Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

OBJECTIVE To analyze the clinical distribution characteristics and drug resistance of Enterobacter cloa-cae in Gansu Province from 2019 to 2023,providing reference for the prevention and control of E.cloacae infec-tions in this region.METHODS Data on the distribution and drug resistance of E.cloacae from hospitals in mem-ber units of the Gansu Antimicrobial Surveillance Network between 2019 and 2023 were collected.In vitro drug susceptibility testing was performed by the Kirby-Bauer disk diffusion(K-B)method,minimum inhibitory con-centration method,and fully automated instrumentation,followed by analysis of the susceptibility results.RESULTS From 2019 to 2023,a total of 402 490 bacterial strains were isolated and cultured in Gansu Province,including 17 417 strains of E.cloacae,with a detection rate of 4.33％.The bacteria were primarily iso-lated from sputum specimens(62.81％),followed by urine(7.37％)and wound pus specimens(6.07％).The de-partmental distribution was dominated by internal medicine(44.96％)and surgery(28.50％).The highest detec-tion rate was observed in the adult group(15-65 years,45.79％).E.cloacae exhibited varying degrees of resist-ance to over 20 antibacterial drugs,but the overall drug resistance rate showed a declining trend(P＜0.05).The highest drug resistance rate was observed for cefazolin(96.40％-98.38％),while the lowest was for tigecycline(0.44％—2.92％).Carbapenem-resistant E.cloacae demonstrated an increasing trend in drug resistance rates,with imipenem resistance ranging from 2.79％to 3.71％(P=0.044)and meropenem resistance ranging from 1.29％to 3.41％(P＜0.05).CONCLUSIONS The isolation rate of E.cloacae in Gansu Province remains stable,with a declining trend in drug resistance to multiple antibacterial drugs.However,the increasing drug resistance to carbapenems warrants attention.

Hepatitis virus is the main pathogen causing liver inflammation and damage. Early detection is crucial for the effective treatment of hepatitis. The detection technology of hepatitis virus has gone through multiple stages, including immunological detection technology and nucleic acid detection technology. The emergence of emerging molecular detection technologies makes its detection more sensitive and convenient, including nanotechnology, Raman spectroscopy technology, microfluidic technology and biosensor technology. The development of these technologies has promoted the early diagnosis of hepatitis, but their clinic applications are still facing challenges. In the future, the development of hepatitis virus detection technology is expected to transform in the form of multidimensional and interdisciplinary innovation process, with its core objectives being the realization of more precise, convenient, and accessible detection methods, thereby comprehensively advancing the progress of hepatitis prevention and control efforts.

Hepatitis virus is the main pathogen causing liver inflammation and damage. Early detection is crucial for the effective treatment of hepatitis. The detection technology of hepatitis virus has gone through multiple stages, including immunological detection technology and nucleic acid detection technology. The emergence of emerging molecular detection technologies makes its detection more sensitive and convenient, including nanotechnology, Raman spectroscopy technology, microfluidic technology and biosensor technology. The development of these technologies has promoted the early diagnosis of hepatitis, but their clinic applications are still facing challenges. In the future, the development of hepatitis virus detection technology is expected to transform in the form of multidimensional and interdisciplinary innovation process, with its core objectives being the realization of more precise, convenient, and accessible detection methods, thereby comprehensively advancing the progress of hepatitis prevention and control efforts.

OBJECTIVE To analyze the clinical distribution characteristics and drug resistance of Enterobacter cloa-cae in Gansu Province from 2019 to 2023,providing reference for the prevention and control of E.cloacae infec-tions in this region.METHODS Data on the distribution and drug resistance of E.cloacae from hospitals in mem-ber units of the Gansu Antimicrobial Surveillance Network between 2019 and 2023 were collected.In vitro drug susceptibility testing was performed by the Kirby-Bauer disk diffusion(K-B)method,minimum inhibitory con-centration method,and fully automated instrumentation,followed by analysis of the susceptibility results.RESULTS From 2019 to 2023,a total of 402 490 bacterial strains were isolated and cultured in Gansu Province,including 17 417 strains of E.cloacae,with a detection rate of 4.33％.The bacteria were primarily iso-lated from sputum specimens(62.81％),followed by urine(7.37％)and wound pus specimens(6.07％).The de-partmental distribution was dominated by internal medicine(44.96％)and surgery(28.50％).The highest detec-tion rate was observed in the adult group(15-65 years,45.79％).E.cloacae exhibited varying degrees of resist-ance to over 20 antibacterial drugs,but the overall drug resistance rate showed a declining trend(P＜0.05).The highest drug resistance rate was observed for cefazolin(96.40％-98.38％),while the lowest was for tigecycline(0.44％—2.92％).Carbapenem-resistant E.cloacae demonstrated an increasing trend in drug resistance rates,with imipenem resistance ranging from 2.79％to 3.71％(P=0.044)and meropenem resistance ranging from 1.29％to 3.41％(P＜0.05).CONCLUSIONS The isolation rate of E.cloacae in Gansu Province remains stable,with a declining trend in drug resistance to multiple antibacterial drugs.However,the increasing drug resistance to carbapenems warrants attention.

Objective To evaluate five types of DIC scoring systems based on sepsis patients,to explore the values of different DIC scoring systems in the occurrence and prognosis of DIC in sepsis patients,and to compare the applicability of different DIC scoring systems for sepsis complicated with DIC.Methods Laboratory indexes and clinical data from sepsis patients who had been hospitalized in Gansu Provincial People's Hospital from December 1,2019 to December 31,2021 were retrospectively analyzed within 24 hours.Five types of DIC scoring systems were used to score,and the difference of diagnostic rate and discharge outcome in sepsis patients with different severity was compared.The ROC curves of five DIC scoring systems were established to evaluate the accu-racy of DIC in sepsis patients.Results The fatality rate of sepsis increased with the severity of sepsis(P<0.05).There were statistically significant differences in discharge outcomes between DIC and non-DIC in the five scoring systems(P<0.05).JMHW,CDSS and part of ISTH were detected in JAAM cases,while ISTH was detected in non-dominant ISTH cases.ISTH,JAAM,JMHW,CDSS,and non-dominant ISTH5 scoring systems were used to diagnose DIC,and absence of full health restoration and death were 3.0,3.8,4.2,3.9,and 3.0 times higher than non-DIC cases,respectively.Conclusion JAAM scoring system has higher diagnostic rate and sensitivity for adult sepsis.CDSS and JMHW scoring systems are more accurate in predicting the prognosis of sepsis patients.

Objective To assess the factors associated with the restoration of spontaneous circulation (ROSC) and 2-year survival prognosis in patients with cardiac arrest (CA) after acute myocardial infarction (AMI),and after ROSC,the effects of various factors on midian survival time and on 2-year survival.Methods In a registry study from January 2005 to January 2015,all consecutive AMI-induced CA patients treated with cardiopulmonary resuscitation (CPR) admitted to our hospital were enrolled.The survivors were followed-up for 2 years.Univariate analysis was applied to evaluate factors associated with rate of ROSC and 2-year survival.Multivariable logistic regression analysis was applied to evaluate statistically significant factors in the univariate analysis.Medians with inter-quartile ranges were used to describe 2-year survival time affected by various factors after ROSC.Kaplan-Meier survival curve analysis was used to evaluate the effect of factors on 2-year survival.Results A total of 254 cases with CA after AMI were enrolled,including 129 cases of ROSC and 71 cases of 2-year survival.Univariate analysis showed age ≥ 70 years,CA occurred during 22:00-8:00,the duration time ofCPR ≥ 15 min and adrenaline dosage ＞ 5 mg were unfavorable predictors of ROSC;while,left ventricular ejection fraction (LVEF) ≥ 40％ before CA,shockable rhythm and percutaneous coronary intervention (PCI) therapy were favorable predictors.Besides,age ≥ 70 years,intubation during CPR,adrenaline dosage ＞ 5 mg and cardiogenic shock were unfavorable predictors of 2-year survival;While,male,normal daily activity before CA and PCI treatment were favorable predictors.Multivariable analysis showed age,the duration of CPR,adrenaline dosage,LVEF before CA,the rhythm during CPR and PCI therapy were independent predictors of ROSC.Age and PCI therapy were independent predictors of 2-year survival.Among patients,the survival time was affected by various factors after ROSC,and the factors with minimum 25％ and small median value were associated with cardiac rupture,cancer,adrenaline dosage ＞ 5 mg and cardiogenic shock.The factor with maximum 25％ value was PCI treatment (216 days).Kaplan-Meier survival analysis suggested that age ≥ 70 years was an unfavorable factor of 2-years survival (Log-rank test,P=0.007);while,PCI treatment was a favorable factor (Log-rank test,P＜0.01).PCI-related prognosis analysis showed that the effectiveness of PCI was related to the timing of PCI,the number of infarctrelated artery and the difference in culprit lesion.Conclusions The age ≥ 70 years was disadvantageous to both ROSC and 2-year survival.PCI treatment was favorable to both ROSC and 2-year survival.

Objective To study primary transfer and secondary transfer of exfoliated cells by handshaking and touching. Methods Firstly, volunteers wash hands , then shake hands between two volunteers, after that each volunteer touch the cleaned glass. Finally, pick up the DNA from the glass. Results STR loci that can be extracted from glasses. Under the same conditions, the number of STR loci obtained by primary transfer is more than that obtained by the secondary transfer. Conclusion Primary transfer and secondary transfer of exfoliated cells could happened by handshaking and touching. Therefore, in forensic work, we should pay great attention to the pollution problems caused by DNA transfer.

Objective To investigate the significance of a comprehensive test on the semen stain in the field of forensic evidence;Methods PSA tests performed on samples obtained supernatant and sediment STR genotyping by differential lysis method;Results Through STR testing,there are inconsistencies with the PSA test results in which 13 cases of false positive and false negative in 1 case.The supernatant was detected in two cases of male component,coeducational 9 cases;Conclusion PSA test strips there are some false positive and false negative rate,test isolated by the difference lysis supernatant can not only increase the success rate of the fine on the semen stain can also as a supplement to bring more valuable information for the semen stain.

OBJECTIVETo determine the effective dose of hepatitis B immunoglobulin (HBIG) for clearing maternally-transmitted hepatitis B virus (HBV) from a newborn.

METHODSFull-term neonates born to HBV-infected mothers were tested for hepatitis B surface antigen (HBsAg) and HBV DNA in venous blood, Individuals with positive results within two hours after birth were selected for study, and divided among two treatment groups: research group receiving HBIG continually adjusted to quantitative levels of neonatal HBsAg and HBV DNA levels; control group receiving standard HBIG 200IU dose. All neonates were also treated with 10 micrograms of recombinant vaccine. The decreases in HBsAg and HBV DNA over 12 months were comparatively analyzed between the two treatment groups.

RESULTSThe two treatment groups (HBIG adjusted vs. standard) were statistically similar in Apgar score (9.38+/-0.49 vs. 9.37+/-0.48), neonate body weight (3458.67+/-374.93 vs. 3558.61+/-322.85 g), maternal age (26.33+/-3.63 vs. 25.33+/-3.03), and initial HBsAg and HBV DNA levels (rank sum test Z = 1.381, and Z = 0.700, respectively) (all, P more than 0.05). Successful clearance of HBV infection within 12 months was achieved in significantly more neonates in the HBIG adjusted therapy group than in the standard therapy group (82.8% vs. 57.4%; x2 = 9.696, P less than 0.05).

CONCLUSIONAdjusting the neonatal HBIG dose according to HBsAg and HBV DNA levels can improve the success rate of clearing maternally-transmitted HBV.

DNA, Viral ; Dose-Response Relationship, Immunologic ; Female ; Hepatitis B ; prevention & control ; therapy ; Hepatitis B Surface Antigens ; blood ; immunology ; Hepatitis B virus ; genetics ; immunology ; Humans ; Immunoglobulins ; administration & dosage ; therapeutic use ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; prevention & control