OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Objective:To analyze the incidence of adverse treatment outcome of rifampicin-resistant tuberculosis (RR-TB) patients and influencing factors in 9 provinces in China.Methods:The information about the basic characteristics, diagnosis and treatment of RR-TB patients registered from January 1, 2017 to December 31, 2021 in 9 provinces (Beijing, Jilin, Shanghai, Jiangsu, Zhejiang, Hubei, Henan, Yunnan and Guizhou) were collected from the tuberculosis information management sub-system of China Disease Control and Prevention Information System for a descriptive analysis, and the influencing factors of adverse treatment outcome were identified by binary logistic regression analysis.Results:In 18 204 RR-TB patients in this study a total of 6 852 had adverse treatment outcomes (37.64%). Treatment failure occurred in 1 031 patients, 1 272 patients died, 2 284 patients were lost to follow-up, and 2 265 patients were not evaluated. The results of multivariate logistic regression analysis showed that being man (a OR=1.54, 95% CI: 1.43-1.66), age ≥65 years (a OR=2.42, 95% CI: 2.20-2.67), being from other ethnic groups (a OR=1.18, 95% CI: 1.03-1.35), being farmer (a OR=1.22, 95% CI: 1.13-1.32), being retired with honours or being retired (a OR=1.16, 95% CI: 1.00-1.35) and being floating population (a OR=1.23, 95% CI: 1.13-1.34), re-treatment (a OR=1.33, 95% CI: 1.24-1.42), long-term treatment therapy (a OR=3.26, 95% CI: 2.52-4.23), living in central provinces (a OR=2.76, 95% CI: 2.55-2.99), living in western provinces (a OR=2.31, 95% CI: 2.08-2.57) were the influencing factors for adverse treatment outcome of RR-TB. Conclusions:The incidence of adverse outcomes in RR-TB patients in 9 provinces in China was higher from 2017 to 2021. There were many influencing factors associated with adverse treatment outcome in RR-TB patients, especially the area specific factors. The national tuberculosis control program should strengthen the follow-up and treatment management of RR-TB in men, the elderly, floating population, people in central and western provinces and other key groups, actively promote the short-term treatment program and improve the allocation of medical resources to reduce the influencing for adverse treatment outcomes in RR-TB patient.

BACKGROUND:Macrophage subtypes exhibit tissue heterogeneity,and the adipose tissue macrophage phenotype is largely influenced by obesity.Local and systemic inflammatory responses caused by obese adipose tissue macrophages are considered a vital pathological mechanism of obesity-associated metabolic diseases.OBJECTIVE:To summarize the inflammatory characteristics of different macrophage subtypes in adipose tissue and their relationship with obesity-associated metabolic diseases,aiming to provide a reference basis for targeting specific macrophage subtypes to explore preventive and treatment strategies for obesity-associated metabolic diseases.METHODS:Literature retrieval was conducted in CNKI and PubMed using Chinese and English search terms "obesity,adipose tissue,adipose tissue macrophage,macrophage polarisation,metabolic diseases." The search results were accepted or excluded according to the inclusion criteria.Ninety-one papers that met the criteria were finally included for review.RESULTS AND CONCLUSION:(1) Macrophages have tissue heterogeneity.Under normal conditions,adipose tissue macrophages are mainly composed of anti-inflammatory M2 resident macrophages,which maintain tissue inflammation homeostasis.Under obese conditions,a large number of foreign infiltrating macrophages surround hypertrophic adipocytes,and most of them exhibit pro-inflammatory characteristics.Therefore,it is believed that adipose tissue macrophages of pro-inflammatory M1 type may actually be a collection of multiple pro-inflammatory subtypes.Further understanding of the characteristics of various pro-inflammatory subtypes helps us to gain a deeper understanding of the mechanisms underlying inflammatory disorders in obese adipose tissue.(2) In obesity,foreign infiltrating macrophages form crown-like structures around hypertrophic adipocytes.Currently,six different subtypes of the crown-like structure have been identified,most of which exhibit pro-inflammatory properties and a few of which possess anti-inflammatory characteristics.Thus,taking full advantage of the anti-inflammatory subtypes while inhibiting the differentiation of the pro-inflammatory subtypes may be a new target for alleviating inflammatory damage in obese adipose tissue.(3) M3,Mme,CD9+and LAM adipose tissue macrophage subtypes have been found to be involved in the occurrence and development of metabolic diseases such as atherosclerosis,diabetes,insulin resistance,and cancer.DARC+and Mfehi adipose tissue macrophage subtypes play a vital role in the treatment of non-alcoholic fatty liver disease,obesity insulin resistance,iron death,and other related metabolic diseases.The above studies further suggest that inflammatory disorders caused by externally infiltrated macrophages in obese adipose tissue are an important pathological basis for obesity-induced metabolic diseases.Further in-depth research on the characteristics of various subtypes has important theoretical and practical significance.

Objective To explore the influencing factors of hypothermia after extraperitoneal laparoscopic radical prostatectomy in prostate cancer patients over 80 years old,so as to improve the effectiveness of treatment.Methods The clinical data of 26 cases of prostate cancer patients over 80 years old who underwent extraperitoneal laparoscopic radical prostatectomy in Shanghai 411 hospital from January 2021 to December 2023 were analyzed retrospectively.The incidence of postoperative hypothermia was investigated.Univariate and multivariate Logistic regression analyses were used to analyze the related factors of postoperative hypothermia in elderly patients.Results The incidence of hypothermia was 61.54%(16/26).Univariate analysis indicated that body mass index(BMI),intraoperative thermal insulation,intraoperative infusion volume,operation time,and anesthesia time were related to the occurrence of postoperative hypothermia in elderly patients(all P<0.05).Multivariate Logistic regression analysis indicated that BMI≤24,intraoperative infusion volume>2 000 ml,anesthesia time>3 h and operation time>2.5 h were high risk factors for postoperative hypothermia in patients over 80 years old.Conclusion The independent influencing factors of hypothermia after extraperitoneal laparoscopic prostatectomy for selected prostate cancer patients over 80 years old are BMI,intraoperative infusion volume,duration of anesthesia,and operation time.These factors should be paid more attention during perioperative period in order to improve clinical safety.

Diabetic chronic wounds are characterized by difficult healing, recurrent progression, and high rates of disability and mortality, which make their clinical treatment a medical challenge urgent to be addressed. However, the complex local microenvironment conditions of chronic wounds, such as high protease activity and persistent inflammatory responses, result in low bioavailability of exogenous cytokines (e.g., chemokine CXCL12) at the wound site, limiting their clinical application. In this study, we utilized Lactobacillus plantarum WCFS1 as the chassis to develop an efficient CXCL12 delivery system based on synthetic biology. Subsequently, we evaluated the role of the engineered probiotic strain in promoting the chronic wound healing in diabetic mice. Firstly, we fused the endogenous secretion signal peptide lp_3050 (SP_{lp_3050}) of L. plantarum WCFS1 and the commonly used secretion signal peptide usp45 (SP_usp45) of lactic acid bacteria with the reporter gene gusA and inserted them into the pTRK892-P_32(pgm) plasmid by molecular cloning. Then, we prepared the engineered strains and characterized the efficacy of the two signal peptides in driving the secretion of GusA. The results showed that SP_{lp_3050} efficiently drove the secretion of GusA in L. plantarum WCFS1, increasing the activity of GusA in the culture supernatant by nearly five times compared with that of SP_{lp_3050}. Further, we fused SP_{lp_3050} and codon-optimized CXCL12 gene to construct an engineered probiotic strain Lpw-CXCL12 for CXCL12 delivery. The results demonstrated that the content of CXCL12 in the culture supernatant reached (13.40±0.20) μg/mL. Finally, we found that the engineered probiotic strain Lpw-CXCL12 accelerated chronic wound healing in a diabetic mouse model. In conclusion, these results support an engineered probiotic strain in promoting diabetic chronic wound healing, providing a new strategy and technological foundation for the management of diabetic chronic wounds in the future.
Probiotics ; Animals ; Chemokine CXCL12/biosynthesis* ; Mice ; Wound Healing ; Lactobacillus plantarum/metabolism* ; Diabetes Mellitus, Experimental/complications* ; Male

Objective:To evaluate the long-term protective efficacy of the recombinant Chinese hamster ovary cell-derived hepatitis B vaccine（CHO-HepB）26 years post-vaccination in the rural China.Methods:Zhengding county，Hebei province was designated as a rural monitoring site for CHO-HepB efficacy. Study participants included individuals born between 1997 and 1999 who had completed the three-dose CHO-HepB primary series without booster doses. A cross-sectional survey was conducted in late 2024 using random sampling. Demographic and vaccination history data were collected via questionnaires，and hepatitis B virus（HBV）serological markers were detected using chemiluminescence. Historical surveillance data were integrated to infer infection statuses of HBsAg-positive individuals and evaluate longitudinal trends in anti-HBs seropositivity and antibody titers.Results:Among 178 participants（mean time since vaccination：26.2 years），the seroprevalence rates were 0.6% for HBsAg（95% CI：0.0%-1.6%），64.6% for anti-HBs（95% CI：57.6%-71.6%），and 1.1% for anti-HBc（95% CI：0.0%-2.7%）. Compared to the pre-vaccination baseline HBsAg positivity of 11.3% in children under 10 years of age，the estimated vaccine protection rate was 95%. Two notable cases were identified：one with concurrent HBsAg and anti-HBc positivity and one with anti-HBs and anti-HBc positivity，suggestive of transient HBV exposure（1999—2009）without chronicity. Natural immune boosting was inferred for the latter case based on anti-HBs titer dynamics. Longitudinal analysis of four prior cross-sectional surveys（2005，2009，2013，and 2017）revealed no significant upward trends in HBsAg and anti-HBc positivity（both P>0.05）over 26 years，while anti-HBs seropositivity declined significantly（ P<0.05）from 6 to 26 years post-vaccination. Conclusion:The CHO-HepB vaccine demonstrates sustained immunological persistence and robust long-term protection up to 26 years post-immunization. Continued emphasis on rigorous implementation of mother-to-child transmission prevention strategies is critical for future hepatitis B control.

Background and aims:Studies indicate that the gut microbiota and its metabolites are involved in the progression of cardiovascular diseases,and enterohepatic circulation plays an important role in this progression.This study aims to identify potential probiotics for the treatment of unstable angina(UA)and elucidate their mechanisms of action.Methods:Initially,the gut microbiota from patients with UA and control was analyzed.To directly assess the effects of Bifidobacterium supplementation,10 patients with UA were enrolled and administered Bifidobacterium(630 mg per intake twice a day for 1 month).The fecal metagenome,serum trimethyl-amine N-oxide(TMAO)levels,and other laboratory parameters were evaluated before and after Bifido-bacterium supplementation.Results:After supplementing with Bifidobacterium for 1 month,there were statistically significant dif-ferences(P＜0.05)in TMAO,aspartate aminotransferase,total cholesterol,and low-density lipoprotein compared to before.Additionally,the abundance of Bifidobacterium longum increased significantly,although the overall abundance of Bifidobacterium did not reach statistical significance.The gut micro-biota,metabolites,and gut-liver axis are involved in the progression of UA,and potential mechanisms should be further studied.Conclusions:Metagenomic analysis demonstrated a reduced abundance of Bifidobacterium in patients with UA.Supplementation with Bifidobacterium restored gut dysbiosis and decreased circulating TMAO levels in patients with UA.This study provides evidence that Bifidobacterium may exert cardiovascular-protective effects through the gut-liver-heart axis.

Objective:To analyze the incidence of adverse treatment outcome of rifampicin-resistant tuberculosis (RR-TB) patients and influencing factors in 9 provinces in China.Methods:The information about the basic characteristics, diagnosis and treatment of RR-TB patients registered from January 1, 2017 to December 31, 2021 in 9 provinces (Beijing, Jilin, Shanghai, Jiangsu, Zhejiang, Hubei, Henan, Yunnan and Guizhou) were collected from the tuberculosis information management sub-system of China Disease Control and Prevention Information System for a descriptive analysis, and the influencing factors of adverse treatment outcome were identified by binary logistic regression analysis.Results:In 18 204 RR-TB patients in this study a total of 6 852 had adverse treatment outcomes (37.64%). Treatment failure occurred in 1 031 patients, 1 272 patients died, 2 284 patients were lost to follow-up, and 2 265 patients were not evaluated. The results of multivariate logistic regression analysis showed that being man (a OR=1.54, 95% CI: 1.43-1.66), age ≥65 years (a OR=2.42, 95% CI: 2.20-2.67), being from other ethnic groups (a OR=1.18, 95% CI: 1.03-1.35), being farmer (a OR=1.22, 95% CI: 1.13-1.32), being retired with honours or being retired (a OR=1.16, 95% CI: 1.00-1.35) and being floating population (a OR=1.23, 95% CI: 1.13-1.34), re-treatment (a OR=1.33, 95% CI: 1.24-1.42), long-term treatment therapy (a OR=3.26, 95% CI: 2.52-4.23), living in central provinces (a OR=2.76, 95% CI: 2.55-2.99), living in western provinces (a OR=2.31, 95% CI: 2.08-2.57) were the influencing factors for adverse treatment outcome of RR-TB. Conclusions:The incidence of adverse outcomes in RR-TB patients in 9 provinces in China was higher from 2017 to 2021. There were many influencing factors associated with adverse treatment outcome in RR-TB patients, especially the area specific factors. The national tuberculosis control program should strengthen the follow-up and treatment management of RR-TB in men, the elderly, floating population, people in central and western provinces and other key groups, actively promote the short-term treatment program and improve the allocation of medical resources to reduce the influencing for adverse treatment outcomes in RR-TB patient.

Objective:To explore the relationship between basic transcription factor 3(BTF3)and glioblastoma multiforme(GBM)cell migra-tion,invasion,and proliferation.Methods:The expression levels of BTF3 in GBM tissues were analyzed using The Cancer Genome Atlas(TCGA),Gene Expression Profiling Interactive Analysis 2(GEPIA2),and The University of ALabama at Birmingham CANcer data analysis Portal(UALCAN)online databases.The effects of inhibiting BTF3 on the malignant biological properties of GBM cells were assessed using the cell scratch,plate colony formation,Cell Counting Kit(CCK)-8,and Transwell assays,and the effect of BTF3 knockdown on Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway-related protein expression levels in GBM cells was determined using Western blot.In addition,GBM cells stably transfected with KD-BTF3 were subcutaneously injected into nude mice,and tumor sizes were analyzed.Western blot was performed to verify the expression of JAK2/STAT3 signaling pathway-related proteins in the tumor tissues.Results:1)BTF3 was highly expressed in GBM cells.2)After BTF3 knockdown,the malignant biological properties of GBM cells were signific-antly decreased.3)After BTF3 knockdown,phosphorylated(p)-JAK2 and p-STAT3 expressions were downregulated,JAK2 and STAT3 expres-sions were unchanged,and p21 expression was increased.4)BTF3 knockdown inhibited GBM tumorigenesis.Therefore,the expression of JAK2/STAT3 signaling pathway-related proteins was consistent with the in vitro results.Conclusions:BTF3 is highly expressed in GBM and regulates the proliferation,migration,and invasion of GBM cells through the JAK2/STAT3 signaling pathway.

BACKGROUND:Macrophage subtypes exhibit tissue heterogeneity,and the adipose tissue macrophage phenotype is largely influenced by obesity.Local and systemic inflammatory responses caused by obese adipose tissue macrophages are considered a vital pathological mechanism of obesity-associated metabolic diseases.OBJECTIVE:To summarize the inflammatory characteristics of different macrophage subtypes in adipose tissue and their relationship with obesity-associated metabolic diseases,aiming to provide a reference basis for targeting specific macrophage subtypes to explore preventive and treatment strategies for obesity-associated metabolic diseases.METHODS:Literature retrieval was conducted in CNKI and PubMed using Chinese and English search terms "obesity,adipose tissue,adipose tissue macrophage,macrophage polarisation,metabolic diseases." The search results were accepted or excluded according to the inclusion criteria.Ninety-one papers that met the criteria were finally included for review.RESULTS AND CONCLUSION:(1) Macrophages have tissue heterogeneity.Under normal conditions,adipose tissue macrophages are mainly composed of anti-inflammatory M2 resident macrophages,which maintain tissue inflammation homeostasis.Under obese conditions,a large number of foreign infiltrating macrophages surround hypertrophic adipocytes,and most of them exhibit pro-inflammatory characteristics.Therefore,it is believed that adipose tissue macrophages of pro-inflammatory M1 type may actually be a collection of multiple pro-inflammatory subtypes.Further understanding of the characteristics of various pro-inflammatory subtypes helps us to gain a deeper understanding of the mechanisms underlying inflammatory disorders in obese adipose tissue.(2) In obesity,foreign infiltrating macrophages form crown-like structures around hypertrophic adipocytes.Currently,six different subtypes of the crown-like structure have been identified,most of which exhibit pro-inflammatory properties and a few of which possess anti-inflammatory characteristics.Thus,taking full advantage of the anti-inflammatory subtypes while inhibiting the differentiation of the pro-inflammatory subtypes may be a new target for alleviating inflammatory damage in obese adipose tissue.(3) M3,Mme,CD9+and LAM adipose tissue macrophage subtypes have been found to be involved in the occurrence and development of metabolic diseases such as atherosclerosis,diabetes,insulin resistance,and cancer.DARC+and Mfehi adipose tissue macrophage subtypes play a vital role in the treatment of non-alcoholic fatty liver disease,obesity insulin resistance,iron death,and other related metabolic diseases.The above studies further suggest that inflammatory disorders caused by externally infiltrated macrophages in obese adipose tissue are an important pathological basis for obesity-induced metabolic diseases.Further in-depth research on the characteristics of various subtypes has important theoretical and practical significance.