Objective:To analyze the etiological characteristics, serotype distribution, drug resistance and molecular typing characteristics based on data collected by active surveillance of foodborne diseases in Shanxi Province from 2021 to 2022.Methods:Fecal and anal swabs for foodborne disease tests were collected from 17 sentinel hospitals in Shanxi Province from 2021 to 2022. The pathogens included Shigella, Salmonella, Vibrio parahaemolyticus and 5 types of diarrheagenic Escherichia coli ( E. coli). The positive strains were identified by mass spectrometry or systematic biochemistry. Salmonella and Shigella were serotyped by slide agglutination, and diarrheagenic E. coli was typed by multiplex fluorescence PCR. Vibrio parahaemolyticus was tested for tlh/ tdh/ trh virulence genes by multiplex fluorescent PCR. All strains were also tested for drug resistance by the microbroth dilution method. Molecular typing was performed by pulsed-field gel electrophoresis (PFGE). Results:A total of 4 481 samples were collected from patients with diarrhea, and 555 target strains were detected, with a detection rate of 12.39%(555/4 481). Among them, there were 365 strains of Salmonella, 175 strains of diarrheagenic E. coli, 15 strains of Vibrio parahaemolyticus, and no Shigella. There were 32 serotypes of Salmonella, and the dominant serotypes were 158 strains of Salmonella senteritidis and 124 strains of Salmonella typhimurium. diarrheagenic E. coli classification: 79 strains of enteroaggregative E. coli, 72 strains of enteropathogenic E. coli, 23 strains of enterotoxic E. coli, 1 strain of enterohemorrhagic E. coli, and none of enteroinvasive E. coli. For Vibrio parahaemolyticus virulence gene carriage, all strains carried tlh; 11 strains (73.33%, 11/15) carried tdh only; 2 strains (13.33%, 2/15) carried trh; 1 strain (6.67%, 1/15) carried both tdh and trh genes; 1 strain (6.67%, 1/15) did not carry these two virulence genes. Antimicrobial resistance tests presented that Salmonella had the highest resistance rate to ampicillin (85.21%, 311/365), followed by naphridic acid (66.58%, 243/365), and multi-drug resistance (78.63%, 287/365), resulting in 135 drug resistance spectrums. The resistance rate of diarrheagenic E. coli to ampicillin was the highest (81.71%, 143/175), followed by tetracycline (67.43%, 118/175), and multi-drug resistance (72.57%, 127/175), resulting in 81 drug resistance spectrums. Vibrio parahaemolyticus had the highest resistance rate to cefazolin (93.33%, 14/15), followed by tetracycline (26.67%, 4/15) and multi-drug resistance (20.00%, 3/15), resulting in 3 drug resistance spectrums. A total of 158 strains of Salmonella enteritidi, 124 strains of Salmonella typhimurium, 13 strains of Salmonella london and 175 strains of DEC were typed by PFGE. Among 470 strains of PFGE typing, 6 strains of DEC were degraded by DNA, while the remaining strains obtained effective PFGE band. Salmonella enteritidi were divided into 64 PFGE band types, Salmonella typhimurium were divided into 115 PFGE band types, Salmonella london were divided into 13 PFGE band types and diarrheagenic E. coli were divided into 165 PFGE band types. Conclusions:Shigella is not detected in the active surveillance, and Salmonella is detected most frequently. Salmonella and diarrheagenic E. coli have the highest resistance rates to ampicillin, and Vibrio parahaemolyticus has the highest resistance rates to cefazolin. The PFGE classification is polymorphic, and the dominant band type is not obvious. The evidence of multi-drug resistance suggests further strengthening monitoring and management of drug resistance.

Objective:To investigate the host and vector composition of pestis and the epidemic situation of pestis among animals in the border port areas of Longchuan County, Yunnan Province.Methods:In September 2022, a survey was conducted on rodents and their surface parasitic fleas in the border port areas of Longchuan County, according to three habitat types: residential areas, agricultural areas, and forest-shrubbery areas. Samples of murine animals organs and their surface parasitic fleas were collected for isolation and identification of Yersinia pestis. Blood samples of plague indicating animals, such as murine animals, dogs and cats were collected, and serum plague F1 antibody was detected by indirect hemagglutination assay. Meanwhile, a retrospective investigation was conducted on the occurrence of self dead rats, sick rats, and suspected cases in the local area from 2018 to 2022 through interviews with farmers. Results:A total of 168 murine animals belonging to 3 orders, 5 families, 10 genera, and 11 species were captured in three habitats in Longchuan County. Among them, the capture rate in residential areas was 5.00% (30/600), with Rattus tanezumi and Suncus murinus as dominant species, with a composition ratio of 50.00% (15/30). The capture rate in agricultural areas was 9.67% (122/1 262), with Rattus tanezumi and Suncus murinus as dominant species, with a composition ratio of 50.82% (62/122) and 44.26% (54/122), respectively. The capture rate in the forest-shrubbery areas was 6.25% (16/256), with Hylomys suillus and Eothenomys eleusis as dominant species, with a composition ratio of 37.50% (6/16) and 31.25% (5/16), respectively. Among the captured murine animals, 20 individuals carried 52 parasitic fleas, belonging to 2 species of 2 genera and 2 families. The total flea infection rate was 11.90% (20/168), and the total flea index was 0.31 (52/168). The dominant specie was Xenopsylla cheopis (90.38%, 47/52). The flea infection rate in residential areas was 33.33% (10/30), and the flea index was 1.23 (37/30). The flea infection rate in agricultural areas was 7.38% (9/122), and the flea index was 0.11 (14/122). The flea infection rate in the forest-shrubbery areas was 6.25% (1/16), and the flea index was 0.06 (1/16). The samples of murine animals and their parasitic fleas obtained were isolated and cultured by Yersinia pestis, and the results were negative. A total of 144 serum samples from murine animals, dogs and cats were separated, and no F1 antibody against pestis was detected. According to interviews and investigations, no abnormal situations such as a large number of self dead rats, sick rats, and suspected cases were found from 2018 to 2022. Conclusions:No plague epidemic has been found in the border port areas of Longchuan County recently. The main host of plague, Rattus tanezumi, and the main vector, Xenopsylla cheopis, remain the dominant species in this area.

Objective To explore the anti-inflammatory mechanism of Tong-Xie-Yao-Fang's intervention on irritable bowel syndrome with diarrhea(IBS-D),the effects of Tong-Xie-Yao-Fang on farnesol receptor(FXR),nuclear factor-κB(NF-κB)and inflammatory factors in IBS-D model rats were observed.Methods Healthy SD rats were randomly divided into blank group(Control group),model group(Model group),low-dose group of Tong-Xie-Yao-Fang(TXYF-L group,4.977 g/kg),middle-dose group of Tong-Xie-Yao-Fang(TXYF-M group,9.954 g/kg),and high-dose group of Tong-Xie-Yao-Fang(TXYF-H group,19.908 g/kg),Pivium bromide group(PWXA group,0.018 g/kg),with 10 rats in each group.Except for the blank group,the IBS-D rat models of liver depression and spleen deficiency were established by chronic restraint stress and senna intragastric administration.After the model was successfully established,the intervention was continued for 14 days according to the corresponding group treatment method.The general situation,diarrhea rate,fecal moisture content,water injection when abdominal wall retraction reflex reaches 3 scores,sugar water preference rate and serum D-xylose level were observed.The morphological and structural changes of rat colon were observed by HE staining.The expression of FXR gene in colon tissue was detected by real-time fluorescence quantitative PCR,the expression of FXR protein and NF-κB protein in colon tissue was detected by protein Western blot,and the levels of serum IL-6,IL-8 and TNF-α were detected by ELISA.Results After the treatment of Tong-Xie-Yao-Fang,the weight of each dosage group of Tong-Xie-Yao-Fang increased,the fecal water content decreased,the sugar water preference rate increased,the water injection volume increased when the rats reached the third grade of abdominal retraction reflex score,the serum D-xylose content increased and the food intake increased.HE staining showed that villous or finger-like structures appeared in the mucosal epithelium of model group,and inflammatory cells infiltrated in the upper mucosa.After treatment,the mucosal epithelium in TXYF-M group was smooth,villous or finger-like structures disappeared,and the infiltration degree of inflammatory cells decreased.Compared with the model group,the expression of FXR mRNA and FXR protein in the colon tissue of rats in the high-dose group of Tong-Xie-Yao-Fang increased significantly,while the concentration of IL-6,IL-8 and TNF-α in serum and the expression of NF-κB protein in the colon tissue of rats in the high-dose group of Tong-Xie-Yao-Fang decreased.Conclusion The mechanism of Tong-Xie-Yao-Fang in treating low-grade inflammation of IBS-D intestinal mucosa may be related to activating the expression of FXR in colon,inhibiting the expression of NF-κB in colon tissue,and then reducing the concentration of pro-inflammatory factors IL-6,IL-8 and TNF-α in serum.

Objective To explore the anti-inflammatory mechanism of Tong-Xie-Yao-Fang's intervention on irritable bowel syndrome with diarrhea(IBS-D),the effects of Tong-Xie-Yao-Fang on farnesol receptor(FXR),nuclear factor-κB(NF-κB)and inflammatory factors in IBS-D model rats were observed.Methods Healthy SD rats were randomly divided into blank group(Control group),model group(Model group),low-dose group of Tong-Xie-Yao-Fang(TXYF-L group,4.977 g/kg),middle-dose group of Tong-Xie-Yao-Fang(TXYF-M group,9.954 g/kg),and high-dose group of Tong-Xie-Yao-Fang(TXYF-H group,19.908 g/kg),Pivium bromide group(PWXA group,0.018 g/kg),with 10 rats in each group.Except for the blank group,the IBS-D rat models of liver depression and spleen deficiency were established by chronic restraint stress and senna intragastric administration.After the model was successfully established,the intervention was continued for 14 days according to the corresponding group treatment method.The general situation,diarrhea rate,fecal moisture content,water injection when abdominal wall retraction reflex reaches 3 scores,sugar water preference rate and serum D-xylose level were observed.The morphological and structural changes of rat colon were observed by HE staining.The expression of FXR gene in colon tissue was detected by real-time fluorescence quantitative PCR,the expression of FXR protein and NF-κB protein in colon tissue was detected by protein Western blot,and the levels of serum IL-6,IL-8 and TNF-α were detected by ELISA.Results After the treatment of Tong-Xie-Yao-Fang,the weight of each dosage group of Tong-Xie-Yao-Fang increased,the fecal water content decreased,the sugar water preference rate increased,the water injection volume increased when the rats reached the third grade of abdominal retraction reflex score,the serum D-xylose content increased and the food intake increased.HE staining showed that villous or finger-like structures appeared in the mucosal epithelium of model group,and inflammatory cells infiltrated in the upper mucosa.After treatment,the mucosal epithelium in TXYF-M group was smooth,villous or finger-like structures disappeared,and the infiltration degree of inflammatory cells decreased.Compared with the model group,the expression of FXR mRNA and FXR protein in the colon tissue of rats in the high-dose group of Tong-Xie-Yao-Fang increased significantly,while the concentration of IL-6,IL-8 and TNF-α in serum and the expression of NF-κB protein in the colon tissue of rats in the high-dose group of Tong-Xie-Yao-Fang decreased.Conclusion The mechanism of Tong-Xie-Yao-Fang in treating low-grade inflammation of IBS-D intestinal mucosa may be related to activating the expression of FXR in colon,inhibiting the expression of NF-κB in colon tissue,and then reducing the concentration of pro-inflammatory factors IL-6,IL-8 and TNF-α in serum.

Objective:To investigate the host and vector composition of pestis and the epidemic situation of pestis among animals in the border port areas of Longchuan County, Yunnan Province.Methods:In September 2022, a survey was conducted on rodents and their surface parasitic fleas in the border port areas of Longchuan County, according to three habitat types: residential areas, agricultural areas, and forest-shrubbery areas. Samples of murine animals organs and their surface parasitic fleas were collected for isolation and identification of Yersinia pestis. Blood samples of plague indicating animals, such as murine animals, dogs and cats were collected, and serum plague F1 antibody was detected by indirect hemagglutination assay. Meanwhile, a retrospective investigation was conducted on the occurrence of self dead rats, sick rats, and suspected cases in the local area from 2018 to 2022 through interviews with farmers. Results:A total of 168 murine animals belonging to 3 orders, 5 families, 10 genera, and 11 species were captured in three habitats in Longchuan County. Among them, the capture rate in residential areas was 5.00% (30/600), with Rattus tanezumi and Suncus murinus as dominant species, with a composition ratio of 50.00% (15/30). The capture rate in agricultural areas was 9.67% (122/1 262), with Rattus tanezumi and Suncus murinus as dominant species, with a composition ratio of 50.82% (62/122) and 44.26% (54/122), respectively. The capture rate in the forest-shrubbery areas was 6.25% (16/256), with Hylomys suillus and Eothenomys eleusis as dominant species, with a composition ratio of 37.50% (6/16) and 31.25% (5/16), respectively. Among the captured murine animals, 20 individuals carried 52 parasitic fleas, belonging to 2 species of 2 genera and 2 families. The total flea infection rate was 11.90% (20/168), and the total flea index was 0.31 (52/168). The dominant specie was Xenopsylla cheopis (90.38%, 47/52). The flea infection rate in residential areas was 33.33% (10/30), and the flea index was 1.23 (37/30). The flea infection rate in agricultural areas was 7.38% (9/122), and the flea index was 0.11 (14/122). The flea infection rate in the forest-shrubbery areas was 6.25% (1/16), and the flea index was 0.06 (1/16). The samples of murine animals and their parasitic fleas obtained were isolated and cultured by Yersinia pestis, and the results were negative. A total of 144 serum samples from murine animals, dogs and cats were separated, and no F1 antibody against pestis was detected. According to interviews and investigations, no abnormal situations such as a large number of self dead rats, sick rats, and suspected cases were found from 2018 to 2022. Conclusions:No plague epidemic has been found in the border port areas of Longchuan County recently. The main host of plague, Rattus tanezumi, and the main vector, Xenopsylla cheopis, remain the dominant species in this area.

Objective:To analyze the etiological characteristics, serotype distribution, drug resistance and molecular typing characteristics based on data collected by active surveillance of foodborne diseases in Shanxi Province from 2021 to 2022.Methods:Fecal and anal swabs for foodborne disease tests were collected from 17 sentinel hospitals in Shanxi Province from 2021 to 2022. The pathogens included Shigella, Salmonella, Vibrio parahaemolyticus and 5 types of diarrheagenic Escherichia coli ( E. coli). The positive strains were identified by mass spectrometry or systematic biochemistry. Salmonella and Shigella were serotyped by slide agglutination, and diarrheagenic E. coli was typed by multiplex fluorescence PCR. Vibrio parahaemolyticus was tested for tlh/ tdh/ trh virulence genes by multiplex fluorescent PCR. All strains were also tested for drug resistance by the microbroth dilution method. Molecular typing was performed by pulsed-field gel electrophoresis (PFGE). Results:A total of 4 481 samples were collected from patients with diarrhea, and 555 target strains were detected, with a detection rate of 12.39%(555/4 481). Among them, there were 365 strains of Salmonella, 175 strains of diarrheagenic E. coli, 15 strains of Vibrio parahaemolyticus, and no Shigella. There were 32 serotypes of Salmonella, and the dominant serotypes were 158 strains of Salmonella senteritidis and 124 strains of Salmonella typhimurium. diarrheagenic E. coli classification: 79 strains of enteroaggregative E. coli, 72 strains of enteropathogenic E. coli, 23 strains of enterotoxic E. coli, 1 strain of enterohemorrhagic E. coli, and none of enteroinvasive E. coli. For Vibrio parahaemolyticus virulence gene carriage, all strains carried tlh; 11 strains (73.33%, 11/15) carried tdh only; 2 strains (13.33%, 2/15) carried trh; 1 strain (6.67%, 1/15) carried both tdh and trh genes; 1 strain (6.67%, 1/15) did not carry these two virulence genes. Antimicrobial resistance tests presented that Salmonella had the highest resistance rate to ampicillin (85.21%, 311/365), followed by naphridic acid (66.58%, 243/365), and multi-drug resistance (78.63%, 287/365), resulting in 135 drug resistance spectrums. The resistance rate of diarrheagenic E. coli to ampicillin was the highest (81.71%, 143/175), followed by tetracycline (67.43%, 118/175), and multi-drug resistance (72.57%, 127/175), resulting in 81 drug resistance spectrums. Vibrio parahaemolyticus had the highest resistance rate to cefazolin (93.33%, 14/15), followed by tetracycline (26.67%, 4/15) and multi-drug resistance (20.00%, 3/15), resulting in 3 drug resistance spectrums. A total of 158 strains of Salmonella enteritidi, 124 strains of Salmonella typhimurium, 13 strains of Salmonella london and 175 strains of DEC were typed by PFGE. Among 470 strains of PFGE typing, 6 strains of DEC were degraded by DNA, while the remaining strains obtained effective PFGE band. Salmonella enteritidi were divided into 64 PFGE band types, Salmonella typhimurium were divided into 115 PFGE band types, Salmonella london were divided into 13 PFGE band types and diarrheagenic E. coli were divided into 165 PFGE band types. Conclusions:Shigella is not detected in the active surveillance, and Salmonella is detected most frequently. Salmonella and diarrheagenic E. coli have the highest resistance rates to ampicillin, and Vibrio parahaemolyticus has the highest resistance rates to cefazolin. The PFGE classification is polymorphic, and the dominant band type is not obvious. The evidence of multi-drug resistance suggests further strengthening monitoring and management of drug resistance.

Objective To investigate the influencing factors of adverse pregnancy outcomes in patients with preeclampsia and the predictive value of serum trace elements in the second trimester.Methods A total of 98 patients with preeclampsia admitted to Qujing First People's Hospital from January 2019 to June 2022 were enrolled in the study.Patients were divided into poor outcome group and good outcome group according to whether they had adverse pregnancy outcomes.The clinical data of all patients enrolled in the study were col-lected and the serum levels of trace elements calcium,copper,zinc and iron were detected in the second trimes-ter.Univariate analysis and multivariate Logistic regression were used to analyze the influencing factors of ad-verse pregnancy outcomes in patients with preeclampsia.The levels of serum trace elements in the second tri-mester of pregnancy were compared between the poor outcome group and the good outcome group.The re-ceiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum trace elements calcium,copper,zinc and iron for adverse pregnancy outcomes in patients with preeclampsia.Results Univari-ate analysis showed that compared with the good outcome group,the poor outcome group had significantly higher systolic blood pressure,24 h urinary protein quantitation,and D-dimer level(P＜0.05)and significantly less gestational age and platelet count at admission(P＜0.05).Multivariate Logistic regression analysis showed that 24 h urinary protein quantification,D-dimer and platelet count were the influencing factors of ad-verse pregnancy outcomes in patients with preeclampsia(P＜0.05).The levels of serum trace elements calci-um,copper,and zinc in the poor outcome group were significantly lower than those in the good outcome group(P＜0.05),and the level of iron was significantly higher than that in the good outcome group(P＜0.05).ROC curve analysis showed that the areas under the curves(AUCs)of serum calcium,copper,zinc,and iron in the second trimester of pregnancy for predicting adverse pregnancy outcomes in preeclampsia patients were 0.830(95％CI:0.780-0.880),0.855(95％CI:0.805-0.905),0.847(0.797-0.897)and 0.861(95％CI:0.811-0.911),respectively.Conclusion Adverse pregnancy outcomes in patients with preeclampsia are re-lated to 24 h urine protein,D-dimer and platelet count.The levels of serum trace elements calcium,copper,zinc and iron in the second trimester of pregnancy change significantly in patients with adverse pregnancy out-comes,which may become predictive markers of adverse pregnancy outcomes.

Objective To explore the relationship between the variability of blood pressure and the occurrence of acute kidney injury(AKI)in patients with hypovolemic shock so as to provide a theoretical basis for early prediction and prevention of AKI.Methods Clinical data of 661 critically ill patients with hypovolemic shock were acquired from the Medical Information Mart for Intensive Care Ⅳ(MIMIC-Ⅳ)database from 2008 to 2022.Data were grouped with the quartile division method,with systolic blood pressure average real variability(SBP-ARV)and diastolic blood pressure average real variability(DBP-ARV)as the continuous or categorical variables.Univariate and multivariate logistic regression analyses were used to examine the relationships of SBP-ARV and DBP-ARV with the occurrence of AKI.Additionally,the relationship between SBP-ARV and the occurrence of AKI was further investigated in subgroups of gender,age,sequential organ failure assessment(SOFA),hypertension,diabetes,and the use of vasopressors after correction of all covariates.Results Logistic regression analysis showed that SBP-ARV,a continuous variable,was independently associated with the occurrence of AKI[OR(95%CI):1.05(1.01～1.10),P=0.024].However,DBP-ARV was not significantly related to the occurrence of AKI.When SBP-ARV was grouped by quartile division,Q4 group had a significantly higher risk of AKI[OR(95%CI):1.83(1.04～3.22),P=0.037]compared with that of Q1 group.Analyses across the subgroups revealed that there was an interaction between SBP-ARV and diabetes(P=0.033).Conclusion For ICU patients with hypovolemic shock,SBP-ARV positively associates with the occurrence of AKI.

Objective To explore the relationship between the variability of blood pressure and the occurrence of acute kidney injury(AKI)in patients with hypovolemic shock so as to provide a theoretical basis for early prediction and prevention of AKI.Methods Clinical data of 661 critically ill patients with hypovolemic shock were acquired from the Medical Information Mart for Intensive Care Ⅳ(MIMIC-Ⅳ)database from 2008 to 2022.Data were grouped with the quartile division method,with systolic blood pressure average real variability(SBP-ARV)and diastolic blood pressure average real variability(DBP-ARV)as the continuous or categorical variables.Univariate and multivariate logistic regression analyses were used to examine the relationships of SBP-ARV and DBP-ARV with the occurrence of AKI.Additionally,the relationship between SBP-ARV and the occurrence of AKI was further investigated in subgroups of gender,age,sequential organ failure assessment(SOFA),hypertension,diabetes,and the use of vasopressors after correction of all covariates.Results Logistic regression analysis showed that SBP-ARV,a continuous variable,was independently associated with the occurrence of AKI[OR(95%CI):1.05(1.01～1.10),P=0.024].However,DBP-ARV was not significantly related to the occurrence of AKI.When SBP-ARV was grouped by quartile division,Q4 group had a significantly higher risk of AKI[OR(95%CI):1.83(1.04～3.22),P=0.037]compared with that of Q1 group.Analyses across the subgroups revealed that there was an interaction between SBP-ARV and diabetes(P=0.033).Conclusion For ICU patients with hypovolemic shock,SBP-ARV positively associates with the occurrence of AKI.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins