Objective To assess the value of acute gastrointestinal injury(AGI)and intestinal fatty acid-binding protein(I-FABP)in the prognosis of liver cirrhotic patients with sepsis.Methods Clinical data of 84 liver cirrhosis patients with sepsis who were admitted to the intensive care unit(ICU)of a hospital from September 2020 to March 2023 were analyzed retrospectively,and 41 patients with decompensated liver cirrhosis during the same period were selected as the control group.Serum I-FABP level in patients was determined with enzyme-linked immunosorbent assay(ELISA).Scores of the model of end-stage liver disease(MELD)and sequential organ failure assessment(SOFA)were calculated.AGI was evaluated based on medical records.30-day and 90-day survival was observed.Correlation among variables was analyzed by Spearman correlation.Risk factors for death in patients with liver cir-rhosis and sepsis was determined by multivariate Cox regression analysis.The optimal cut-off value was determined by receiver operating characteristic(ROC)curve,and the diagnostic efficacy was compared through the area under the ROC curve(AUC).Results Both AGI grading and I-FABP level in liver cirrhosis patients with sepsis were higher than those in the control group(both P＜0.05).I-FABP level was correlated with procalcitonin(PCT),MELD,and SOFA scores in patients with liver cirrhosis and sepsis(all P＜0.05).AGI grading was positively cor-related with SOFA score(P=0.038).The 30-day and 90-day mortality of patients in the liver cirrhosis with sepsis group were 25.0％(n=21)and 35.7％(n=30),respectively.Multivariate Cox regression analysis showed that baseline I-FABP and SOFA scores were independently correlated with 30-day and 90-day survival,and the I-FABP quartile showed good prognostic differentiation efficacy.ROC curve showed that I-FABP could significantly improve the predictive effect of SOFA score on the prognosis of patients.Conclusion AGI grading and I-FABP level in liver cirrhosis patients with sepsis are elevated significantly.Serum I-FABP is associated with the prognosis of patient and can improve the predictive efficacy of SOFA score for survival.

BACKGROUND:Steroid-induced osteonecrosis of the femoral head is a refractory disease in the field of orthopedics.There is no definitive idea to fully explain its pathogenesis.With the increased research on the active ingredients of Panax notoginseng interfering with the signaling pathways related to various diseases,the active ingredients of Panax notoginseng that treat steroid-induced necrosis of the femoral head via the regulation of relevant signaling pathways have gradually become a hot research topic. OBJECTIVE:To systematically summarize the literature on the pathological mechanism of steroid-induced osteonecrosis of the femoral head and the regulation of signaling pathways by the active ingredients of Panax notoginseng in recent years,thereby providing a reference for the follow-up study on the active ingredients of Panax notoginseng in the treatment of this disease. METHODS:CNKI,WanFang,and PubMed were searched for relevant literature with the key words of"glucocorticoid,steroid-induced osteonecrosis of the femoral head,pathological mechanism,signaling pathway,Panax notoginseng,active ingredient"in Chinese and English.Documents related to the pathological mechanism of steroid-induced osteonecrosis of the femoral head as well as related to the intervention of active ingredients of Panax notoginseng on the signaling pathway of steroid-induced osteonecrosis of the femoral head were retrieved.A total of 63 documents were finally included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:The main ingredients of Panax notoginseng include Panax notoginseng saponins,ginsenoside,Panax notoginseng saponins,quercetin,kaempferol,etc.Panax notoginseng saponins,ginsenoside Rb1 and quercetin can promote bone repair and angiogenesis by acting on the transforming growth factor-β/bone morphogenetic protein pathway.Panax notoginseng saponins,ginsenoside CK and kaempferol can promote osteogenic differentiation and lipid metabolism by acting on the Wnt/β-catenin pathway.Panax notoginseng saponins and Panax notoginseng saponins R1/R2 act on the MAPK pathway to inhibit osteoclastogenesis and promote bone repair.Panax notoginseng saponins,ginsenoside Rb2 and quercetin can inhibit osteoclast proliferation and promote osteoblastic differentiation by acting on the RANKL/RANK/OPG pathway.Panax notoginseng saponins,quercetin and kaempferol can repair vascular injury and promote osteogenesis by acting on the hypoxia-inducible factor-1α pathway.Panax notoginseng saponins R1,quercetin combined with hydroxyapatite nanoparticles,Panax notoginseng saponins combined with polyethylene-L-lactic acid and other biomaterials have good research prospects in the treatment of steroid-induced osteonecrosis of the femoral head.The active ingredients of Panax notoginseng can regulate the signaling pathways related to steroid-induced osteonecrosis of the femoral head through various mechanisms,and play an active intervention role in the disease.However,the depth and breadth of relevant research are insufficient at present,and the future research should be based on the existing mechanism to explore the specific mechanism of Panax notoginseng regulating different pathways and the interaction between pathways,which will be beneficial to the multi-development of the active ingredients of Panax notoginseng in the treatment of steroid-induced osteonecrosis of the femoral head.

Objective:To construct and validate the best predictive model for 28-day death risk in patients with septic shock based on different supervised machine learning algorithms.Methods:The patients with septic shock meeting the Sepsis-3 criteria were selected from Medical Information Mart for Intensive Care-Ⅳ v2.0 (MIMIC-Ⅳ v2.0). According to the principle of random allocation, 70% of these patients were used as the training set, and 30% as the validation set. Relevant predictive variables were extracted from three aspects: demographic characteristics and basic vital signs, serum indicators within 24 hours of intensive care unit (ICU) admission and complications possibly affecting indicators, functional scoring and advanced life support. The predictive efficacy of models constructed using five mainstream machine learning algorithms including decision tree classification and regression tree (CART), random forest (RF), support vector machine (SVM), linear regression (LR), and super learner [SL; combined CART, RF and extreme gradient boosting (XGBoost)] for 28-day death in patients with septic shock was compared, and the best algorithm model was selected. The optimal predictive variables were determined by intersecting the results from LASSO regression, RF, and XGBoost algorithms, and a predictive model was constructed. The predictive efficacy of the model was validated by drawing receiver operator characteristic curve (ROC curve), the accuracy of the model was assessed using calibration curves, and the practicality of the model was verified through decision curve analysis (DCA).Results:A total of 3?295 patients with septic shock were included, with 2?164 surviving and 1?131 dying within 28 days, resulting in a mortality of 34.32%. Of these, 2?307 were in the training set (with 792 deaths within 28 days, a mortality of 34.33%), and 988 in the validation set (with 339 deaths within 28 days, a mortality of 34.31%). Five machine learning models were established based on the training set data. After including variables at three aspects, the area under the ROC curve (AUC) of RF, SVM, and LR machine learning algorithm models for predicting 28-day death in septic shock patients in the validation set was 0.823 [95% confidence interval (95% CI) was 0.795-0.849], 0.823 (95% CI was 0.796-0.849), and 0.810 (95% CI was 0.782-0.838), respectively, which were higher than that of the CART algorithm model (AUC = 0.750, 95% CI was 0.717-0.782) and SL algorithm model (AUC = 0.756, 95% CI was 0.724-0.789). Thus above three algorithm models were determined to be the best algorithm models. After integrating variables from three aspects, 16 optimal predictive variables were identified through intersection by LASSO regression, RF, and XGBoost algorithms, including the highest pH value, the highest albumin (Alb), the highest body temperature, the lowest lactic acid (Lac), the highest Lac, the highest serum creatinine (SCr), the highest Ca 2+, the lowest hemoglobin (Hb), the lowest white blood cell count (WBC), age, simplified acute physiology score Ⅲ (SAPSⅢ), the highest WBC, acute physiology score Ⅲ (APSⅢ), the lowest Na +, body mass index (BMI), and the shortest activated partial thromboplastin time (APTT) within 24 hours of ICU admission. ROC curve analysis showed that the Logistic regression model constructed with above 16 optimal predictive variables was the best predictive model, with an AUC of 0.806 (95% CI was 0.778-0.835) in the validation set. The calibration curve and DCA curve showed that this model had high accuracy and the highest net benefit could reach 0.3, which was significantly outperforming traditional models based on single functional score [APSⅢ score, SAPSⅢ score, and sequential organ failure assessment (SOFA) score] with AUC (95% CI) of 0.746 (0.715-0.778), 0.765 (0.734-0.796), and 0.625 (0.589-0.661), respectively. Conclusions:The Logistic regression model, constructed using 16 optimal predictive variables including pH value, Alb, body temperature, Lac, SCr, Ca 2+, Hb, WBC, SAPSⅢ score, APSⅢ score, Na +, BMI, and APTT, is identified as the best predictive model for the 28-day death risk in patients with septic shock. Its performance is stable, with high discriminative ability and accuracy.

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 understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

Objective To investigate the effect of radiation on cardiomyocyte apoptosis and its related mechanism.Methods Rat H9C2 cardiomyocytes were divided into blank control group,X-ray irradiation group(X-ray group),X-ray irradiation+microRNA(miRNA)-134-5p inhibitor group(X-inhibitor group)and X-ray irradiation+miRNA-134-5p inhibitor negative control group(X-NC group).H9C2 cardiomyocytes were irradiated with 6 Gy X-ray,and the changes of various indexes were detected 48 h after irradiation.Cell viability was detected by cell counting kit 8 assay.The apoptosis rate was detected by flow cytometry and Hoechst 33342 staining.The level of reactive oxygen species(ROS)in cells was detected by DCFH-DA fluorescence probe.The mitochondrial membrane potential was detected by JC-1 method.The activity of superoxide dismutase(SOD)and the level of malondialdehyde(MDA)in cells were measured by kits.The expression of miRNA-134-5p was detected by quantitative polymerase chain reaction.The protein expression of brain-derived neurotrophic factor(BDNF),protein kinase B(Akt),phosphorylated Akt(p-Akt),Bcl2 and Bax was detected by Western blotting.Results Compared with the blank control group,in the X-ray group the levels of ROS and MDA were significantly increased,the activity of SOD was significantly decreased,the decreased percentage in mitochondrial membrane potential was significantly increased,the number of micronuclei of DNA damage was significantly increased,and the apoptosis rate was significantly increased(all P＜0.01).Compared with the X-ray group,all the indexes of the X-inhibitor group were reversed(P＜0.05 or P＜0.01),while there was no significant difference in the above parameters in the X-NC group(all P＞0.05).Compared with the blank control group,the X-ray group had a significant increase in the miRNA-134-5p level and significant reductions in the protein level of BDNF,Bcl2/Bax ratio,and p-Akt/Akt ratio(all P＜0.01).Compared with the X-ray group,the X-inhibitor group had a significant reduction in the level of miRNA-134-5p and significant increases in the protein level of BDNF,Bcl2/Bax ratio,and p-Akt/Akt ratio(all P＜0.01),and there was no significant difference in all parameters in the X-NC group(all P＞0.05).Conclusion X-ray irradiation can induce oxidative stress,mitochondrial damage,and DNA damage,eventually leading to apoptosis in rat cardiomyocytes,and the mechanism may involve miRNA-134-5p/BDNF/Akt signaling pathway.

AIM:This study examined the inhibitory effect of peiminine on the human colonic adenocarcino-ma cell line SW480 and explored the underlying mechanisms.METHODS:SW480 and human normal colonic epithelial CCD-841CoN cells were treated with different concentrations of peiminine and subjected to the CCK-8 assay to select the optimal treatment time and concentration of the compound.SW480 cell migration and invasion were evaluated by the wound-healing and Transwell assays.Cell cycle progression was analyzed by flow cytometry.The expression levels of cell cycle-related proteins were examined by Western blot.SW480 xenograft tumor model was established in nude mice to ex-amine the effect of peiminine on tumor growth and the expression of cell cycle-related proteins in vivo.RESULTS:Peimi-nine(110 mg/L)significantly inhibited the proliferation of SW480 cells compared with the control group(P<0.01),caused cell cycle arrest at G1 phase,and significantly downregulated the expression of cyclin dependent kinase 2(CDK2),CDK4,CDK6,cyclin D1,p-Rb/Rb,E2F1,E2F3,and E2F4(P<0.05).Peiminine inhibited SW480 xenograft tumor growth,prolonged the survival of model mice,and affected the expression of CDK2,CDK4,CDK6,and cyclin D1 in tu-mor tissues.CONCLUSION:Peiminine promotes G1 phase arrest by down-regulating the expression of CDK2,CDK4,CDK6,and cyclin D1,thereby inhibiting the proliferation of SW480 cells.

AIM:To explore the effect and mechanism of action of the aqueous extract of Fritillaria ussuriensis(FU-AE)against nonalcoholic fatty liver disease(NAFLD).METHODS:The association between Fritillaria ussuriensis Maxir.(FU)and NAFLD was analyzed by network pharmacology.A mouse model of NAFLD was induced in mice by high fat diet(HFD)+10%fructose drinking water,and three doses of Fritillaria ussuriensis aqueous extract were given to the mice for intervention.Colorimetric assay was used for detection of aspartate aminotransferase(AST),alanine aminotrans-ferase(ALT),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)levels in the serum of experimental mice.Hematoxylin and eosin staining was used to as-sess the pathological and histological changes in the liver of mice and to clarify the anti-NAFLD effect of aqueous extracts of Fritillaria ussuriensis.Liver tissue proteins were extracted,and expression of proteins related to the AMP-activated pro-tein kinase(AMPK)/acetyl-CoA carboxylase(ACC)pathway was detected by Western blot to clarify the mechanism of an-ti-NAFLD action of Fritillaria ussuriensis.The microbial composition of cecum contents was explored using 16S rRNA se-quencing to reveal the modulatory effect of the aqueous extract of Fritillaria ussuriensis on the structure of intestinal flora in mice with nonalcoholic fatty liver disease.RESULTS:Aqueous extract of Fritillaria ussuriensis(high dose)ameliorated exogenous adipocyte infiltration in the liver of mice with NAFLD(P<0.05).AST,ALT,TG,TC and LDL-C levels were significantly decreased(P<0.05)and HDL-C levels were significantly increased(P<0.05)in the high-dose group.Aque-ous extract of Fritillaria ussuriensis(high dose)significantly increased expression of phosphorylated AMPKα,AMPKα,and phosphorylated ACC in the livers of the model mice(P<0.05),significantly reduced expression of ACC(P<0.05),and significantly increased the relative abundance of the potentially beneficial bacteria Faecalibaculum rodentium,Lacto-bacillus johnsonii,Akkermansia muciniphila(P<0.05).CONCLUSION:Aqueous extract of Fritillaria ussuriensis may ameliorate NAFLD in mice by activating the AMPK/ACC pathway and modulating the structure of intestinal flora.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.