Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

OBJECTIVE: To explore whether hydrocortisone can improve the prognosis of patients with severe community-acquired pneumonia (sCAP) by Meta-analysis. METHODS: Randomized controlled trial (RCT) on hydrocortisone in the treatment of sCAP were extracted from the database including PubMed, Cochrane library, Web of Science, and Embase, and the search time was up to April 29, 2023. The patients in the standard treatment group received standard treatment such as antibiotics and supportive care, while those in the hydrocortisone group received hydrocortisone treatment on the basis of standard treatment. Meta-analysis was used to compare the mortality, duration of mechanical ventilation, mechanical ventilation rate and incidence of adverse reactions (hyperglycemia, gastrointestinal bleeding, secondary infection) between the two groups. The risk of literature bias was assessed. The studies that might have publication bias were corrected by the subtraction and complementation method. At the same time, trial sequential analysis (TSA) was conducted. RESULTS: A total of 5 RCTs involving 1 031 patients were finally enrolled, including 494 patients in the standard treatment group and 537 patients in the hydrocortisone group. Among the 5 studies, the research site of 2 studies was in the mixed ward. Considering the inclusion characteristics of the study population, there was doubt whether its research object was sCAP patients, which might have a certain impact on the results and introduce potential bias. Meta-analysis showed that the mortality in the hydrocortisone group was significantly lower than that in the standard treatment group [6.0% vs. 14.0%; odds ratio (OR) = 0.38, 95% confidence interval (95%CI) was 0.25-0.59, P < 0.01; I² = 9%]. The studies that were asymmetric were corrected by the reduction and supplementation method. Even after filling the missing studies, hydrocortisone could still reduce the death risk of the patient (OR = 0.49, 95%CI was 0.32-0.73, P < 0.01; I² = 31%). TSA showed that the average mortality of the standard treatment group was about 14.0%, and that of the hydrocortisone group was about 6.0%, with a relative risk reduction (RRR) = 57%. The calculated sample size was 699 cases, and the actual sample size was 1 031 cases. The actual sample size exceeded the required sample size, and the Z-curve crossed the O'Brien-Fleming boundary and the curve corresponding to P = 0.05, it meant that hydrocortisone could effectively reduce the mortality of sCAP. Compared with the standard treatment group, no statistical difference in the duration of mechanical ventilation was found in the hydrocortisone group [mean difference (MD) = -3.26, 95%CI was -6.72-0.21, P = 0.07; I² = 0%], but the 8-day mechanical ventilation rate was significantly lowered (19.5% vs. 55.4%; OR = 0.24, 95%CI was 0.12-0.45, P < 0.01; I² = 0%), and also no significantly difference was found in the incidence of hyperglycemia (54.3% vs. 44.6%, OR = 1.26, 95%CI was 0.56-2.84, P = 0.58; I² = 61%), gastrointestinal bleeding (2.5% vs. 3.6%; OR = 0.70, 95%CI was 0.34-1.46, P = 0.34; I² = 0%) and secondary infection (9.2% vs. 11.5%; OR = 0.46, 95%CI was 0.06-3.35, P = 0.45; I² = 53%). CONCLUSION Hydrocortisone can reduce the mortality rate of sCAP patients, decrease their need for mechanical ventilation, and does not increase the risk of hyperglycemia, gastrointestinal bleeding, or secondary infections.
Humans ; Hydrocortisone/therapeutic use* ; Community-Acquired Infections/drug therapy* ; Pneumonia/drug therapy* ; Randomized Controlled Trials as Topic ; Respiration, Artificial ; Community-Acquired Pneumonia

Hepatocellular carcinoma （HCC） is a malignant tumor with high incidence and mortality rates in China， and advanced HCC is a difficult issue in current treatment. Immune checkpoint inhibitor （ICI）， as an emerging treatment regimen， has shown a certain effect in clinical practice， but there are still problems such as low overall response rate and a high incidence rate of immune-related adverse events （irAEs）. Traditional Chinese medicine exhibits unique advantages in the treatment of advanced HCC. Through a retrospective analysis of related studies in recent years， this article shows that traditional Chinese medicine combined with ICI can control disease progression， prolong survival time， and reduce irAEs in the treatment of advanced HCC through the synergistic effect between multiple components， targets， and pathways. The potential mechanism of this treatment modality may involve various aspects such as the direct inhibition of tumor cells and the regulation of immune system and intestinal flora.

ObjectiveTo investigate the core influencing factors for quality of life in patients with primary biliary cholangitis through a systematic review， and to provide an evidence-based basis for understanding such factors. MethodsThe databases including CNKI， Wanfang Data， CBM， VIP， PubMed， Embase， Web of Science， Ovid， Scopus， and Medline were searched for articles assessing the influencing factors for quality of life in patients with primary biliary cholangitis using PBC-40 scale published up to January 11， 2025. Quality assessment was conducted using the scale compiled by the Agency for Healthcare Research and Quality， and then a qualitative evaluation was performed for the basic situation of the studies included in the analysis. ResultsA total of 11 articles were included， and the results showed that age， sex， albumin， alkaline phosphatase， gamma-glutamyl transferase， direct bilirubin， total bilirubin， total bile acid， alanine aminotransferase， aspartate aminotransferase， body mass index， and high-density lipoprotein cholesterol were important influencing factors for quality of life in patients with primary biliary cholangitis. ConclusionInfluencing factors include demographic features， liver function parameters， and physical and metabolic indicators； however， due to the limited number of studies， more high-quality large-sample studies are needed in the future.

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.

Cholelithiasis, a prevalent disease of the digestive system, is characterized by its intricate and diverse mechanisms, which are influenced by a complex interplay of genetic, environmental, lifestyle, and other factors. Recently, with the widespread application of molecular biology techniques, the role of the biliary tract microecological environment in the pathogenesis of gallstones has garnered increasing attention. This review includes the most recent and pertinent literature on the association between biliary tract microecology and gallstones, summarizing the latest research advancements in this field. Furthermore, it delves into the role of the biliary tract microecology in the formation of both cholesterol and pigment gallstones.

Objective:To compare the effects of high-power and conventional power atrial fibrillation ablation on intraoperative acute pulmonary vein isolation, postoperative troponin levels, and atrial fibrillation recurrence.Methods:A retrospective selection was conducted on 105 patients with paroxysmal atrial fibrillation admitted to the Baoding NO.1 Central Hospital from January 2017 to December 2020. According to different treatment methods, they were divided into a high-power ablation group of 52 cases and a conventional power ablation group of 53 cases. The intraoperative rate of single circle acute pulmonary vein isolation, the recovery of electrical conduction after acute pulmonary vein isolation, and the location and number of points that need to be added were compared between the two groups; At the same time, two groups were compared in terms of surgical time, ablation time, surgical radiation exposure time and radiation dose, intraoperative complications postoperative cardiac troponin levels at 12 hours, and recurrence of atrial fibrillation within 1 year after ablation.Results:The intraoperative single loop pulmonary vein isolation rate and postoperative troponin levels in the high-power atrial fibrillation ablation group were higher than those in the conventional atrial fibrillation ablation group (all P<0.05). The surgical time, ablation time, and the number of sites and points that need to be added during surgery were less than those in the conventional atrial fibrillation ablation group (all P<0.05). There was no statistically significant difference in the incidence of intraoperative complications and postoperative atrial fibrillation recurrence between the two groups (all P>0.05). Conclusions:High power atrial fibrillation ablation has a higher single loop acute pulmonary vein isolation rate, fewer patch sites and points, shorter surgical time, and greater ablation damage compared to conventional ablation, and the clinical efficacy of the two groups is similar after surgery.

Objective:To explore the efficacy and safety of endoscopic radial incision (ERI) for congenital membranous duodenal stenosis (MDS).Methods:The clinical data of 13 children with MDS receiving ERI in the Department of Gastroenterology of Xi'an Children's Hospital from May 2017 to December 2021 were reviewed and analyzed. The perioperative management, surgical procedures, postoperative complications and follow-up were summarized.Results:There were 5 boys and 8 girls with a median disease duration of 8 (2-20) months, and the median age of diagnosis was 13 months (5-30 months). The septum of 10 cases (10/13) was located in the descending part of the duodenum, and that of 3 cases (3/13) in the horizontal part. The papilla of 1 case (1/13) opened on the septum, that of 3 cases (3/13) within 5 cm of the mouth side of the septum, and that of 9 cases (9/13) within 5 cm of the anal side of the septum. The median diameter of the septal aperture was 3 mm (2-6 mm). All 13 children successfully underwent ERI with a median operation time of 20 min (15-32 min). The average surgical incision was 3 strokes (2-4 strokes), and the endoscope with outer diameter 9.9 mm could pass stenosis after ERI. The median incision diameter was 10 mm (10-12 mm). All patients achieved relief of clinical symptoms after ERI. One patient (1/13) suffered from the postoperative delayed bleeding, which was stopped by endoscopic titanium clamping. No intestinal perforation or duodenal papilla injury occurred, and median postoperative hospital stay was 6 days (5-10 days). The upper gastrointestinal angiogram and gastroscopy were repeated 3 months after ERI, and the median diameter of stenosis was 12 mm (10-15 mm), which was significantly dilated compared with before. The mean body weight increase at 1 month after ERI was 1.20 kg (0.50-1.80 kg), and the mean body weight increase at 3 months was 3.50 kg (2.50-4.00 kg), which reached the normal body weight of the same age.Conclusion:ERI is safe and effective for the treatment of MDS in children, and shows good clinical application and promotion value.

Tumor metastasis is the major cause of death for tumor patients and the key bottleneck of clinical treatment. In recent years， basic and clinical studies have recognized that tumor microenvironment （TME） is highly correlated with tumor metastasis， which provides hope for anti-metastatic drug development and clinical treatment. At present， the mainstream studies on TME represented by immune checkpoint inhibitors （ICIs） mainly focus on the rectification of immune function of T cells and B cells. However， a large number of studies have shown that the significance of other members of TME for tumor metastasis cannot be ignored， which greatly reflects the progress of anti-metastatic research based on TME regulation. This review focused on tumor metastasis， summarized the mechanism of action of non-T and non-B immune cells ［tumor-associated macrophages （TAMs） and tumor-associated neutrophils （TANs）］ and non-immune members ［vascular endothelial cells （ECs）， tumor-associated fibroblasts （CAFs）， and blood platelet］ in the process of tumor metastasis in TME based on the literature over the recent five years， and explored their key value in the treatment of metastasis. At the treatment level， this review focused on the perspective of the integration of frontier and traditional methods and took the functional homeostasis remodeling of TME as the entry point to summarize the activity and mechanism of traditional Chinese medicine （TCM） regulation of non-T and non-B immune cells and non-immune members and highlight its advantages and characteristics in clinical intervention of metastasis. This review helps to break through the limitations of over-reliance on T and B immune cells in anti-metastatic research， make the research rely on a wider range of cell groups， explore the potential value of TME in anti-metastatic drug intervention， and enrich the idea and strategy of understanding the anti-metastatic pharmacological activity. The review is also expected to provide a broader vision for the research and development of new anti-metastatic drugs.