BACKGROUND Hip fractures account for 23.8%of all fractures in patients over the age of 75 years.More than half of these patients are older than 80 years.Bipolar hemiarthroplasty(BHA)was established as an effective man...BACKGROUND Hip fractures account for 23.8%of all fractures in patients over the age of 75 years.More than half of these patients are older than 80 years.Bipolar hemiarthroplasty(BHA)was established as an effective management option for these patients.Various approaches can be used for the BHA procedure.However,there is a high risk of postoperative dislocation.The conjoined tendon-preserving posterior(CPP)lateral approach was introduced to reduce postoperative dislocation rates.AIM To evaluate the effectiveness and safety of the CPP lateral approach for BHA in elderly patients.METHODS We retrospectively analyzed medical data from 80 patients with displaced femoral neck fractures who underwent BHA.The patients were followed up for at least 1 year.Among the 80 patients,57(71.3%)were female.The time to operation averaged 2.3 d(range:1-5 d).The mean age was 80.5 years(range:67-90 years),and the mean body mass index was 24.9 kg/m^(2)(range:17-36 kg/m^(2)).According to the Garden classification,42.5%of patients were typeⅢand 57.5%of patients were typeⅣ.Uncemented bipolar hip prostheses were used for all patients.Torn conjoined tendons,dislocations,and adverse complications during and after surgery were recorded.RESULTS The mean postoperative follow-up time was 15.3 months(range:12-18 months).The average surgery time was 52 min(range:40-70 min)with an average blood loss of 120 mL(range:80-320 mL).The transfusion rate was 10%(8 of 80 patients).The gemellus inferior was torn in 4 patients(5%),while it was difficult to identify in 2 patients(2.5%)during surgery.The posterior capsule was punctured by the fractured femoral neck in 3 patients,but the conjoined tendon and the piriformis tendon remained intact.No patients had stem varus greater than 3 degrees or femoral fracture.There were no patients with stem subsidence more than 5 mm at the last follow-up.No postoperative dislocations were observed throughout the follow-up period.No significance was found between preoperative and postoperative mean Health Service System scores(87.30±2.98 vs 86.10±6.10,t=1.89,P=0.063).CONCLUSION The CPP lateral approach can effectively reduce the incidence of postoperative dislocation without increasing perioperative complications.For surgeons familiar with the posterior lateral approach,there is no need for additional surgical instruments,and it does not increase surgical difficulty.展开更多
Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early d...Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early detection and geneticallyfocused treatment of neonatal diabetes and maturity-onset diabetes of theyoung can significantly improve long-term health and well-being. The etiology ofmonogenic diabetes in childhood is primarily attributed to genetic variationsaffecting the regulatory genes responsible for beta-cell activity. In rare instances,mutations leading to severe insulin resistance can also result in the developmentof diabetes. Individuals diagnosed with specific types of monogenic diabetes,which are commonly found, can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguishindividuals with type 1 or 2 diabetes from those more prone to monogenicdiabetes. Genetic screening with appropriate findings and interpretations isessential to establish a prognosis and to guide the choice of therapies andmanagement of these interrelated ailments. This review aims to design a comprehensiveliterature summarizing genetic insights into monogenetic diabetes inchildren and adolescents as well as summarizing their diagnosis and management.展开更多
Diabetes mellitus (DM) is a chronic metabolic condition characterized predominantlyby hyperglycemia. The most common causes contributing to the pathophysiologyof diabetes are insufficient insulin secretion, resistance...Diabetes mellitus (DM) is a chronic metabolic condition characterized predominantlyby hyperglycemia. The most common causes contributing to the pathophysiologyof diabetes are insufficient insulin secretion, resistance to insulin’stissue-acting effects, or a combination of both. Over the last 30 years, the globalprevalence of diabetes increased from 4% to 6.4%. If no better treatment or cure isfound, this amount might climb to 430 million in the coming years. The major fact-ors of the disease’s deterioration include age, obesity, and a sedentary lifestyle.Finding new therapies to manage diabetes safely and effectively without jeopardizingpatient compliance has always been essential. Among the medicationsavailable to manage DM on this journey are glucagon-like peptide-1 agonists,thiazolidinediones, sulphonyl urease, glinides, biguanides, and insulin-targetingreceptors discovered more than 10 years ago. Despite the extensive preliminarystudies, a few clinical observations suggest this process is still in its early stages.The present review focuses on targets that contribute to insulin regulation andmay be employed as targets in treating diabetes since they may be more efficientand secure than current and traditional treatments.展开更多
BACKGROUND Parathyroid carcinoma(PC)is a rare,slow-growing malignant tumor and a rare cause of primary hyperfunctioning of the parathyroid,with a highly variable clinical course,depending on the aggressiveness of the ...BACKGROUND Parathyroid carcinoma(PC)is a rare,slow-growing malignant tumor and a rare cause of primary hyperfunctioning of the parathyroid,with a highly variable clinical course,depending on the aggressiveness of the individual tumor and the degree of hypercalcemia.CASE SUMMARY The aim of this report is to summarize the diagnosis and treatment of three cases of PC and to review and conclude aspects regarding the three collected cases with reference to other relevant cases to explore the value of ultrasound in the diagnosis of PC.All three patients had hypercalcemia,consisting of a high serum calcium level and a high level of parathyroid hormone that was>2-fold(even>30-fold)of the normal upper limit.The ultrasonographic findings of the parathyroid gland showed that the glands were all>30 mm,and the internal echo was uneven.All patients underwent surgery.PC in three cases was confirmed by routine histopathology and immunohistochemistry.CONCLUSION As clinical signs and laboratory results are nonspecific,it is difficult to diagnose PC preoperatively,so imaging examinations are often needed.展开更多
Background:It has been demonstrated that thymosinβ4(Tβ4)could inflect the severity of acute-on-chronic hepatitis B liver failure(ACHBLF),but the relationship between its methylation status and the prognosis of liver...Background:It has been demonstrated that thymosinβ4(Tβ4)could inflect the severity of acute-on-chronic hepatitis B liver failure(ACHBLF),but the relationship between its methylation status and the prognosis of liver failure is not clear.This study aimed to determine Tβ4 promoter methylation status in patients with ACHBLF and to evaluate its prognostic value.Methods:The study recruited 115 patients with ACHBLF,80 with acute-on-chronic hepatitis B pre-liver failure(pre-ACHBLF),and 86 with chronic hepatitis B(CHB).In addition,there were 36 healthy controls(HCs)from the Department of Hepatology,Qilu Hospital of Shandong University.The 115 patients with ACHBLF were divided into three subgroups:33 with early stage ACHBLF(E-ACHBLF),42 with mid-stage ACHBLF(M-ACHBLF),and 40 with advanced stage ACHBLF(A-ACHBLF).Tβ4 promoter methylation status in peripheral blood mononuclear cells(PBMCs)was measured by methylation-specific polymerase chain reaction,and mRNA was detected by quantitative real-time polymerase chain reaction.Results:Methylation frequency of Tβ4 was significantly higher in patients with ACHBLF than in those with pre-ACHBLF,CHB or HCs.However,expression of Tβ4 mRNA showed the opposite trend.In patients with ACHBLF,Tβ4 promoter methylation status correlated negatively with mRNA levels.The 3-month mortality of ACHBLF in the methylated group was significantly higher than that in the unmethylated group.Also,Tβ4 promoter methylation frequency was lower in survivors than in non-survivors.When used to predict the 1-,2-,and 3-month incidence of ACHBLF,Tβ4 methylation status was better than the model for end-stage liver disease(MELD)score.The predictive value of Tβ4 methylation was higher than that of MELD score for the mortality of patients with E-ACHBLF and M-ACHBLF,but not for A-ACHBLF.Conclusions:Tβ4 methylation might be an important early marker for predicting disease incidence and prognosis in patients with ACHBLF.展开更多
BACKGROUND Impaired glucose tolerance(IGT)is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes.When IGT occurs,insulin sensitivity decreases,causing a redu...BACKGROUND Impaired glucose tolerance(IGT)is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes.When IGT occurs,insulin sensitivity decreases,causing a reduction in insulin secretion and an increase in glucagon secretion.Recently,vascular endothelial growth factor B(VEGFB)has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity.Therefore,we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion,thus contributing to the prevention and cure of prediabetes.AIM To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT.METHODS We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression.Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay,and the protein expression of phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)was determined using western blot.Further,mRNA expression of forkhead box protein O1,phosphoenolpyruvate carboxykinase,and glucose-6 phosphatase was detected via quantitative polymerase chain reaction,and the correlation between the expression of proteins was analyzed via bioinformatics.RESULTS In mice with IGT and VEGFB knockout,glucagon secretion increased,and the protein expression of PI3K/AKT decreased dramatically.Further,in mice with VEGFB overexpression,glucagon levels declined,with the activation of the PI3K/AKT signaling pathway.CONCLUSION VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.展开更多
Nonalcoholic fatty liver disease(NAFLD)refers to fatty liver disease caused by liver injury factors other than alcohol.The disease is characterized by diffuse fat infiltration,including simple steatosis(no inflammator...Nonalcoholic fatty liver disease(NAFLD)refers to fatty liver disease caused by liver injury factors other than alcohol.The disease is characterized by diffuse fat infiltration,including simple steatosis(no inflammatory fat deposition),nonalcoholic fatty hepatitis,liver fibrosis,and so on,which may cause liver cirrhosis,liver failure,and even liver cancer in the later stage of disease progression.At present,the pathogenesis of NAFLD is still being studied.The"two-hit"theory,represented by lipid metabolism disorder and inflammatory reactions,is gradually enriched by the"multiple-hit"theory,which includes multiple factors,such as insulin resistance and adipocyte dysfunction.In recent years,vascular endothelial growth factor B(VEGFB)has been reported to have the potential to regulate lipid metabolism and is expected to become a novel target for ameliorating metabolic diseases,such as obesity and type 2 diabetes.This review summarizes the regulatory role of VEGFB in the onset and development of NAFLD and illustrates its underlying molecular mechanism.In conclusion,the signaling pathway mediated by VEGFB in the liver may provide an innovative approach to the diagnosis and treatment of NAFLD.展开更多
Objective:To observe the anti-tumor effect of matrine combined with cisplatin on U14 rat models of cervical cancer.Methods:A total of 80 female Kunming rats were used to establish U14 rat models of cervical cancer and...Objective:To observe the anti-tumor effect of matrine combined with cisplatin on U14 rat models of cervical cancer.Methods:A total of 80 female Kunming rats were used to establish U14 rat models of cervical cancer and then divided into groups Ⅰ,Ⅱ,Ⅲ and Ⅳ,with 20 rats in each.For Group Ⅰ,the control group,injection of normal saline was given around the tumors.For Group Ⅱ,injection of 2 mg/kg cisplatin was given around the tumors.For Group Ⅲ,injection of 75 mg/kg matrine was given around the tumors while the combined injection of matrine and cisplatin was given for Group Ⅳ with the same doses as Groups Ⅱand Ⅲ.The animals were sacrificed 10 d after the injection and tumors were taken out for the comparisons of tumor weights after injection and calculation of anti-tumor rates,while thymus and spleen were taken for thymus index and spleen index.Blood in eyeball was collected for determination of changes in serum creatinine and urea nitrogen levels.Sections of tumor issue were prepared and morphological changes in tumor tissue cells were observed by using immunohistochemistry technique.Results:After injection,the thymus index and spleen index in Groups Ⅲ and Ⅳ were significantly higher than those in Groups Ⅰ and Ⅱ(P<0.05)while the two indexes in Group Ⅱ were significantly lower than Group Ⅰ(P<0.05).The tumor weights in Groups Ⅱ and Ⅳ were significantly smaller than those in Groups Ⅰ and Ⅲ(P<0.05) with significantly higher anti-tumor rates than Groups Ⅰ and Ⅲ(P<0.05).The serum creatinine and urea nitrogen levels in Groups Ⅲ and Ⅳ were significantly lower than Group Ⅱ(P<0.05) and the two indicators in Group Ⅲ were significantly lower than those in Group Ⅳ(P<0.05).The observation under the histological microscope showed densely arranged tumor cells in Group Ⅰ,growing as a crumby structure and diffuse appearance,with hyperchromatic and large nuclei,and abundant cytoplasm.In the case of Group Ⅱ,it showed less tumor cells,with extensive degenerative necrosis,sparse arrangement and karyopyknosis as well as karyoclasis.For Group Ⅲ,necrosis of tumor cells in different sizes and heterogeneous color in nuclei were observed.For Group Ⅳ,the number of tumor cells was significantly smaller than Groups Ⅰ and Ⅲ and the tumor cells presented an appearance of crumby structure as cancer nests,with more proliferation of connective tissue.Conclusions:The treatment of matrine combined with cisplatin can significantly improve the anti-tumor effect on U14 rats with cervical cancer,which can be a new option for the treatment for cervical cancer.展开更多
BACKGROUND The prevalence of type 2 diabetes mellitus(T2DM)is rising rapidly in rural areas,and lifestyle interventions can effectively reduce the blood glucose levels of patients with T2DM.However,current dietary and...BACKGROUND The prevalence of type 2 diabetes mellitus(T2DM)is rising rapidly in rural areas,and lifestyle interventions can effectively reduce the blood glucose levels of patients with T2DM.However,current dietary and exercise guidelines are still at experimental stages and are difficult for subjects to understand and implement.The Human Metabolism Analyzer provides real life interventions for the prevention and treatment of T2DM,and our pilot research has demonstrated its effectiveness and good compliance.AIM To investigate the effect of and compliance with lifestyle interventions in rural patients with T2DM.METHODS A total of ten rural villages were randomly selected in Chaoshui Township,Penglai City,Shandong Province,China,to conduct health screening among residents aged 50 years or older.Each rural village represented a group,and 12 patients with T2DM were randomly selected from each group(total:120)to participate in this study and receive real life lifestyle interventions and medication guidance.Lifestyle interventions included changing the meal order(A),postprandial activities(B),resistance exercise(C),and reverse abdominal breathing(D).Diabetes education was conducted at least once a month with a weekly phone follow-up to monitor exercise and diet.Waist circumference,blood pressure,body mass index(BMI),motor function,body composition,fasting blood glucose,and glycated hemoglobin(HbA1c)were analyzed before and 3 mo after the intervention.Moreover,patient compliance and adjustments of hypoglycemic drugs were evaluated.RESULTS A total of 109 subjects completed the study.The compliance rates for lifestyle interventions A,B,C,and D were 57.79%,60.55%,64.22%,and 75.23%,respectively.Among the subjects who received hypoglycemic drugs,the dose was reduced 2 to 3 times based on blood glucose in 54(67.50%)subjects and was tapered and discontinued in 5(6.25%)subjects within 3 mo,with no significant fluctuations in blood glucose after dose reduction and withdrawal.After lifestyle interventions,waist circumference,BMI,fasting blood glucose,and HbA1c significantly decreased(P<0.001);motor function and body composition also significantly improved(P<0.001).CONCLUSION For patients with T2DM,compliance to real-life lifestyle interventions is good,and the interventions significantly improve metabolic indicators such as waist circumference,BMI,blood pressure,HbA1c,body composition,and motor function.Some patients are able to taper or discontinue hypoglycemic drugs.展开更多
AIM: To investigate the relationship between ARID1 A expression and clinicopathologic parameters, as well as its prognostic value, for patients with intrahepatic cholangiocarcinoma(IHCC).METHODS: We assessed ARID1 A p...AIM: To investigate the relationship between ARID1 A expression and clinicopathologic parameters, as well as its prognostic value, for patients with intrahepatic cholangiocarcinoma(IHCC).METHODS: We assessed ARID1 A protein and m RNA expression in IHCC tissues and paracarcinomatous(PC) tissues from 57 patients with IHCC using western blot and quantitative real-time reverse transcription polymerase chain reaction, respectively. We used Fisher's exact and χ2 tests to analyze relationships between clinicopathological parameters and ARID1 A expression. The Kaplan-Meier method and Cox regression were used to analyze survival.RESULTS: The mean ARID1 A protein level in IHCC tissues was 1.16 ± 0.36 relative units(RU), which was significantly lower than that in PC tissues(1.26 ± 0.21 RU, P < 0.01) and NL tissues(1.11 ± 0.31, P < 0.001).The mean ARID1 A m RNA level in IHCC tissues(1.20 ± 0.18) was also lower than that in PC tissues(1.27 ± 0.15, P < 0.001) and normal liver tissues(1.15 ± 0.34, P < 0.001). Low ARID1 A expression was significantly associated with tumor nodules, vein invasion, and recurrence. Median overall survival(OS) and disease-free survival(DFS) for the low ARID1 A expression group was 15.0 and 7.0 mo, respectively, which were significantly shorter than those for the high ARID1 A expression group at 25.0 and 22.0 mo(OS: P < 0.01; DFS: P < 0.001), respectively. Low ARID1 A expression was significantly associated with worse OS(HR = 3.967, 95%CI: 1.299-12.118, P = 0.016) in multivariate analyses.CONCLUSION: Low expression of ARID1 A is associated with poor prognosis in patients with IHCC, and thus may be a potential prognostic biomarker candidate in IHCC.展开更多
Objective: To study the preventive and therapeutic effect of N-Acetyl-L-cysteine on infection-associated preterm labor in mice. Methods: A total of 66 C57BL/6 inbred strain pregnant mice were selected and randomly div...Objective: To study the preventive and therapeutic effect of N-Acetyl-L-cysteine on infection-associated preterm labor in mice. Methods: A total of 66 C57BL/6 inbred strain pregnant mice were selected and randomly divided into groups A, B and C, with 22 cases in each group. Group A, B and C were regarded as model group, prevention group and treatment group, respectively. The model of infection-associated preterm labor was built by intraperitoneal injection of Escherichia coli. Ten mice of each group were taken and observed the preterm birth rates and live birth rates, respectively. Three mice of each group were killed at 3 h, 6 h, 12 h and 24 h after building the model. Their uterus tissues were collected and the expressions of the AP-1 and MCP-1 in those tissues were assayed with immunohistochemical method and the expressions of NF- kappa Bp65 and TNF- protein in the placenta tissues of those mice were also detected with immunohistochemical method. Results: The pretem: birth rates of mice in groups B and C were significantly lower than that in group A, while their live birth rates were distinctly higher than that in group A (P<0.05); the expressions of the AP-1 and MCP-1 in the uterus tissues and NF- kappa Bp65 and TNF- protein in the placenta tissues of mice in groups B and C were evidently lower than those in group A (P<0.05); the comparison of the expressions of the NF- kappa Bp65 and TNF- between group B and C showed no statistical differences (P>0.05). Conclusions: N-Acetyl-L-cysteine can lower the incidence rate of infection-associated preterm labor by prohibiting the activation of the protein AP-1/MCP-1 and decreasing the expression of NF- kappa Bp65 and TNF- in the pregnant tissues of premature mice to reduce the inflammatory reactions.展开更多
AIM: To compare kinesin family member 1B(KIF1B) expression with clinicopathologic parameters and prognosis in hepatocellular carcinoma(HCC) patients.METHODS: KIF1 B protein and m RNA expression was assessed in HCC and...AIM: To compare kinesin family member 1B(KIF1B) expression with clinicopathologic parameters and prognosis in hepatocellular carcinoma(HCC) patients.METHODS: KIF1 B protein and m RNA expression was assessed in HCC and paracarcinomatous(PC) tissues from 68 patients with HCC using Western blot and quantitative real-time reverse transcription-PCR, respectively. Student's t-tests were used to analyze relationships between clinicopathologic parameters and KIF1 B expression, the Kaplan-Meier method was used to analyze survival outcomes, and the log-rank test was used to compare survival differences between groups.RESULTS: Mean protein and m RNA levels of KIF1 B were similar between HCC and PC tissues. However, HCC tissues with vein invasions had significantly lower KIF1 B protein levels compared to those without vein invasions(2.30 ± 0.82 relative units vs 2.77 ± 0.84 relative units, P < 0.05). KIF1 B protein levels in HCC tissues from patients with recurrence during the followup period were significantly lower than those without recurrence(2.31 ± 0.92 relative units vs 2.80 ± 0.80 relative units, P < 0.05). However, KIF1 B protein and m RNA expression in HCC patients was not associated with other clinicopathologic parameters. Ratios of KIF1 B m RNA expression in HCC tissues to those in PC tissues were correlated with overall survival(13.5 mo vs 20.0 mo, P < 0.05) and disease-free survival(11.5 mo vs 19.5 mo, P < 0.05).CONCLUSION: Downregulation of KIF1 B in HCC tissues is associated with poor prognosis; additional clinical studies are needed to confirm whether KIF1 B can serve as a prognostic marker.展开更多
BACKGROUND Osteoarthritis is a major source of pain,disability,and socioeconomic cost worldwide.Osteonecrosis is a disabling disorder that frequently occurs in the younger population aged from 20-50 years.The compound...BACKGROUND Osteoarthritis is a major source of pain,disability,and socioeconomic cost worldwide.Osteonecrosis is a disabling disorder that frequently occurs in the younger population aged from 20-50 years.The compound Eucommia bone tonic granules,a traditional Chinese medicine,can alleviate the damage of osteoarthritis and osteonecrosis.AIM To investigate the potential role of the compound Eucommia bone tonic granules(Eucommia)in the treatment of patients with osteoarthritis and osteonecrosis.METHODS One-hundred forty osteoarthritis and osteonecrosis cases admitted to our hospital from January 2013 to December 2017 were selected.Patients were divided into two groups:Eucommia-meloxicam group and meloxicam group.Clinical efficacy and the Western Ontario and McMaster Universities Arthritis Index(WOMAC)score were evaluated according to the evaluation criteria of orthopedic diseases.The levels of bone-GLA protein,interleukin-17,recombinant human S100 calcium binding protein A12,sphingosine 1-phosphate,cystatin C,creatinine,and hemoglobin in peripheral blood were determined.RESULTS The total effective rate in the two osteoarthritis groups was not different,but the total effective rate in the two osteonecrosis groups was significantly different.The overall efficacy of Eucommia-meloxicam group was superior to that of the meloxicam group.WOMAC showed that pain,stiffness,and dysfunction in the two groups of osteoarthritis and osteonecrosis before and after treatment were significantly different.The concentration of recombinant human S100 calcium binding protein A12,sphingosine 1-phosphate,cystatin C,creatinine,and hemoglobin before and after treatment in the Eucommia-meloxicam group and meloxicam group of osteoarthritis and osteonecrosis were significantly different,and the two treatment groups were significantly different from each other for osteoarthritis.CONCLUSION Our findings indicate that Eucommia can effectively enhance the curative effect of meloxicam,and the combination of Eucommia and meloxicam is superior to meloxicam alone.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a major cause of cancer-related mortality worldwide.Transcatheter arterial chemoembolization(TACE)has been performed as a palliative treatment for patients with HCC.However,H...BACKGROUND Hepatocellular carcinoma(HCC)is a major cause of cancer-related mortality worldwide.Transcatheter arterial chemoembolization(TACE)has been performed as a palliative treatment for patients with HCC.However,HCC is easy to recur after TACE.Magnetic resonance imaging(MRI)has clinical potential in evaluating the TACE treatment effect for patients with liver cancer.However,traditional MRI has some limitations.AIM To explore the clinical potential of diffusion kurtosis imaging(DKI)in predicting recurrence and cellular invasion of the peritumoral liver zone of HCC after TACE.METHODSSeventy-six patients with 82 HCC nodules were recruited in this study and underwent DKI afterTACE. According to pathological examinations or the overall modified response evaluationcriteria in solid tumors (mRECIST) criterion, 48 and 34 nodules were divided into true progressionand pseudo-progression groups, respectively. The TACE-treated area, peritumoral liver zone, andfar-tumoral zone were evaluated on DKI-derived metric maps. Non-parametric U test and receiveroperating characteristic curve (ROC) analysis were used to evaluate the prediction performance ofeach DKI metric between the two groups. The independent t-test was used to compare each DKImetric between the peritumoral and far-tumoral zones of the true progression group.RESULTSDKI metrics, including mean diffusivity (MD), axial diffusivity (DA), radial diffusivity (DR), axialkurtosis (KA), and anisotropy fraction of kurtosis (Fak), showed statistically different valuesbetween the true progression and pseudo-progression groups (P < 0.05). Among these, MD, DA,and DR values were higher in pseudo-progression lesions than in true progression lesions,whereas KA and FAk values were higher in true progression lesions than in pseudo-progressionlesions. Moreover, for the true progression group, the peritumoral zone showed significantlydifferent DA, DR, KA, and FAk values from the far-tumoral zone. Furthermore, MD values of theliver parenchyma (peritumoral and far-tumoral zones) were significantly lower in the trueprogression group than in the pseudo-progression group (P < 0.05).CONCLUSIONDKI has been demonstrated with robust performance in predicting the therapeutic response ofHCC to TACE. Moreover, DKI might reveal cellular invasion of the peritumoral zone by moleculardiffusion-restricted change.展开更多
BACKGROUND Type 2 diabetes(T2 D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance,resulting in an increase in blood glucose.However,the mechanism...BACKGROUND Type 2 diabetes(T2 D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance,resulting in an increase in blood glucose.However,the mechanism involved in this lack of insulin secretion is unclear.The level of vascular endothelial growth factor B(VEGF-B) is significantly increased in T2 D patients.The inactivation of VEGF-B could restore insulin sensitivity in db/db mice by reducing fatty acid accumulation.It is speculated that VEGF-B is related to pancreatic β-cell dysfunction and is an important factor affecting β-cell secretion of insulin.As an in vitro model of normal pancreatic β-cells,the MIN6 cell line can be used to analyze the mechanism of insulin secretion and related biological effects.AIM To study the role of VEGF-B in the insulin secretion signaling pathway in MIN6 cells and explore the effect of VEGF-B on blood glucose regulation.METHODS The MIN6 mouse pancreatic islet β-cell line was used as the model system.By administering exogenous VEGF-B protein or knocking down VEGF-B expression in MIN6 cells,we examined the effects of VEGF-B on insulin secretion,Ca2+ and cyclic adenosine monophosphate(cAMP) levels,and the insulin secretion signaling pathway.RESULTS Exogenous VEGF-B inhibited the secretion of insulin and simultaneously reduced the levels of Ca2+ and cAMP in MIN6 cells.Exogenous VEGF-B also reduced the expression of phospholipase C gamma 1(PLCγ1),phosphatidylinositol 3-kinase(PI3 K),serine/threonine kinase(AKT),and other proteins in the insulin secretion pathway.Upon knockdown of VEGF-B,MIN6 cells exhibited increased insulin secretion and Ca2+ and cAMP levels and upregulated expression of PLCγ1,PI3 K,AKT,and other proteins.CONCLUSION VEGF-B can regulate insulin secretion by modulating the levels of Ca2+ and cAMP.VEGF-B involvement in insulin secretion is related to the expression of PLCγ1,PI3 K,AKT,and other signaling proteins.These results provide theoretical support and an experimental basis for the study of VEGF-B in the pathogenesis of T2 D.展开更多
BACKGROUND Multiple system atrophy(MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15(GDF15) is i...BACKGROUND Multiple system atrophy(MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15(GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA.AIM To determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson’s disease(PD) patients and healthy controls.METHODS A case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzymelinked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysiswas used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD.RESULTS Serum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls(P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels(P = 0.043 and 0.000;respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients(cutoff: 470.42 pg/m L, sensitivity: 85.7%, specificity: 88.0%;cutoff: 1075.91 pg/m L, sensitivity:51.0%, specificity: 96.0%;respectively).CONCLUSION Serum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.展开更多
In this study, we treated PC12 cells with 0-20 μM amyloid-β peptide (25-35) for 24 hours to induce cytotoxicity, and found that 5-20 μM amyloid-β peptide (25-35) decreased PC12 cell viability, but adenosine tr...In this study, we treated PC12 cells with 0-20 μM amyloid-β peptide (25-35) for 24 hours to induce cytotoxicity, and found that 5-20 μM amyloid-β peptide (25-35) decreased PC12 cell viability, but adenosine triphosphate-sensitive potassium channel activator diazoxide suppressed the decrease in PC12 cell viability induced by amyloid-β peptide (25-35). Diazoxide protected PC12 cells against amyloid-β peptide (25-35)-induced increases in mitochondrial membrane potential and intracellular reactive oxygen species levels. These protective effects were reversed by the selective mitochondrial adenosine triphosphate-sensitive potassium channel blocker 5-hydroxydecanoate. An inducible nitric oxide synthase inhibitor, Nw-nitro-L-arginine, also protected PC12 cells from amyloid-β peptide (25-35)-induced increases in both mitochondrial membrane potential and intracellular reactive oxygen species levels. However, the H202-degrading enzyme catalase could not reverse the amyloid-β peptide (25-35)-induced increase in intracellular reactive oxygen species. A 24-hour exposure to amyloid-13 peptide (25-35) did not result in apoptosis or necrosis, suggesting that the increases in both mitochondrial membrane potential and reactive oxygen species levels preceded cell death. The data suggest that amyloid-β peptide (25-35) cytotoxicity is associated with adenosine triphosphate-sensitive potassium channels and nitric oxide. Regulation of adenosine triphosphate-sensitive potassium channels suppresses PC12 cell cytotoxicity induced by amyloid-β peptide (25-35).展开更多
BACKGROUND: Dysfunction of knee joint is a common sequela after fracture of femur. The key of avoiding or decreasing dysfunction lies in early prevention, muscular practices of isometric contraction and functional exe...BACKGROUND: Dysfunction of knee joint is a common sequela after fracture of femur. The key of avoiding or decreasing dysfunction lies in early prevention, muscular practices of isometric contraction and functional exercises of knee joint as soon as possible. It is an essential component part of rehabilitation care for functional recovery of patients with fracture of femur.展开更多
Insulin resistance(IR)is the common pathophysiological basis of many metabolic diseases.IR is characterized by decreased glucose uptake in skeletal muscle and adipose tissue,especially in skeletal muscle.Skeletal musc...Insulin resistance(IR)is the common pathophysiological basis of many metabolic diseases.IR is characterized by decreased glucose uptake in skeletal muscle and adipose tissue,especially in skeletal muscle.Skeletal muscle is the main target tissue of glucose uptake under insulin stimulation.Glucose uptake by skeletal muscle is complex,and it is controlled by many pathways.The PI3K/AKt/GSK-1 signaling pathway is not only the main pathway for insulin signal transduction but also an important mechanism for regulating blood glucose.From the binding of insulin to its receptors on the surface of target cells to the transportation of glucose from extracellular fluid to skeletal muscle,a series of signal transduction processes is completed,any of which potentially affects the physiological effects of insulin and leads to IR.Resistance exercise(RT)can reduce skeletal muscle IR and effectively improve blood glucose control and glycosylated hemoglobin level in patients with type 2 diabetes mellitus(T2DM).However,the exact mechanism by which RT improves skeletal muscle IR remains unclear.Therefore,this paper discusses the above problems by tracking the progress of the literature to deepen the correlation between RT and skeletal muscle insulin sensitivity and provide further evidence for the application of exercise therapy in IR.In conclusion,RT mainly improves insulin sensitivity of skeletal muscle by increasing muscle mass,microvascular blood flow,and glucose transporter-4 expression in skeletal muscle,as well as by reducing lipid accumulation and inflammation in skeletal muscle.Thus,it is potentially useful in the prevention and treatment of T2DM.展开更多
文摘BACKGROUND Hip fractures account for 23.8%of all fractures in patients over the age of 75 years.More than half of these patients are older than 80 years.Bipolar hemiarthroplasty(BHA)was established as an effective management option for these patients.Various approaches can be used for the BHA procedure.However,there is a high risk of postoperative dislocation.The conjoined tendon-preserving posterior(CPP)lateral approach was introduced to reduce postoperative dislocation rates.AIM To evaluate the effectiveness and safety of the CPP lateral approach for BHA in elderly patients.METHODS We retrospectively analyzed medical data from 80 patients with displaced femoral neck fractures who underwent BHA.The patients were followed up for at least 1 year.Among the 80 patients,57(71.3%)were female.The time to operation averaged 2.3 d(range:1-5 d).The mean age was 80.5 years(range:67-90 years),and the mean body mass index was 24.9 kg/m^(2)(range:17-36 kg/m^(2)).According to the Garden classification,42.5%of patients were typeⅢand 57.5%of patients were typeⅣ.Uncemented bipolar hip prostheses were used for all patients.Torn conjoined tendons,dislocations,and adverse complications during and after surgery were recorded.RESULTS The mean postoperative follow-up time was 15.3 months(range:12-18 months).The average surgery time was 52 min(range:40-70 min)with an average blood loss of 120 mL(range:80-320 mL).The transfusion rate was 10%(8 of 80 patients).The gemellus inferior was torn in 4 patients(5%),while it was difficult to identify in 2 patients(2.5%)during surgery.The posterior capsule was punctured by the fractured femoral neck in 3 patients,but the conjoined tendon and the piriformis tendon remained intact.No patients had stem varus greater than 3 degrees or femoral fracture.There were no patients with stem subsidence more than 5 mm at the last follow-up.No postoperative dislocations were observed throughout the follow-up period.No significance was found between preoperative and postoperative mean Health Service System scores(87.30±2.98 vs 86.10±6.10,t=1.89,P=0.063).CONCLUSION The CPP lateral approach can effectively reduce the incidence of postoperative dislocation without increasing perioperative complications.For surgeons familiar with the posterior lateral approach,there is no need for additional surgical instruments,and it does not increase surgical difficulty.
文摘Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early detection and geneticallyfocused treatment of neonatal diabetes and maturity-onset diabetes of theyoung can significantly improve long-term health and well-being. The etiology ofmonogenic diabetes in childhood is primarily attributed to genetic variationsaffecting the regulatory genes responsible for beta-cell activity. In rare instances,mutations leading to severe insulin resistance can also result in the developmentof diabetes. Individuals diagnosed with specific types of monogenic diabetes,which are commonly found, can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguishindividuals with type 1 or 2 diabetes from those more prone to monogenicdiabetes. Genetic screening with appropriate findings and interpretations isessential to establish a prognosis and to guide the choice of therapies andmanagement of these interrelated ailments. This review aims to design a comprehensiveliterature summarizing genetic insights into monogenetic diabetes inchildren and adolescents as well as summarizing their diagnosis and management.
文摘Diabetes mellitus (DM) is a chronic metabolic condition characterized predominantlyby hyperglycemia. The most common causes contributing to the pathophysiologyof diabetes are insufficient insulin secretion, resistance to insulin’stissue-acting effects, or a combination of both. Over the last 30 years, the globalprevalence of diabetes increased from 4% to 6.4%. If no better treatment or cure isfound, this amount might climb to 430 million in the coming years. The major fact-ors of the disease’s deterioration include age, obesity, and a sedentary lifestyle.Finding new therapies to manage diabetes safely and effectively without jeopardizingpatient compliance has always been essential. Among the medicationsavailable to manage DM on this journey are glucagon-like peptide-1 agonists,thiazolidinediones, sulphonyl urease, glinides, biguanides, and insulin-targetingreceptors discovered more than 10 years ago. Despite the extensive preliminarystudies, a few clinical observations suggest this process is still in its early stages.The present review focuses on targets that contribute to insulin regulation andmay be employed as targets in treating diabetes since they may be more efficientand secure than current and traditional treatments.
文摘BACKGROUND Parathyroid carcinoma(PC)is a rare,slow-growing malignant tumor and a rare cause of primary hyperfunctioning of the parathyroid,with a highly variable clinical course,depending on the aggressiveness of the individual tumor and the degree of hypercalcemia.CASE SUMMARY The aim of this report is to summarize the diagnosis and treatment of three cases of PC and to review and conclude aspects regarding the three collected cases with reference to other relevant cases to explore the value of ultrasound in the diagnosis of PC.All three patients had hypercalcemia,consisting of a high serum calcium level and a high level of parathyroid hormone that was>2-fold(even>30-fold)of the normal upper limit.The ultrasonographic findings of the parathyroid gland showed that the glands were all>30 mm,and the internal echo was uneven.All patients underwent surgery.PC in three cases was confirmed by routine histopathology and immunohistochemistry.CONCLUSION As clinical signs and laboratory results are nonspecific,it is difficult to diagnose PC preoperatively,so imaging examinations are often needed.
基金supported by grants from the Key Project of the Chinese Ministry of Science and Technology(2017ZX102022022)the National Natural Science Foundation of China(81970522)the Key Research and Development Project of Shandong Province(2019GSF108023).
文摘Background:It has been demonstrated that thymosinβ4(Tβ4)could inflect the severity of acute-on-chronic hepatitis B liver failure(ACHBLF),but the relationship between its methylation status and the prognosis of liver failure is not clear.This study aimed to determine Tβ4 promoter methylation status in patients with ACHBLF and to evaluate its prognostic value.Methods:The study recruited 115 patients with ACHBLF,80 with acute-on-chronic hepatitis B pre-liver failure(pre-ACHBLF),and 86 with chronic hepatitis B(CHB).In addition,there were 36 healthy controls(HCs)from the Department of Hepatology,Qilu Hospital of Shandong University.The 115 patients with ACHBLF were divided into three subgroups:33 with early stage ACHBLF(E-ACHBLF),42 with mid-stage ACHBLF(M-ACHBLF),and 40 with advanced stage ACHBLF(A-ACHBLF).Tβ4 promoter methylation status in peripheral blood mononuclear cells(PBMCs)was measured by methylation-specific polymerase chain reaction,and mRNA was detected by quantitative real-time polymerase chain reaction.Results:Methylation frequency of Tβ4 was significantly higher in patients with ACHBLF than in those with pre-ACHBLF,CHB or HCs.However,expression of Tβ4 mRNA showed the opposite trend.In patients with ACHBLF,Tβ4 promoter methylation status correlated negatively with mRNA levels.The 3-month mortality of ACHBLF in the methylated group was significantly higher than that in the unmethylated group.Also,Tβ4 promoter methylation frequency was lower in survivors than in non-survivors.When used to predict the 1-,2-,and 3-month incidence of ACHBLF,Tβ4 methylation status was better than the model for end-stage liver disease(MELD)score.The predictive value of Tβ4 methylation was higher than that of MELD score for the mortality of patients with E-ACHBLF and M-ACHBLF,but not for A-ACHBLF.Conclusions:Tβ4 methylation might be an important early marker for predicting disease incidence and prognosis in patients with ACHBLF.
基金Supported by the National Natural Science Foundation of China,No.31771284Basic Research Project of Yantai Science and Technology Innovation and Development Plan,No.2022JCYJ026+1 种基金Natural Science Foundation of Shandong province,No.ZR202111250163Yantai Science and Technology Plan Project,No.2022YD062.
文摘BACKGROUND Impaired glucose tolerance(IGT)is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes.When IGT occurs,insulin sensitivity decreases,causing a reduction in insulin secretion and an increase in glucagon secretion.Recently,vascular endothelial growth factor B(VEGFB)has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity.Therefore,we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion,thus contributing to the prevention and cure of prediabetes.AIM To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT.METHODS We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression.Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay,and the protein expression of phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)was determined using western blot.Further,mRNA expression of forkhead box protein O1,phosphoenolpyruvate carboxykinase,and glucose-6 phosphatase was detected via quantitative polymerase chain reaction,and the correlation between the expression of proteins was analyzed via bioinformatics.RESULTS In mice with IGT and VEGFB knockout,glucagon secretion increased,and the protein expression of PI3K/AKT decreased dramatically.Further,in mice with VEGFB overexpression,glucagon levels declined,with the activation of the PI3K/AKT signaling pathway.CONCLUSION VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.
文摘Nonalcoholic fatty liver disease(NAFLD)refers to fatty liver disease caused by liver injury factors other than alcohol.The disease is characterized by diffuse fat infiltration,including simple steatosis(no inflammatory fat deposition),nonalcoholic fatty hepatitis,liver fibrosis,and so on,which may cause liver cirrhosis,liver failure,and even liver cancer in the later stage of disease progression.At present,the pathogenesis of NAFLD is still being studied.The"two-hit"theory,represented by lipid metabolism disorder and inflammatory reactions,is gradually enriched by the"multiple-hit"theory,which includes multiple factors,such as insulin resistance and adipocyte dysfunction.In recent years,vascular endothelial growth factor B(VEGFB)has been reported to have the potential to regulate lipid metabolism and is expected to become a novel target for ameliorating metabolic diseases,such as obesity and type 2 diabetes.This review summarizes the regulatory role of VEGFB in the onset and development of NAFLD and illustrates its underlying molecular mechanism.In conclusion,the signaling pathway mediated by VEGFB in the liver may provide an innovative approach to the diagnosis and treatment of NAFLD.
基金Supported by special program of molecular genetics medicine for women and children's health,National Center for Women and Children's Health.China Centers for Disease Control with Grant No.FY-ZX-ZD-0059
文摘Objective:To observe the anti-tumor effect of matrine combined with cisplatin on U14 rat models of cervical cancer.Methods:A total of 80 female Kunming rats were used to establish U14 rat models of cervical cancer and then divided into groups Ⅰ,Ⅱ,Ⅲ and Ⅳ,with 20 rats in each.For Group Ⅰ,the control group,injection of normal saline was given around the tumors.For Group Ⅱ,injection of 2 mg/kg cisplatin was given around the tumors.For Group Ⅲ,injection of 75 mg/kg matrine was given around the tumors while the combined injection of matrine and cisplatin was given for Group Ⅳ with the same doses as Groups Ⅱand Ⅲ.The animals were sacrificed 10 d after the injection and tumors were taken out for the comparisons of tumor weights after injection and calculation of anti-tumor rates,while thymus and spleen were taken for thymus index and spleen index.Blood in eyeball was collected for determination of changes in serum creatinine and urea nitrogen levels.Sections of tumor issue were prepared and morphological changes in tumor tissue cells were observed by using immunohistochemistry technique.Results:After injection,the thymus index and spleen index in Groups Ⅲ and Ⅳ were significantly higher than those in Groups Ⅰ and Ⅱ(P<0.05)while the two indexes in Group Ⅱ were significantly lower than Group Ⅰ(P<0.05).The tumor weights in Groups Ⅱ and Ⅳ were significantly smaller than those in Groups Ⅰ and Ⅲ(P<0.05) with significantly higher anti-tumor rates than Groups Ⅰ and Ⅲ(P<0.05).The serum creatinine and urea nitrogen levels in Groups Ⅲ and Ⅳ were significantly lower than Group Ⅱ(P<0.05) and the two indicators in Group Ⅲ were significantly lower than those in Group Ⅳ(P<0.05).The observation under the histological microscope showed densely arranged tumor cells in Group Ⅰ,growing as a crumby structure and diffuse appearance,with hyperchromatic and large nuclei,and abundant cytoplasm.In the case of Group Ⅱ,it showed less tumor cells,with extensive degenerative necrosis,sparse arrangement and karyopyknosis as well as karyoclasis.For Group Ⅲ,necrosis of tumor cells in different sizes and heterogeneous color in nuclei were observed.For Group Ⅳ,the number of tumor cells was significantly smaller than Groups Ⅰ and Ⅲ and the tumor cells presented an appearance of crumby structure as cancer nests,with more proliferation of connective tissue.Conclusions:The treatment of matrine combined with cisplatin can significantly improve the anti-tumor effect on U14 rats with cervical cancer,which can be a new option for the treatment for cervical cancer.
文摘BACKGROUND The prevalence of type 2 diabetes mellitus(T2DM)is rising rapidly in rural areas,and lifestyle interventions can effectively reduce the blood glucose levels of patients with T2DM.However,current dietary and exercise guidelines are still at experimental stages and are difficult for subjects to understand and implement.The Human Metabolism Analyzer provides real life interventions for the prevention and treatment of T2DM,and our pilot research has demonstrated its effectiveness and good compliance.AIM To investigate the effect of and compliance with lifestyle interventions in rural patients with T2DM.METHODS A total of ten rural villages were randomly selected in Chaoshui Township,Penglai City,Shandong Province,China,to conduct health screening among residents aged 50 years or older.Each rural village represented a group,and 12 patients with T2DM were randomly selected from each group(total:120)to participate in this study and receive real life lifestyle interventions and medication guidance.Lifestyle interventions included changing the meal order(A),postprandial activities(B),resistance exercise(C),and reverse abdominal breathing(D).Diabetes education was conducted at least once a month with a weekly phone follow-up to monitor exercise and diet.Waist circumference,blood pressure,body mass index(BMI),motor function,body composition,fasting blood glucose,and glycated hemoglobin(HbA1c)were analyzed before and 3 mo after the intervention.Moreover,patient compliance and adjustments of hypoglycemic drugs were evaluated.RESULTS A total of 109 subjects completed the study.The compliance rates for lifestyle interventions A,B,C,and D were 57.79%,60.55%,64.22%,and 75.23%,respectively.Among the subjects who received hypoglycemic drugs,the dose was reduced 2 to 3 times based on blood glucose in 54(67.50%)subjects and was tapered and discontinued in 5(6.25%)subjects within 3 mo,with no significant fluctuations in blood glucose after dose reduction and withdrawal.After lifestyle interventions,waist circumference,BMI,fasting blood glucose,and HbA1c significantly decreased(P<0.001);motor function and body composition also significantly improved(P<0.001).CONCLUSION For patients with T2DM,compliance to real-life lifestyle interventions is good,and the interventions significantly improve metabolic indicators such as waist circumference,BMI,blood pressure,HbA1c,body composition,and motor function.Some patients are able to taper or discontinue hypoglycemic drugs.
文摘AIM: To investigate the relationship between ARID1 A expression and clinicopathologic parameters, as well as its prognostic value, for patients with intrahepatic cholangiocarcinoma(IHCC).METHODS: We assessed ARID1 A protein and m RNA expression in IHCC tissues and paracarcinomatous(PC) tissues from 57 patients with IHCC using western blot and quantitative real-time reverse transcription polymerase chain reaction, respectively. We used Fisher's exact and χ2 tests to analyze relationships between clinicopathological parameters and ARID1 A expression. The Kaplan-Meier method and Cox regression were used to analyze survival.RESULTS: The mean ARID1 A protein level in IHCC tissues was 1.16 ± 0.36 relative units(RU), which was significantly lower than that in PC tissues(1.26 ± 0.21 RU, P < 0.01) and NL tissues(1.11 ± 0.31, P < 0.001).The mean ARID1 A m RNA level in IHCC tissues(1.20 ± 0.18) was also lower than that in PC tissues(1.27 ± 0.15, P < 0.001) and normal liver tissues(1.15 ± 0.34, P < 0.001). Low ARID1 A expression was significantly associated with tumor nodules, vein invasion, and recurrence. Median overall survival(OS) and disease-free survival(DFS) for the low ARID1 A expression group was 15.0 and 7.0 mo, respectively, which were significantly shorter than those for the high ARID1 A expression group at 25.0 and 22.0 mo(OS: P < 0.01; DFS: P < 0.001), respectively. Low ARID1 A expression was significantly associated with worse OS(HR = 3.967, 95%CI: 1.299-12.118, P = 0.016) in multivariate analyses.CONCLUSION: Low expression of ARID1 A is associated with poor prognosis in patients with IHCC, and thus may be a potential prognostic biomarker candidate in IHCC.
基金supported by the special plan of maternal and child health molecular genetic medicine of Maternal and Child Health Care Center in Chinese Center for Discase Control and Prevention(Grant No.FY-ZX-ZD-0059)
文摘Objective: To study the preventive and therapeutic effect of N-Acetyl-L-cysteine on infection-associated preterm labor in mice. Methods: A total of 66 C57BL/6 inbred strain pregnant mice were selected and randomly divided into groups A, B and C, with 22 cases in each group. Group A, B and C were regarded as model group, prevention group and treatment group, respectively. The model of infection-associated preterm labor was built by intraperitoneal injection of Escherichia coli. Ten mice of each group were taken and observed the preterm birth rates and live birth rates, respectively. Three mice of each group were killed at 3 h, 6 h, 12 h and 24 h after building the model. Their uterus tissues were collected and the expressions of the AP-1 and MCP-1 in those tissues were assayed with immunohistochemical method and the expressions of NF- kappa Bp65 and TNF- protein in the placenta tissues of those mice were also detected with immunohistochemical method. Results: The pretem: birth rates of mice in groups B and C were significantly lower than that in group A, while their live birth rates were distinctly higher than that in group A (P<0.05); the expressions of the AP-1 and MCP-1 in the uterus tissues and NF- kappa Bp65 and TNF- protein in the placenta tissues of mice in groups B and C were evidently lower than those in group A (P<0.05); the comparison of the expressions of the NF- kappa Bp65 and TNF- between group B and C showed no statistical differences (P>0.05). Conclusions: N-Acetyl-L-cysteine can lower the incidence rate of infection-associated preterm labor by prohibiting the activation of the protein AP-1/MCP-1 and decreasing the expression of NF- kappa Bp65 and TNF- in the pregnant tissues of premature mice to reduce the inflammatory reactions.
文摘AIM: To compare kinesin family member 1B(KIF1B) expression with clinicopathologic parameters and prognosis in hepatocellular carcinoma(HCC) patients.METHODS: KIF1 B protein and m RNA expression was assessed in HCC and paracarcinomatous(PC) tissues from 68 patients with HCC using Western blot and quantitative real-time reverse transcription-PCR, respectively. Student's t-tests were used to analyze relationships between clinicopathologic parameters and KIF1 B expression, the Kaplan-Meier method was used to analyze survival outcomes, and the log-rank test was used to compare survival differences between groups.RESULTS: Mean protein and m RNA levels of KIF1 B were similar between HCC and PC tissues. However, HCC tissues with vein invasions had significantly lower KIF1 B protein levels compared to those without vein invasions(2.30 ± 0.82 relative units vs 2.77 ± 0.84 relative units, P < 0.05). KIF1 B protein levels in HCC tissues from patients with recurrence during the followup period were significantly lower than those without recurrence(2.31 ± 0.92 relative units vs 2.80 ± 0.80 relative units, P < 0.05). However, KIF1 B protein and m RNA expression in HCC patients was not associated with other clinicopathologic parameters. Ratios of KIF1 B m RNA expression in HCC tissues to those in PC tissues were correlated with overall survival(13.5 mo vs 20.0 mo, P < 0.05) and disease-free survival(11.5 mo vs 19.5 mo, P < 0.05).CONCLUSION: Downregulation of KIF1 B in HCC tissues is associated with poor prognosis; additional clinical studies are needed to confirm whether KIF1 B can serve as a prognostic marker.
文摘BACKGROUND Osteoarthritis is a major source of pain,disability,and socioeconomic cost worldwide.Osteonecrosis is a disabling disorder that frequently occurs in the younger population aged from 20-50 years.The compound Eucommia bone tonic granules,a traditional Chinese medicine,can alleviate the damage of osteoarthritis and osteonecrosis.AIM To investigate the potential role of the compound Eucommia bone tonic granules(Eucommia)in the treatment of patients with osteoarthritis and osteonecrosis.METHODS One-hundred forty osteoarthritis and osteonecrosis cases admitted to our hospital from January 2013 to December 2017 were selected.Patients were divided into two groups:Eucommia-meloxicam group and meloxicam group.Clinical efficacy and the Western Ontario and McMaster Universities Arthritis Index(WOMAC)score were evaluated according to the evaluation criteria of orthopedic diseases.The levels of bone-GLA protein,interleukin-17,recombinant human S100 calcium binding protein A12,sphingosine 1-phosphate,cystatin C,creatinine,and hemoglobin in peripheral blood were determined.RESULTS The total effective rate in the two osteoarthritis groups was not different,but the total effective rate in the two osteonecrosis groups was significantly different.The overall efficacy of Eucommia-meloxicam group was superior to that of the meloxicam group.WOMAC showed that pain,stiffness,and dysfunction in the two groups of osteoarthritis and osteonecrosis before and after treatment were significantly different.The concentration of recombinant human S100 calcium binding protein A12,sphingosine 1-phosphate,cystatin C,creatinine,and hemoglobin before and after treatment in the Eucommia-meloxicam group and meloxicam group of osteoarthritis and osteonecrosis were significantly different,and the two treatment groups were significantly different from each other for osteoarthritis.CONCLUSION Our findings indicate that Eucommia can effectively enhance the curative effect of meloxicam,and the combination of Eucommia and meloxicam is superior to meloxicam alone.
基金the Greater Bay Area Institute of Precision Medicine,No.KCH2310094Shanghai Sailing Program,No.22YF1405000+1 种基金Research Startup Fund of Huashan Hospital Fudan University,No.2021QD035and Clinical Research Plan of SHDC,No.SHDC2020CR3020A.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a major cause of cancer-related mortality worldwide.Transcatheter arterial chemoembolization(TACE)has been performed as a palliative treatment for patients with HCC.However,HCC is easy to recur after TACE.Magnetic resonance imaging(MRI)has clinical potential in evaluating the TACE treatment effect for patients with liver cancer.However,traditional MRI has some limitations.AIM To explore the clinical potential of diffusion kurtosis imaging(DKI)in predicting recurrence and cellular invasion of the peritumoral liver zone of HCC after TACE.METHODSSeventy-six patients with 82 HCC nodules were recruited in this study and underwent DKI afterTACE. According to pathological examinations or the overall modified response evaluationcriteria in solid tumors (mRECIST) criterion, 48 and 34 nodules were divided into true progressionand pseudo-progression groups, respectively. The TACE-treated area, peritumoral liver zone, andfar-tumoral zone were evaluated on DKI-derived metric maps. Non-parametric U test and receiveroperating characteristic curve (ROC) analysis were used to evaluate the prediction performance ofeach DKI metric between the two groups. The independent t-test was used to compare each DKImetric between the peritumoral and far-tumoral zones of the true progression group.RESULTSDKI metrics, including mean diffusivity (MD), axial diffusivity (DA), radial diffusivity (DR), axialkurtosis (KA), and anisotropy fraction of kurtosis (Fak), showed statistically different valuesbetween the true progression and pseudo-progression groups (P < 0.05). Among these, MD, DA,and DR values were higher in pseudo-progression lesions than in true progression lesions,whereas KA and FAk values were higher in true progression lesions than in pseudo-progressionlesions. Moreover, for the true progression group, the peritumoral zone showed significantlydifferent DA, DR, KA, and FAk values from the far-tumoral zone. Furthermore, MD values of theliver parenchyma (peritumoral and far-tumoral zones) were significantly lower in the trueprogression group than in the pseudo-progression group (P < 0.05).CONCLUSIONDKI has been demonstrated with robust performance in predicting the therapeutic response ofHCC to TACE. Moreover, DKI might reveal cellular invasion of the peritumoral zone by moleculardiffusion-restricted change.
基金Supported by National Natural Science Foundation of China,No.31771284National Natural Science Foundation of China Youth Project,No.31702024+1 种基金Major Basic Research Project of Shandong Provincial Natural Science Foundation,No.ZR2019ZD27Shandong Province Higher Educational Science and Technology Plan Project,No.J17KA258。
文摘BACKGROUND Type 2 diabetes(T2 D) is characterized by insufficient insulin secretion caused by defective pancreatic β-cell function or insulin resistance,resulting in an increase in blood glucose.However,the mechanism involved in this lack of insulin secretion is unclear.The level of vascular endothelial growth factor B(VEGF-B) is significantly increased in T2 D patients.The inactivation of VEGF-B could restore insulin sensitivity in db/db mice by reducing fatty acid accumulation.It is speculated that VEGF-B is related to pancreatic β-cell dysfunction and is an important factor affecting β-cell secretion of insulin.As an in vitro model of normal pancreatic β-cells,the MIN6 cell line can be used to analyze the mechanism of insulin secretion and related biological effects.AIM To study the role of VEGF-B in the insulin secretion signaling pathway in MIN6 cells and explore the effect of VEGF-B on blood glucose regulation.METHODS The MIN6 mouse pancreatic islet β-cell line was used as the model system.By administering exogenous VEGF-B protein or knocking down VEGF-B expression in MIN6 cells,we examined the effects of VEGF-B on insulin secretion,Ca2+ and cyclic adenosine monophosphate(cAMP) levels,and the insulin secretion signaling pathway.RESULTS Exogenous VEGF-B inhibited the secretion of insulin and simultaneously reduced the levels of Ca2+ and cAMP in MIN6 cells.Exogenous VEGF-B also reduced the expression of phospholipase C gamma 1(PLCγ1),phosphatidylinositol 3-kinase(PI3 K),serine/threonine kinase(AKT),and other proteins in the insulin secretion pathway.Upon knockdown of VEGF-B,MIN6 cells exhibited increased insulin secretion and Ca2+ and cAMP levels and upregulated expression of PLCγ1,PI3 K,AKT,and other proteins.CONCLUSION VEGF-B can regulate insulin secretion by modulating the levels of Ca2+ and cAMP.VEGF-B involvement in insulin secretion is related to the expression of PLCγ1,PI3 K,AKT,and other signaling proteins.These results provide theoretical support and an experimental basis for the study of VEGF-B in the pathogenesis of T2 D.
基金Supported by National Natural Science Foundation of China,No.81771373Key Research and Development Plan of Zibo City,No.2019ZC010169 and No.2019ZC010166.
文摘BACKGROUND Multiple system atrophy(MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15(GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA.AIM To determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson’s disease(PD) patients and healthy controls.METHODS A case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzymelinked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysiswas used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD.RESULTS Serum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls(P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels(P = 0.043 and 0.000;respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients(cutoff: 470.42 pg/m L, sensitivity: 85.7%, specificity: 88.0%;cutoff: 1075.91 pg/m L, sensitivity:51.0%, specificity: 96.0%;respectively).CONCLUSION Serum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.
基金supported by the Project Sponsored by Yantai Science and Technology Bureau,China,No.2010232
文摘In this study, we treated PC12 cells with 0-20 μM amyloid-β peptide (25-35) for 24 hours to induce cytotoxicity, and found that 5-20 μM amyloid-β peptide (25-35) decreased PC12 cell viability, but adenosine triphosphate-sensitive potassium channel activator diazoxide suppressed the decrease in PC12 cell viability induced by amyloid-β peptide (25-35). Diazoxide protected PC12 cells against amyloid-β peptide (25-35)-induced increases in mitochondrial membrane potential and intracellular reactive oxygen species levels. These protective effects were reversed by the selective mitochondrial adenosine triphosphate-sensitive potassium channel blocker 5-hydroxydecanoate. An inducible nitric oxide synthase inhibitor, Nw-nitro-L-arginine, also protected PC12 cells from amyloid-β peptide (25-35)-induced increases in both mitochondrial membrane potential and intracellular reactive oxygen species levels. However, the H202-degrading enzyme catalase could not reverse the amyloid-β peptide (25-35)-induced increase in intracellular reactive oxygen species. A 24-hour exposure to amyloid-13 peptide (25-35) did not result in apoptosis or necrosis, suggesting that the increases in both mitochondrial membrane potential and reactive oxygen species levels preceded cell death. The data suggest that amyloid-β peptide (25-35) cytotoxicity is associated with adenosine triphosphate-sensitive potassium channels and nitric oxide. Regulation of adenosine triphosphate-sensitive potassium channels suppresses PC12 cell cytotoxicity induced by amyloid-β peptide (25-35).
文摘BACKGROUND: Dysfunction of knee joint is a common sequela after fracture of femur. The key of avoiding or decreasing dysfunction lies in early prevention, muscular practices of isometric contraction and functional exercises of knee joint as soon as possible. It is an essential component part of rehabilitation care for functional recovery of patients with fracture of femur.
基金National Natural Science Foundation of China Youth Project,No.31702024Shandong Province Higher Educational Science and Technology Plan Project,No.J17KA258.
文摘Insulin resistance(IR)is the common pathophysiological basis of many metabolic diseases.IR is characterized by decreased glucose uptake in skeletal muscle and adipose tissue,especially in skeletal muscle.Skeletal muscle is the main target tissue of glucose uptake under insulin stimulation.Glucose uptake by skeletal muscle is complex,and it is controlled by many pathways.The PI3K/AKt/GSK-1 signaling pathway is not only the main pathway for insulin signal transduction but also an important mechanism for regulating blood glucose.From the binding of insulin to its receptors on the surface of target cells to the transportation of glucose from extracellular fluid to skeletal muscle,a series of signal transduction processes is completed,any of which potentially affects the physiological effects of insulin and leads to IR.Resistance exercise(RT)can reduce skeletal muscle IR and effectively improve blood glucose control and glycosylated hemoglobin level in patients with type 2 diabetes mellitus(T2DM).However,the exact mechanism by which RT improves skeletal muscle IR remains unclear.Therefore,this paper discusses the above problems by tracking the progress of the literature to deepen the correlation between RT and skeletal muscle insulin sensitivity and provide further evidence for the application of exercise therapy in IR.In conclusion,RT mainly improves insulin sensitivity of skeletal muscle by increasing muscle mass,microvascular blood flow,and glucose transporter-4 expression in skeletal muscle,as well as by reducing lipid accumulation and inflammation in skeletal muscle.Thus,it is potentially useful in the prevention and treatment of T2DM.