Analysis of 72 patients with colorectal high-grade neuroendocrine neoplasms from three Chinese hospitals

BACKGROUND Colorectal high-grade neuroendocrine neoplasms(HGNENs)are rare and constitute less than 1%of all colorectal malignancies.Based on their morphological differentiation and proliferation identity,these neoplasms present heterogeneous clinicopathologic features.Opinions regarding treatment strategies for and improvement of the clinical outcomes of these patients remain controversial.AIM To delineate the clinicopathologic features of and explore the prognostic factors for this rare malignancy.METHODS This observational study reviewed the data of 72 consecutive patients with colorectal HGNENs from three Chinese hospitals between 2000 and 2019.The clinicopathologic characteristics and follow-up data were carefully collected from their medical records,outpatient reexaminations,and telephone interviews.A survival analysis was conducted to evaluate their outcomes and to identify the prognostic factors for this disease.RESULTS According to the latest recommendations for the classification and nomenclature of colorectal HGNENs,61(84.7%)patients in our cohort had poorly differentiated neoplasms,which were categorized as high-grade neuroendocrine carcinomas(HGNECs),and the remaining 11(15.3%)patients had well differentiated neoplasms,which were categorized as high-grade neuroendocrine tumors(HGNETs).Most of the neoplasms(63.9%)were located at the rectum.More than half of the patients(51.4%)presented with distant metastasis at the date of diagnosis.All patients were followed for a median duration of 15.5 mo.In the entire cohort,the median survival time was 31 mo,and the 3-year and 5-year survival rates were 44.3%and 36.3%,respectively.Both the univariate and multivariate analyses demonstrated that increasing age,HGNEC type,and distant metastasis were risk factors for poor clinical outcomes.CONCLUSION Colorectal HGNENs are rare and aggressive malignancies with poor clinical outcomes.However,patients with younger age,good morphological differentiation,and without metastatic disease can have a relatively favorable prognosis.

Emergency Biosafety Management Practice in Laboratory of Shelter Hospital

At the end of 2019,the novel coronavirus infection outbroke in Wuhan,Hubei Province.On Feb.2,2020,Wuhan,as the worst-hit region,began to build“shelter hospital”rapidly to treat patients with mild ilness.The shelter hospital has multiple functions such as emergency treatment,surgical treatment and clinical test,which can adapt to emergency medical rescue tasks.Based on the characteristics that shelter hospital only treats patients with mild ilness,tests of shelter laboratory,including coronavirus nucleic acid detection,IgM/IgG antibody serology detection,monitoring and auxiliary diagnosis and/or a required blood routine,urine routine,C-reactive protein,calcitonin original,biochemical indicators(liver enzymes,myocardial enzymes,renal function,etc.)and blood coagulation function test etc,were used to provide important basis for the diagnosis and treatment of the disease.In order to ensure laboratory biosafety,it is necessary to first evaluate the harm level of various specimens.In the laboratory biosafety management,the harm level assessment of microorganisms is the core work of biosafety,which is of great significance to guarantee biosafety.As an emergency deployment afcted by the environment,shelter laboratory must possess strong mobility.This paper will explore how to combine the biosafety model of traditional laboratory with the particularity of shelter laboratory to carry out effective work in response to the current epidemic.

Spread of Staphylococcus aureus between medical staff and high-frequency contact surfaces in a large metropolitan hospital

Objective:To examine whether bacteria are transferred between the hands of medical staff and high-frequency contact surfaces within and between departments of a major metropolitan hospital,and to further analyze the patterns of cross-transmission.Methods:Microbiological samples were collected from the hands of 112 hospital employees as well as from 120 high-frequency contact surfaces in four hospital departments.Samples were collected on agar plates,analyzed for the presence of Staphylococcus aureus or methicillin-resistant S.aureus(MRSA)by standard microbiology testing,and partially genotyped using pulsed-field gel electrophoresis.Results:Genetically identical MRSA was identified on the surface of an electrocardiography device in the medical intensive care unit and on the same type of device in the neurosurgical unit.Genetically similar S.aureus was identified on an infusion pump in the medical intensive care unit and on the hands of several doctors in a different department who regularly use that pump.Genetically identical S.aureus was also identified on bedside rail restraint in the medical intensive care unit and on the hands of the nurse in the neurosurgical unit.Finally,genetically similar MRSA was identified both on the surface of an electrocardiography device and on the suction apparatus in the medical intensive care unit.Conclusion:Cross-contamination of S.aureus or MRSA on medical workers'hands and contact surfaces was demonstrated within and between departments of a large metropolitan hospital.Improvements are needed in medical staff hygiene habits and in the cleaning of highfrequency contact surfaces to help prevent and control nosocomial infections.

Investigation on the Clinical Readiness of Nurses’Evidence-Based Practice in a 3A-Level General Hospital in Beijing

Objective:To understand the evidence-based practice readiness of developing evidence application projects in a 3A-level general hospital in Beijing,to identify barriers to evidence-based practice and to promote the successful application of evidence.Methods:All the clinical nurses who were going to participate in the application units of the evidence-based practice project were selected as the survey objects,and the self-made“Basic Information Questionnaire”and“Clinical Readiness to Evidence-based Nursing Assessment(CREBNA)”were used to conduct the survey.The total amounts and subscales were calculated.The factors that influence the score of the total scale were scored and analyzed.Results:The CREBNA total score was(119.87±19.18),the evidence subscale score was(47.94±8.54),the organizational environmental subscale score was(36.09±6.11),and the facilitator subscale score was(35.83±7.56).Univariate analysis showed that the total score of the scale was related to years of work,scientific research experience,knowledge of evidence-based care,and participation in evidence-based practice.Conclusion:The current evidence-based practice preparation situation is good.It is feasible to carry out evidence-based practice activities in the hospital.The follow-up development plan should be made based on the corresponding obstacle factors.

Analysis of cancer pain in hospitals in Beijing,China

Objective:This study aimed to survey the characteristics and treatments of cancer pain in Beijing hospitals,China.Methods:At 20:00 on December 22,2009,there conducted a questionnaire survey in 2238 patients with malignant tumors of 26 hospitals in Beijing,and the survey results were statistically analyzed.Results:The 531 cases in 2238 patients had pained and 121 cases (22.79%) had outbreak pain with one week.At 20:00 on December 22,2009,199 cases (38%) in the above-mentioned 531 pain patients suffered the moderate to severe pain (pain scores ≥ 4).The number of pain (pain scores ≥ 4) patients in the consecutive three days from December 20 to December 22 were 150.Conclusion:In the 531 cancer pain patients of the surveyed hospitals,38% of the patients were not satisfied with the pain control.Doctors believed that the main reason for pain not controlled was the non-standard treatment,but patients considered to be afraid of addiction.

FK506 contributes to peripheral nerve regeneration by inhibiting neuroinflammatory responses and promoting neuron survival

FK506(Tacrolimus)is a systemic immunosuppressant approved by the U.S.Food and Drug Administration.FK506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain unclear.In this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function recovery.These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.

Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration.However,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear.This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury.The functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent assay.Axonal debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian degeneration.Macrophage inflammatory factor expression in different polarization states was detected using a protein chip.The results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 polarization.The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention.Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in vitro.Thus,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

Influenza and pneumococcal vaccination coverage and associated factors in patients hospitalized with acute exacerbations of COPD in China:Findings from real-world data

Background:Influenza and pneumococcal vaccination are a priority in patients with chronic obstructive pulmonary disease(COPD).However,limited information is available on vaccination coverage among patients with acute exacerbations of COPD(AECOPD)in China.This study aimed to determine the rates and associated factors of influenza and pneumococcal vaccination in patients hospitalized with AECOPD.Methods:Baseline data from a national,multicenter,hospital-based study that included adult inpatients with AECOPD between 2017 and 2021 were analyzed.The outcomes of interest were the influenza vaccination in the past year and the pneumococcal vaccination in the past 5 years.To ensure national representativeness,rates were weighted according to the distribution of hospital levels and types enrolled in this study.Multivariable Poisson regression based on mixed-effects models were used to determine the associated factors.The independent variables included the region and hospital features where the participants were located,sociodemographic characteristics(age,sex,rural/urban residence,education,etc.),and clinical indicators(COPD disease history,lung function parameters,comorbidities,etc.).The treatment profiles of the vaccinated and unvaccinated participants were compared.Results:Of 6949 eligible participants,the weighted rates of influenza/pneumococcal,influenza,and pneumococcal vaccination were 2.72%(95%confidence interval[CI]:2.34%-3.10%),2.09%(95%CI:1.76%-2.43%),and 1.25%(95%CI:0.99%-1.51%),respectively.In multivariable models,age≥60 years(60-69 years,odds ratio[OR]:1.90,95%CI:1.11-3.25;≥80 years,OR:2.00,95%CI:1.06-3.78),geographical regions(Northern China relative to Eastern China,OR:5.09,95%CI:1.96-13.21),urban residence(OR:1.69,95%CI:1.07-2.66),a higher education level(junior high school,OR:1.77,95%CI:1.21-2.58;senior high school or above,OR:2.61,95%CI:1.69-4.03),former smoking(OR:1.79,95%CI:1.15-2.79),and regular inhaled medication treatment(OR:3.28,95%CI:2.29-4.70)were positively associated with vaccination.Patients who had experienced severe exacerbations in the past year were less likely to be vaccinated(OR:0.65,95%CI:0.45-0.96).Compared with unvaccinated participants,vaccinated participants adhered better to pharmacological and non-pharmacological treatment.Conclusions:Influenza and pneumococcal vaccination coverage are extremely low.Urgent measures are necessary to increase vaccination coverage among inpatients with AECOPD in China.

Age-specific differences in the association between prediabetes and cardiovascular diseases in China:A national cross-sectional study

BACKGROUND Cardiovascular disease(CVD)is a leading cause of morbidity and mortality worldwide,the global burden of which is rising.It is still unclear the extent to which prediabetes contributes to the risk of CVD in various age brackets among adults.To develop a focused screening plan and treatment for Chinese adults with prediabetes,it is crucial to identify variations in the connection between prediabetes and the risk of CVD based on age.AIM To examine the clinical features of prediabetes and identify risk factors for CVD in different age groups in China.METHODS The cross-sectional study involved a total of 46239 participants from June 2007 through May 2008.A thorough evaluation was conducted.Individuals with prediabetes were categorized into two groups based on age.Chinese atherosclerotic CVD risk prediction model was employed to evaluate the risk of developing CVD over 10 years.Random forest was established in both age groups.SHapley Additive exPlanation method prioritized the importance of features from the perspective of assessment contribution.RESULTS In total,6948 people were diagnosed with prediabetes in this study.In prediabetes,prevalences of CVD were 5(0.29%)in the younger group and 148(2.85%)in the older group.Overall,11.11%of the younger group and 29.59% of the older group were intermediate/high-risk of CVD for prediabetes without CVD based on the Prediction for ASCVD Risk in China equation in ten years.In the younger age group,the 10-year risk of CVD was found to be more closely linked to family history of CVD rather than lifestyle,whereas in the older age group,resident status was more closely linked.CONCLUSION The susceptibility to CVD is age-specific in newly diagnosed prediabetes.It is necessary to develop targeted approaches for the prevention and management of CVD in adults across various age brackets.

To explore the mechanism of Yigong San anti-gastric cancer and immune regulation

BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear.AIM To explore the mechanism of YGS anti-gastric cancer and immune regulation.METHODS Firstly,collect the active ingredients and targets of YGS,and the differentially expressed genes of gastric cancer.Secondly,constructed a protein-protein interaction network between the targets of drugs and diseases,and screened hub genes.Then the clinical relevance,mutation and repair,tumor microenvironment and drug sensitivity of the hub gene were analyzed.Finally,molecular docking was used to verify the binding ability of YGS active ingredient and hub genes.RESULTS Firstly,obtained 55 common targets of gastric cancer and YGS.The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6,EGFR,MMP2,MMP9 and TGFB1 as the hub genes.The 5 hub genes were involved in gastric carcinogenesis,staging,typing and prognosis,and their mutations promote gastric cancer progression.Finally,molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets.CONCLUSION YGS has the effect of anti-gastric cancer and immune regulation.

Xuebijing improves intestinal microcirculation dysfunction in septic rats by regulating the VEGF-A/PI3K/Akt signaling pathway

BACKGROUND:This study aims to explore whether Xuebijing(XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.METHODS:A rat model of sepsis was established by cecal ligation and puncture(CLP).A total of 30 male SD rats were divided into four groups:sham group,CLP group,XBJ + axitinib group,and XBJ group.XBJ was intraperitoneally injected 2 h before CLP.Hemodynamic data(blood pressure and heart rate) were recorded.The intestinal microcirculation data of the rats were analyzed via microcirculation imaging.Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the serum levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α) in the rats.Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats.The expression of vascular endothelial growth factor A(VEGF-A),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt) in the small intestine was analyzed via Western blotting.RESULTS:XBJ improved intestinal microcirculation dysfunction in septic rats,alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa,and reduced the systemic inflammatory response.Moreover,XBJ upregulated the expression of VEGF-A,p-PI3K/total PI3K,and p-Akt/total Akt in the rat small intestine.CONCLUSION:XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.

Carbon-based nanomaterials cause toxicity by oxidative stress to the liver and brain in Sprague-Dawley rats

Carbon-based nanomaterials have important research significance in various disciplines,such as composite materials,nanoelectronic devices,biosensors,biological imaging,and drug delivery.Recently,the human and ecological risks associated with carbon-based nanomaterials have received increasing attention.However,the biological safety of carbon based nanomaterials has not been systematically studied.In this study,we used different types of carbon materials,namely,graphene oxide(GO),single-walled carbon nanotubes(SWCNTs),and multiwalled carbon nanotubes(MWCNTs),as models to observe their distribution and oxidative damage in vivo.The results of Histopathological and ultrastructural examinations indicated that the liver and lungs were the main accumulation targets of these nanomaterials.SR-μ-XRF analysis revealed that SWCNTs and MWCNTs might be present in the brain.This shows that the three types of carbon-based nanomaterials could cross the gas-blood barrier and eventually reach the liver tissue.In addition,SWCNTs and MWCNTs could cross the blood-brain barrier and accumulate in the cerebral cortex.The increase in ROS and MDA levels and the decrease in GSH,SOD,and CAT levels indicated that the three types of nanomaterials might cause oxidative stress in the liver.This suggests that direct instillation of these carbon-based nanomaterials into rats could induce ROS generation.In addition,iron(Fe)contaminants in these nanomaterials were a definite source of free radicals.However,these nanomaterials did not cause obvious damage to the rat brain tissue.The deposition of selenoprotein in the rat brain was found to be related to oxidative stress and Fe deficiency.This information may support the development of secure and reasonable applications of the studied carbon-based nanomaterials.

Comprehensive analysis of gene mutations and mismatch repair in Chinese colorectal cancer patients

BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing factors in Chinese patients have not been thoroughly described.AIM To analyze the clinicopathological features of KRAS,NRAS,BRAF,and PIK3CA mutations and the DNA MMR status in CRC.METHODS We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital.MMR proteins were tested using immunohistochemical analysis,and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction.Microsatellite status was determined using an MSI detection kit.Statistical analyses were conducted using SPSS software and logistic regression.RESULTS The KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 44.6%,3.4%,3.7%,and 3.9% of CRC patients,respectively.KRAS mutations were more likely to occur in patients with moderate-to-high differentiation.BRAF mutations were more likely to occur in patients with right-sided CRC,poorly differentiated,or no perineural invasion.Deficient MMR(dMMR)was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas.KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 29.6%,1.1%,8.1%,and 22.3% of patients with dMMR,respectively.The dMMR was more likely to occur in patients with a family history of CRC,aged<50 years,right-sided CRC,poorly differentiated histology,no perineural invasion,and with carcinoma in situ,stage I,or stage II tumors.CONCLUSION This study analyzed the molecular profiles of KRAS,NRAS,BRAF,PIK3CA,and MMR/MSI in CRC,identifying key influencing factors,with implications for clinical management of CRC.

Global current research status and future hotspots in osteoporotic fracture based on bibliometric assessment and visualization techniques

BACKGROUND In the past decade,the evolution of themes in the field of osteoporotic fractures has changed from epidemiology and prediction of long-term morbidity,risk assessment of osteoporotic fractures,and zoledronic acid and denosumab in the treatment of osteoporosis to treatment guidelines for osteoporosis and the side effects caused by anti-osteoporotic drugs.AIM To understand the trends and hotspots in osteoporotic fracture research.METHODS Original articles were retrieved between January 1,2010,and December 31,2019,from the Web of Science Core Collection database.CiteSpace software facilitated the analysis and visualization of scientific productivity and emerging trends.RESULTS Nine studies were identified using bibliometric indices,including citation,centrality,and sigma value,which might indicate a growing trend.Through clustering,we identified six major hot subtopics.Using burst analysis,top-5 references with the strongest bursting strength after 2017 were identified,indicating a future hotspot in this field.CONCLUSION Current hot subtopics in osteoporotic fracture research include atypical femoral fractures,androgen deprivation therapy,denosumab discontinuation,hip fractures,trabecular bone score(TBS),and bone phenotype.Management and prevention of secondary fractures in patients with osteoporotic fractures,TBSs,and long-term administration strategy for zoledronic acid are expected to become research hotspots.

Transcriptome sequencing reveals novel biomarkers and immune cell infiltration in esophageal tumorigenesis

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those in the NOR group,IL-1βand IL-6 were upregulated,while IL-10 was downregulated in the LGIN,HGIN,and CA groups.Moreover,the expression of the representative key genes,such as S100a8 and Krt6b,was verified in external human samples,and the results of immunohistochemical staining were consistent with the findings in mice.CONCLUSION We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions.In addition,we found that macrophage infiltration and abnormal alterations in the levels of inflam-mation-associated cytokines,such as IL-1β,IL-6,and IL-10,in the peripheral blood may be closely associated with the development of ESCC.

Clinical evolution of antisynthetase syndrome-associated interstitial lung disease after COVID-19 in a man with Klinefelter syndrome:A case report

BACKGROUND This study presents a case of rapidly developing respiratory failure due to antisynthetase syndrome(AS)following coronavirus disease 2019(COVID-19)in a 33-year-old man diagnosed with Klinefelter syndrome(KS).CASE SUMMARY A 33-year-old man with a diagnosis of KS was admitted to the Department of Pulmonary and Critical Care Medicine of a tertiary hospital in China for fever and shortness of breath 2 wk after the onset of COVID-19.Computed tomography of both lungs revealed diffuse multiple patchy heightened shadows in both lungs,accompanied by signs of partial bronchial inflation.Metagenomic next-generation sequencing of the bronchoalveolar lavage fluid suggested absence of pathogen.A biopsy specimen revealed organizing pneumonia with alveolar septal thickening.Additionally,extensive auto-antibody tests showed strong positivity for anti-SSA,anti-SSB,anti-Jo-1,and anti-Ro-52.Following multidisciplinary discussions,the patient received a final diagnosis of AS,leading to rapidly progressing respiratory failure.CONCLUSION This study underscores the clinical progression of AS-associated interstitial lung disease subsequent to viral infections such as COVID-19 in patients diagnosed with KS.

Novel compound heterozygous mutations in the hemojuvelin gene in a juvenile hemochromatosis patient:A case report

BACKGROUND Juvenile hemochromatosis(JH)is an early-onset,rare autosomal recessive disorder of iron overload observed worldwide that leads to damage in multiple organs.Pathogenic mutations in the hemojuvelin(HJV)gene are the major cause of JH.CASE SUMMARY A 34-year-old male Chinese patient presented with liver fibrosis,diabetes,hypogonadotropic hypogonadism,hypophysis hypothyroidism,and skin hyperpigmentation.Biochemical test revealed a markedly elevated serum ferritin level of 4329μg/L and a transferrin saturation rate of 95.4%.Targeted exome sequencing and Sanger sequencing revealed that the proband had a novel mutation c.863G>A(p.R288Q)in the HJV gene which was transmitted from his father,and two known mutations,c.18G>C(p.Q6H)and c.962_963delGCinsAA(p.C321*)in cis,which were inherited from his mother.The p.R288W mutation was previously reported to be pathogenic for hemochromatosis,which strongly supported the pathogenicity of p.R288Q reported for the first time in this case.After 72 wk of intensive phlebotomy therapy,the patient achieved a reduction in serum ferritin to 160.5μg/L.The patient's clinical symptoms demonstrated a notable improvement.CONCLUSION This study highlights the importance of screening for hemochromatosis in patients with diabetes and hypogonadotropic hypogonadism.It also suggests that long-term active phlebotomy could efficiently improve the prognosis in severe JH.

Research progress on dynamic monitoring of ctDNA and drug resistance related concomitant mutations in non-small cell lung cancer

Owing to significantly prolonged survival,targeted therapy has become standardized recommendation for advanced non-small cell lung cancer patients with mutated driver genes.However,the genetic status of lung cancer patients is dynamic.By dynamically monitoring the evolution of genes status,differential genes and concomitant genes related to progressive disease could be confirmed early,so as to achieve a more accurate and comprehensive insight of the whole process management of targeted therapy for lung cancer patients.Under the guidance of accurate genetic testing results,it is helpful to provide patients with more effective,long-term,and stable individualized targeted therapy.

Chinese herbal medicine for the treatment of endocrine therapyrelated osteoporosis among patients with breast cancer:A systematic review and meta-analysis

Objective:To assess the efficacy and safety of combining traditional Chinese medicine(TCM),specifically Chinese herbal medicine(CHM),with Western medicine(WM),compared to WM alone to treat breast cancer endocrine therapy-related osteoporosis(BCET-OP)by meta-analysis.Methods:Thirty-eight randomized controlled trials involving 2170 participants were analyzed.Eight databases were searched for articles published between inception and December 2023.Quality assessment was performed using the Risk of Bias 2 tool.Results:Significant increases were observed in the TCM-WM group in lumbar vertebrae bone mineral density(BMD)(P<.001,mean difference(MD)=0.07,95%confidence interval(CI):0.06 to 0.08),lumbar vertebrae T-score(P=.0005,MD=0.21,95%CI:0.09 to 0.33)and collum femoris BMD(P=.01,MD=0.10,95%CI:0.02 to 0.19).No significant difference was observed between the groups in the collum femoris T-score and estradiol levels.Bone gla-protein levels were significantly increased in the TCM-WM group(P=.0002,MD=0.52,95%CI:0.25 to 0.79).Beta-CrossLaps decreased significantly in the TCM-WM group(P=.0008,MD=−0.10,95%CI:−0.16 to−0.04).No significant difference was observed between the TCM-WM and WM groups in alkaline phosphatase,in procollagen type I N-terminal propeptide,and in the Kupperman index.The visual analog score(VAS)was decreased in the TCM-WM group compared to the WM group(P<.001,MD=−1.40,95%CI:−1.94 to−0.87).No significant difference in adverse events was observed between the two groups.Conclusion:Combining CHM with WM in patients with BCET-OP significantly improved BMD,T-score,and certain bone turnover markers and reduced the VAS score,indicating potential benefits for bone health and related pain.Adverse event analysis revealed no differences between the groups,supporting the feasibility of the combination therapy.However,further research,particularly in diverse populations,is required.

Associations between remnant cholesterol levels and mortality in patients with diabetes

BACKGROUND Dyslipidemia is frequently present in patients with diabetes.The associations of remnant cholesterol and mortality remains unclear in patients with diabetes.AIM To explore the associations of remnant cholesterol with all-cause and cardiovas-cular mortality in patients with diabetes.METHODS This prospective cohort study included 4740 patients with diabetes who par-ticipated in the National Health and Nutrition Examination Survey from 1999 through 2018.Remnant cholesterol was used as the exposure variable,and all-cause and cardiovascular mortality were considered outcome events.Outcome data were obtained from the National Death Index,and all participants were followed from the interview date until death or December 31,2019.Multivariate proportional Cox regression models were used to explore the associations between exposure and outcomes,in which remnant cholesterol was modeled as both a categorical and a continuous variable.Restricted cubic splines(RCSs)were calculated to assess the nonlinearity of associations.Subgroup(stratified by sex,age,body mass index,and duration of diabetes)and a series of sensitivity analyses were performed to evaluate the robustness of the associations.RESULTS During a median follow-up duration of 83 months,1370 all-cause deaths and 389 cardiovascular deaths were documented.Patients with remnant cholesterol levels in the third quartile had a reduced risk of all-cause mortality[hazard ratio(HR)95%confidence interval(CI):0.66(0.52-0.85)];however,when remnant cholesterol was modeled as a continuous variable,it was associated with increased risks of all-cause[HR(95%CI):1.12(1.02-1.21)per SD]and cardiovascular[HR(95%CI):1.16(1.01-1.32),per SD]mortality.The RCS demonstrated nonlinear associations of remnant cholesterol with all-cause and cardiovascular mortality.Subgroup and sensitivity analyses did not reveal significant differences from the above results.CONCLUSION In patients with diabetes,higher remnant cholesterol was associated with increased risks of all-cause and cardiovascular mortality,and diabetes patients with slightly higher remnant cholesterol(0.68-1.04 mmol/L)had a lower risk of all-cause mortality.