Chronic subdural hematoma(CSDH)is a disease characterized by capsuled blood products that progressively occupy the intracranial space,causing intracranial hypertension and compression in the brain.CSDH frequently occu...Chronic subdural hematoma(CSDH)is a disease characterized by capsuled blood products that progressively occupy the intracranial space,causing intracranial hypertension and compression in the brain.CSDH frequently occurs in all demographics,especially in the elderly,but the pathogenesis of CSDH remains unclear.In this review,we discuss the origin,development,and current treatment strategies of CSDH.For thefirst time,we analyzed the cellular and molecular compositions of hematoma membranes with a focus on neomembrane formation,a complex early-stage interactive event in hematoma pathogenesis.We hypothesize that in patients with CSDH,dural border cells(DBCs)might be induced to synthesize collagen or serum proteins might accumulate at the dura and arachnoid layers at the site of injury,thereby encapsulating the hemorrhage.Membrane formation may trigger inflammatory responses after subdural hemorrhage,promotingfibroblast-involved extracellular matrix(ECM)deposition and aberrant angiogenesis within the outer membrane.Consequently,ECM deposition and angiogenesis mutually influence each other and are modulated by inflammatory processes.By illustrating the complex and interactive mechanism of neomembrane formation,we aim to provide a novel insight into CSDH pathogenesis and propose directions for future research as well as advancements in treatment strategies for this disease.展开更多
BACKGROUND:This study aims to evaluate the eff ect of continuous renal replacement therapy(CRRT)on inflammation-related anemia,iron metabolism,and the prognosis in sepsis patients with acute kidney injury(AKI).METHODS...BACKGROUND:This study aims to evaluate the eff ect of continuous renal replacement therapy(CRRT)on inflammation-related anemia,iron metabolism,and the prognosis in sepsis patients with acute kidney injury(AKI).METHODS:Sepsis patients with AKI were prospectively enrolled and randomized into the CRRT and control groups.The clinical and laboratory data on days 1,3 and 7 after intensive care unit(ICU)admission were collected.The serum interleukin(IL)-6,hepcidin,erythropoietin,ferritin,and soluble transferrin receptor(sTfR)were determined by enzyme-linked immunosorbent assay.The Sequential Organ Failure Assessment(SOFA)score and 28-day mortality were recorded.Data were analyzed using Pearson’s Chi-square test or Fisher’s exact test(categorical variables),and Mann-Whitney U-test or t-test(continuous variables).RESULTS:The hemoglobin and serum erythropoietin levels did not signifi cantly diff er between the CRRT and control groups though gradually decreased within the first week of ICU admission.On days 3 and 7,the serum IL-6,hepcidin,ferritin,and red blood cell distribution width significantly decreased in the CRRT group compared to the control group(all P<0.05).On day 7,the serum iron was significantly elevated in the CRRT group compared to the control group(P<0.05).However,the serum sTfR did not signifi cantly diff er between the groups over time.In addition,the SOFA scores were signifi cantly lower in the CRRT group compared to the control group on day 7.The 28-day mortality did not signifi cantly diff er between the control and CRRT groups(38.0%vs.28.2%,P=0.332).CONCLUSION:CRRT might have beneficial effects on the improvement in inflammationrelated iron metabolism and disease severity during the fi rst week of ICU admission but not anemia and 28-day mortality in sepsis patients with AKI.展开更多
To investigate the expression of osteopontin (OPN) and its receptor integrin αvβ3 in the placental tissue from pregnant women complicated with preeclampsia, the expression of OPN and αvβ3 in the placenta of the ...To investigate the expression of osteopontin (OPN) and its receptor integrin αvβ3 in the placental tissue from pregnant women complicated with preeclampsia, the expression of OPN and αvβ3 in the placenta of the pregnant women with preeclampsia and healthy pregnant women was detected by immunohistochemistry, Western blotting and RT-PCR. Our results showed that OPN and αvβ3 protein were expressed in the placenta from normal pregnant woman and those with preeclampsia. OPN was located in the placental syncytiotrophoblasts and the cytoplasm of capillary endothelial cells and integrin αvβ3 was mainly expressed on the surface of trophoblast cells. Expression of OPN and integrin αvβ3 in the placental tissue from preeclampsia subjects was significantly lower than that from the control group (P〈0.05). Compared with the control group, expression of OPN in the placental tissue from preeclampsia group was significantly lower (P〈0.05) but there was no significant difference in the expression of αv and β3 between the preeclampsia group and the controls. It is concluded that OPN and its receptor integrin αvβ3 may be involved in the pathogenesis of preeclampsia.展开更多
BACKGROUND The ideal depth of general anesthesia should achieve the required levels of hypnosis,analgesia,and muscle relaxation while minimizing physiologic responses to awareness.The choice of anesthetic strategy in ...BACKGROUND The ideal depth of general anesthesia should achieve the required levels of hypnosis,analgesia,and muscle relaxation while minimizing physiologic responses to awareness.The choice of anesthetic strategy in patients with coronary heart disease(CHD)undergoing major noncardiac surgery is becoming an increasingly important issue as the population ages.This is because general anesthesia is associated with a risk of perioperative cardiac complications and death,and this risk is much higher in people with CHD.AIM To compare hemodynamic function and cardiovascular event rate between etomidate-and propofol-based anesthesia in patients with CHD.METHODS This prospective study enrolled consecutive patients(American Society of Anesthesiologists grade II/III)with stable CHD(New York Heart Association class I/II)undergoing major noncardiac surgery.The patients were randomly allocated to receive either etomidate/remifentanil-based or propofol/remifentanil-based general anesthesia.Randomization was performed using a computer-generated random number table and sequentially numbered,opaque,sealed envelopes.Concealment was maintained until the patient had arrived in the operating theater,at which point the consulting anesthetist opened the envelope.All patients,data collectors,and data analyzers were blinded to the type of anesthesia used.The primary endpoints were the occurrence of cardiovascular events(bradycardia,tachycardia,hypotension,ST-T segment changes,and ventricular premature beats)during anesthesia and cardiac troponin I level at 24 h.The secondary endpoints were hemodynamic parameters,bispectral index,and use of vasopressors during anesthesia.RESULTS The final analysis included 40 patients in each of the propofol and etomidate groups.The incidences of bradycardia,hypotension,ST-T segment changes,and ventricular premature beats during anesthesia were significantly higher in the propofol group than in the etomidate group(P<0.05 for all).The incidence of tachycardia was similar between the two groups.Cardiac troponin I levels were comparable between the two groups both before the induction of anesthesia and at 24 h after surgery.When compared with the etomidate group,the propofol group had significantly lower heart rates at 3 min after the anesthetic was injected(T1)and immediately after tracheal intubation(T2),lower systolic blood pressure at T1,and lower diastolic blood pressure and mean arterial pressure at T1,T2,3 min after tracheal intubation,and 5 min after tracheal intubation(P<0.05 for all).Vasopressor use was significantly more in the propofol group than in the etomidate group during the induction and maintenance periods(P<0.001).CONCLUSION In patients with CHD undergoing noncardiac major surgery,etomidate-based anesthesia is associated with fewer cardiovascular events and smaller hemodynamic changes than propofol-based anesthesia.展开更多
In this study,we compared the efficacy of mitoxantrone in combination with intermediate-dose cytarabine(HAM) with that of high-dose cytarabine alone(Hi DAC) as consolidation regimens in non-acute promyelocytic leu...In this study,we compared the efficacy of mitoxantrone in combination with intermediate-dose cytarabine(HAM) with that of high-dose cytarabine alone(Hi DAC) as consolidation regimens in non-acute promyelocytic leukemia(APL) acute myeloid leukemia patients with favorable and intermediate cytogenetics.A total of 62 patients from Shenzhen People's Hospital were enrolled in this study.All patients enrolled received standard induction chemotherapy and achieved the first complete remission(CR1).In these patients,24 received Hi DAC and 38 received HAM as consolidation.The median relapse free survival(RFS) and overall survival(OS) were similar between these two consolidation regimens.Even in subgroup analysis according to risk stratification,the combination regimen conferred no benefit in longterm outcome in patients with favorable or intermediate cytogenetics.However,in patients receiving HAM regimen,the lowest neutrophil count was lower,neutropenic period longer,neutropenic fever rate higher,and more platelet transfusion support was required.HAM group also tended to have higher rate of sepsis than Hi DAC group.According to our results,we suggest that combination treatment with mitoxantrone and intermediate-dose cytarabine has limited value as compared to Hi DAC,even in young non-APL AML patients with favorable and intermediate cytogenetics.展开更多
BACKGROUND There are many disputes about the definition,diagnosis,therapy,and prognosis of collision tumors.CASE SUMMARY We describe a rare patient with a collision tumor consisting of neuroendocrine carcinoma(NEC)and...BACKGROUND There are many disputes about the definition,diagnosis,therapy,and prognosis of collision tumors.CASE SUMMARY We describe a rare patient with a collision tumor consisting of neuroendocrine carcinoma(NEC)and squamous cell carcinoma(SCC)in the nasal cavity and paranasal sinus.She received operation,concurrent chemoradiotherapy,and then two cycles of palliative chemotherapy.Follow-up at 12 mo after diagnosis showed that this patient experienced a complete response with no signs of recurrence or metastasis.A literature review of previous 26 cases diagnosed with collision tumor of NEC and SCC in the head and neck was also undertaken.CONCLUSION It is challenging to manage collision tumors because there are two morphologically and etiologically distinct tumors.Well-designed multimodality therapy including surgery and chemoradiotherapy might lead to a long survival in these patients.展开更多
Background: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine(CQ) has played an i...Background: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine(CQ) has played an indispensable role, however, its mechanism of action(MoA) is not fully understood.Methods: We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling(ABPP) and mass spectrometry-coupled cellular thermal shift assay(MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic assays.Results: We developed a novel clickable, photo-affinity chloroquine analog probe(CQP) which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photocrosslinked with CQP which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. At the same time, we identified 8 proteins as the most potential hits which were commonly identified by both methods.Conclusions: We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its well-known inhibitory effect of hemozoin formation. This is the first report of identifying CQ antimalarial targets by a parallel usage of labeled(ABPP)and label-free(MS-CETSA) methods.展开更多
Electric signals from a chest skin electrode can be conducted to the heart and activate contraction. In the present study, normal and diabetic rabbits were stimulated by skin electrode on the abnormal bladder projecti...Electric signals from a chest skin electrode can be conducted to the heart and activate contraction. In the present study, normal and diabetic rabbits were stimulated by skin electrode on the abnormal bladder projection area using three levels of exporting voltage (5.84 V, 8.00 V, and 11.00 V). Results demonstrated significantly attenuated electric signals from both groups, in particular the diabetes group. The skin electrode signals were conducted to the bladders, and all vesical signals increased according to strength of stimulating signals from the skin electrode, However, vesical signals from diabetic rabbits were less than those from normal rabbits at the same stimulating strength of exporting voltage. Vesical pressures from the two groups increased along with increased vesical signals, but vesical pressure was less those from diabetic rabbits than in normal rabbits (basic status and different stimulating levels). Linear correlation analysis showed a significantly positive correlation between vesical pressure and signal. These results demonstrated that electric signals from skin electrodes resulted in increased vesical pressure, and vesical pressure increased along with stimulation strength.展开更多
Dear Editor,P igmented paravenous chorioretinal atrophy(PPCRA), which was first described by Hewiston-Brown in 1937, is a rare pigmentary retinopathy affecting the retina and choroid;most patients mainly manifest symm...Dear Editor,P igmented paravenous chorioretinal atrophy(PPCRA), which was first described by Hewiston-Brown in 1937, is a rare pigmentary retinopathy affecting the retina and choroid;most patients mainly manifest symmetrical retinal choroid in both eyes, except for a small number of patients with monocular manifestations[1].展开更多
Objective:To explore the targels and molecular mechanism of Gancao Yangyin Decoction(甘草养阴汤,GCYYD)based on network pharmacology.Methods:The effective chemical components of 7 kinds of Chinese materia medica in GCY...Objective:To explore the targels and molecular mechanism of Gancao Yangyin Decoction(甘草养阴汤,GCYYD)based on network pharmacology.Methods:The effective chemical components of 7 kinds of Chinese materia medica in GCYYD and their relevant targets were obtai ned through the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)and the encyelopedia of traditional Chinese medicine(ETCM).The aging-related targets were obtained through GeneCards database.The targets related to the effective chemical components were mapped with the aging-related targets,and the gene targets of GCY YD for intervening in aging were obtained.The protein interaction network diagram of GCY YD interfering with aging was drawn through String database and Cytoscape 3.7.1 software,and the core target genes were screened.The potential targets obtained were analyzed by gene ontology(GO)biological function enrichment analysis and kyoto encyelopedia of genes and genomes(KEGG)pathway enrichment analysis.Results:Totally 130 effective chemical components of the 7 kinds of Chinese materia medica of GCYYD and 276 related targets were obtained from TCMSP and ETCM databases.Totally 216 aging-related targets were obtained through GeneCards database.There were 63 target genes intervening in aging in GCYYD,with core target genes ALB,AKTI,TNF,L 6,MMP-3,VEGFA,CASP5,etc.Through biological function and signaling pathway enrichment analyses for the target genes with R software,147 KEGG signaling pathways were found,mainly related to age-RAGE signaling pathway in diabetic complications,proteoglycans in cancer,fluid shear stress and atherosclero-sis,HIF-1 signaling pathway,human cytomegalovirus infection,celluar senescence,prostate cancer,bladder cancer,elte.Conclusion:GCYYD can intervene in aging through"multicomponents-mulitargets-multipath-ways",which lays foundation for further experimental research.展开更多
Mg alloys have mechanical properties compatible with human bones.However,their rapid degradation and associated foreign body reactions in vivo significantly limit their application for human implants.In this study,thr...Mg alloys have mechanical properties compatible with human bones.However,their rapid degradation and associated foreign body reactions in vivo significantly limit their application for human implants.In this study,three differently processed Mg alloys,pure Mg(PM),cold extruded Mg alloy AZ31(CE AZ31),and fully annealed AZ31 Mg alloy(FA AZ31)were comparatively investigated for their potential as implants using a rat model.All three implanted Mg alloys do not show any impact on hepato-and renal function,nor any signs of observable changes to vital organs.Proteomics analysis of tissues directly contacting the implants 2.5 months post implantation revealed that FA AZ31 activates very few inflammation and immune associated signaling pathways;while the CE AZ31 and PM produce more significant inflammatory responses as confirmed by cytokine array analyses.Further,FA AZ31 activated pathways for cell organization and development that may improve the recovery of injured tissues.Structurally,EBSD analysis reveals that the FA AZ31 alloy has a higher ratio of first-order pyramidal orientated(10–11){10–1–2}grain texture with a value of 0.25,while PM and CE AZ31 alloys have lower ratios of first-order pyramidal orientated texture with the values of 0.16 and 0.17,respectively.This is associated with recovery and recrystallisation during annealing which promotes grain texture which exhibits enhanced degradation behaviours and induces a more limited immune response in vivo.In conclusion,the FA AZ31 demonstrated better biocompatibility and corrosion resistance and is a promising candidate for metal-based degradable implants which warrants further investigation.展开更多
Cirrhosis with portal hypertension is a common disease which has a significant impact on the quality of patients' life. Esophagogastric devascularization(EGDV) has been demonstrated to be an effective method to tre...Cirrhosis with portal hypertension is a common disease which has a significant impact on the quality of patients' life. Esophagogastric devascularization(EGDV) has been demonstrated to be an effective method to treat portal hypertension, however certain complications are associated with it. The purpose of this study was to evaluate the effectiveness and clinical outcome of the selective EGDV(sEGDV) for the treatment of portal hypertension. The study was conducted prospectively from Jan. 1 2011 to Dec. 31, 2012, and 180 patients were randomized to the sEGDV group(n=90) or the non-sEGDV(n-sEGDV) group(n=90). Patients' demographics, preoperative lab test results and operative details were comparable between the two groups. Postoperative and short-term complications were analyzed in two groups. There was statistically significant difference(P〈0.01) in the PVF reduction between the two groups. Post-operative complications showed no statistically significant difference between the two groups in the incidence of bleeding, ascites, acute portal vein thrombosis, fever and hepatic encephalopathy. Mortality between two groups was comparable. The incidence of splenic fossa effusion after the surgery was lower in sEGDV group than in n-sEGDV group. There were no significant differences in the short-term follow-up data such as esophageal varices and portal hypertensive gastropathy(P〉0.05). It is suggested that sEGDV is a safe, simple and effective surgical procedure. It has both the advantages of the shunt and devascularization because it preserves body's voluntary diversion. With the advantage of low incidence of postoperative complications, it is an ideal surgical approach for the treatment of portal hypertension.展开更多
AIM:To investigate the surgical outcomes of patients with chronic angle-closure glaucoma(CACG)treated with phacoemulsification(phaco)/endocyclophotocoagulation(ECP)with and without endoscopic goniosynechialysis(E-GSL)...AIM:To investigate the surgical outcomes of patients with chronic angle-closure glaucoma(CACG)treated with phacoemulsification(phaco)/endocyclophotocoagulation(ECP)with and without endoscopic goniosynechialysis(E-GSL).METHODS:A retrospective,nonrandomized,comparative case series was conducted.Patients with CACG who underwent phaco in combination with either ECP alone(ECP group)or GSL with ECP(E-GSL group)from 2018 to 2019 were followed for 12mo and reviewed.Clinical features and outcomes were identified and analyzed.The ECP and E-GSL groups were matched in age and baseline intraocular pressure(IOP).Changes in IOP,mean of visual acuity(VA),peripheral anterior synechiae(PAS)formation,and the number of glaucoma medications was examined.RESULTS:The ECP group included 32 eyes of 27 patients,and the E-GSL group included 32 eyes of 26 patients.The preoperative baseline IOP was 22.18±6.48 mm Hg in the ECP group and 22.95±6.71 mm Hg in the E-GSL group(P=0.644).The mean IOP reduction was 26.2%in the ECP group and 41.6%in the E-GSL group at 12mo.The mean postoperative VA(log MAR units)at 12mo was 0.47 in the ECP group and 0.36 in the E-GSL group.The reduction in PAS formation and the number of glaucoma medications was also higher in the ECP group than E-GSL group at 12mo.CONCLUSION:The phaco/ECP and phaco/E-GSL groups both achieve a significant reduction in IOP without complications associated with traditional glaucoma filtration surgeries.展开更多
BACKGROUND Liver cirrhosis is the main cause of portal hypertension.The leading cause of death in patients with liver cirrhosis is its most common complication,esophageal variceal bleeding(EVB).Endoscopic variceal lig...BACKGROUND Liver cirrhosis is the main cause of portal hypertension.The leading cause of death in patients with liver cirrhosis is its most common complication,esophageal variceal bleeding(EVB).Endoscopic variceal ligation(EVL)is recommended by many guidelines to treat EVB and prevent rebleeding;however,esophageal ulcers occur after treatment.Delayed healing of ulcers and unhealed ulcers lead to high rebleeding and mortality rates.Thus,the prevention of early postoperative rebleeding is of great significance in improving the quality of life and prognosis of patients.AIM To evaluate the efficacy of aluminum phosphate gel(APG)plus a proton pump inhibitor(PPI)in the prevention of early rebleeding after EVL in patients with EVB.METHODS The medical records of 792 patients who were diagnosed with EVB and in whom bleeding was successfully stopped by EVL at Shenzhen People’s Hospital,Guangdong Province,China from January 2015 to December 2020 were collected.According to the study inclusion and exclusion criteria,401 cases were included in a PPI-monotherapy group(PPI group),and 377 cases were included in a PPI and APG combination therapy(PPI+APG)group.We compared the incidence rates of early rebleeding and other complications within 6 wk after treatment between the two groups.The two-sample t-test,Wilcoxon rank-sum test,and chisquared test were adopted for statistical analyses.RESULTS No significant differences in age,sex,model for end-stage liver disease score,coagulation function,serum albumin level,or hemoglobin level were found between the two groups.The incidence of early rebleeding in the PPI+APG group(9/337;2.39%)was significantly lower than that in the PPI group(30/401;7.48%)(P=0.001).Causes of early rebleeding in the PPI group were esophageal ulcer(3.99%,16/401)and esophageal varices(3.49%,14/401),while those in the PPI+APG group were also esophageal ulcers(5/377;1.33%)and esophageal varices(4/377;1.06%);such causes were significantly less frequent in the PPI+APG group than in the PPI group(P=0.022 and 0.024,respectively).The early mortality rate within 6 wk in both groups was 0%,which was correlated with the timely rehospitalization of all patients with rebleeding and the conduct of emergency endoscopic therapy.The incidence of adverse events other than early bleeding in the PPI+APG group(28/377;7.43%)was significantly lower than that in the PPI group(63/401;15.71%)(P<0.001).The incidence of chest pain in the PPI+APG group(9/377;2.39%)was significantly lower than that in the PPI group(56/401;13.97%)(P<0.001).The incidence of constipation in the PPI+APG group(16/377;4.24%)was significantly higher than that in the PPI group(3/401;0.75%)(P=0.002)but constipation was relieved after patients drank more water or took lactulose.In the PPI and PPI+APG groups,the incidence rates of spontaneous peritonitis within 6 wk after discharge were 0.50%(2/401)and 0.53%(2/377),respectively,and those of hepatic encephalopathy were 0.50%(2/401)and 0.27%(1/377),respectively,presenting no significant difference(P>0.999).CONCLUSION PPI+APG combination therapy significantly reduces the incidence of early rebleeding and chest pain in patients with EVB after EVL.展开更多
Objective: To explore the roles of the expression of the co-stimulatory molecule, B7-2, and the co-inhibitory molecule, PD-L1, on peripheral blood mononuclear cells in the mechanism of immunotolerance in chronic hepa...Objective: To explore the roles of the expression of the co-stimulatory molecule, B7-2, and the co-inhibitory molecule, PD-L1, on peripheral blood mononuclear cells in the mechanism of immunotolerance in chronic hepatitis B virus infection. Methods: Thirty HBV infected patients in the immunoreactive phase and 20 patients in the immunotolerant phase were enrolled in the study, while 20 healthy volunteers were used as controls. RT- PCR and real-time PCR methods were used to detect the expression levels of B7-2 and PD-L1 mRNA in peripheral blood mononuclear cells in chronic HBV infected patients. Results: The B7-2 expression in irnrnunoreactive and immunotolerant patients was significantly lower than that in the controls (P all 〈 0.01 ); B7-2 expression in immunoreactive patients was significantly lower than in immunotolerant patients (P 〈 0.01). PD-L1 expression in irnmunoreactive patients and immunotolerant patients was significantly higher than that in normal controls (P all 〈 0.01). The PD-L1/BT-2 ratios in immunoreactive and immunotolerant patients were significantly higher than that of the healthy controls (P all 〈 0.01); the PD-L1/ B7-2 ratio was significantly higher in the immunoreactive patients than in the immunotolerant patients (P 〈 0.01). Conclusion: In chronic HBV infection, changes in the expression of co-stimulatory and co-inhibitory molecules imply a protective adjustment against the patient' s immune response that may result in increased immunotolerance and persistent HBV infection.展开更多
Tumor metastasis is a hallmark of colorectal cancer(CRC),in which exosome plays a crucial role with its function in intercellular communication.Plasma exosomes were collected from healthy control(HC)donors,localized p...Tumor metastasis is a hallmark of colorectal cancer(CRC),in which exosome plays a crucial role with its function in intercellular communication.Plasma exosomes were collected from healthy control(HC)donors,localized primary CRC and liver-metastatic CRC patients.We performed proximity barcoding assay(PBA)for single-exosome analysis,which enabled us to identify the alteration in exosome subpopulations associated with CRC progression.By in vitro and in vivo experiments,the biological impact of these subpopulations on cancer proliferation,migration,invasion,and metastasis was investigated.The potential application of exosomes as diagnostic biomarkers was evaluated in 2 independent validation cohorts by PBA.Twelve distinct exosome subpopulations were determined.We found 2 distinctly abundant subpopulations:one ITGB3-positive and the other ITGAM-positive.The ITGB3-positive cluster is rich in liver-metastatic CRC,compared to both HC group and primary CRC group.On the contrary,ITGAM-positive exosomes show a large-scale increase in plasma of HC group,compared to both primary CRC and metastatic CRC groups.Notably,both discovery cohort and validation cohort verified ITGB3+exosomes as potential diagnostic biomarker.ITGB3+exosomes promote proliferation,migration,and invasion capability of CRC.In contrast,ITGAM+exosomes suppress CRC development.Moreover,we also provide evidence that one of the sources of ITGAM+exosomes is macrophage.ITGB3+exosomes and ITGAM+exosomes are proven 2 potential diagnostic,prognostic,and therapeutic biomarkers for management of CRC.展开更多
With the continuous improvement and development of modern network information technology and the continuous improvement of people’s demands for health care,the traditional health care model has evolved,giving birth t...With the continuous improvement and development of modern network information technology and the continuous improvement of people’s demands for health care,the traditional health care model has evolved,giving birth to a new telemedicine health care model.Telemedicine refers to the comprehensive application of information technology for medical information transmission and long-distance communication between different places.It integrates medicine,computer technology,and communication technology for remote monitoring,diagnosis,consultation,case discussion,teaching,and surgery as well as a series of medical activities.With the continuous development of communication technology,telemedicine is also constantly changing.As a relatively novel technology,telemedicine is sought after by major hospitals.With the advancement of internet technology,digitization and informatization have been gradually applied in telemedicine,but due to various factors,telemedicine still has great limitations.This paper summarized the development status of telemedicine;discussed in detail the development of telemedicine at home and abroad;reviewed the application of telemedicine as well as the feasibility and limitations of its promotion and development;and put forward an outlook for the future development of telemedicine.展开更多
Postmenopausal osteoporosis is a common bone metabolic disorder characterized by deterioration of the bone microarchitecture,leading to an increased risk of fractures.Recently,circular RNAs(circ RNAs)have been demonst...Postmenopausal osteoporosis is a common bone metabolic disorder characterized by deterioration of the bone microarchitecture,leading to an increased risk of fractures.Recently,circular RNAs(circ RNAs)have been demonstrated to play pivotal roles in regulating bone metabolism.However,the underlying functions of circ RNAs in bone metabolism in postmenopausal osteoporosis remain obscure.Here,we report that circ Stag1 is a critical osteoporosis-related circ RNA that shows significantly downregulated expression in osteoporotic bone marrow mesenchymal stem cells(BMSCs)and clinical bone tissue samples from patients with osteoporosis.Overexpression of circ Stag1 significantly promoted the osteogenic capability of BMSCs.Mechanistically,we found that circ Stag1 interacts with human antigen R(Hu R),an RNA-binding protein,and promotes the translocation of Hu R into the cytoplasm.A high cytoplasmic level of Hu R led to the activation of the Wnt signaling pathway by stabilizing and enhancing low-density lipoprotein receptor-related protein 5/6(Lrp5/6)andβ-catenin expression,thereby stimulating the osteogenic differentiation of BMSCs.Furthermore,overexpression of circ Stag1 in vivo by circ Stag1-loaded adeno-associated virus(circ Stag1-AAV)promoted new bone formation,thereby preventing bone loss in ovariectomized rats.Collectively,we show that circ Stag1 plays a pivotal role in promoting the regeneration of bone tissue via Hu R/Wnt signaling,which may provide new strategies to prevent bone metabolic disorders such as postmenopausal osteoporosis.展开更多
Natural products are an important source of new drugs for the treatment of various diseases.However,developing natural productbased new medicines through random moiety modification is a lengthy and costly process,due ...Natural products are an important source of new drugs for the treatment of various diseases.However,developing natural productbased new medicines through random moiety modification is a lengthy and costly process,due in part to the difficulties associated with comprehensively understanding the mechanism of action and the side effects.Identifying the protein targets of natural products is an effective strategy,but most medicines interact with multiple protein targets,which complicate this process.In recent years,an increasing number of researchers have begun to screen the target proteins of natural products with chemical proteomics approaches,which can provide a more comprehensive array of the protein targets of active small molecules in an unbiased manner.Typically,chemical proteomics experiments for target identification consist of two key steps:(1)chemical probe design and synthesis and(2)target fishing and identification.In recent decades,five different types of chemical proteomic probes and their respective target fishing methods have been developed to screen targets of molecules with different structures,and a variety of protein identification approaches have been invented.Presently,we will classify these chemical proteomics approaches,the application scopes and characteristics of the different types of chemical probes,the different protein identification methods,and the advantages and disadvantages of these strategies.展开更多
基金This research was funded by Guangdong Natural Science Foundation(2020A1515010289)Shenzhen Key Medical Discipline Construction Fund(Shenzhen Key Medical Discipline 2020-2024)Shenzhen Science and Technology Innovation Foundation(Shenzhen Technology Key Project JSGG20211029095400001).
文摘Chronic subdural hematoma(CSDH)is a disease characterized by capsuled blood products that progressively occupy the intracranial space,causing intracranial hypertension and compression in the brain.CSDH frequently occurs in all demographics,especially in the elderly,but the pathogenesis of CSDH remains unclear.In this review,we discuss the origin,development,and current treatment strategies of CSDH.For thefirst time,we analyzed the cellular and molecular compositions of hematoma membranes with a focus on neomembrane formation,a complex early-stage interactive event in hematoma pathogenesis.We hypothesize that in patients with CSDH,dural border cells(DBCs)might be induced to synthesize collagen or serum proteins might accumulate at the dura and arachnoid layers at the site of injury,thereby encapsulating the hemorrhage.Membrane formation may trigger inflammatory responses after subdural hemorrhage,promotingfibroblast-involved extracellular matrix(ECM)deposition and aberrant angiogenesis within the outer membrane.Consequently,ECM deposition and angiogenesis mutually influence each other and are modulated by inflammatory processes.By illustrating the complex and interactive mechanism of neomembrane formation,we aim to provide a novel insight into CSDH pathogenesis and propose directions for future research as well as advancements in treatment strategies for this disease.
基金funded by the Shenzhen Key Medical Discipline Construction Fund(S ZXK046)the National Nature Science Foundation of China(81571869).
文摘BACKGROUND:This study aims to evaluate the eff ect of continuous renal replacement therapy(CRRT)on inflammation-related anemia,iron metabolism,and the prognosis in sepsis patients with acute kidney injury(AKI).METHODS:Sepsis patients with AKI were prospectively enrolled and randomized into the CRRT and control groups.The clinical and laboratory data on days 1,3 and 7 after intensive care unit(ICU)admission were collected.The serum interleukin(IL)-6,hepcidin,erythropoietin,ferritin,and soluble transferrin receptor(sTfR)were determined by enzyme-linked immunosorbent assay.The Sequential Organ Failure Assessment(SOFA)score and 28-day mortality were recorded.Data were analyzed using Pearson’s Chi-square test or Fisher’s exact test(categorical variables),and Mann-Whitney U-test or t-test(continuous variables).RESULTS:The hemoglobin and serum erythropoietin levels did not signifi cantly diff er between the CRRT and control groups though gradually decreased within the first week of ICU admission.On days 3 and 7,the serum IL-6,hepcidin,ferritin,and red blood cell distribution width significantly decreased in the CRRT group compared to the control group(all P<0.05).On day 7,the serum iron was significantly elevated in the CRRT group compared to the control group(P<0.05).However,the serum sTfR did not signifi cantly diff er between the groups over time.In addition,the SOFA scores were signifi cantly lower in the CRRT group compared to the control group on day 7.The 28-day mortality did not signifi cantly diff er between the control and CRRT groups(38.0%vs.28.2%,P=0.332).CONCLUSION:CRRT might have beneficial effects on the improvement in inflammationrelated iron metabolism and disease severity during the fi rst week of ICU admission but not anemia and 28-day mortality in sepsis patients with AKI.
基金supported by a grant from Shenzhen Municipal Science and Technology Program (No 200802107)a grant for medical research programs from the Health Department of Guangdong Province (No A2009593)
文摘To investigate the expression of osteopontin (OPN) and its receptor integrin αvβ3 in the placental tissue from pregnant women complicated with preeclampsia, the expression of OPN and αvβ3 in the placenta of the pregnant women with preeclampsia and healthy pregnant women was detected by immunohistochemistry, Western blotting and RT-PCR. Our results showed that OPN and αvβ3 protein were expressed in the placenta from normal pregnant woman and those with preeclampsia. OPN was located in the placental syncytiotrophoblasts and the cytoplasm of capillary endothelial cells and integrin αvβ3 was mainly expressed on the surface of trophoblast cells. Expression of OPN and integrin αvβ3 in the placental tissue from preeclampsia subjects was significantly lower than that from the control group (P〈0.05). Compared with the control group, expression of OPN in the placental tissue from preeclampsia group was significantly lower (P〈0.05) but there was no significant difference in the expression of αv and β3 between the preeclampsia group and the controls. It is concluded that OPN and its receptor integrin αvβ3 may be involved in the pathogenesis of preeclampsia.
基金Supported by Shenzhen Municipal Science and Technology Foundation,No.JCYJ20170307100314152Shenzhen Health Research Fund,No.SZLY2018011, No.SZXJ2017029+2 种基金Guangdong Medical Research Fund,No.A2018008 and No.A2019382Scientific Research Fund of Shenzhen People’s Hospital,No.SYLY201706and Shenzhen Key Medical Discipline Construction Fund,No.SZXK012.
文摘BACKGROUND The ideal depth of general anesthesia should achieve the required levels of hypnosis,analgesia,and muscle relaxation while minimizing physiologic responses to awareness.The choice of anesthetic strategy in patients with coronary heart disease(CHD)undergoing major noncardiac surgery is becoming an increasingly important issue as the population ages.This is because general anesthesia is associated with a risk of perioperative cardiac complications and death,and this risk is much higher in people with CHD.AIM To compare hemodynamic function and cardiovascular event rate between etomidate-and propofol-based anesthesia in patients with CHD.METHODS This prospective study enrolled consecutive patients(American Society of Anesthesiologists grade II/III)with stable CHD(New York Heart Association class I/II)undergoing major noncardiac surgery.The patients were randomly allocated to receive either etomidate/remifentanil-based or propofol/remifentanil-based general anesthesia.Randomization was performed using a computer-generated random number table and sequentially numbered,opaque,sealed envelopes.Concealment was maintained until the patient had arrived in the operating theater,at which point the consulting anesthetist opened the envelope.All patients,data collectors,and data analyzers were blinded to the type of anesthesia used.The primary endpoints were the occurrence of cardiovascular events(bradycardia,tachycardia,hypotension,ST-T segment changes,and ventricular premature beats)during anesthesia and cardiac troponin I level at 24 h.The secondary endpoints were hemodynamic parameters,bispectral index,and use of vasopressors during anesthesia.RESULTS The final analysis included 40 patients in each of the propofol and etomidate groups.The incidences of bradycardia,hypotension,ST-T segment changes,and ventricular premature beats during anesthesia were significantly higher in the propofol group than in the etomidate group(P<0.05 for all).The incidence of tachycardia was similar between the two groups.Cardiac troponin I levels were comparable between the two groups both before the induction of anesthesia and at 24 h after surgery.When compared with the etomidate group,the propofol group had significantly lower heart rates at 3 min after the anesthetic was injected(T1)and immediately after tracheal intubation(T2),lower systolic blood pressure at T1,and lower diastolic blood pressure and mean arterial pressure at T1,T2,3 min after tracheal intubation,and 5 min after tracheal intubation(P<0.05 for all).Vasopressor use was significantly more in the propofol group than in the etomidate group during the induction and maintenance periods(P<0.001).CONCLUSION In patients with CHD undergoing noncardiac major surgery,etomidate-based anesthesia is associated with fewer cardiovascular events and smaller hemodynamic changes than propofol-based anesthesia.
基金supported by grants from the Basic Research Project of Shenzhen Science and Technology Program(No.JYCJ20150403101146307,No.JCYJ20150403101028195 and No.JCYJ20160422145031770)the National Natural Science Foundation of China(No.81600168)
文摘In this study,we compared the efficacy of mitoxantrone in combination with intermediate-dose cytarabine(HAM) with that of high-dose cytarabine alone(Hi DAC) as consolidation regimens in non-acute promyelocytic leukemia(APL) acute myeloid leukemia patients with favorable and intermediate cytogenetics.A total of 62 patients from Shenzhen People's Hospital were enrolled in this study.All patients enrolled received standard induction chemotherapy and achieved the first complete remission(CR1).In these patients,24 received Hi DAC and 38 received HAM as consolidation.The median relapse free survival(RFS) and overall survival(OS) were similar between these two consolidation regimens.Even in subgroup analysis according to risk stratification,the combination regimen conferred no benefit in longterm outcome in patients with favorable or intermediate cytogenetics.However,in patients receiving HAM regimen,the lowest neutrophil count was lower,neutropenic period longer,neutropenic fever rate higher,and more platelet transfusion support was required.HAM group also tended to have higher rate of sepsis than Hi DAC group.According to our results,we suggest that combination treatment with mitoxantrone and intermediate-dose cytarabine has limited value as compared to Hi DAC,even in young non-APL AML patients with favorable and intermediate cytogenetics.
基金Supported by National Natural Science Foundation of China,No.81802732.
文摘BACKGROUND There are many disputes about the definition,diagnosis,therapy,and prognosis of collision tumors.CASE SUMMARY We describe a rare patient with a collision tumor consisting of neuroendocrine carcinoma(NEC)and squamous cell carcinoma(SCC)in the nasal cavity and paranasal sinus.She received operation,concurrent chemoradiotherapy,and then two cycles of palliative chemotherapy.Follow-up at 12 mo after diagnosis showed that this patient experienced a complete response with no signs of recurrence or metastasis.A literature review of previous 26 cases diagnosed with collision tumor of NEC and SCC in the head and neck was also undertaken.CONCLUSION It is challenging to manage collision tumors because there are two morphologically and etiologically distinct tumors.Well-designed multimodality therapy including surgery and chemoradiotherapy might lead to a long survival in these patients.
基金suppor ted by the National Key Research and Development Program of China(2020YFA0908000)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202002)+2 种基金the National Natural Science Foundation of China(82074098,82003814)the CACMS Innovation Fund(CI2021A05101)the Fundamental Research Funds for the Central public welfare research institutes(ZZ14-YQ-050,ZZ14-YQ-051,ZZ14-ND-010,ZZ15-ND-10 and ZZ14-FL-002)。
文摘Background: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine(CQ) has played an indispensable role, however, its mechanism of action(MoA) is not fully understood.Methods: We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling(ABPP) and mass spectrometry-coupled cellular thermal shift assay(MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic assays.Results: We developed a novel clickable, photo-affinity chloroquine analog probe(CQP) which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photocrosslinked with CQP which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. At the same time, we identified 8 proteins as the most potential hits which were commonly identified by both methods.Conclusions: We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its well-known inhibitory effect of hemozoin formation. This is the first report of identifying CQ antimalarial targets by a parallel usage of labeled(ABPP)and label-free(MS-CETSA) methods.
基金supported by a grant from the Science and Technology Bureau of Shenzhen (Shenzhen Pro-ject of Science and Technology in 2010), No. 201001003
文摘Electric signals from a chest skin electrode can be conducted to the heart and activate contraction. In the present study, normal and diabetic rabbits were stimulated by skin electrode on the abnormal bladder projection area using three levels of exporting voltage (5.84 V, 8.00 V, and 11.00 V). Results demonstrated significantly attenuated electric signals from both groups, in particular the diabetes group. The skin electrode signals were conducted to the bladders, and all vesical signals increased according to strength of stimulating signals from the skin electrode, However, vesical signals from diabetic rabbits were less than those from normal rabbits at the same stimulating strength of exporting voltage. Vesical pressures from the two groups increased along with increased vesical signals, but vesical pressure was less those from diabetic rabbits than in normal rabbits (basic status and different stimulating levels). Linear correlation analysis showed a significantly positive correlation between vesical pressure and signal. These results demonstrated that electric signals from skin electrodes resulted in increased vesical pressure, and vesical pressure increased along with stimulation strength.
基金Supported by Shenzhen-Hong Kong Cofunded Projects (Category A)(No.SGDX20190920110403741)Guangdong Basic and Applied Basic Research Foundation (No.2022A1515012326)+2 种基金Shenzhen Key Medical Discipline Construction Fund (No.SZXK038)Shenzhen Fund for Guangdong Provincial High level Clinical Key Specialties (No.SZGSP014)Shenzhen Science and Technology Program (No.JSGG20201102174200001)。
文摘Dear Editor,P igmented paravenous chorioretinal atrophy(PPCRA), which was first described by Hewiston-Brown in 1937, is a rare pigmentary retinopathy affecting the retina and choroid;most patients mainly manifest symmetrical retinal choroid in both eyes, except for a small number of patients with monocular manifestations[1].
基金We thank for the funding support from the General Project of the National Natural Science Foundation of China(8197060898)。
文摘Objective:To explore the targels and molecular mechanism of Gancao Yangyin Decoction(甘草养阴汤,GCYYD)based on network pharmacology.Methods:The effective chemical components of 7 kinds of Chinese materia medica in GCYYD and their relevant targets were obtai ned through the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)and the encyelopedia of traditional Chinese medicine(ETCM).The aging-related targets were obtained through GeneCards database.The targets related to the effective chemical components were mapped with the aging-related targets,and the gene targets of GCY YD for intervening in aging were obtained.The protein interaction network diagram of GCY YD interfering with aging was drawn through String database and Cytoscape 3.7.1 software,and the core target genes were screened.The potential targets obtained were analyzed by gene ontology(GO)biological function enrichment analysis and kyoto encyelopedia of genes and genomes(KEGG)pathway enrichment analysis.Results:Totally 130 effective chemical components of the 7 kinds of Chinese materia medica of GCYYD and 276 related targets were obtained from TCMSP and ETCM databases.Totally 216 aging-related targets were obtained through GeneCards database.There were 63 target genes intervening in aging in GCYYD,with core target genes ALB,AKTI,TNF,L 6,MMP-3,VEGFA,CASP5,etc.Through biological function and signaling pathway enrichment analyses for the target genes with R software,147 KEGG signaling pathways were found,mainly related to age-RAGE signaling pathway in diabetic complications,proteoglycans in cancer,fluid shear stress and atherosclero-sis,HIF-1 signaling pathway,human cytomegalovirus infection,celluar senescence,prostate cancer,bladder cancer,elte.Conclusion:GCYYD can intervene in aging through"multicomponents-mulitargets-multipath-ways",which lays foundation for further experimental research.
基金supported in part by JSPS research grant(No.P16718)Natural Science Foundation of Guangdong Province(No.2020A1515010855)+2 种基金National Science Foundation of China(31971355)Genecology MCR Seed Funding of University of the Sunshine CoastDeng Feng Project of Foshan First People’s Hospital(2019A008)。
文摘Mg alloys have mechanical properties compatible with human bones.However,their rapid degradation and associated foreign body reactions in vivo significantly limit their application for human implants.In this study,three differently processed Mg alloys,pure Mg(PM),cold extruded Mg alloy AZ31(CE AZ31),and fully annealed AZ31 Mg alloy(FA AZ31)were comparatively investigated for their potential as implants using a rat model.All three implanted Mg alloys do not show any impact on hepato-and renal function,nor any signs of observable changes to vital organs.Proteomics analysis of tissues directly contacting the implants 2.5 months post implantation revealed that FA AZ31 activates very few inflammation and immune associated signaling pathways;while the CE AZ31 and PM produce more significant inflammatory responses as confirmed by cytokine array analyses.Further,FA AZ31 activated pathways for cell organization and development that may improve the recovery of injured tissues.Structurally,EBSD analysis reveals that the FA AZ31 alloy has a higher ratio of first-order pyramidal orientated(10–11){10–1–2}grain texture with a value of 0.25,while PM and CE AZ31 alloys have lower ratios of first-order pyramidal orientated texture with the values of 0.16 and 0.17,respectively.This is associated with recovery and recrystallisation during annealing which promotes grain texture which exhibits enhanced degradation behaviours and induces a more limited immune response in vivo.In conclusion,the FA AZ31 demonstrated better biocompatibility and corrosion resistance and is a promising candidate for metal-based degradable implants which warrants further investigation.
基金supported by grants from Doctoral Research Funding of the Education Department(No.20120142120048)Natural Science Foundation of Hubei Province(No.2012FFB02308)Special Research of the Health Department of Hubei Province(No.XF2010-16)
文摘Cirrhosis with portal hypertension is a common disease which has a significant impact on the quality of patients' life. Esophagogastric devascularization(EGDV) has been demonstrated to be an effective method to treat portal hypertension, however certain complications are associated with it. The purpose of this study was to evaluate the effectiveness and clinical outcome of the selective EGDV(sEGDV) for the treatment of portal hypertension. The study was conducted prospectively from Jan. 1 2011 to Dec. 31, 2012, and 180 patients were randomized to the sEGDV group(n=90) or the non-sEGDV(n-sEGDV) group(n=90). Patients' demographics, preoperative lab test results and operative details were comparable between the two groups. Postoperative and short-term complications were analyzed in two groups. There was statistically significant difference(P〈0.01) in the PVF reduction between the two groups. Post-operative complications showed no statistically significant difference between the two groups in the incidence of bleeding, ascites, acute portal vein thrombosis, fever and hepatic encephalopathy. Mortality between two groups was comparable. The incidence of splenic fossa effusion after the surgery was lower in sEGDV group than in n-sEGDV group. There were no significant differences in the short-term follow-up data such as esophageal varices and portal hypertensive gastropathy(P〉0.05). It is suggested that sEGDV is a safe, simple and effective surgical procedure. It has both the advantages of the shunt and devascularization because it preserves body's voluntary diversion. With the advantage of low incidence of postoperative complications, it is an ideal surgical approach for the treatment of portal hypertension.
文摘AIM:To investigate the surgical outcomes of patients with chronic angle-closure glaucoma(CACG)treated with phacoemulsification(phaco)/endocyclophotocoagulation(ECP)with and without endoscopic goniosynechialysis(E-GSL).METHODS:A retrospective,nonrandomized,comparative case series was conducted.Patients with CACG who underwent phaco in combination with either ECP alone(ECP group)or GSL with ECP(E-GSL group)from 2018 to 2019 were followed for 12mo and reviewed.Clinical features and outcomes were identified and analyzed.The ECP and E-GSL groups were matched in age and baseline intraocular pressure(IOP).Changes in IOP,mean of visual acuity(VA),peripheral anterior synechiae(PAS)formation,and the number of glaucoma medications was examined.RESULTS:The ECP group included 32 eyes of 27 patients,and the E-GSL group included 32 eyes of 26 patients.The preoperative baseline IOP was 22.18±6.48 mm Hg in the ECP group and 22.95±6.71 mm Hg in the E-GSL group(P=0.644).The mean IOP reduction was 26.2%in the ECP group and 41.6%in the E-GSL group at 12mo.The mean postoperative VA(log MAR units)at 12mo was 0.47 in the ECP group and 0.36 in the E-GSL group.The reduction in PAS formation and the number of glaucoma medications was also higher in the ECP group than E-GSL group at 12mo.CONCLUSION:The phaco/ECP and phaco/E-GSL groups both achieve a significant reduction in IOP without complications associated with traditional glaucoma filtration surgeries.
基金Natural Science Foundation of Guangdong Province of China,No.2018A0303130278.
文摘BACKGROUND Liver cirrhosis is the main cause of portal hypertension.The leading cause of death in patients with liver cirrhosis is its most common complication,esophageal variceal bleeding(EVB).Endoscopic variceal ligation(EVL)is recommended by many guidelines to treat EVB and prevent rebleeding;however,esophageal ulcers occur after treatment.Delayed healing of ulcers and unhealed ulcers lead to high rebleeding and mortality rates.Thus,the prevention of early postoperative rebleeding is of great significance in improving the quality of life and prognosis of patients.AIM To evaluate the efficacy of aluminum phosphate gel(APG)plus a proton pump inhibitor(PPI)in the prevention of early rebleeding after EVL in patients with EVB.METHODS The medical records of 792 patients who were diagnosed with EVB and in whom bleeding was successfully stopped by EVL at Shenzhen People’s Hospital,Guangdong Province,China from January 2015 to December 2020 were collected.According to the study inclusion and exclusion criteria,401 cases were included in a PPI-monotherapy group(PPI group),and 377 cases were included in a PPI and APG combination therapy(PPI+APG)group.We compared the incidence rates of early rebleeding and other complications within 6 wk after treatment between the two groups.The two-sample t-test,Wilcoxon rank-sum test,and chisquared test were adopted for statistical analyses.RESULTS No significant differences in age,sex,model for end-stage liver disease score,coagulation function,serum albumin level,or hemoglobin level were found between the two groups.The incidence of early rebleeding in the PPI+APG group(9/337;2.39%)was significantly lower than that in the PPI group(30/401;7.48%)(P=0.001).Causes of early rebleeding in the PPI group were esophageal ulcer(3.99%,16/401)and esophageal varices(3.49%,14/401),while those in the PPI+APG group were also esophageal ulcers(5/377;1.33%)and esophageal varices(4/377;1.06%);such causes were significantly less frequent in the PPI+APG group than in the PPI group(P=0.022 and 0.024,respectively).The early mortality rate within 6 wk in both groups was 0%,which was correlated with the timely rehospitalization of all patients with rebleeding and the conduct of emergency endoscopic therapy.The incidence of adverse events other than early bleeding in the PPI+APG group(28/377;7.43%)was significantly lower than that in the PPI group(63/401;15.71%)(P<0.001).The incidence of chest pain in the PPI+APG group(9/377;2.39%)was significantly lower than that in the PPI group(56/401;13.97%)(P<0.001).The incidence of constipation in the PPI+APG group(16/377;4.24%)was significantly higher than that in the PPI group(3/401;0.75%)(P=0.002)but constipation was relieved after patients drank more water or took lactulose.In the PPI and PPI+APG groups,the incidence rates of spontaneous peritonitis within 6 wk after discharge were 0.50%(2/401)and 0.53%(2/377),respectively,and those of hepatic encephalopathy were 0.50%(2/401)and 0.27%(1/377),respectively,presenting no significant difference(P>0.999).CONCLUSION PPI+APG combination therapy significantly reduces the incidence of early rebleeding and chest pain in patients with EVB after EVL.
文摘Objective: To explore the roles of the expression of the co-stimulatory molecule, B7-2, and the co-inhibitory molecule, PD-L1, on peripheral blood mononuclear cells in the mechanism of immunotolerance in chronic hepatitis B virus infection. Methods: Thirty HBV infected patients in the immunoreactive phase and 20 patients in the immunotolerant phase were enrolled in the study, while 20 healthy volunteers were used as controls. RT- PCR and real-time PCR methods were used to detect the expression levels of B7-2 and PD-L1 mRNA in peripheral blood mononuclear cells in chronic HBV infected patients. Results: The B7-2 expression in irnrnunoreactive and immunotolerant patients was significantly lower than that in the controls (P all 〈 0.01 ); B7-2 expression in immunoreactive patients was significantly lower than in immunotolerant patients (P 〈 0.01). PD-L1 expression in irnmunoreactive patients and immunotolerant patients was significantly higher than that in normal controls (P all 〈 0.01). The PD-L1/BT-2 ratios in immunoreactive and immunotolerant patients were significantly higher than that of the healthy controls (P all 〈 0.01); the PD-L1/ B7-2 ratio was significantly higher in the immunoreactive patients than in the immunotolerant patients (P 〈 0.01). Conclusion: In chronic HBV infection, changes in the expression of co-stimulatory and co-inhibitory molecules imply a protective adjustment against the patient' s immune response that may result in increased immunotolerance and persistent HBV infection.
基金the National Natural Science Foundation of China(82000779,31971061)Taishan Pandeng Scholar Program of Shandong Province(tspd20210321)。
文摘Tumor metastasis is a hallmark of colorectal cancer(CRC),in which exosome plays a crucial role with its function in intercellular communication.Plasma exosomes were collected from healthy control(HC)donors,localized primary CRC and liver-metastatic CRC patients.We performed proximity barcoding assay(PBA)for single-exosome analysis,which enabled us to identify the alteration in exosome subpopulations associated with CRC progression.By in vitro and in vivo experiments,the biological impact of these subpopulations on cancer proliferation,migration,invasion,and metastasis was investigated.The potential application of exosomes as diagnostic biomarkers was evaluated in 2 independent validation cohorts by PBA.Twelve distinct exosome subpopulations were determined.We found 2 distinctly abundant subpopulations:one ITGB3-positive and the other ITGAM-positive.The ITGB3-positive cluster is rich in liver-metastatic CRC,compared to both HC group and primary CRC group.On the contrary,ITGAM-positive exosomes show a large-scale increase in plasma of HC group,compared to both primary CRC and metastatic CRC groups.Notably,both discovery cohort and validation cohort verified ITGB3+exosomes as potential diagnostic biomarker.ITGB3+exosomes promote proliferation,migration,and invasion capability of CRC.In contrast,ITGAM+exosomes suppress CRC development.Moreover,we also provide evidence that one of the sources of ITGAM+exosomes is macrophage.ITGB3+exosomes and ITGAM+exosomes are proven 2 potential diagnostic,prognostic,and therapeutic biomarkers for management of CRC.
基金the Natural Science Foundation of Beijing(Grant Nos.Z190024 and 12019B1002)the China National Key Research and Development Program(Grant No.2020AAA0105005)。
文摘With the continuous improvement and development of modern network information technology and the continuous improvement of people’s demands for health care,the traditional health care model has evolved,giving birth to a new telemedicine health care model.Telemedicine refers to the comprehensive application of information technology for medical information transmission and long-distance communication between different places.It integrates medicine,computer technology,and communication technology for remote monitoring,diagnosis,consultation,case discussion,teaching,and surgery as well as a series of medical activities.With the continuous development of communication technology,telemedicine is also constantly changing.As a relatively novel technology,telemedicine is sought after by major hospitals.With the advancement of internet technology,digitization and informatization have been gradually applied in telemedicine,but due to various factors,telemedicine still has great limitations.This paper summarized the development status of telemedicine;discussed in detail the development of telemedicine at home and abroad;reviewed the application of telemedicine as well as the feasibility and limitations of its promotion and development;and put forward an outlook for the future development of telemedicine.
基金The Shenzhen Municipal Science and Technology Innovation Committee Project(JCYJ20190806160407178,JCYJ20180305164544288,JSGG20180504170427135,SGLH20180625141602256,JCYJ20180305164659637)the Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration(ZDSYS20200811143752005)supported this work。
文摘Postmenopausal osteoporosis is a common bone metabolic disorder characterized by deterioration of the bone microarchitecture,leading to an increased risk of fractures.Recently,circular RNAs(circ RNAs)have been demonstrated to play pivotal roles in regulating bone metabolism.However,the underlying functions of circ RNAs in bone metabolism in postmenopausal osteoporosis remain obscure.Here,we report that circ Stag1 is a critical osteoporosis-related circ RNA that shows significantly downregulated expression in osteoporotic bone marrow mesenchymal stem cells(BMSCs)and clinical bone tissue samples from patients with osteoporosis.Overexpression of circ Stag1 significantly promoted the osteogenic capability of BMSCs.Mechanistically,we found that circ Stag1 interacts with human antigen R(Hu R),an RNA-binding protein,and promotes the translocation of Hu R into the cytoplasm.A high cytoplasmic level of Hu R led to the activation of the Wnt signaling pathway by stabilizing and enhancing low-density lipoprotein receptor-related protein 5/6(Lrp5/6)andβ-catenin expression,thereby stimulating the osteogenic differentiation of BMSCs.Furthermore,overexpression of circ Stag1 in vivo by circ Stag1-loaded adeno-associated virus(circ Stag1-AAV)promoted new bone formation,thereby preventing bone loss in ovariectomized rats.Collectively,we show that circ Stag1 plays a pivotal role in promoting the regeneration of bone tissue via Hu R/Wnt signaling,which may provide new strategies to prevent bone metabolic disorders such as postmenopausal osteoporosis.
基金support from the National Natural Science Foundation of China(81903588,81803456 and 81841001)the Major National Science and Technology Program of China for Innovative Drug(2017ZX09101002-001-001-05)+5 种基金the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZXKT18003)the Natural Science Foundation of Jiangsu Province(BK20190799,China)the Science and Technology Foundation of Shenzhen(JCYJ20180305164128430)the International Cooperation Foundation of Shenzhen(GJHZ20180928171602104)the Shenzhen Economic and Information Committee“Innovation Chain and Industry Chain”integration special support plan project(20180225112449943)the Shenzhen Public Service Platform on Tumor Precision Medicine and Molecular Diagnosis.
文摘Natural products are an important source of new drugs for the treatment of various diseases.However,developing natural productbased new medicines through random moiety modification is a lengthy and costly process,due in part to the difficulties associated with comprehensively understanding the mechanism of action and the side effects.Identifying the protein targets of natural products is an effective strategy,but most medicines interact with multiple protein targets,which complicate this process.In recent years,an increasing number of researchers have begun to screen the target proteins of natural products with chemical proteomics approaches,which can provide a more comprehensive array of the protein targets of active small molecules in an unbiased manner.Typically,chemical proteomics experiments for target identification consist of two key steps:(1)chemical probe design and synthesis and(2)target fishing and identification.In recent decades,five different types of chemical proteomic probes and their respective target fishing methods have been developed to screen targets of molecules with different structures,and a variety of protein identification approaches have been invented.Presently,we will classify these chemical proteomics approaches,the application scopes and characteristics of the different types of chemical probes,the different protein identification methods,and the advantages and disadvantages of these strategies.