OBJECTIVE To establish the high-performance liquid chromatography （HPLC） fingerprint of Sagina japonica ， and to establish a quantitative analysis of multi-components by single-marker （QAMS） method for simultaneous determination of six componen ts in S. japonica ， aiming to provide references for the quality control of this medicinal herb. METHODS HPLC method was used to establish the fingerprints of 12 batches （No. S1-S12） of S . japonica according to Similarity Evaluation System of Chromatographic Fingerprint of Traditional Chinese Medicine . The similarity evaluation and identification of common peaks were conducted， followed by cluster analysis （CA） and principal component analysis （PCA） for 12 batches of samples. Using vicenin-2 as internal reference， the contents of p-hydroxy cinnamic acid， apigenin-6-C-arabinoside-8-C-glucoside， isoorientin， vitexin and 20-hydroxyecdysone were determined by QAMS method. The results were then compared with those obtained by the external standard method. RESULTS The similarities of HPLC fingerprints for 12 batches of S . japonica ranged from 0.828-0.998. A total of 17 common peaks were calibrated， and 6 common peaks were identified. Specifically， peak 5 was identified as vicenin-2， peak 7 as p-hydroxycinnamic acid， peak 10 as apigenin-6-C-arabinoside-8-C-glucoside， peak 11 as isoorientin， peak 13 as vitexin， and peak 15 as 20-hydroxyecdysone. The results of CA showed that S1-S5， S7 and S9-S11 were clustered into one category， S6 was clustered into one category， and S8 and S12 were clustered into one category. The results of PCA revealed that the accumulative contribution rate of the four main components was 89.430%. The content ranges measured by QAMS method for p-hydroxy cinnamic acid， apigenin-6-C-arabinoside-8-C-glucoside， isoorientin， vitexin and 20-hydroxyecdysone were 0.017 4-0.269 4， 0.568 8-4.240 3， 0.503 2-5.040 3， 0.024 0-0.132 0 and 2.551 3-4.881 1 mg/g， respectively. There was no significant difference in the contents of components measured between QAMS method and the external standard method （ P ＞0.05）. CONCLUSIONS The established HPLC fingerprint and QAMS method can be used for quality evaluation and quality control of S . japonica.

Objective To analyze the dynamic change in placental growth factor(PLGF)level in patients with preeclampsia(PE)and its role in predicting pregnancy outcomes.Methods A retrospective cohort study was conducted on 198 PE patients admitted to Department of Obstetrics of Tianjin Beichen Hospital from January 2021 to January 2024.Among them,151 cases were identified as non-severe PE and 47 cases as severe PE.During the same period,another 100 healthy pregnant women were included in the department and served as the control group.According to the final pregnancy status of the PE patients,they were divided into an adverse outcome group(88 cases)and a good outcome group(110 cases).Locally Weighted Scatterplot Smoothing(LOWESS)was used to analyze the relationship between vascular endothelial function indicators and PLGF level.Logistic regression was employed to identify the influencing factors for adverse pregnancy outcomes.Receiver operating characteristic(ROC)curve was plotted to evaluate the value of PLGF level for predicting adverse pregnancy outcomes in patients with non-severe PE and severe PE.Results The PLGF level was in a peak shape at different gestational weeks,relatively low at 28～29+6 weeks of gestation,gradually increasing with the increment of gestational weeks,reaching a peak at 30～31+6 weeks of gestation,and then gradually decreased(P<0.05).The PLGF level was gradually reduced in the control group,non-severe PE group,and severe PE group in turn(P<0.05).LOWESS analysis showed that the PLGF level exhibited certain nonlinear relationship with soluble fms-like tyrosine kinase receptor 1(sFlt-1),vascular endothelial growth factor(VEGF),nitric oxide(NO),thrombomodulin(TM),thromboxane A2(TXA2),and Von Willebrand factor(VwF).The results of logistic regression analysis indicated that after gradually eliminating collinearity confounding factors and adjusting for each covariate,there was still an independent correlation between the PLGF level at 28～29+6 gestational weeks and pregnancy outcome(OR=0.593,95%CI:0.583～0.778,P<0.001).After converting the PLGF level into a binary variable,there was an independent correlation between high PLGF level and pregnancy outcome(OR=0.773,95%CI:0.671～0.885,P<0.001).Compared with the quintile with the lowest PLGF(Q1),as the PLGF level gradually increased(Q2 to Q5),the correlation effect values were(OR=0.765,95%CI:0.639～0.837,P=0.092),(OR=0.752,95%CI:0.624～0.818,P=0.056),(OR=0.696,95%CI:0.615～0.813,P=0.027),and(OR=0.642,95%CI:0.591～0.733,P<0.001),and the trend test was statistically significant(Ptrend<0.001).ROC curve analysis revealed that the area under the ROC curve(AUC)of serum PLGF level at 28-29+6 gestational weeks in predicting adverse pregnancy outcomes in non-severe PE patients was 0.830(95%CI:0.635～0.917),the optimal critical threshold was 75.47 ng/L,the sensitivity was 88.37%,the specificity was 71.30%,the positive predictive value was 55.07%,and the negative predictive value was 93.90%.Its AUC value of the level for the prediction in patients with severe PE was 0.874(95%CI:0.677～0.923),the optimal critical threshold was 38.53 ng/L,the sensitivity was 88.89%,the specificity was 50.00%,the positive predictive value was 97.56%,and the negative predictive value was 16.67%.Conclusion At 28～29+6 gestational weeks,PLGF has an independent correlation with pregnancy outcomes and shows a good predictive performance for adverse pregnancy outcomes in patients with non-severe PE and severe PE.

Objective To explore the pharmacokinetic characteristics of sufentanil in individuals with normal body mass index(BMI),overweight BMI,and different CYP3A4/5 enzyme genotypes.Methods The patients receiving laparoscopic surgery under general anesthesia in the First Affiliated Hospital of Army Medical University from November 2020 to September 2021 were prospectively recruited in this study.Before the operation,the oral swabs were collected from all the patients for genotyping using the human CYP3A4/5 gene kit.Based on the potential impact of combination of their polymorphisms on sufentanil metabolism and the proportion of different genotype combinations of CYP3A4/5 enzymes,the patients were divided into groups I(3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation),II(3A4 heterozygous mutation+3A5 heterozygous mutation),and III(3A4 wild type or 3A4 heterozygous mutation+3A5 wild type).According to their BMI,they were also assigned into a normal body weight group(18.5～24.0 kg/m2)and an overweight group(24～<28 kg/m2),and the differences in drug metabolism parameters were statistically analyze between the 2 groups.After routine general anesthesia induction(sufentanil 0.5 μg/kg),venous blood samples were collected to detect the changes in its concentration using high performance liquid chromatography-mass spectrometry(HPLC-MS).The pharmacokinetic data of sufentanil were calculated between the normal BMI group and overweight group in all participants and between the 2 body weight groups among those with different genotype combinations.Results Among the 90 participants completing the blood drug concentration test,8 patients had their blood samples contaminated(including 1 case with an anesthesia duration of<2 h),and 3 were excluded due to low weight or overweight.Eventually,79 participants were included in the pharmacokinetic analysis on the normal body weight group and the overweight group.Compared with the normal body weight group,the central compartment volume of distribution in the overweight group was significantly reduced(P<0.05),while no obvious differences were observed between the 2 groups in terms of peripheral compartment volume of distribution,total clearance rate,peripheral compartment clearance rate,distribution half-life,clearance half-life,and area under the blood concentration-time curve.In group Ⅰ(n=26),the overweight patients(n=13)had significantly reduced central compartment volume of distribution,peripheral compartment volume of distribution,and peripheral compartment clearance rate when compared with the normal body weight patients(n=13)(P<0.05),while no differences were observed in other pharmacokinetic parameters.In groups Ⅱ(n=25)and Ⅲ(n=28),the overweight patients and normal body weight patients had no statistical differences in all pharmacokinetic parameters.Conclusion Among the patients with the same genotype combination of CYP3A4/5 mutations,there was no difference in the metabolism of sufentanil between the overweight and normal weight patients.Additionally,in the population of 3A4 homozygous mutation or 3A4 heterozygous mutation+3A5 homozygous mutation,the overweight patients have smaller peripheral distribution range of sufentanil,and weakened metabolic process.

Objective:To investigate the clinical distribution characteristics changes in antimicrobial resistance, and carbapenemase resistance genes of Klebsiella pneumoniae isolated from children in Chongqing region during the period of January 2019 to December 2024, providing a basis for the rational use of antibiotics and the prevention and control of nosocomial infections.Methods:An observational study was conducted to retrospectively analyze 5 020 Klebsiella pneumoniae (KP) isolates detected in four hospitals of the Southwest Pediatric Laboratory Specialty Alliance. Antimicrobial susceptibility testing was performed by the minimum inhibitory concentration method combined with the disk diffusion method. Results were interpreted according to the 2024 Clinical and Laboratory Standards Institute (CLSI) standards. Carbapenemase resistance genes were detected by polymerase chain reaction (PCR) combined with Sanger sequencing. WHONET 5.6 was used for resistance analysis and SPSS 19.0 for statistical analysis. The chi-square test was used to assess trends in resistance rates, ESBL detection rates, and resistance rates of different CRKP carbapenemase genotypes from 2019 to 2024. Statistical significance was confirmed if the two-tailed P-value was <0.05. Results:A total of 5 020 strains were isolated, with a detection rate of 5.1% (5 020/99 063). The majority were from sputum (59.2%, 2 970/5 020), followed by pus (17.1%, 857), urine (9.7%, 487), venous blood (6.5%, 326), secretions (2.6%, 130), and other specimens (5.0%, 250).The lowest resistance rate was to amikacin (3.8%), followed by levofloxacin (10.9%), imipenem (19.1%), and meropenem (19.9%). Resistance rates to cefoperazone/sulbactam ( χ2=9.982 0, P=0.001 6), piperacillin/tazobactam ( χ2=10.110 0, P=0.001 5), ceftazidime ( χ2=3.849 0, P=0.049 8), cefotaxime ( χ2=7.605 0, P=0.005 8), cefepime ( χ2=13.510 0, P=0.000 2), aztreonam ( χ2=6.457 0, P=0.011 1), imipenem ( χ2=4.672 0, P=0.030 7), and levofloxacin ( χ2=7.555 0, P=0.006 0) showed an annual increasing trend. The main carbapenemase genes were blaNDM-5 (42.2%, 127/301), blaNDM-1 (33.9%, 102/301), and blaKPC-2 (17.3%, 52/301). Patients with KPC-2-producing strains (median age, 240 days) were older than those with NDM-1/NDM-5-producing strains (median age, 40 days) ( χ2=22.620 0, P<0.000 1). In neonatal wards, the detection rate of NDM-KP was higher than that of KPC-KP (64.6%, 148/229 vs. 26.9%, 14/52, χ2=24.680 0, P<0.000 1), whereas in ICUs, it was lower (6.1%, 14/229 vs. 26.9%, 14/52, χ2=20.450 0, P<0.000 1). Conclusion:In Chongqing region, the isolation rate of K. pneumoniae from sputum was the highest with most cases from neonatal wards. Resistance to carbapenems showed an upward trend. BlaNDM-5 was the predominant genotype in pediatric CRKP. Patients with KPC-KP were older than those with NDM-KP. NDM-KP predominated in neonatal wards, while KPC-KP predominated in ICUs, with KPC-KP showing higher antimicrobial resistance.

Objective To analyze the predictive value of bispectral index(BIS)dynamic changes for hypotension after laparoscopic surgery in elderly patients with primary liver cancer.Methods 197 elderly patients with primary liver cancer who underwent laparoscopic surgery in the hospital from November 2021 to July 2024 were selected as the research subjects,and all patients received general anesthesia,and their perioperative BIS was monitored.The patients were divided into a hypotension group and a non hypotension group based on the occur-rence of hypotension after laparoscopic surgery.The general information and the BIS at 5 minutes before anesthesia induction(T0),5 minutes after anesthesia induction(T1),30 minutes after the start of surgery(T2)and the end of surgery(T3)in the two groups were compared.The influencing factors of hypotension after laparoscopic surgery in elderly patients with primary liver cancer were analyzed through Logistic regression analysis,and the predictive value of BIS for hypotension after laparoscopic surgery in elderly patients with primary liver cancer were analyzed through receiver operating characteristic(ROC)curve.Results 51 patients were experienced hypotension after laparoscopic surgery among 197 elderly patients with primary lung cancer,and the incidence rate was 25.89％.The proportion of hypertension and operative time in the hypotension group were higher than those in the non hypoten-sion group(P<0.05),while the levels of albumin(ALB)and BIS at T2 and T3 were lower than those in the non hypertension group(P<0.05).logistic regression analysis showed that hypertension,long operative time,low ALB level,low BIS value at T2 and low BIS value at T3 were all risk factors for hypotension after laparoscopic surgery in elderly patients with primary liver cancer(P<0.05).The sensitivity,specificity and area under curve(AUC)of BIS combined prediction of hypotension after laparoscopic surgery in elderly patients with primary liver cancer at T2 and T3 were 92.16％,78.08％and 0.902％respectively,and the sensitivity and AUC were higher than those single prediction(P<0.05),but the specificity was similar to that of single prediction.Conclusion The predictive value of BIS at 30 minutes after the start of surgery and the end of surgery for hypotension after laparoscopic surgery in elderly patients with primary liver cancer are good,and the joint prediction of this two can further enhance the predictive value.

OBJECTIVE To investigate the distribution and drug resistance of the pathogens isolated from sterile body fluids in a hospital so as to provide reference for clinical treatment of the infections.METHODS The sterile body fluids specimens that were cultured positive for pathogens were retrospectively collected from a three-A hos-pital of Jiangxi Province between 2016 and 2023.The distribution and drug resistance of the isolated pathogens were observed.RESULTS Totally 16,658 strains of pathogens were isolated from the sterile body fluid speci-mens in 2016-2023,among which gram-negative bacteria accounted for 51.74％.The species of bacteria that ranked the top 5 places were as follows:Escherichia coli,Klebsiella pneumoniae,Staphylococcus epidermidis,Staphylococcus hominis,and Staphylococcus aureus.The isolation rates of methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococcus were 28.32％and 74.94％,respectively;the strains maintained high sensitivity to linezolid and vancomycin,with the drug resistance rates no more than 2.50％.The drug resistance rates of Enterococcus faecium and Enterococcus faecalis to linezolid and vancomycin were always less than 4.20％.Among the species of Enterobacter,the drug resistance rates of the E.coli strains to meropenem declined from 17.65％to 5.94％;conversely,the drug resistance rate of the K.pneumoniae strains to carbapenems reached high up to 54.36％,showing an upward trend on the whole.Among the non-fermenting gram-negative bacteria,the drug resistance rate of the A.baumannii strains to carbapenems remained high(about 80.00％);while the drug resistance rates of the P.aeruginosa strains to meropenem dropped from 60.71％down to 24.32％.CONCLUSIONS The gram-negative bacteria are dominant among the pathogens isolated from the ster-ile body fluids in the hospital between 2016 and 2023.Although some major species of drug-resistant pathogens are effectively under control,the pathogens isolated from the sterile body fluid specimens maintain varying degree of drug resistance to various types of antibiotics.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective To explore and analyze the characteristics and transmission routes of carbapenem-resistant Klebsiella pneumoniae(CRKP)strains in intensive care unit(ICU).Methods From January to October 2023,17 clinical infection isolates(clinical infection group),5 active screening isolates(active screening group),and 7 envi-ronmental isolates(environmental group)of CRKP in the liver surgery ICU of a hospital were selected and analyzed by whole-genome sequencing.The differences in resistance genes,virulence genes,and sequence typing(ST)were compared,and transmission routes were analyzed based on the phylogenetic tree.Results 29 strains of CRKP car-ried 4-18 resistance genes and 52-98 virulence genes,respectively.There were no statistically significant diffe-rences in genotype distribution of resistance genes,the number of virulence genes,and gene types among three groups of CRKP(all P＞0.05).ST showed that 29 CRKP strains mainly consisted of two categories:ST11 and ST15.Based on the phylogenetic tree constructed from the core genome,there were 7 highly homologous groups of CRKP,among which 4 groups had clear epidemiological associations.Conclusion CRKP in ICU carries more re-sistance and virulence genes,and some strains are highly homologous in ST and phylogenetic tree,which may lead to cross transmission.In the future,prevention and control measures should be strengthened to reduce the trans-mission of CRKP.

Purpose To investigate the value of non-invasive preoperative prediction of programmed death ligand 1 expression status in extrahepatic cholangiocarcinoma using MRI radiomics combined with clinical features through nomograms.Materials and Methods A retrospective collection was made of 87 cases of extrahepatic cholangiocarcinoma diagnosed through surgical pathology in the Affiliated Hospital of Southwest Medical University from January 2011 to December 2021.These were randomly divided into training and testing sets at a 7∶3 ratio.Using 3D-Slicer software,regions of interest were manually delineated layer-by-layer on MRI images,and radiomic features were extracted.Data normalization,feature dimensionality reduction and selection were then performed.A Gaussian naive Bayes classifier was used to construct the radiomics model,and radiomics scores were obtained.Multivariate Logistic regression was used to screen clinical features,and individual clinical and combined models were constructed.The predictive performances of the three models were evaluated using the area under the receiver operating characteristic curve(AUC),and the goodness of fit and clinical net benefit of the combined model nomogram were assessed through calibration and decision curves.Results Nine radiomic features and three clinical features were finally selected.The clinical features included alanine transaminase(P=0.020),aspartate transaminase(P=0.025)and total bilirubin(P=0.026).The predictive performance of the combined model(training set AUC 0.813,testing set AUC 0.818)was superior to that of the individual clinical model(training set AUC 0.711,testing set AUC 0.705)and the radiomics model(training set AUC 0.769,testing set AUC 0.767).Calibration and decision curves indicated good fit and better clinical net benefit for the combined model nomogram.Conclusion Based on preoperative multi-sequence MRI images and the radiomics score,along with alanine transaminase,aspartate transaminase and total bilirubin as clinical features,the constructed combined model nomogram effectively predicts the programmed death ligand 1 expression status in extrahepatic cholangiocarcinoma.This provides guidance for the precise and personalized immunotherapy for patients.

Objective To analyze the predictive value of bispectral index(BIS)dynamic changes for hypotension after laparoscopic surgery in elderly patients with primary liver cancer.Methods 197 elderly patients with primary liver cancer who underwent laparoscopic surgery in the hospital from November 2021 to July 2024 were selected as the research subjects,and all patients received general anesthesia,and their perioperative BIS was monitored.The patients were divided into a hypotension group and a non hypotension group based on the occur-rence of hypotension after laparoscopic surgery.The general information and the BIS at 5 minutes before anesthesia induction(T0),5 minutes after anesthesia induction(T1),30 minutes after the start of surgery(T2)and the end of surgery(T3)in the two groups were compared.The influencing factors of hypotension after laparoscopic surgery in elderly patients with primary liver cancer were analyzed through Logistic regression analysis,and the predictive value of BIS for hypotension after laparoscopic surgery in elderly patients with primary liver cancer were analyzed through receiver operating characteristic(ROC)curve.Results 51 patients were experienced hypotension after laparoscopic surgery among 197 elderly patients with primary lung cancer,and the incidence rate was 25.89％.The proportion of hypertension and operative time in the hypotension group were higher than those in the non hypoten-sion group(P<0.05),while the levels of albumin(ALB)and BIS at T2 and T3 were lower than those in the non hypertension group(P<0.05).logistic regression analysis showed that hypertension,long operative time,low ALB level,low BIS value at T2 and low BIS value at T3 were all risk factors for hypotension after laparoscopic surgery in elderly patients with primary liver cancer(P<0.05).The sensitivity,specificity and area under curve(AUC)of BIS combined prediction of hypotension after laparoscopic surgery in elderly patients with primary liver cancer at T2 and T3 were 92.16％,78.08％and 0.902％respectively,and the sensitivity and AUC were higher than those single prediction(P<0.05),but the specificity was similar to that of single prediction.Conclusion The predictive value of BIS at 30 minutes after the start of surgery and the end of surgery for hypotension after laparoscopic surgery in elderly patients with primary liver cancer are good,and the joint prediction of this two can further enhance the predictive value.