ObjectiveTo investigate the mechanism by which Feixin decoction treats hypoxic pulmonary hypertension （HPH） by regulating the peroxisome proliferator-activated receptor gamma （PPARγ）/nuclear factor-kappa B （NF-κB）/NOD-like receptor pyrin domain containing 3 （NLRP3） signaling pathway. MethodsForty-eight male SD rats were randomly allocated into normal， hypoxia， and low-， medium- and high-dose （5.85， 11.7， 23.4 g·kg^-1， respectively） Feixin decoction groups， with 8 rats in each group. Except the normal group， the remaining five groups were placed in a hypoxia chamber with an oxygen concentration of （10.0±0.5）% for 8 h per day， 28 days， and administrated with corresponding drugs during the modeling process. After 4 weeks of treatment， echocardiographic parameters ［pulmonary artery acceleration time （PAT）， pulmonary artery ejection time （PET）， right ventricular anterior wall thickness （RVAWd）， and tricuspid annular plane systolic excursion （TAPSE）］ were measured for each group. The right ventricular systolic pressure （RVSP） was measured by the right heart catheterization method， and the right ventricular hypertrophy index （RVHI） was calculated by weighing the heart. The pathological changes in pulmonary arterioles were observed by hematoxylin-eosin staining. The co-localization of α-smooth muscle actin （α-SMA） with NLRP3， N-terminal gasdermin D （N-GSDMD）， and cysteinyl aspartate-specific proteinase-1 （Caspase-1） in pulmonary arteries was detected by immunofluorescence. The protein levels of PPARγ， NF-κB， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， N-GSDMD， interleukin-1β （IL-1β）， interleukin-18（IL-18）， and cleaved Caspase-1 in the lung tissue was determined by Western blot. The ultrastructural changes in pulmonary artery smooth muscle cells （PASMCs） were observed by transmission electron microscopy. ResultsCompared with the normal group， the hypoxia group showed increased RVSP and RVHI （P<0.01）， decreased right heart function （P<0.01）， increased pulmonary vascular remodeling （P<0.01）， increased co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 in pulmonary arterioles （P<0.01）， up-regulated protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， a down-regulated protein level of PPARγ （P<0.05， P<0.01）， and pyroptosis in PASMCs. Compared with the hypoxia group， Feixin decoction reduced RVSP and RVHI， improved the right heart function and ameliorated pulmonary vascular remodeling （P<0.05， P<0.01）， decreased the co-localization of α-SMA with NLRP3， N-GSDMD， and Caspase-1 （P<0.05， P<0.01）， down-regulated the protein levels of NF-κB， NLRP3， ASC， N-GSDMD， IL-1β， IL-18， and cleaved Caspase-1 in the lung tissue （P<0.05， P<0.01）， up-regulated the protein level of PPARγ （P<0.05， P<0.01）， and alleviated pyroptosis in PASMCs. ConclusionFeixin decoction can ameliorate pulmonary vascular remodeling and right heart dysfunction in chronically induced HPH rats by regulating pyroptosis in PASMCs through the PPARγ/NF-κB/NLRP3 pathway.

Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

Aim To screen and study the effects of Tao Hong Si Wu decoction(THSWD)-mediated treat-ment on circular RNA(circRNA)expression profiles in rats with middle cerebral artery occlusion(MCAO),and investigate the possible roles and molecular mecha-nisms of THSWD.Methods Next-generation RNA sequencing was conducted to identify circRNA expres-sion profiles in MCAO rats after treatment with THSWD and compared with the MCAO model group and control group.Bioinformatics analysis was performed to predict the potential target microRNAs and mRNAs.Gene On-tology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses for the potential target mRNAs were applied to explore the potential roles of differentially expressed circRNAs.RT-qPCR was performed to verify circRNAs with significant differences in expression.Results We identified 87 significantly differentially expressed circRNAs between the MCAO group versus the control group,and 86 sig-nificantly differentially expressed circRNAs between the MCAO group versus the THSWD group.respective-ly.Among them,17 circRNAs induced by the MCAO model were reversed via treatment with THSWD.To demonstrate the roles of mRNAs targeted by DECs,the GO and KEGG databases were used.Further analysis revealed that five circRNAs may play important roles in the development of MCAO.Conclusions The com-prehensive expression profile of circRNAs in rats with middle cerebral artery occlusion after THSWD treat-ment is determined for the first time,suggesting that the therapeutic effect of THSWD on MCAO may be a-chieved by regulating the expression of circRNAs.

Mongolian medicine external treatment,which called five kinds of treatment in ancient time,is a kind of exter-nal treatment including fire moxibustion,poultice,soaking and other therapies.The therapy was gradually developed and per-fected in the course of Mongolian people's long-term struggle against diseases,which has characteristics of small trauma and suitable for long-term application.In this paper,the research progress of external treatment of orthopedic diseases in Mongolian medicine in recent years was summarized,and it was concluded that external treatment of orthopedic diseases in Mongolian medicine had distinct characteristics and accurate efficacy.However,there are still deficiencies in the standardization of clini-cal operation and the study of the mechanism of therapeutic action,which need further research and improvement.

Objective To investigate the effect of intravenous infusion of low-dose remifentanil on obese scarred uterine puerperae undergoing cesarean section under epidural anesthesia.Methods A total of 87 obese scarred uterine puerperae undergoing cesarean section under epidural anesthesia were selected as the study subjects,and they were randomly divided into the conventional group(n=43)and the remifentanil group(n=44).From the beginning of skin incision,puerperae of the conventional group and the remifentanil group were intravenously injected with normal saline and low-dose remifentanil respectively until the end of the operation.The vital signs,pain and comfort scores,intraoperative complications of puerperae,and status of newborns were compared between the two groups at different points during the operation.Results During fetal extraction and peritoneal exploration,the heart rate,mean arterial pressure and pain scores of puerperae in the remifentanil group were lower than those in the conventional group,and the differences were statistically significant(P<0.05);the intraoperative comfort score of puerperae in the remifentanil group was higher than that in the conventional group,and the difference was statistically significant(P<0.05).The incidence of nausea and vomiting of puerperae in the remifentanil group was lower than that in the conventional group,and the difference was statistically significant(P<0.05).There was no significant difference in the Apgar score at 1 minute and 5 minutes after delivery,requiring initial resuscitation or pH value of umbilical vein blood between newborns delivered by puerperae of the two groups(P>0.05).Conclusion Intravenous infusion of 0.05 μg·kg-1·min-1 low-dose remifentanil not only significantly reduces intraoperative pain and improves comfort of obese scarred uterine puerperae undergoing cesarean section under epidural anesthesia,but also helps to reduce the incidence of adverse reactions and ensure maternal and infant safety.

Objective:To investigate the value of transrectal ultrasonography(TRUS)in the detection of clinically significant prostate cancer(CsPCa)in patients with intravesical prostatic protrusion(IPP).Methods:We retrospectively analyzed the data on 128 patients undergoing TRUS-guided prostate biopsy in the General Hospital of Eastern Theater Command and Jiangsu Province Hospi-tal from January 2019 to December 2022.We measured the size of and graded IPP,compared the clinicopathological and ultrasono-graphic features of the patients in the CsPCa group(Gleason score≥7)and those in the control group(Gleason score<7),and ana-lyzed the correlation of the IPP grades with the detection rate of CsPCa by multivariate logistic regression analysis.Results:The prostate volume was significantly higher in the CsPCa group than in the control([51.3±12.1]vs[43.5±11.3]ml,P<0.05),whilethe PSAdensity(PSAD)remarkablylowerin the former than in the latter([0.45±1.92]vs[0.59±2.14]ng/ml,P<0.05)and so was the detection rate of CsPCa in the patients with IPP grade3 than in those with IPP grades0,1 and2(56.0%vs 85.4%,87.1%and 80.6%,P<0.05).Spearman correlation analysis showed that the Gleason score was correlated positively with the prostate volume(r=0.612)but negatively with PSAD(r=-0.735)and the IPP grade(r=-0.619)(P<0.05).Logis-tic regression analysis indicated that IPP grade3(OR:0.690,95%CI:0.380-0.995,P=0.032)was an independent protective factor for CsPCa.Conclusion:CsPCa is significantly correlated with the IPP grade,and the detection rate of CsPCa by TRUS-guided biopsy is lower in patients with IPP grade 3 than in those with IPP grades 0-2.Therefore,special attention should be paid to false negative probability in case of high-grade IPP.

AIM To investigate the consistency of chemical constituents between formula granules and standard decoction of Coptidis Rhizoma.METHODS Eighteen batches of standard decoctions were prepared,after which the extraction rate and contents,transfer rates of magnolflorine,jatrorrhizine,columbamine,epiberberine,coptisine,palmatine,berberin were determined,HPLC characteristic chromatograms were established.RESULTS There were 11 common peaks in the characteristic chromatograms of 18 batches of standard decoctions and 24 batches of formula granules with the similarities of 0.861-1.000,which were clusterd into two categories.The formula granules and standard decoction demonstrated approximated extraction rate and contents,transfer rates of index constituents.CONCLUSION The chemical constituents between formula granules and standard decoction of Coptidis Rhizoma display good consistency,which can provide references for the quality control,process research and clinical application of the former.

Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.

AIM:This study utilized CRISPR/Cas9 technology to create Retnlb floxp knock-in mice,followed by the application of the Cre-LoxP recombination system to generate intestinal epithelial-specific Retnlb gene knockout mice(Retnlb-CKO).This model was developed to investigate the pathogenic mechanisms of Retnlb in inflammatory bowel disease.METHODS:Female and male C57BL/6N mice,aged 8 weeks with the Retnlbflox/+genotype,were housed togeth-er for breeding.Offsprings were screened to identify those with the Retnlbflox/flox genotype.These mice were then crossed with Vil1-Cre transgenic mice,which express Cre recombinase specifically in intestinal epithelial cells,resulting in Retnlb-flox/+,Cre+mice.Subsequent crosses between Retnlbflox/+,Cre+mice and Retnlbflox/flox mice produced Retnlbflox/flox,Cre+mice(Retnlb-CKO).Six 8-week-old Retnlbflox/flox,Cre+mice and their littermate Retnlbflox/flox mice were selected for experiments.RT-qPCR and immunohistochemistry were used to assess Retnlb mRNA and protein levels in colonic epithelium.Phenotypic observa-tions included body length,weight,diet,and reproductive capability.Tissue-to-body weight ratios were calculated to ana-lyze growth and development.Intestinal barrier integrity and colonic expression of inflammatory factors were evaluated.RESULTS:The conditional gene knockout mouse model with specific deletion of Retnlb in intestinal epithelial cells was successfully established and validated through genetic identification,mRNA and protein analysis.Compared to Retnlbflox/flox mice,Retnlb-CKO mice exhibited no significant differences in body length,weight,diet,or reproductive capability.There were no differences in the ratios of heart,liver,spleen,lung,kidney,and colon weight to body weight,nor were there morphological differences in various tissues.However,the mRNA expression of tight junction proteins ZO-1,Occlu-din,and Claudin3 in colon tissues of Retnlb-CKO mice was significantly reduced(P<0.01).PAS staining and immunohis-tochemistry revealed a significant decrease in the number of goblet cells and lysozyme-positive cells in the colon tissues of Retnlb-CKO mice(P<0.01).HE staining showed no obvious pathological change in colon tissues of Retnlb-CKO mice.RT-qPCR further demonstrated a significant downregulation of pro-inflammatory factors NLRP3,interleukin-6(IL-6),IL-1β,and tumor necrosis factor-α(TNF-α)in colon tissues(P<0.01),along with significant downregulation of inflamma-tion signaling pathway proteins TLR4,MyD88,and NF-κB(P<0.01).CONCLUSION:A conditional colon epithelial cell Retnlb gene knockout mouse model was successfully constructed and validated.The absence of Retnlb in colon cells led to impaired intestinal barrier function,decreased mRNA expression of pro-inflammatory factors in colon tissue,and downregulation of mRNA expression of inflammatory pathway proteins TLR4,MyD88,and NF-κB.

Objective To understand the prevalence characteristics of influenza and changes of influenza virus strains,and provide reference for the prevention and control of influenza in the province.Methods Surveillance da-ta about influenza in Hunan Province from 2014 to 2023 were exported from China Influenza Surveillance Informa-tion System.Differences in the percentage of influenza-like illness(ILI)cases(percentage of influenza-like cases[ILI％]in outpatient and emergency department visits)among different years and different populations,as well as the positive rate of influenza virus in ILI specimens were compared.Results From 2014 to 2023,over 2.65 million cases of ILI were reported,with an ILI％of 4.70％.ILI％among different years presented statistically significant differences(P＜0.001).People aged 0-14 years old were the main population with ILI,accounting for 82.90％.The positive rate of influenza virus in ILI specimens was 14.14％,the positive rate of influenza virus among diffe-rent years and age groups were both significantly different(both P＜0.001).The main prevalent influenza strains from 2014 to 2023 included types A(H1N1),A(H3N2),B(Victoria),and B(Yamagata),alternating among di-fferent years.However,type B(Yamagata)strains were not detected from 2020 to 2023.There were basically two influenza prevalence seasons every year,namely winter-spring and summer.Conclusion People＜15 years old are the main population of influenza,and the prevalence peaks are in winter-spring and summer.From 2021 to 2023,the prevalence alternates mainly among 3 types:A(H1N1),A(H3N2),and B(Victoria).