Immune checkpoint inhibitors are effective tumor treatment agents with survival benefits.However,immune toxicity to various organs has become a new challenge in clinical practice.The cardiac involvement can be presented as heart failure,arrhythmia(atrial fibrillation,atrioventricular block,bundle branch block,ventricular tachycardia,etc.),myocardial-pericarditis,myocardiopathy,and sudden cardiac death,etc.This patient developed abnormally increased myocardial enzymes,impaired cardiac function,and atrioventricular block after 1-month treatment with tislelizumab.Endomyocardial biopsy examination confirmed the diagnosis of immune checkpoint inhibitor-associated myocarditis.Through the diagnosis,treatment,and review of relevant literatures of this case,we wish to improve the understanding of immune checkpoint inhibitor-associated myocarditis,and therefore improve the diagnosis and treatment of immune checkpoint inhibitor-associated myocarditis for clinicians.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To investigate the predictive value of serum circular RNA(circRNA)CDYL and circRNA ACAP2 expression levels for major adverse cardiovascular events(MACE)in pa-tients with acute myocardial infarction(AMI).Methods A total of 98 AMI patients were enrolled into the observation group,and divided into MACE group(n=45)and no-MACE group(n=53)based on whether they experienced MACE.Another 98 healthy individuals who underwent physical ex-amination during the same period were selected as the control group.The expression levels of serum cir-cRNA CDYL and circRNA ACAP2 were compared among groups.Multivariate logistic regression analysis was used to identify factors influencing the occurrence of MACE in AMI patients.Receiver operating characteristic(ROC)curve analysis was conducted to evaluate the predictive value of serum circRNA CDYL and circRNA ACAP2 levels for MACE in AMI patients.Results The serum circRNA CDYL level in the observation group was significantly lower than that in the control group,while the circRNA ACAP2 level was significantly higher(P＜0.05).The circRNA CDYL level in the MACE group was significantly lower,and the circRNA ACAP2 level was significantly higher than that in the no-MACE group(P＜0.05).Heart rate and circRNA ACAP2 were identified as independent risk factors for MACE in AMI patients,whereas circRNA CDYL served as independent protective factor(P＜0.05).The area under the ROC curve(AUC)for predicting MACE in AMI patients using se-rum circRNA CDYL,circRNA ACAP2 and their combination were 0.814,0.821 and 0.921,re-spectively.The sensitivity and specificity of combined prediction using serum circRNA CDYL and circRNA ACAP2 were 91.11％and 79.25％,respectively.The combined prediction efficacy of serum circRNA CDYL and circRNA ACAP2 was superior to their individual prediction(Zcombined-circRNA CDYL=1.975,Zcombined-circRNAACAP2=2.064,P=0.048,0.039).Conclusion Serum circRNA CDYL lev-el is down-regulated and circRNA ACAP2 level is up-regulated in AMI patients,and circRNA ACAP2 is an independent risk factor for MACE,while circRNA CDYL is a independent protective factor.The combined value of circRNA CDYL and circRNA ACAP2 in predicting the occurrence of MACE is higher.

The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose-catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16 ℃ in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni-NTA affinity column.Size-exclusion chromatography and SDS-PAGE analysis demonstrated that the puri-fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD+as a coenzyme to NADP+.The optimal temperature and pH of the TeXDH were 40 ℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26％of the initial enzyme activity,while the divalent metal ions Mg2+or Ca2+could recover the enzyme activity of TeXDH,reaching 103.32％and 110.69％of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn2+,Ni2+,Cu2+,Zn2+,Co2+,and Cd2+significantly inhibited the activity of TeXDH.ICP-MS and molecular doc-king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn2+ions and 1 mol/L Mg2+ion.Further-more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.

The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose-catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16 ℃ in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni-NTA affinity column.Size-exclusion chromatography and SDS-PAGE analysis demonstrated that the puri-fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD+as a coenzyme to NADP+.The optimal temperature and pH of the TeXDH were 40 ℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26％of the initial enzyme activity,while the divalent metal ions Mg2+or Ca2+could recover the enzyme activity of TeXDH,reaching 103.32％and 110.69％of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn2+,Ni2+,Cu2+,Zn2+,Co2+,and Cd2+significantly inhibited the activity of TeXDH.ICP-MS and molecular doc-king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn2+ions and 1 mol/L Mg2+ion.Further-more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.

Immune checkpoint inhibitors are effective tumor treatment agents with survival benefits.However,immune toxicity to various organs has become a new challenge in clinical practice.The cardiac involvement can be presented as heart failure,arrhythmia(atrial fibrillation,atrioventricular block,bundle branch block,ventricular tachycardia,etc.),myocardial-pericarditis,myocardiopathy,and sudden cardiac death,etc.This patient developed abnormally increased myocardial enzymes,impaired cardiac function,and atrioventricular block after 1-month treatment with tislelizumab.Endomyocardial biopsy examination confirmed the diagnosis of immune checkpoint inhibitor-associated myocarditis.Through the diagnosis,treatment,and review of relevant literatures of this case,we wish to improve the understanding of immune checkpoint inhibitor-associated myocarditis,and therefore improve the diagnosis and treatment of immune checkpoint inhibitor-associated myocarditis for clinicians.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

An online sample decomposition and detection method for high-throughput determination of Se content in organic samples was established based on oxygen combustion combined with hydride generation atomic fluorescence spectrometry.The sole product of Se in oxygen combustion,SeO2,was quantitatively captured on the walls of the combustion flask in an open system.It was then eluted online and reacted in situ with 10％(V/V)HC1 carrier solution and 2％(m/V)NaBH4 reductant solution within the combustion flask.After optimization,for a maximum sample processing amount of 0.2 g,the sample analysis throughput was 20 sample/h.The detection limit(LOD,3SD)for Se reached 0.012 mg/kg,and the relative standard deviations for parallel determinations(RSDs,n=6)was 1.7％.The analytical results of certified reference materials,scallop(GBW10024)and chicken(GBW10018),were consistent with the certified values,and the analytical results of real samples were in good agreement with those obtained by traditional wet digestion.

The prevalence rate of nonalcoholic fatty liver disease(NAFLD)reaches up to 30%around the world,and the disease has a serious impact on human health and constitutes a public health burden.Due to difficulties in the diagnosis and monitoring of NAFLD,it is important to identify potential drug targets and biomarkers,and multi-omics techniques hold great promise in the search for early diagnostic markers,therapeutic targets,and outcome and prognostic assessment of NAFLD.This article reviews the research advances in multi-omics techniques in the field of NAFLD in recent years,in order to provide a richer theoretical basis and new strategies for the prevention and treatment of NAFLD.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.