Objective Exploring the mechanism of"Wushen acupuncture"in alleviating chronic fatigue in rats from the perspective of mitophagy.Methods Forty male Wistar rats were randomly allocated into a normal group and a modeling group,where the latter employed a protocol combining exhaustive swimming with tail-clamping stimuli to induce a rat model of chronic fatigue.Post-modeling,the normal group was subdivided randomly into a blank group and a presumed control group with specifics requiring clarification.Meanwhile,the modeling group was further randomized into a model group,a"Wushen acupuncture"group that underwent acupuncture at the Baihui and Sishencong points,and a non-acupoint control group,in which acupuncture was applied to 5 mm behind houshencong which is non-meridian,non-acupoint sites on the rats' heads and necks.The modeling and treatment outcomes in rats are assessed via the tail suspension test.Protein relative expression levels of adenosine 5'-monophosphate-activated protein kinase(AMPK),mammalian target of rapamycin(mTOR),and peroxisome proliferator-activated receptor γ coactivator 1-alpha(PGC-1α)in rat skeletal muscle were detected using Western blot.Meanwhile,the relative mRNA expression levels of PTEN induced putative kinase 1(PINK1)and Parkin were measured by Real-Time PCR.Results In contrast to the baseline cohort,rats in the induced fatigue model displayed a reduction in struggles,struggle duration,swaying frequency,and swaying duration(P<0.05).When juxtaposed against the fatigue-induced model group,the"Wushen acupuncture"intervention cohort manifested a substantial increase in these behavioral parameters(P<0.05).Furthermore,relative to the"Wushen acupuncture"intervention group,the non-acupoint control cohort showed a decrease in struggles,struggle duration,swaying frequency,and swaying duration(P<0.05).Versus the baseline group,the fatigue-induced model cohort demonstrated a marked decrease in the relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA in skeletal muscle tissue(P<0.05),alongside an increase in mTOR protein expression(P<0.05).Compared to the fatigue-induced model group,the"Wushen acupuncture"intervention led to an increase in the relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA(P<0.05),and a decrease in mTOR protein expression(P<0.05).When juxtaposed against the"Wushen acupuncture"intervention group,the non-acupoint control cohort showed decreased relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA(P<0.05),and increased mTOR protein expression(P<0.05).Conclusion The"Wushen acupuncture"have been shown to enhance the alleviation of chronic fatigue symptoms in rat models and modulate the functionality of mitochondrial autophagy.This therapeutic effect is believed to be mechanistically linked to the regulation of both the PINK1/Parkin pathway and the AMPK/mTOR signaling cascade.

Objective Exploring the mechanism of"Wushen acupuncture"in alleviating chronic fatigue in rats from the perspective of mitophagy.Methods Forty male Wistar rats were randomly allocated into a normal group and a modeling group,where the latter employed a protocol combining exhaustive swimming with tail-clamping stimuli to induce a rat model of chronic fatigue.Post-modeling,the normal group was subdivided randomly into a blank group and a presumed control group with specifics requiring clarification.Meanwhile,the modeling group was further randomized into a model group,a"Wushen acupuncture"group that underwent acupuncture at the Baihui and Sishencong points,and a non-acupoint control group,in which acupuncture was applied to 5 mm behind houshencong which is non-meridian,non-acupoint sites on the rats' heads and necks.The modeling and treatment outcomes in rats are assessed via the tail suspension test.Protein relative expression levels of adenosine 5'-monophosphate-activated protein kinase(AMPK),mammalian target of rapamycin(mTOR),and peroxisome proliferator-activated receptor γ coactivator 1-alpha(PGC-1α)in rat skeletal muscle were detected using Western blot.Meanwhile,the relative mRNA expression levels of PTEN induced putative kinase 1(PINK1)and Parkin were measured by Real-Time PCR.Results In contrast to the baseline cohort,rats in the induced fatigue model displayed a reduction in struggles,struggle duration,swaying frequency,and swaying duration(P<0.05).When juxtaposed against the fatigue-induced model group,the"Wushen acupuncture"intervention cohort manifested a substantial increase in these behavioral parameters(P<0.05).Furthermore,relative to the"Wushen acupuncture"intervention group,the non-acupoint control cohort showed a decrease in struggles,struggle duration,swaying frequency,and swaying duration(P<0.05).Versus the baseline group,the fatigue-induced model cohort demonstrated a marked decrease in the relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA in skeletal muscle tissue(P<0.05),alongside an increase in mTOR protein expression(P<0.05).Compared to the fatigue-induced model group,the"Wushen acupuncture"intervention led to an increase in the relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA(P<0.05),and a decrease in mTOR protein expression(P<0.05).When juxtaposed against the"Wushen acupuncture"intervention group,the non-acupoint control cohort showed decreased relative expression levels of AMPK,PGC-1α,PINK1,and Parkin mRNA(P<0.05),and increased mTOR protein expression(P<0.05).Conclusion The"Wushen acupuncture"have been shown to enhance the alleviation of chronic fatigue symptoms in rat models and modulate the functionality of mitochondrial autophagy.This therapeutic effect is believed to be mechanistically linked to the regulation of both the PINK1/Parkin pathway and the AMPK/mTOR signaling cascade.

Objective:To analyze the risk factors for the development of moderate to severe liver fibrosis in male metabolic syndrome (MetS) patients.Methods:In this study, a single-center retrospective study was conducted to select 414 male patients with MetS who were diagnosed by physical examination at the First Affiliated Hospital of Zhengzhou University from January 2022 to November 2023. The patients were classified into MetS with no/slight hepatic fibrosis group (MetS F0-1 group, 294 cases) and MetS with moderate to severe hepatic fibrosis group (MetS F2-4 group, 120 cases) according to the results of liver hardness test. The independent risk factors for the development of moderate-to-severe liver fibrosis in male MetS patients were explored by univariate and multivariate analyses of whether they had diabetes, and the levels of body mass index (BMI), serum glutamate aminotransferase (ALT), aspartate aminotransferase (AST), glutamyltransferase (GGT), and uric acid.Results:Compared with the MetS F0-1 group, theMets F2-4 group had the characteristics of high obesity rate, high diabetes rate and high serum ALT, AST. GGT and uric acid levels (all P<0.05). One-way regression analysis revealed that those with diabetes mellitus ( OR=2.891, 95% CI: 1.627-5.138), high BMI ( OR=1.276, 95% CI: 1.191-1.368), high level of serum ALT ( OR=1.024, 95% CI: 1.015-1.034), AST ( OR=1.052, 95% CI: 1.032-1.072), GGT ( OR=1.011, 95% CI: 1.005-1.016) and uric acid ( OR=1.003, 95% CI: 1.001-1.006) were the risk factors for the development of moderate-to-severe hepatic fibrosis in male patients with MetS, whereas a multifactorial regression analysis found that the presence of diabetes ( OR=5.561, 95% CI: 2.706-11.428), high BMI ( OR=1.271, 95% CI: 1.177-1.372) and high serum uric acid ( OR=1.004, 95% CI: 1.001-1.007) were the independent risk factors for the development of moderate-to-severe hepatic fibrosis in male MetS patients. Conclusion:Diabetes, high BMI and high level of serum uric acid are independent risk factors for the development of moderate-to-severe hepatic fibrosis in male patients with MetS.

Objective To analyze the correlation between inflammation,nutritional indicators and hy-poproteinemia in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Meth-ods The clinical data of patients with AECOPD admitted to the Department of Respiratory and Critical Care Medicine of the First Affiliated Hospital of Xiamen University from January 2020 to September 2022 were ret-rospectively analyzed,and the patients were divided into the hypoproteinemia group(n=73)and the non-hy-poproteinemia group(n=141)according to whether the serum albumin(ALB)was lower than 35 g/L.The clinical data,inflammatory indicators and nutritional indicators of the two groups were compared,Spearman correlation analysis was performed,and binary logistic regression analysis was performed to analyze the influ-encing factors of patients with AECOPD complicated with hypoproteinemia.Results There were statistically significant differences in age,length of hospital stay,and body weight between the two groups(P＜0.05).There were no significant differences in gender,number of hospitalizations in the past 1 year,height,diabetes,hypertension and proportion of coronary heart disease(P＞0.05).Compared with the non-hypoproteinemia group,the hypoproteinemia group had longer hospital stays and higher levels of C-reactive protein,neutrophil/albumin ratio(NAR),neutrophil to lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR),and systemic immunoinflammatory index(SII).The prognostic nutritional index(PNI),body mass index(BMI),hemoglo-bin and total protein levels were lower,and the difference was statistically significant(P＜0.05).Body weight,BMI,hemoglobin,total protein,PNI and AECOPD patients with hypoproteinemia were negatively cor-related(P＜0.05),while age,length of hospital stay,C-reactive protein,NAR,NLR,PLR,SII and AECOPD patients with hypoproteinemia were positively correlated(P＜0.05).Binary logistic regression analysis showed that PNI,SII and NLR were the influencing factors of hypoproteinemia in AECOPD patients.Conclusion In clinical practice,attention should be paid to and timely correction of hypoproteinemia in pa-tients with AECOPD,improvement of inflammatory indicators and nutritional status of patients,and preven-tion of acute exacerbation.

Glycosite-specific antibody‒drug conjugatess (gsADCs), harnessing Asn297 N-glycan of IgG Fc as the conjugation site for drug payloads, usually require multi-step glycoengineering with two or more enzymes, which limits the substrate diversification and complicates the preparation process. Herein, we report a series of novel disaccharide-based substrates, which reprogram the IgG glycoengineering to one-step synthesis of gsADCs, catalyzed by an endo-N-acetylglucosaminidase (ENGase) of Endo-S2. IgG glycoengineering via ENGases usually has two steps: deglycosylation by wild-type (WT) ENGases and transglycosylation by mutated ENGases. But in the current method, we have found that disaccharide LacNAc oxazoline can be efficiently assembled onto IgG by WT Endo-S2 without hydrolysis of the product, which enables the one-step glycoengineering directly from native antibodies. Further studies on substrate specificity revealed that this approach has excellent tolerance on various modification of 6-Gal motif of LacNAc. Within 1 h, one-step synthesis of gsADC was achieved using the LacNAc-toxin substrates including structures free of bioorthogonal groups. These gsADCs demonstrated good homogeneity, buffer stability, in vitro and in vivo anti-tumor activity. This work presents a novel strategy using LacNAc-based substrates to reprogram the multi-step IgG glycoengineering to a one-step manner for highly efficient synthesis of gsADCs.

Objective To compare the characteristic of high permeability dialysis(HPD) and conventional hemodialysis(CHD) and to study whether HPD was more effectively in elimination of the macromolecular, medium and small molecule urinary endotoxin in uremia than CHD.Method 48 cases of hemodialysis patients were randomly divided into two groups: HPD group(26 cases)given by high permeability dialysis, and CHD group(22 cases)given by conventional hemodialysis dialyzer. Two groups were observed prospectively for 2 years and renal function , electrolytes, ? 2 microglubulin, amino acid, protein concentration, endotoxin in blood serum were detected before and after hemodialysis respectively.Results The clearance rates of blood creatinine, blood urea nitrogen, uric acid , ? 2 microglubulin in HPD group were better than that of CHD group. Serum amino acid, endotoxin, serum phosphorum changes were no statistical significance after hemodialysis in two groups. Protein concentration after hemodialysis was higher than that before hemodialysis in two groups. Conclusions High permeability dialysis has all virtues of conventional hemodialysis dialysis and can clear macromolecular and medium molecule endotoxin, but conventional hemodialysis can not do.