Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective To observe the effect of Bushen Huoxue formula on interleukin-17(IL-17)in rats with recurrent spontaneous abortion(RSA).Methods RS A model rats were constructed by intraperitoneal injection of estradiol benzoate.Forty RSA model rats were randomly divided into model group,control group and experimental-L,-H groups,with 10 rats per group.Another 10 healthy pregnant rats were set as blank group.The experimental-L,-H groups were given 7.77 and 15.54 g·kg-1 of Bushen Huoxue formula solution by gavage.The control group was given 2.10 mg·kg-1of dydrogesterone solution by gavage.The blank group and the model group were given equal amount of 0.9％NaCl by gavage.The dose of administration for the five groups was 10 mL·kg-1,once a day,for 9 days.The number of live fetuses,embryo loss,and embryo loss rate in each group were observed.The proportion of Th 17 cells in the peripheral blood was detected by flow cytometry.The expression levels of interleukin-6(IL-6),IL-17 and IL-23 proteins in the decidual tissues were detected by Western blotting.Results The number of live fetuses in the experimental-H,control,model and blank groups were 11.50±2.84,11.50±3.10,6.30±1.25 and 12.50±3.24;the number of embryos lost were 1.80±0.42,1.90±0.57,4.90±1.37 and 0;the rates of embryo loss were(14.01±4.52)％,(14.79±6.06)％,(43.50±9.49)％and 0;the proportions of Th17 cells in the peripheral blood were(3.12±0.47)％,(3.10±0.59)％,(5.31±1.16)％and(2.54±0.71)％;the relative expression levels of IL-6 protein were 0.19±0.04,0.18±0.05,0.85±0.16 and 0.11±0.03;the relative expression levels of IL-17 protein were 0.28±0.04,0.29±0.05,0.84±0.12 and 0.09±0.01;the relative expression levels of IL-23 protein were 0.35±0.04,0.34±0.06,0.90±0.11 and 0.08±0.01,respectively.Comparing experimental-H group and model group,comparing control group and blank group,the above indexes were statistically significant(all P＜0.05).Conclusion Bushen Huoxue formula can reduce embryo loss,improve placental tissue pathology,reduce Th 17 cell proportion and its related cytokines IL-6,IL-17,IL-23 expression in rats with RSA.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

AIM To investigate the effects and mechanism of Shenxiao Jiedu Tongluo Recipe on renal AIM 2-mediated pyroptosis of a golden hamster model of diabetic nephropathy(DN).METHODS Fifty male golden hamsters of SPF grade were randomly divided into the control group and the model group.The golden hamsters of the model group successfully developed into DN models by feeding of high glucose and high fat diet and intraperitoneal injection of STZ were further randomly assigned into the model group,the enagliflozin group(10 mg/kg),and the low-dose and the high-dose Shenxiao Jiedu Tongluo Recipe groups(12.8,25.6 g/kg)for 8 weeks gavage of the corresponding administration.The golden hamsters had their levels of fasting blood glucose,24 h-UTP,serum TC,LDL-C,Scr,and Sur detected by automatic biochemical analyzer;their serum SOD activity and MDA level detected by biochemical method;their serum levels of IL-1β,IL-18,and TNF-α detected by ELISA method;their pathomorphological changes of kidney tissue observed by HE and PAS staining;their protein expressions of ROS and γH2AX detected by immunofluorescence or immunohistochemistry;and their renal protein expressions of AIM 2,caspase-1 and GSDMD detected by Western blot and immunohistochemistry.RESULTS Compared with the control group,the model group showed atrophic glomeruli;enlarged glomerular capsule cavity;mesangial expansion;edema and necrosis in the dilated renal tubules;increased levels of fasting blood glucose,24 h-UTP,serum TC,LDL-C,Scr,Sur,IL-1β,IL-18,TNF-α,MDA and renal protein expressions of ROS,γH2AX,AIM2,caspase-1,GSDMD(P＜0.01);and decreased serum SOD activity(P＜0.01).Compared with the model group,the high-dose Shenxiao Jiedu Tongluo Recipe group and the enagliflozin group displayed improved renal histopathology,decreased levels of 24 h-UTP,serum TC,LDL-C,Scr,Sur,IL-1β,IL-18,TNF-α,MDA and renal protein expressions of ROS,γH2AX,AIM2,caspase-1,GSDMD(P＜0.05,P＜0.01);and increased serum SOD activity(P＜0.01).CONCLUSION Shenxiao Jiedu Tongluo Recipe can inhibit AIM 2-mediated cell death and alleviate renal inflammatory damage in golden hamsters by inhibiting their expression of ROS-dsDNA-AIM 2 signal pathway to attain reduction of their renal ROS level,DNA damage of renal intrinsic cells,and synthesis of AIM 2 inflammatory corpuscles as well.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

OBJECTIVE: To observe the therapeutic effects and underlying mechanism of baicalin against colon cancer. METHODS: The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and CT26. WT were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network pharmacology. Furthermore, molecular docking and drug affinity responsive target stability (DARTS) analysis were performed to confirm the interaction between potential targets and baicalin. Finally, the mechanisms predicted by in silico analyses were experimentally verified in-vitro and in-vivo. RESULTS: Baicalin significantly inhibited proliferation, invasion, migration, and induced apoptosis in MC38 and CT26 cells (all P<0.01). Additionally, baicalin caused cell cycle arrest at the S phase, while the G₀/G₁ phase was detected in the tiny portion of the cells. Subsequent network pharmacology analysis identified 6 therapeutic targets associated with baicalin, which potentially affect various pathways including 39 biological processes and 99 signaling pathways. In addition, molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A (CDKN2A), protein kinase B (AKT), caspase 3, and mitogen-activated protein kinase (MAPK). In vitro, the expressions of CDKN2A, MAPK, and p-AKT were suppressed by baicalin in MC38 and CT26 cells. In vivo, baicalin significantly reduced the tumor size and weight (all P<0.01) in the colon cancer mouse model via inactivating p-AKT, CDKN2A, cyclin dependent kinase 4, cyclin dependent kinase 2, interleukin-1, tumor necrosis factor α, and activating caspase 3 and mouse double minute 2 homolog signaling (all P<0.05). CONCLUSION Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer.
Flavonoids/pharmacology* ; Colonic Neoplasms/prevention & control* ; Animals ; Cell Line, Tumor ; Molecular Docking Simulation ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Cyclin-Dependent Kinase Inhibitor p16/metabolism* ; Mice ; Mice, Inbred BALB C ; Cell Movement/drug effects* ; Humans ; Gene Expression Regulation, Neoplastic/drug effects* ; Cell Cycle Checkpoints/drug effects*

Objective To explore the changing patterns of electrocardiogram(ECG)and echocardiography in healthy young people during their descent from high altitude to the plain.Methods A prospective cohort study was carried out.Fifty-five healthy young volunteers who had migrated to an altitude of 4800-5500 m on the Qinghai-Tibet Plateau within one year were recruited as the plateau-migration group.ECG examinations were performed at an altitude of 3700 m(first time),on the 5th day after returning to 1300 m(second time),and on the 15th day after returning to 1300 m(third time).Echocardiography was conducted at 3700 m and on the 5th day after returning to 1300 m.A plain control group of 55 healthy youngsters from the plains(1300 m)was matched.The results of ECG and echocardiography between the two groups were compared.Results Intragroup analysis of the plateau-migration group revealed that compared with the first ECG results,the number of normal ECGs decreased in the second and third ECG results(P<0.05),and the proportions of sinus rhythm irregularity,sinus bradycardia,and U-wave appearance increased(P<0.05).There was no statistically significant difference in abnormal ECG results between the second and third ECGs(P>0.05).Compared with plain control group,there was no significant difference in the abnormal results of the first ECG of plateau-migration group(P>0.05).In the second and third ECG results,the number of normal ECGs was significantly reduced,and the proportions of sinus bradycardia,sinus rhythm irregularity,and U-wave appearance were significantly increased compared with plain control group(P<0.001).Intragroup analysis of plateau-migration group revealed that compared with the first ECG,the heart rate decreased in the second and third ECGs(P<0.05 or<0.001).Compared with plain control group,in the first ECG of plateau-migration group,the PR interval was significantly prolonged,the QTc interval was shortened,and the QRS axis degree was increased(P<0.05).In the second ECG,the heart rate significantly decreased,the PR interval was prolonged,and the QTc interval was shortened(P<0.05).In the third ECG,the heart rate decreased,the PR interval was prolonged,the QTc interval was shortened,and the QRS axis degrees was increased(P<0.05).The QRS axis of the first,second,and third ECGs of plateau-migration group was statistically significantly different from that of plain control group(P<0.001).Intragroup analysis of plateau-migration group showed that compared with the first echocardiogram,the left ventricular end-systole diameter,left ventricular end-diastolic diameter,and left atrial anteroposterior diameter all significantly increased in the second echocardiogram(P<0.001).Compared with plain control group,in the first echocardiogram of plateau-migration group,the left ventricular end-systole diameter and right atrial transection diameter significantly decreased,the right ventricular transection diameter significantly increased,and the left ventricular fractional shortening rate(FS)significantly decreased(P<0.05);In the second echocardiogram,the left atrial anteroposterior diameter,right atrial transverse diameter,and right ventricular transverse diameter all significantly increased,and FS increased(P<0.05).Conclusions In healthy young people returning from high altitude to the plain,as the altitude decreased,the heart rate significantly drops.The number of people with frontal QRS axis right deviation significantly reduces.The number of normal ECGs significantly decreases,while the numbers of people with sinus bradycardia,sinus arrhythmias,and U-wave appearance significantly increase.During high-altitude stay,the left ventricular systolic and diastolic function is affected to some extent.

This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid β oxidation in the liver.
Rats ; Male ; Animals ; Non-alcoholic Fatty Liver Disease/genetics* ; Sterol Regulatory Element Binding Protein 1/metabolism* ; Diet, High-Fat/adverse effects* ; Diosgenin/metabolism* ; Chaperonin 60/therapeutic use* ; Rats, Sprague-Dawley ; Liver ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Triglycerides ; RNA, Messenger/metabolism* ; Simvastatin/therapeutic use* ; Body Weight ; Lipid Metabolism ; Mammals/metabolism*

The study investigated the effect of Buyang Huanwu Decoction(BYHWD) on endogenous biomarkers in the urine of rats with chronic inflammation induced by lipopolysaccharide(LPS) using ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS), aiming to elucidate the molecular mechanism underlying the therapeutic effect of BYHWD on chronic inflammation from a metabolomics perspective. Male SD rats were randomly divided into a normal group, a model group, and low-, medium-, and high-dose BYHWD groups(7.5, 15, and 30 g·kg~(-1)). The model group and BYHWD groups received tail intravenous injection of LPS(200 μg·kg~(-1)) on the first day of each week, followed by oral administration of BYHWD once a day for four consecutive weeks. Urine samples were collected at the end of the administration period, and UPLC-Q-TOF-MS was used to analyze the metabolic profiles of the rat urine in each group. Multivariate statistical analysis methods such as principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to analyze the effect of BYHWD on endogenous metabolites. One-way ANOVA and variable importance for the projection(VIP) were used to screen for potential biomarkers related to chronic inflammation. The identified biomarkers were subjected to pathway and enrichment analysis using MetaboAnalyst 5.0. A total of 25 potential biomarkers were screened and identified in the rat urine in this experiment. Compared with the normal group, the model group showed significant increases in the levels of 14 substances(P<0.05) and significant decreases in the levels of 11 substances(P<0.05). BYHWD was able to effectively reverse the trend of most endogenous biomarkers. Compared with the model group, BYHWD significantly down-regulated 13 biomarkers(P<0.05) and up-regulated 10 biomarkers(P<0.05). The metabolic products were mainly related to the biosynthesis of pantothenic acid and coenzyme A, tryptophan metabolism, retinol metabolism, and propionate metabolism. BYHWD has therapeutic effect on chronic inflammation induced by LPS, which may be related to its ability to improve the levels of endogenous metabolites, enhance the body's anti-inflammatory and antioxidant capabilities, and restore normal metabolic activity.
Rats ; Male ; Animals ; Chromatography, High Pressure Liquid/methods* ; Lipopolysaccharides ; Rats, Sprague-Dawley ; Metabolomics/methods* ; Inflammation/drug therapy* ; Biomarkers/urine*