AIM:Using bioinformatics analysis and experiment validation to explore the differential expres-sion genes related to abnormal lipid metabolism in hepatocellular carcinoma(HCC)and the molecular mechanism of pachymaran affecting pyroptosis through squalene epoxidase(SQLE)/nucleotide-binding oligomerization domain-like re-ceptor protein 3(NLRP3)/gasdermin D(GSDMD)signaling pathway.METHODS:(1)The GEO,GSEA,DAVID,STRING and GEPIA databases were employed to screen abnormal lipid metabolism-related differentially expressed genes in HCC.(2)The tumor tissues from HCC patients(n=9)were collected to verify the differential expression of SQLE.(3)The inhibitory effect of pachymaran on the viability of human HCC cell line HepG2 was measured by CCK-8 assay.(4)The HepG2 cells were divided into control group and pachymaran(800 mg/L)group.The cell migration was analyzed by wound-healing assay,and RT-qPCR was used to measure SQLE mRNA expression.(5)The HepG2 cells with overexpres-sion of SQLE(OE-SQLE)were divided into 5 groups as follows:control group,overexpression negative control(OE-NC)group,OE-SQLE group,OE-NC+pachymaran group,and OE-SQLE+pachymaran group.The mRNA and protein expres-sion levels of SQLE and pyroptosis-related factors were determined by RT-qPCR and Western blot.Colorimetric method and ELISA were used to measure lactate dehydrogenase(LDH),interleukin-1β(IL-1β)and IL-18 levels.The necrosis of HepG2 cells was analyzed by flow cytometry.RESULTS:The SQLE gene was screened through bioinformatics analysis,and its mRNA expression was significantly increased in tumor tissues from HCC patients(P＜0.01).In cell experiments,treatment with 800 mg/L pachymaran for 48 h had a significant inhibitory effect on HepG2 cell viability,and the expres-sion of SQLE mRNA was reduced(P＜0.01).After overexpression of SQLE,the mRNA and protein levels of pyroptosis-re-lated factors,necrotic rate,and LDH,IL-1β and IL-18 levels were significantly decreased(P＜0.05).After treatment with pachymaran,the above indicators were significantly increased(P＜0.05).CONCLUSION:The SQLE is abnormal-ly highly expressed in HCC,and pachymaran can affect the growth of HCC cells by activating the NLRP3/GSDMD pyropto-sis pathway through SQLE.

Objective To understand the distribution of ecological suitability of Scutellaria baicalensis Georgi;To screen the main ecological factors affecting its distribution;To predict its suitable planting area in China.Methods A total of 231 batches of Scutellaria baicalensis Georgi were collected through the fourth national survey of TCM resources.The environment information of sampling points were recorded,and 55 ecological factors were analyzed by MaxEnt model and GIS.Results Rainfall,vegetation type and soil types had a greater influence on the distribution of Scutellaria baicalensis Georgi.The ecological suitable areas of Scutellaria baicalensis Georgi mainly concentrated in the eastern part of Shaanxi Province,the western part of Hebei Province and most areas of Chengde,the most part of Shanxi Province,the western part of Beijing,the western part of Liaoning Province,the central and eastern part of Shandong Province,the junction of Jiangsu and Anhui Province,the northern part of Yunnan Province,and the eastern and southern part of Sichuan Province.Conclusion The ecological suitability areas of Scutellaria baicalensis Georgi were classified in this study,and the results could provide reference for the selection of cultivation areas of Scutellaria baicalensis Georgi.

Objective:To investigate the diagnostic efficacy of miR-9 and miR-195-3p for primary hepatic carcinoma (PHC), and the changes in miR-9 and miR-195-3p levels after interventional therapy.Methods:A total of 123 cases of PHC patients and 30 cases of liver cirrhosis patients attending Tangshan People's Hospital from May 2019 to May 2020 were selected as the PHC group and the liver cirrhosis group, respectively, and 50 people who were physically healthy during the same period were selected as the healthy group. Serum miR-9 and miR-195-3p levels were detected by real-time quantitative PCR. The relationship between serum miR-9 and miR-195-3p levels and clinical-pathological characteristics of PHC patients was analyzed. Receiver operator characteristic (ROC) curve was applied to analyze the diagnostic efficacy of miR-9 and miR-195-3p for PHC. The changes in serum miR-9 and miR-195-3p levels in PHC patients before and after transcatheter arterial chemoembolization (TACE) were compared.Results:There were statistically significant differences in serum miR-9 (0.99±0.10, 1.31±0.28, 1.68±0.43) and miR-195-3p (0.97±0.10, 0.83±0.22, 0.63±0.18) levels among the healthy group, liver cirrhosis group, and PHC group ( F=69.78, P<0.001; F=74.82, P<0.001), with serum miR-9 levels increased successively and miR-195-3p levels decreased successively among the three groups (all P<0.05). There were statistically significant differences in serum miR-9 ( t=7.45, P<0.001; t=5.32, P<0.001; t=4.96, P<0.001) and miR-195-3p ( t=16.17, P<0.001; t=4.21, P<0.001; t=7.53, P<0.001) levels in PHC patients with different maximum diameters of tumor, clinical stages and degrees of differentiation. ROC curve analysis showed that the area under the curve (AUC) for the combined differential diagnosis of liver cirrhosis and PHC by serum miR-9 and miR-195-3p testing was 0.919, which was higher than the AUC for the differential diagnosis of serum miR-9 (AUC: 0.712, Z=4.38, P<0.001) and miR-195-3p (AUC: 0.844, Z=2.04, P=0.042) alone. After TACE treatment, serum miR-9 levels decreased (1.39±0.21 vs. 1.68±0.43, t=14.22, P<0.001) and miR-195-3p levels increased (0.78±0.22 vs. 0.63±0.18, t=14.84, P<0.001) in patients compared to pre-treatment levels. Conclusion:Serum miR-9 level is increased and miR-195-3p level is decreased in patients with PHC compared with patients with liver cirrhosis and healthy subjects, and the combination of the two has high differential diagnostic efficacy for liver cirrhosis and PHC. After TACE treatment, serum miR-9 level is decreased and miR-195-3p level is increased in PHC patients.

convalescents, and to screen for broad-spectrum neutralizing antibodies against the SARS-CoV-2 RBD. Methods Using biotinylated RBD as a molecular probe, flow cytometry was employed to perform single-cell sorting of B cells from peripheral blood mononuclear cells (PBMCs) of convalescents. The obtained B cells were lysed and subjected to reverse transcription, followed by nested PCR amplification of the heavy and light chains of antibodies was conducted using random primers. The amplified products were cloned into corresponding expression vectors, and the respective matched heavy-light chain plasmids were co-transfected into 293F cells for expression. Monoclonal antibodies were then purified using Protein A column chromatography. Neutralization experiments were conducted with the wild-type (WT) pseudovirus, and antibodies with IC50<0.1 μg/mL were selected for further testing of neutralizing breadth and potency against the wild-type (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and currently prevalent pseudovirus strains (XBB, BA.5, BF.7). Results A total of 21 RBD-specific monoclonal B cells were obtained from two recovered patients, resulting in the isolation of 13 pairs of antibody light/heavy chains. Nine antibodies were successfully expressed, with P1-A1, P1-B6, and P1-B9 exhibiting IC50 values below 0.1 μg/mL against the pseudovirus of the wild-type strain (WT). Specifically, P1-B6 effectively neutralized the wild-type strain (WT), Beta variant (B.1.351), and Delta variant (B.1.617.2), with IC50 values reaching 0.01 μg/mL. P1-B9 demonstrated effective neutralization against the wild-type strain (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and Gamma variant (P.1) pseudoviruses, with IC50 values of 0.42 μg/mL, 0.63 μg/mL, 0.28 μg/mL, and 2.50 μg/mL, respectively. Additionally, P1-B6 exhibited good neutralization against BA.5 and BF.7 pseudoviruses, with IC50 values of 0.06 μg/mL and 0.09 μg/mL, respectively. Conclusions Infection with the SARS-CoV-2 WT strain can induce the generation of neutralizing antibodies with broad-spectrum activity. Generating these broadly neutralizing antibodies does not require an excessively high somatic hypermutation. The obtained antibodies can be used as candidates for SARS-CoV-2 diagnosis and prevention.

Objectives:Fenofibric acid is extracted from the widely used hypolipemic fenofibrate,nowadays being approved for marketing around numerous nations and regions,nonetheless not in China.Present trial evaluated the efficacy and safety in the Chinese hypertriglyceridemia population. Methods:This is a multi-center,randomized,double-blind,placebo-controlled phase Ⅲ clinical trial.Patients from 3 different cohorts,including severe hypertriglyceridemia(HTG),moderate HTG and mixed-dyslipidemia(MD),were randomized at 1:1 ratio to receive fenofibric acid 135 mg or placebo daily for 12 weeks.The primary endpoint was the percentage change of triglyceridemia(TG)from baseline at week 12.Secondary endpoints were the percentage changes of other blood lipid indexes.At the same time,the incidence of medical adverse events was observed. Results:Among the three cohorts of patients with severe HTG(n=52),moderate HTG(n=23)and MD(n=52),the TG levels in the fenofibric acid-treated group decreased by(49.12±29.19)%,(49.95±25.19)%and(49.79±19.28)%,respectively from baseline to 12 weeks,while the corresponding placebo groups decreased by(18.88±40.69)%,(8.11±29.86)%and increased by(10.42±73.04)%,respectively from baseline to 12 weeks.The differences between treatment and placebo groups were statistically significant(P<0.017 for severe HTG cohort,P<0.05 for moderate and MD cohort).The high-density lipoprotein cholesterol(HDL-C)in the fenofibric acid-treated group increased by(25.51±21.45)%,(24.55±24.73)%,and(23.60±27.38)%,and the placebo group increased by(1.91±20.42)%,(2.40±9.32)%and(7.13±19.12)%,respectively,the differences between the two groups were statistically significant(all P<0.05).In the fenofibric acid group,adverse events with incidence>5%included upper respiratory tract infection(10.9%),abdominal pain(6.3%),and increased serum creatinine levels(6.3%),rates of adverse events were similar between the two groups(P>0.05). Conclusions:Fenofibric acid can significantly reduce triglycerides and elevate HDL-C levels safely in Chinese patients with severe to moderate HTG without statin or MD patients on top of statin therapy.

Oligonucleotide drugs have experienced accelerated development in the past 10 years, and some of them have been used in clinical treatment. Because of its convenient design, flexible sequence, and high specificity, it is expected to solve the “undruggable” challenge of many targets which are difficult in drug development. Moreover, its clinical transformation period and cost are relatively low, which makes oligonucleotide drug become the frontier of emerging biotechnology drug discovery. Brain diseases include a series of incurable diseases, such as neurodegenerative diseases, glioma, and motor neuron diseases. Many of them are age-related and regarded as aging-associated brain diseases. Due to the complex etiology, many targets are difficult to be drugged. At the same time, the existence of the barrier system “blood-brain barrier” in the brain makes most drugs unable to achieve effective accumulation at brain lesions, and many small molecule drugs have failed in clinical transformation. The specificity and sequence flexibility of oligonucleotide acid drugs provide new possibilities for drug development, but they also face the challenge of brain delivery. Although a variety of oligonucleotide drugs have been used in the medical market, brain-targeted oligonucleotide drugs are still extremely rare. This article reviewed recent advances and discussed key topics and clinical transformation challenges in this field, such as clinical approval cases, bottlenecks of brain-targeted delivery and current strategies, as well as potential targets for aging-related brain diseases.

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.

This study was aimed at investigating the antimicrobial susceptibility and genomic characteristics of multidrug resistant diarrheagenic Escherichia coli isolated from human and food samples in Henan Province from 2017 to 2022.A total of 101 strains of multidrug resistant diarrheagenic E.coli were subjected to antimicrobial susceptibility testing with the broth di-lution method.Whole genome sequencing was performed to analyze the antimicrobial resistance genes,multilocus sequence typ-ing,and plasmid types.The sequencing data were used to construct a phylogenetic tree based on core genome single-nucleotide polymorphisms(cgSNPs).The isolates showed the highest resistance to ampicillin(87.1％),followed by tetracycline(79.2％)and nalidixic acid(64.4％).The resistance rate to cefotaxime was 38.6％.All 101 strains were classified into 60 STs,among which ST10,ST1491,and ST38 were dominant.Moreover,23 distinct plasmid replicons were identified,among which IncFIB was dominant.Diverse antimicrobial resistance genes(including quinolone,aminoglycoside,β-lactamase,and tetracycline)were identified.Insertion sequences(IS26,IS903B,and ISECP 1)were identified in upstream and downstream analysis of the gene context of the extended-spectrum β-lactamase bla CTX-M-14 and bla CTX-M-55 genes.In conclusion,multidrug resistant diarrhea-genic Escherichia coli isolated from clinical and food samples in Henan Province showed high genetic diversity and high antimi-crobial resistance.The dissemination of blaCTX-M carried by the strains was shown to be associated with the insertion sequence(IS).

This study was aimed at studying the phenotypic and molecular characteristics of a Salmonella Grumpensis isolate from a patient with diarrhea in Shanghai,to provide evi-dence for the prevention of salmonellosis.Biochemical identifi-cation,serum agglutination testing,antimicrobial susceptibility testing,and whole genome sequencing(WGS)were performed on isolate 2023JD76.Global Salmonella Grumpensis genome sequences were searched and downloaded for serotyping predic-tion,multilocus sequence typing(MLST),prediction of anti-microbia resistance genes and virulence genes,and phylogenetic analysis of 2023JD76.The 2023JD76 strain was identified as Salmonella Grumpensis(13,23:d:1,7)with ST2060,and was susceptible to 20 antimicrobial agents.Strain 2023JD76 carried the aminoglycoside resistance gene aac(6')-Iaa and five types of virulence genes:the adhesion genes csg and rat;the secretion and transport genes sip and inv;the typhoid toxin genes cdt and plt;the invasive gene nutrient metabolism factor mgt;and the antimicrobial peptide resistance factor mig.Global S.Grumpensis strains harbored ten types of antimicrobial resistance genes whose prevalence ranged from 58.33％to 100％.The global genome sequences of S.Grumpensis were divided into two lineages.Lineage I was dominated by ST751(88.89％,16/18),and lineage Ⅱ was dominated by ST2060(89.47％,17/19).The genome sequence of strain 2023JD76 belonged to lineage Ⅱ,and was closely related to the genome sequences from human fecal and human cerebrospinal fluid.This study provides the first report of a S.Grumpensis isolate from the stool of a patient with diarrhea in China.Considerable variability in antimicrobial resistance genes was observed among genome sequences from different sources,and the strains harbored a substantial number of virulence genes.Enhanced surveillance should be emphasized to prevent a potential risk of global dissemination.

Background and purpose:Effective treatment for cervical cancer patients is one of the global strategies to eliminate cervical cancer.By analyzing the metastasis characteristics and survival status of patients with distant metastasis of cervical cancer from a hospital-based cancer registry data,our study provided real-world evidence for better survival of cervical cancer and finally eliminating cervical cancer.Methods:A total of 572 cervical cancer patients who had metastasis cancer at the initial diagnosis or developed distant metastasis during follow-up in Fudan University Shanghai Cancer Center from 2008 to 2017 were included in this study.Medical records review,telephone visits and death registry data linkage were applied in collecting endpoint data.The first follow-up date was the diagnose date of metastasis,and the last follow-up date was November 1,2020.Kaplan-Meier method was applied in evaluating the 1-,3-and 5-year overall survival(OS)rates for overall and site-specific patients.Results:The median follow-up time was 38.93 months,and 348 cases died during the follow-up.72.55%were single site metastasis,and 27.45%were multiple metastases.Among all metastatic sites,the proportion of lung metastasis was the highest,41.26%,15.21%to bone,and 11.54%to liver.After metastasis,the 1-year,3-year and 5-year OS rates were 62.29%(95%CI:62.25-62.33),33.13%(95%CI:33.08-33.18)and 23.42%(95%CI:23.37-23.47),respectively.In single site metastasis,1-year OS was the highest after metastasis to the lung(72.52%).Besides,there was no significant difference among different metastatic sites,both in 3-year and 5-year OS.Conclusion:The most frequent distant metastatic sites of cervical cancer are lung,bone and liver.The survival rate after metastasis is poor.Further research with systematic treatment strategy is required for better survival.