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.

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

Postoperative pain seriously affects the recovery process of patients, resulting in prolonged hospital stay and increased care costs. Appropriate application of patient-controlled analgesia devices can effectively relieve perioperative acute pain. In 1994 patient-controlled analgesia began to be used in Peking Union Medical College Hospital, and the Acute Pain Service Working Group was established in 2004. With the cooperation of anesthesiologists and specialist nurses, the group jointly has implemented the whole process and standardized management based on patient-controlled analgesia, and constantly improved and innovated working methods, laying a solid foundation for the development of postoperative pain management. This paper systematically reviews and summarizes the work from the aspects of clinical focus, nursing management experience, promotion and dissemination of pain treatment concepts, and development of acute pain service model under the new situation, with the hope of providing valuable reference for comprehensively strengthening pain management in the process of diagnosis and treatment, and enhancing patients' satisfaction with perioperative analgesia services.

Objective To study the changes in peripheral blood T lymphocytes in patients with ankylosing spondylitis and their correlation with the disease's severity and prognosis.Methods We selected 120 patients with ankylosing spondylitis treated between January 2020 and March 2023 as the research group and 120 healthy people who had medical examinations in the same period as the health group.We detected the changes in CD4+,CD8+and CD4+/CD8+values of peripheral blood T lymphocyte subsets with flow cytometry,compared the differences in T lymphocyte subsets between the two groups,and analyzed the correlation with the disease severity of the patients.All the 120 patients with ankylosing spondylitis were followed up for 6 months after treatment to assess their prognosis.General information and T lymphocyte sub-groups CD4+,CD8+level,CD4+/CD8+value changes were compared among patients with different prognosis.We analyzed the value of T lymphocyte sub-groups in predicting the prognosis of patients with ankylosing spondylitis.Results In the research group CD4+and CD4+/CD8+were lower but CD8 1 was higher than those in the healthy group(P＜0.05).CD4+and CD4+/CD8 were lower but CD8+was higher in patients with advanced ankylosing spondylitis than in early and mid-term patients(P＜0.05).The ROC curve analysis showed that the AUC of CD4+,CD8+,and CD4+/CD8+combined diagnosis of ankylosing spondylitis patients was 0.878,with higher diagnostic sensitivity than that of the single diagnosis(P＜0.05).In the poor prognosis group,CD8+was higher than that in the excellent prognosis group,but CD4+and CD4+/CD8 value were lower than the latter(P＜0.05).The results of Pearson test showed that CD4+and CD4+/CD8+were negatively correlated with the prognosis of patients with ankylosing spondylitis(r=-0.568,-0.656,P＜0.001).CD8+was positively correlated with the prognosis of patients with ankylosing spondylitis(r=0.623,P＜0.001).ROC curve analysis showed that the AUC of the combined diagnosis of CD4+,CD8+and CD4+/CD8+for ankylosing spondylitis patients was 0.910,and the diagnostic sensitivity was higher than that of single diagnosis(P＜0.05).Conclusion The abnormal levels of peripheral blood T lymphocyte subsets in patients with ankylosing spondylitis are closely related to the severity and prognosis of the disease,and can be used as a reference indicator for diagnosing the severity and prognosis of ankylosing spondylitis.

Objective:To analyze the epidemiological characteristics of rabies in China from 2007 to 2023, and to provide reference evidence for tailoring strategies to facilitate the elimination of rabies in the country.Methods:Case data from 2007 to 2023 were obtained from China′s National Notifiable Infectious Disease Reporting Information System, and the spatial, temporal, and demographic features of cases were analyzed.Results:From 2007 to 2023, a total of 18 751 human rabies cases were reported in China, with an average annual incidence rate of 0.08 per 100 000. The average annual percentage change (AAPC) in incidence rate was -18.58% (95% CI: -21.32% to -15.75%, P<0.05), with three significant turning points in 2011, 2018, and 2021. Based on the trend of the epidemic, Chinese provinces can be roughly divided into five categories. The geographical range affected by rabies has decreased from 23 provinces and 984 counties (districts) in 2007 to 17 provinces and 101 counties (districts) in 2023. Since 2019, the high-incidence counties (districts) have been mainly concentrated in the southwestern part of Hunan, the southern part of Henan, and the western part of Anhui. Fourteen provinces have reported no cases for at least two consecutive years. Males (70.24%) and farmers (72.18%) were the main affected groups, and the proportion of cases aged 65 and above increased from 17.43% in 2007 to 36.07% in 2023. Conclusions:The incidence of rabies in China has changed from endemic in many areas to sporadic, with the remaining endemic regions mainly located in parts of the middle and lower reaches of the Yangtze River. The main vulnerable groups are middle-aged and elderly farmers. The current prevention and control measures can effectively curb the transmission of rabies, but the decline of cases has slowed down recently.

Sarcopenia is a major factor affecting the health and quality of life of the patients undergoing hemodialysis.Exercise can effectively ameliorate sarcopenia in these patients.However,the type,intensity,time,and frequency of exercise influence the effect of exercise.This review describes the effects of different exer-cise prescriptions on sarcopenia in the patients undergoing hemodialysis.It aims to assist medical staff in develo-ping personalized exercise prescriptions,guiding patients to engage in exercise,and provide effective strategies for the prevention and treatment of sarcopenia in the patients undergoing hemodialysis.

β-elemene has been observed to exert inhibitory effects on a multitude of tumors,primarily through multiple pathways such as the inhibition of cancer cell proliferation and the induction of apoptosis.The present study is designed to elucidate the role and underlying mechanisms of β-elemene in the thera-peutic intervention of non-small cell lung cancer(NSCLC).Both in vitro and in vivo experimental models corroborate the inhibitory potency of β-elemene on NSCLCs.Our findings indicate that β-elemene fa-cilitates the maturation of miR-127-3p by inhibiting CBX8.Functioning as an upstream regulator of MAPK4,miR-127-3p deactivates the Akt/mTOR/p70S6K pathway by targeting MAPK4,thereby inducing autophagy in NSCLCs.Additionally,β-elemene augments the packaging of miR-127-3p into exosomes via SYNCRIP.Exosomal miR-127-3p further stimulates M1 polarization of macrophages by suppressing ZC3H4.Taken together,the detailed understanding of the mechanisms through which β-elemene in-duces autophagy in NSCLCs and facilitates M1 polarization of macrophages provides compelling scientific evidence supporting its potential utility in NSCLC treatment.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

AIM:Bone morphogenetic protein 7(BMP7)reduces the expression of Yes-related protein 1(YAP1)by down-regulating Ajuba level and decreasing extracellular matrix(ECM)deposition.This study aimed to inves-tigate the influence of these factors on modifying the degree of renal fibrosis in rats with diabetic nephropathy.METH-ODS:Eighteen Sprague-Dawley(SD)rats were randomly divided into three groups:the normal control(NC)group,the diabetes mellitus(DM)group,and the DM group treated with BMP7 overexpressing adeno-associated virus(DM+rAAV-BMP7).Each group consisted of six rats.Diabetic kidney disease(DKD)was established in the DM and DM+rAAV-BMP7 groups by injecting 55 mg/kg streptozotocin(STZ)via the tail vein.NRK-52E cells were divided into three groups:the normal glucose(NG)group,the high glucose(HG)group,and the high glucose group treated with recombinant hu-man BMP7(HG+rhBMP7)group.Pathological changes in renal tissues were observed using hematoxylin and eosin(HE)and Sirius red staining.Immunohistochemical staining was performed to examine the expression sites of Ajuba and YAP1 in the renal cortex.Western blot analysis was conducted to determine the expression levels of BMP7,Ajuba,YAP1,colla-gen type Ⅲ(Col-Ⅲ),and fibronectin(FN)in the rat renal cortex and NRK-52E cells.RT-qPCR was used to measure the mRNA levels of Ajuba and YAP1 in the rat renal cortex.RESULTS:Biochemical indices revealed significantly ele-vated levels of blood glucose,serum creatinine,triglycerides,total cholesterol,and 24-hour urinary protein in the DM group compared to the NC group(P<0.05).In the DM+rAAV-BMP7 group,the levels of serum creatinine,24-hour uri-nary protein,triglycerides,and total cholesterol were lower than those in the DM group(P<0.05).Pathological staining demonstrated that the renal interstitium of the DM group exhibited inflammatory cell infiltration,fibrous tissue,collagen fi-ber deposition,disordered renal tubule arrangement,atrophy,and vacuolar degeneration,which were ameliorated in the DM+rAAV-BMP7 group.Immunohistochemistry revealed that Ajuba and YAP1 were mainly expressed in the cytoplasm and nucleus,with high expression in the cytoplasm of the DM group,which was significantly decreased in the DM+rAAV-BMP7 group.Western blot results indicated that the protein levels of FN,Col-Ⅲ,Ajuba,and YAP1 were up-regulated in the DM and the HG groups(P<0.05),but significantly down-regulated in the DM+rAAV-BMP7 group(P<0.05).RT-qP-CR results demonstrated that the mRNA levels of Ajuba and YAP1 were higher in the DM group and significantly lower in the DM+rAAV-BMP7 group(P<0.05).CONCLUSION:The overexpression of BMP7 can ameliorate renal fibrosis in rats with DKD.This effect is likely mediated by the down-regulation of Ajuba,reduction of YAP1 expression,and subse-quent inhibition of ECM deposition.