ObjectiveTo investigate the risk factors for bleeding within 5 days and 2 weeks after endoscopic variceal ligation （EVL） or endoscopic cyanoacrylate injection （ECI） for the treatment of esophagogastric varices in patients with liver cirrhosis， as well as the safety of EVL/ECI in patients with thrombocytopenia. MethodsA total of 489 patients with liver cirrhosis and esophagogastric varices who underwent EVL/ECI in Guangzhou Eighth People’s Hospital， Guangzhou Medical University， from January 2018 to December 2023 were enrolled as subjects， and according to the presence or absence of bleeding after surgery， they were divided into bleeding group and non-bleeding group. The risk factors for bleeding within 5 days and 2 weeks after surgery were analyzed. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between groups， and the chi-square test or the continuity-corrected chi-square test was used for comparison of categorical data between groups； the receiver operating characteristic （ROC） curve was plotted to determine the cut-off value of MELD score； a multivariate logistic regression analysis was used to identify the independent risk factors for postoperative bleeding. ResultsThere were no significant differences in the bleeding rates within 5 days and 2 weeks after EVL/ECI between the 386 patients with a platelet count of ≥50×10⁹/L and the 103 patients with a platelet count of （25 — 49）×10⁹/L （5 days： 1.94% vs 2.85%， P=0.870； 2 weeks： 2.91% vs 4.92%， P=0.544）. The overall bleeding rate was 2.66% （13/489） and 4.50% （22/489）， respectively， within 5 days and 2 weeks after EVL/ECI. The multivariate logistic regression analysis showed that MELD score was an independent risk factor for bleeding within 5 days （odds ratio ［OR］=3.726， 95% confidence interval ［CI］： 1.214 — 11.429， P=0.021） and 2 weeks （OR=5.760， 95%CI： 1.779 — 18.651， P=0.003） after EVL/ECI， while hemoglobin （Hb） was a protective factor against bleeding within 5 days （OR=0.972， 95%CI： 0.948 — 0.996， P=0.025） and 2 weeks （OR=0.976， 95%CI： 0.957 — 0.995， P=0.016） after surgery； portal vein tumor thrombus （OR=2.667， 95%CI： 1.000 — 7.117， P=0.050） was an independent risk factor for bleeding within 2 weeks after surgery， while platelet count ［（25 — 49）×10⁹/L］ was not a risk factor for postoperative bleeding （P>0.05）. ConclusionBoth EVL and ECI have good safety in patients with liver diseases and grade 3 thrombocytopenia. MELD score is an independent risk factor for bleeding within 5 days and 2 weeks after EVL/ECI， while Hb is a protective factor； portal vein tumor thrombus is an independent risk factor for bleeding within 2 weeks after surgery.

OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors （DTIs） in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital（the Affiliated Hospital of UESTC）， a multidisciplinary working group was formed comprising experts from multiple fields， including clinical pharmacy， cardiac surgery， obstetrics， pediatrics and evidence-based medicine. Through literature review and the Delphi method， clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” （PICO） framework；systematic searches were conducted in CJFD， PubMed， Embase and other databases. Relevant evidence from randomized controlled trials，cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected （with a consensus rate exceeding 90%）， resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations， including children， pregnant women， patients with hepatic or renal impairment， patients with mesenteric venous thrombosis， and individuals with thrombophilia. These recommendations clarify the preferred agents， dosing ranges， monitoring parameters， and safety management strategies for parenteral DTIs in these special populations. 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 special populations.

BACKGROUND:Acupuncture at Xinshu(BL 15)can significantly improve cardiac function and protect myocardial cells in acute myocardial ischemia,but the effect and mechanism of thread embedding treatment at Xinshu(BL 15)on cardiac function in acute myocardial ischemia are yet unclear.Nuclear factor κB activation often appears as an intranuclear translocation of the P65 isoform,and activation of the nuclear factor κB signaling pathway is marked by elevated P65 levels.OBJECTIVE:To explore the effects of thread embedding pretreatment at Xinshu(BL 15)on cardiac function and the expression levels of interleukin-10,tumor necrosis factor-α,P65 genes and proteins in rats with acute myocardial ischemia.METHODS:Thirty-two male Sprague-Dawley rats were randomly divided into a blank group,a model group,a Xinshu(BL 15)acupoint group,and a non-meridian/non-acupoint group using a random number table method,with eight rats in each group.Rat models of acute myocardial ischemia were established in the latter three groups.The Xinshu(BL 15)acupoint group had thread embedding at Xinshu(BL 15)for 14 days,followed by subcutaneous injection of isoproterenol hydrochloride into the back to establish an acute myocardial ischemia rat model.The non-meridian/non-acupoint group had local thread embedding for 14 days,and the rest procedures were the same as above.In the model group,Xinshu(BL 15)was only marked,and the rest procedures were the same as above.In the blank group,Xinshu(BL 15)was only marked,and then an equal amount of physiological saline was injected subcutaneously into the back.After 24 hours of modeling,electrocardiogram and cardiac ultrasound were performed.Abdominal aorta blood was extracted for detection of serum creatine kinase and creatine kinase isoenzyme levels using enzyme-linked immunosorbent assay.Subsequently,the rats were euthanized and samples were collected.Hematoxylin-eosin and TUNEL staining were used to observe the pathological changes of myocardial tissue and the apoptosis of myocardial cells.Real-time fluorescence quantitative PCR(RT-qPCR)and western blot were used to detect the mRNA and protein expression of tumor necrosis factor-α,interleukin-10,and P65 in myocardial tissue respectively.RESULTS AND CONCLUSION:(1)Electrocardiogram:Compared with the blank group,the model group,non-meridian/non-acupoint group,and Xinshu(BL 15)acupoint group had significantly elevated ST segment in lead Ⅱ of the electrocardiogram.(2)Cardiac ultrasound:Compared with the model group,the Left ventricular end-systolic dimension in the Xinshu(BL 15)acupoint group were significantly reduced(P＜0.05),while left ventricular ejection fraction and left ventricular fractional shortening rate were significantly increased(P＜0.05).(4)Serum creatine kinase and creatine kinase isoenzyme:Compared with the model group,the Xinshu(BL 15)acupoint group showed a significant decrease in serum creatine kinase and creatine kinase isoenzyme levels(P＜0.05).(4)Hematoxylin-eosin staining:Compared with the model group,the arrangement of myocardial fibers in the Xinshu(BL 15)acupoint group was basically neat,with less edema and a small amount of inflammatory cell infiltration.(5)TUNEL staining:Compared with the model group,the fluorescence intensity of myocardial cell apoptosis in the Xinshu(BL 15)acupoint group was significantly reduced,and its apoptosis rate was significantly reduced(P＜0.05).(6)RT-qPCR and western blot:Compared with the model group,the myocardial tissue interleukin-10 level in the Xinshu(BL 15)acupoint group was significantly increased(P＜0.05),while tumor necrosis factor-α and P65 levels were significantly decreased(P＜0.05).These findings indicate that thread embedding pretreatment at Xinshu(BL 15)can improve cardiac function in rats with acute myocardial ischemia,and its mechanism of action may be related to the inhibition of the activation of the nuclear factor-κB signaling pathway.

BACKGROUND:Acupuncture at Xinshu(BL 15)can significantly improve cardiac function and protect myocardial cells in acute myocardial ischemia,but the effect and mechanism of thread embedding treatment at Xinshu(BL 15)on cardiac function in acute myocardial ischemia are yet unclear.Nuclear factor κB activation often appears as an intranuclear translocation of the P65 isoform,and activation of the nuclear factor κB signaling pathway is marked by elevated P65 levels.OBJECTIVE:To explore the effects of thread embedding pretreatment at Xinshu(BL 15)on cardiac function and the expression levels of interleukin-10,tumor necrosis factor-α,P65 genes and proteins in rats with acute myocardial ischemia.METHODS:Thirty-two male Sprague-Dawley rats were randomly divided into a blank group,a model group,a Xinshu(BL 15)acupoint group,and a non-meridian/non-acupoint group using a random number table method,with eight rats in each group.Rat models of acute myocardial ischemia were established in the latter three groups.The Xinshu(BL 15)acupoint group had thread embedding at Xinshu(BL 15)for 14 days,followed by subcutaneous injection of isoproterenol hydrochloride into the back to establish an acute myocardial ischemia rat model.The non-meridian/non-acupoint group had local thread embedding for 14 days,and the rest procedures were the same as above.In the model group,Xinshu(BL 15)was only marked,and the rest procedures were the same as above.In the blank group,Xinshu(BL 15)was only marked,and then an equal amount of physiological saline was injected subcutaneously into the back.After 24 hours of modeling,electrocardiogram and cardiac ultrasound were performed.Abdominal aorta blood was extracted for detection of serum creatine kinase and creatine kinase isoenzyme levels using enzyme-linked immunosorbent assay.Subsequently,the rats were euthanized and samples were collected.Hematoxylin-eosin and TUNEL staining were used to observe the pathological changes of myocardial tissue and the apoptosis of myocardial cells.Real-time fluorescence quantitative PCR(RT-qPCR)and western blot were used to detect the mRNA and protein expression of tumor necrosis factor-α,interleukin-10,and P65 in myocardial tissue respectively.RESULTS AND CONCLUSION:(1)Electrocardiogram:Compared with the blank group,the model group,non-meridian/non-acupoint group,and Xinshu(BL 15)acupoint group had significantly elevated ST segment in lead Ⅱ of the electrocardiogram.(2)Cardiac ultrasound:Compared with the model group,the Left ventricular end-systolic dimension in the Xinshu(BL 15)acupoint group were significantly reduced(P＜0.05),while left ventricular ejection fraction and left ventricular fractional shortening rate were significantly increased(P＜0.05).(4)Serum creatine kinase and creatine kinase isoenzyme:Compared with the model group,the Xinshu(BL 15)acupoint group showed a significant decrease in serum creatine kinase and creatine kinase isoenzyme levels(P＜0.05).(4)Hematoxylin-eosin staining:Compared with the model group,the arrangement of myocardial fibers in the Xinshu(BL 15)acupoint group was basically neat,with less edema and a small amount of inflammatory cell infiltration.(5)TUNEL staining:Compared with the model group,the fluorescence intensity of myocardial cell apoptosis in the Xinshu(BL 15)acupoint group was significantly reduced,and its apoptosis rate was significantly reduced(P＜0.05).(6)RT-qPCR and western blot:Compared with the model group,the myocardial tissue interleukin-10 level in the Xinshu(BL 15)acupoint group was significantly increased(P＜0.05),while tumor necrosis factor-α and P65 levels were significantly decreased(P＜0.05).These findings indicate that thread embedding pretreatment at Xinshu(BL 15)can improve cardiac function in rats with acute myocardial ischemia,and its mechanism of action may be related to the inhibition of the activation of the nuclear factor-κB signaling pathway.

ObjectiveTo analyze the potential risk of infection sources during the consolidation phase of schistosomiasis elimination in Lushan County (a mountainous region) of Sichuan Province, and to provide prevention and control strategies for the consolidation of schistosomiasis elimination achievements in mountainous areas. MethodsIn 2024, one to two villages with historically severe epidemics were selected in the heavily endemic townships of Lushan County as monitoring sites to carry out monitoring for wild animal feces, domestic animals, wild rats, free-roaming dogs, local residents, and mobile populations. Follow-up monitoring for previously infected individuals was carried out in Caoping Village of Siyan Town. Statistical analyses were performed to assess the risks associated with infection sources. ResultsA total of 115 fecal samples from 13 species of wildlife were incubated, with all negative. Blood tests were conducted on 492 cattle, 34 sheep, and 261 dogs, with all negative. A total of 2 520 rodent traps were set, capturing 67 wild rats with a capture rate of 2.66%, and no positive wild rats were found upon dissection. The activity track of 25 loose dogs was 2 212 meters at the farthest, 236 meters at the nearest, and 744 meters on average. a total of 68 wild droppings (all dog feces) were picked up along the way, with all negative. Blood tests were performed on 3 540 local population, yielding 39 blood-positive cases with a blood positive rate of 1.1%. Fecal examinations were conducted on 193 individuals, with all negative. A total of 315 blood tests were performed on the mobile population, identifying 1 positive case with a blood-positive rate of 0.32%. One person received a fecal examination, with zero positive. A follow-up survey of 505 previously infected individuals revealed 5 blood-positive cases, with a positive rate of 0.99%. Fecal examinations were conducted on 15 individuals, with all negative. ConclusionIn this investigation, no local or imported sources of schistosomiasis transmission were found. However, there was a wide variety and a large number of potential sources of infection in the local area. It is necessary to actively explore regional monitoring models for schistosomiasis elimination flexibly adjust prevention and control strategies according to local conditions, achieve precise prevention and control, and consolidate the achievements of elimination.

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

ObjectiveTo investigate the effects of Buzhong Yiqitang on the abnormal expression of pulmonary surfactant-associated protein C （SFTPC） and lung injury induced by chronic intermittent hypoxia （CIH） and the mechanism of action. MethodsForty healthy adult male SPF-grade C57BL/6 mice were randomly allocated into five experimental groups： a normoxia group， a CIH group， and low-， medium-， and high-dose Buzhong Yiqitang groups， with eight mice in each group. During the modeling， mice in the normoxia group were housed under standard oxygen concentrations， while the CIH and all Buzhong Yiqitang groups were placed in a hypoxic chamber for 8 h daily over 35 d. Prior to each chamber session， mice in the low-， medium-， and high-dose Buzhong Yiqitang groups were administered decoctions by gavage at corresponding doses （8.1， 16.2， 32.4 g·kg^-1·d^-1 of crude drug， respectively）， while those in normoxia and CIH groups received an equivalent volume of saline by gavage. The general conditions of the mice were recorded before and after the experiment. Pulmonary function was assessed using a non-invasive detection system. Serum SFTPC levels were measured using enzyme-linked immunosorbent assay （ELISA）. Histopathological changes in lung tissue were evaluated using hematoxylin-eosin （HE） staining. Apoptosis in lung tissue was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL）. Protein expression of SFTPC， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， protein kinase R-like endoplasmic reticulum kinase （PERK）， phosphorylated PERK （p-PERK）， eukaryotic initiation factor 2α （eIF2α）， phosphorylated eIF2α （p-eIF2α）， activating transcript factor 4 （ATF4）， and CCAAT/enhancer-binding protein homologous protein （CHOP） in lung tissue was analyzed by Western blot. Immunofluorescence staining was employed to assess the expression of SFTPC and CHOP proteins in lung tissue. ResultsCompared to those in the normoxia group， mice in the CIH group showed significantly impaired pulmonary function and increased histopathological lung injury scores （P<0.05， P<0.01）. Serum SFTPC levels increased， while SFTPC expression in lung tissue was reduced （P<0.05， P<0.01）. The rate of apoptotic cells in lung tissue increased， and the expression of endoplasmic reticulum stress markers p-PERK， p-eIF2α， ATF4， and CHOP was upregulated （P<0.05， P<0.01）. Compared with the CIH group， Buzhong Yiqitang intervention improved pulmonary function indicators and decreased the histopathological lung injury scores （P<0.05， P<0.01）. Serum SFTPC levels were decreased， and lung tissue SFTPC expression was recovered （P<0.05， P<0.01）. The apoptotic rate of lung tissue cells was significantly reduced， with downregulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2 expression （P<0.05， P<0.01）. Activation and expression of p-PERK， p-eIF2α， ATF4， and CHOP were also decreased （P<0.05， P<0.01）. ConclusionBuzhong Yiqitang can alleviate lung injury and improve pulmonary function by reducing lung cell apoptosis and enhancing alveolar surfactant secretion， which may be related to the modulation of the PERK/eIF2α/ATF4/CHOP signaling pathway.

The gut microbiota plays a crucial role in regulating energy metabolism and obesity progression through mechanisms involving short-chain fatty acid and bile acid metabolism pathways. Obese individuals often exhibit gut microbiota dysbiosis, which can influence lipid metabolism and insulin sensitivity through microbial metabolites and signaling mechanisms. Dietary, pharmaceutical, and bariatric metabolism surgery can modulate the gut microbial, strongly correlating with weight reduction and metabolic benefits. Emerging microbiome-modulating strategies, such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, can restore microbial homeostasis and improve bile acid processing, but results differ among people. Moreover, the structural specificity of dietary fibers enables targeted microbial modulation, which provide new perspectives for developing anti-obesity therapies. This review summarizes the mechanisms of interaction between gut microbiota and the host and the clinical research progress in obesity intervention.

Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.