Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

BACKGROUND:Connexin 43(Cx43),which is thought to be engaged in the gap junction process and build the structural groundwork for the development of direct material signaling channels between cells,is crucial for maintaining the homeostatic balance of tissue metabolism.Recent research,however,has revealed fresh information about its distinct hemichannel function and highlighted the significance of its subcellular localization and self-fragmentation for cellular physiological activities and pathological processes. OBJECTIVE:To systematically summarize the molecular characteristics and expression of Cx43 in a variety of cells,concentrate on the pathological and physiological roles of channel-dependent Cx43 and channel-independent Cx43,and investigate the potential value in disease treatment by reviewing the pertinent literature in the database. METHODS:The Chinese and English keywords were"gap junction,connexin 43(Cx43),hemichannel,channel-dependent Cx43,channel-independent Cx43,extracellular vesicles(EVs),mitochondria,GJA1-20k",which were searched in PubMed and CNKI.Finally,81 articles were selected for review. RESULTS AND CONCLUSION:(1)The canonical role of Cx43 is to form a gap junction channel.Channel-dependent Cx43 has primarily involved in disease physiopathological processes by directly constituting gap junction channels,but full attention should be paid to the issue of its structural and functional integrity.Adhesion is a crucial characteristic of gap junctions,which are strongly associated with barrier-like diseases.(2)The non-canonical role of Cx43 is non-gap junction channel-dependent effect.In addition to being localized at the plasma membrane,inner mitochondrial membrane,extracellular vesicle surface,and other structures,Cx43 hexamer has also been found to play a role in positive pro-inflammatory mechanisms,mitochondrial functional metabolism,and targeted uptake of extracellular vesicles in inflammatory diseases.Selective shortened segments control mitochondrial homeostasis by encouraging the polymerization of peri-mitochondrial actin and are involved in the targeted translocation of full-length Cx43 to intracellular structural domains.(3)The development of targeted medicines and the solving of issues like the mechanism of seed cell transformation in tissue engineering-based therapies are both made possible by these two categories of impacts.The interactions of various types of Cx43,however,are frequently not fully taken into account in some of the existing original studies,which confuses the overall characteristics and skews the results.(4)It is necessary to systematically frame the physiological characteristics of Cx43 in different forms and its potential mechanisms in various diseases,so as to provide a reference for the exploration of the Cx43 integrity mechanism and the diagnosis and treatment of multiple diseases.

Objective:The purpose of this study is to explore in depth the mechanism of the impact of brain drain on organizational cohesion,with a view to cracking the vicious circle problem caused by brain drain in the northeast region and eliminating the unfavorable factors affecting the core cohesion of public health institutions.Methods:A combination of convenience sampling and snowball sampling was used to survey11 912 valid questionnaires,and the data were systematically analyzed using descriptive statistics,regression analysis,and moderated mediated effects analysis.Results:Brain drain has a significant negative effect on organizational cohesion(β=-1.29,P<0.001);and role overload partially mediates between the two,with a significant mediating effect(effect value=-0.56,95%CI=-0.67～-0.46),and the indirect effect accounts for 43.4%of the total effect;and monthly income significantly moderates the effect of brain drain on organizational cohesion through role overload(β=1.00,P<0.001).Conclusion:It is recommended to alleviate the sense of role overload among public health personnel by adjusting the level of salary and benefits,and to reduce the negative impact of brain drain by adopting long-term incentive mechanisms and other strategies,thus enhancing organizational cohesion and providing theoretical and practical guidance for relevant institutions.

Objective:To explore whether transjugular intrahepatic portosystemic shunt (TIPS) can improve the prognosis of esophagogastric variceal bleeding (EGVB) combined with sarcopenia in cirrhotic patients.Methods:A retrospective cohort study was performed. A total of 464 cases with cirrhotic EGVB who received standard or TIPS treatment between January 2017 and December 2019 were selected. Regular follow-up was performed for the long-term after treatment. The primary outcome was transplantation-free survival. The secondary endpoints were rebleeding and overt hepatic encephalopathy (OHE). The obtained data were statistically analyzed. The t-test and Wilcoxon rank-sum test were used to compare continuous variables between groups. The χ2 test, or Fisher's exact probability test, was used to compare categorical variables between groups. Results:The age of the included patients was 55.27±13.86 years, and 286 cases were male. There were 203 cases of combined sarcopenia and 261 cases of non-combined sarcopenia. The median follow-up period was 43 months. The two groups had no statistically significant difference in follow-up time. There was no statistically significant difference in transplant-free survival between the TIPS group and the standard treatment group in the overall cohort ( HR=1.31, 95% CI: 0.97-1.78, P=0.08). The TIPS patient group with cirrhosis combined with sarcopenia had longer transplant-free survival (median survival: 47.76 vs. 52.45, χ2=4.09; HR=1.55, 95 CI: 1.01~2.38, P=0.04). There was no statistically significant difference in transplant-free survival between the two kinds of treatments for patients without sarcopenia ( HR=1.22, 95% CI: 0.78~1.88, P=0.39). Rebleeding time was prolonged in TIPS patients with or without sarcopenia combination (patients without combined sarcopenia: median rebleeding time: 39.48 vs. 53.61, χ2=18.68; R=2.47, 95 CI: 1.67~3.65, P<0.01; patients with sarcopenia: median rebleeding time: 39.91 vs. 50.68, χ2=12.36; HR=2.20, 95 CI: 1.42~3.40, P<0.01). TIPS patients had an increased 1-year OHE incidence rate compared to the standard treatment group (sarcopenia patients: 6.93% vs. 16.67%, χ2=3.87, P=0.049; patients without sarcopenia combination: 2.19% vs. 9.68%, χ2=8.85, P=0.01). There was no statistically significant difference in the long-term OHE incidence rate between the two kinds of treatment groups ( P>0.05). Conclusion:TIPS can significantly prolong transplant-free survival compared to standard treatment as a secondary prevention of EGVB concomitant with sarcopenia in patients with cirrhosis. However, its advantage is not prominent for patients with cirrhosis in EGVB without sarcopenia.

Objective:To explore the gene microarray of patients with ankylosing spondylitis in GEO database by using various bioinformatics methods, and to explore the possible targets and mechanisms of action.Methods:The GEO database was searched with "ankylosing spondylitis" the keyword, and the expression profile of genes related to AS was selected as the research object. Standard difference analysis, weighted co-expression analysis and gene set enrichment analysis were conducted to construct the disease set. GO and KEGG enrichment analysis were performed on the disease sets. The NCC algorithm identifies the first five key genes. THP-1 cells were implanted into RPMI-1640 culture medium containing 10% fetal bovine serum to multiply and construct the cell model of AS in vitro. The expression levels of 5 key genes were detected by qRT-PCR and Western blot. The experimental measurement data were expressed as mean± standard deviation, and the t test was used in comparison between the two groups. Results:One thousand six hundred and sixty seven disease genes were analyzed, functional annotation was mainly concentrated in 689 molecular components of cytoplasmic ribosomes, ribosomal subunits, ribosomes, cytoplasmic large ribosomal subunits, the structural composition of ribosomal REDOX enzyme activity, 1 002 molecular functions of NADH dehydrogenase activity, NADH dehydrogenase activity, and 5 764 molecular processes of mRNA catabolism and RNA catabolism The physical process involved 1 002 signaling pathways involved in Alzheimer′s disease, Prion disease, Parkinson′s disease, and the first 5 key genes were identified as RPS11, RPL4, RPL37A, RPS23, and RPS9. The experimental results were obtained by t test. The results showed that TNF-α mRNA ( t=5.59, P=0.001) and protein ( t=20.14, P<0.001) were significantly increased, indicating that LPS had induced inflammatory response in THP-1 cells, while RPL37AmRNA ( t=5.87, P=0.001), RPS11 mRNA ( t=3.88, P=0.008), RPS23 mRNA ( t=2.64, P=0.038), RPL37A protein ( t=3.18, P=0.030), RPS11 protein ( t=11.26, P<0.001), RPS23 protein ( t=5.64, P<0.001), increased, while RPS9 mRNA ( t=3.16, P=0.020), RPL4 mRNA ( t=2.54, P=0.044), RPS9 protein ( t=5.85, P<0.001) and RPL4 ( t=2.93, P=0.040) protein expressions decreased. RPL23 stimulated the joint synovial tissue to produce effect-T lymphocytes and release a large number of IL-2 and other inflammatory cytokines. RPS9 acts on the early stages of ribosomogenesis, and knocking down RPS9 reduced overall protein synthesis. RPL4 interacted with TTC22 protein to enhance the binding of WTAP mRNA to RPL4, which was associated with immune diseases. The nucleoprotein OGFOD1 catalyzed the hydroxylation of RPS23 and participated in the inflammatory process. The chromosome conformation confirmed the single nucleotide polymorphism function of IL23R genomic locus in AS disease. Conclusion:Ribosomal protein may be an important target for exploring the mechanism of AS inflammation.

Humans ; Thyroid Cancer, Papillary/pathology* ; Lymphatic Metastasis/pathology* ; Neck/pathology* ; Lymph Nodes/pathology* ; Thyroid Neoplasms/pathology* ; Retrospective Studies ; Neck Dissection ; Thyroidectomy

Cobalt/toxicity* ; Computational Biology ; Kidney/drug effects* ; Kidney Diseases/genetics* ; Humans

Objective: To investigate the potential risk factors for occult lateral cervical lymph node metastasis (LNM) to levels Ⅲ and Ⅳ in patients with papillary thyroid carcinoma (PTC) and the necessity of super-selective lateral lymph node dissection for patients harboring these metastases. Methods: This prospective study included PTC patients who were operated by the same surgeon in the Department of Head and Neck Surgery of Cancer Hospital, Chinese Academy of Medical Sciences from October 2015 through October 2019. Preoperative ultrasound and enhanced Computer Tomography (CT) did not denote suspected enlarged lymph nodes in the lateral neck. All patients underwent lymph node dissection in levels Ⅲ and Ⅳ on the basis of original thyroid collar incision after LNM to level Ⅵ was confirmed by preoperative fine needlebiopsy or intraoperative frozen pathology. Results: Of all 143 patients, 74 (51.7%) had occult LNM in levels Ⅲ and Ⅳ confirmed by postoperative pathology. The average number of metastasized lymph nodes in levels Ⅲ and Ⅳ was 2.64±1.80, and that in level Ⅵ was 3.77±3.27. There was a significant linear positive correlation between the number of metastasized lymph nodes in level Ⅵ and that in levels Ⅲ and Ⅳ (r=0.341, P<0.001). That the metastasized lymph nodes in level Ⅵ equals three was the best predictor of occult lateral LNM to levels Ⅲ and Ⅳ. Univariate analysis showed that age <55 years, tumor size ≥2.0 cm, number of metastasized lymph nodes in level Ⅵ ≥3, and percentage of metastasized lymph nodes in the total number of dissected lymph nodes in level Ⅵ >50% were associated with occult LNM in levels Ⅲ and Ⅳ (P<0.05). Multivariate analysis showed that number of metastasized lymph nodes in level Ⅵ≥3 was an independent risk factor for occult LNM in levels Ⅲ and Ⅳ (P=0.006). Conclusions: Age, tumor size and LNM in level Ⅵ were associated with occult lateral LNM in PTC patients. Lymph node dissection in levels Ⅲ and Ⅳ could be considered for selective patients, since it will help to avoid secondary operation for residual tumor or recurrence resulted from insufficient treatment without increasing the incidence of complications or affecting patients' appearances.

Objective: To investigate the potential risk factors for occult lateral cervical lymph node metastasis (LNM) to levels Ⅲ and Ⅳ in patients with papillary thyroid carcinoma (PTC) and the necessity of super-selective lateral lymph node dissection for patients harboring these metastases. Methods: This prospective study included PTC patients who were operated by the same surgeon in the Department of Head and Neck Surgery of Cancer Hospital, Chinese Academy of Medical Sciences from October 2015 through October 2019. Preoperative ultrasound and enhanced Computer Tomography (CT) did not denote suspected enlarged lymph nodes in the lateral neck. All patients underwent lymph node dissection in levels Ⅲ and Ⅳ on the basis of original thyroid collar incision after LNM to level Ⅵ was confirmed by preoperative fine needlebiopsy or intraoperative frozen pathology. Results: Of all 143 patients, 74 (51.7%) had occult LNM in levels Ⅲ and Ⅳ confirmed by postoperative pathology. The average number of metastasized lymph nodes in levels Ⅲ and Ⅳ was 2.64±1.80, and that in level Ⅵ was 3.77±3.27. There was a significant linear positive correlation between the number of metastasized lymph nodes in level Ⅵ and that in levels Ⅲ and Ⅳ (r=0.341, P<0.001). That the metastasized lymph nodes in level Ⅵ equals three was the best predictor of occult lateral LNM to levels Ⅲ and Ⅳ. Univariate analysis showed that age <55 years, tumor size ≥2.0 cm, number of metastasized lymph nodes in level Ⅵ ≥3, and percentage of metastasized lymph nodes in the total number of dissected lymph nodes in level Ⅵ >50% were associated with occult LNM in levels Ⅲ and Ⅳ (P<0.05). Multivariate analysis showed that number of metastasized lymph nodes in level Ⅵ≥3 was an independent risk factor for occult LNM in levels Ⅲ and Ⅳ (P=0.006). Conclusions: Age, tumor size and LNM in level Ⅵ were associated with occult lateral LNM in PTC patients. Lymph node dissection in levels Ⅲ and Ⅳ could be considered for selective patients, since it will help to avoid secondary operation for residual tumor or recurrence resulted from insufficient treatment without increasing the incidence of complications or affecting patients' appearances.

Objective: To investigate the prevalence of dyslipidemia among adults in Moyu County, Hotan Prefecture, Xinjiang Uygur Autonomous Region, so as to provide insights into the management of dyslipidemia. Methods: The physical examination data of permanent residents at ages of 18 years and older were collected from Moyu County from 2018 to 2019, including demographic features, height, body weight, blood pressure and blood biochemical parameter measurements. The epidemiological characteristics of dyslipidemia were analyzed among residents. Results: Totally 166 142 adults were investigated, with a mean age of (41.08±15.72) years. There were 77 744 men (46.76%), 34 728 obese adults (20.90%), 5 776 adults with diabetes (3.48%) and 26 294 adults with hypertension (15.83%). The levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were (1.38±0.98), (4.13±1.19), (1.31±0.41) and (2.25±0.77) mmol/L, respectively. The prevalence of dyslipidemia was 29.72%, and the detection rates of high TG, high TC, low-HDL-C and high LDL-C were 9.73%, 4.59%, 19.65% and 1.99%, respectively. The prevalence of dyslipidemia was higher in men than in women (33.97% vs. 25.98%; χ2=1 264.729, P<0.001), and the prevalence increased with age (χ2=539.382, P<0.001) and body mass index (χ2=3 601.833, P<0.001). The prevalence of dyslipidemia was 35.48% among patients with hypertension (χ2=497.251, P<0.001) and 46.07% among patients with diabetes (χ2=766.142, P<0.001). There were 9 059 adults with two and more abnormal blood lipid indexes (18.35%), and the detection rates of two and more abnormal blood lipid indexes were 26.50%, 24.14% and 33.15% among patients with obesity, hypertension and diabetes, respectively. Conclusions The prevalence of dyslipidemia among adults in Moyu County is lower than the national level, and low-HDL cholesterolemia is the most common type of dyslipidemia. The prevalence of dyslipidemia is high among patients with obesity, hypertension and diabetes mellitus, in whom abnormality of multiple blood lipid indexes is measured.