BACKGROUND:Resveratrol is a natural antioxidant extracted from plants.Its mechanism of improving exercise-induced fatigue mainly focuses on the protective effect against oxidative stress and inflammation.In this study,the protective mechanism of resveratrol on exercise-induced fatigue was mainly discussed from the perspective of gluconeogenesis. OBJECTIVE:To investigate the effect of resveratrol on gluconeogenesis in exercise-induced fatigue rats. METHODS:After 1 week of adaptive training,male Sprague-Dawley rats were randomly divided into 4 groups with 12 rats in each group:blank control group,resveratrol group,exercise group,resveratrol + exercise group.Weight-bearing swimming training was used to simulate long-term medium-high intensity exercise.After swimming with a weight of 5%for 1 hour every day,50 mg/kg resveratrol solution or the same volume of dimethyl sulfoxide solvent were given orally,6 days a week,for a total of 6 weeks.Samples were collected 24 hours after the last exercise,and the levels of urea nitrogen,creatine kinase,blood glucose,liver glycogen and lactic acid and pyruvate in liver tissue were detected by the kit.The activity of phosphoenolpyruvate carboxykinase was detected by microassay,and the activity of glucose-6-phosphatase was detected by enzyme-linked immunosorbent assay.Real-time fluorescence quantitative PCR was used to detect the gene expression of silent information regulator 1,cAMP-response element binding protein and peroxisome proliferator-activated receptor-γ coactivator-1α. RESULTS AND CONCLUSION:In the exercise group,plasma urea nitrogen and creatine kinase levels of rats were significantly increased(both P<0.05),liver lactate and pyruvate levels and lactate/pyruvate ratio were significantly increased(all P<0.01),and blood glucose and liver glycogen contents were significantly decreased(both P<0.01).Resveratrol supplementation could effectively improve the above conditions.Exercise significantly decreased the activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase(P<0.01,P<0.05),and resveratrol supplementation significantly increased the activity of phosphoenolpyruvate carboxykinase in liver tissue(P<0.01).The mRNA expression levels of silent information regulator 1,cAMP-response element binding protein and peroxisome proliferator-activated receptor-γ coactivator-1α in liver tissue of the exercise group were significantly decreased(all P<0.01),while resveratrol supplementation could significantly increase the gene expression levels of this pathway.To conclude,resveratrol can relieve exercise-induced fatigue caused by long-term medium-high intensity exercise,and its mechanism may be related to up-regulating the gluconeogenesis regulatory pathway,improving rate-limiting enzyme activity,promoting liver gluconeogenesis,and increasing blood glucose and liver glycogen levels.

BACKGROUND:Studies have shown that resveratrol can relieve exercise-induced fatigue and protect the heart,but its action mechanism needs further study. OBJECTIVE:To explore the protective effect and regulatory mechanism of resveratrol on ventricular remodeling in exercise-induced fatigue rats. METHODS:Totally 48 male Sprague-Dawley rats were randomly divided into four groups,with 12 rats in each group.Rats in the blank control group were fed conventionally.After one week of adaptive training,rats in the exercise-related fatigue group and exercise-related fatigue with resveratrol supplement group were trained by 6-week weight-bearing swimming(5%body mass lead block fixed in the tail,70%-80%maximal oxygen uptake intensity),6 days a week,60 minutes a day.Rats in the resveratrol supplement group and exercise-related fatigue with resveratrol supplement group were given resveratrol(50 mg/kg per day)by gavage one hour after exercise intervention.Blank control group and exercise-related fatigue group were given the same volume of 2%dimethyl sulfoxide,6 days a week,once a day for 6 weeks.The body mass and heart mass of the rats were measured 24 hours after the last intervention.Plasma creatine kinase isoenzyme,cardiac troponin 1,pyruvate dehydrogenase and uncoupling protein 1 levels in myocardial tissue were determined by ELISA.The mRNA expression levels of ventricular remodeling-related factor Foxp1,transforming growth factor β1 and endothelin 1 were detected by RT-PCR. RESULTS AND CONCLUSION:Compared with the blank control group,the body mass of rats decreased and the heart mass increased in the exercise-related fatigue group(P＜0.05).Compared with the exercise-related fatigue group,the body mass and heart mass of the rats reduced in the exercise-related fatigue with resveratrol supplement group(P＜0.05).Compared with the blank control group,the levels of creatine kinase isoenzyme,cardiac troponin 1 and uncoupling protein 1 increased(P＜0.01),and the level of pyruvate dehydrogenase decreased(P＜0.01)in the exercise-related fatigue group.Compared with the exercise-related fatigue group,the levels of creatine kinase isoenzyme,myocardial troponin 1 and uncoupling protein 1 decreased(P＜0.05),and the level of pyruvate dehydrogenase increased(P＜0.05)in the exercise-related fatigue with resveratrol supplement group.Compared with the blank control group,the expression of the Foxp1 gene decreased(P＜0.01),and the expression of transforming growth factor β1 and endothelin 1 gene increased(P＜0.01)in the myocardium of the exercise-related fatigue group.Compared with the exercise-related fatigue group,the expression of the Foxp1 gene in the myocardium of the exercise-related fatigue with resveratrol supplement group increased(P＜0.01),while the expression of the transforming growth factor β1 and endothelin 1 gene decreased(P＜0.05).It is suggested that exercise-induced fatigue can promote myocardial adaptability and cause compensatory hypertrophy.Resveratrol can improve myocardial injury and energy metabolism and delay ventricular energy remodeling in rats.This effect may be related to the regulation of Foxp1/transforming growth factor β1/endothelin 1 signaling pathway.

Background and objective Small cell lung cancer(SCLC)is known as recalcitrant cancer with high malignancy and heterogeneity.Immunotherapy has changed the treatment pattern of extensive-disease SCLC(ED-SCLC),but the beneficiary population is limited.Therefore,exploring new therapeutic strategies is an urgent clinical problem to be solved for SCLC.SCLC is characterized by highly active glycolytic metabolism and pyruvate kinase Ml(PKM1)is one of the isozymes of PK,an important rate-limiting enzyme in glycolysis pathway.Previous studies have shown that PKM1 is related to autophagy and drug sensitivity,however,how PKM1 regulates drug sensitivity in SCLC and its mechanism remain unclear.The aim of this study was to investigate the biological functions of PKM1 in SCLC,including its effects on proliferation,migra-tion,autophagy,drug sensitivity,and expression of neuroendocrine(NE)-related markers in SCLC.Methods Western blot was used to detect the expression level of PKM1 in SCLC cells.PKM1 gene-overexpressed SCLC cell lines were constructed by stable lentivirus transfection.Proliferation of cells and drug sensitivity were detected by MTT,and migration ability of cells was determined by Transwell.The level of autophagy was detected by flow cytometry.Western blot was used to determine the expression levels of NE-related proteins.Results PKM1 was differentially expressed among various SCLC cell lines,and was lower in H1092 cells(P＜0.01).Compared with the control group,there was no significant difference in proliferation level of PKM1 overexpressing H1092 cell,but the migration ability was significantly increased(P＜0.001),the drug sensitivity was re-duced,and the level of autophagy was inhibited(P＜0.001).Additionally,overexpression of PKM1 could upregulate the expres-sion of non-neuroendocrine(non-NE)-related proteins(P＜0.01)and decrease the expression of NE-related proteins(P＜0.01).Conclusion PKM1 was differentially expressed in SCLC cell lines,and high expression of PKM1 did not affect the prolifera-tion,but affected the migration of SCLC cells.PKM1 might affect drug sensitivity by inhibiting autophagy and regulating the expression of NE markers.These results provide a theoretical basis for exploring the role of PKM1 in SCLC.

Objective To observe the effectiveness and safety of Regional Citrate Anticoagulation(RCA)in CRRT combined with artificial liver treatment.Methods Clinical data of 54 sessions of CRRT linked with artificial liver treatment using RCA in 21 patients with acute on chronic liver failure(ACLF)combined with acute kidney injury(AKI)admitted to our center from December 2019 to June 2023 were collected..The improvement of liver and kidney function indicators,anticoagulant effect and adverse reactions of citric acid,and patient outcomes were observed and analyzed before and after treatment.Results The 54 cases of liver and renal function indexes were improved,which showed a statistically significant difference(P<0.05);All 54 cases of CRRT linked artificial liver treatment were successfully completed,and no obvious blood clots were found in the extracorporeal circulation tubing,filters,and adsorbers;There was no statistically significant difference(P>0.05)in the total calcium and ionized calcium levels of all patients at each stage of artificial liver treatment compared to before treatment;However,three cases of CRRT combined with PE and one case of CRRT combined with DPMAS+LPE experienced citrate accumulation after treatment,which returned to normal after 24 hours of timely correction and supplemen-tation;The 30-day survival rate of the 21 patients was 13 survivors,5 deaths,and 3 discharged automatically.Conclusion Under strict monitoring and timely adjustment,the application of RCA in CRRT series artificial liver treatment is safe and feasible,and is worthy of clinical promotion.

Dry eye,also known as keratoconjunctivitis sicca,is clinically manifested as dry eyes,itching,burning,blurred vision and other symptoms,which seriously affects the life quality of patients.In recent years,the incidence of dry eye has increased year by year,and it has become one of the common clinical diseases in ophthalmology.At present,the treatment methods of dry eye mainly include drug treatment,surgical treatment and clinical nursing,among which drug is the most commonly used method for the treatment of dry eye.Therefore,this paper summarizes the application and research progress of clinical medication of dry eye based on permeation pathways and inflammatory pathways in recent years,so as to provide some ideas for the follow-up treatment of dry eye and drug development.

ObjectiveThis study aimed to investigate the HIV genotypic subtypes and molecular transmission clusters among men who have sex with men （MSM） with newly reported HIV infections in Dehong Dai and Jingpo Autonomous Prefecture （Dehong Prefecture）， Yunnan Province， China， between 2010 and 2019. The study aimed to identify potential high-risk transmitters and provide reference data for screening， management， and intervention of infection sources. MethodsPlasma samples from newly reported HIV-positive MSM individuals in Dehong Prefecture between 2010 and 2019 were collected. The viral pol gene fragments were amplified， sequenced， and genotyped. Genetic distances （GD） between pairwise sequences were analyzed and calculated. MEGA 7.0 and Gephi were used for phylogenetic and molecular transmission network analysis. ResultsA total of 159 newly reported HIV infections among MSM were included in the study， with successful genotyping of 100 cases. Nine HIV-1 subtypes were identified， with the most prevalent being CRF01_AE subtype （52%）， followed by CRF07_BC subtype （31%）， CRF55_01B subtype （10%）， and others （7%）. Cluster analysis revealed a total network access rate of 67%， forming three transmission clusters. CRF01_AE subtype formed two transmission clusters with 38 and 3 infected individuals， while CRF07_BC subtypes formed one transmission cluster with 26 infected individuals. The transmission network within the CRF01_AE clusters exhibited a more complex relationship. Significant differences in educational level were observed between the two main transmission clusters. ConclusionThe predominant HIV subtypes among newly reported MSM cases in Dehong Prefecture between 2010 and 2019 were CRF01_AE and CRF07_BC. Significant cultural differences are observed between the main transmission clusters. Continued monitoring of genotypic subtypes and targeted interventions within transmission clusters are warranted.

BACKGROUND/OBJECTIVES: To investigate the effect and regulatory mechanism of resveratrol supplementation on the mitochondrial energy metabolism of rats with exerciseinduced fatigue.MATERIALS/METHODS: Forty-eight Sprague-Dawley male rats were divided randomly into a blank control group (C), resveratrol group (R), exercise group (E), and exercise and resveratrol group (ER), with 12 rats in each group. Group ER and group E performed 6-wk swimming training with 5% wt-bearing, 60 min each time, 6 days a wk. Group ER was given resveratrol 50 mg/kg by gavage one hour after exercise; group R was only given resveratrol 50 mg/kg by gavage; group C and group E were fed normally. The same volume of solvent was given by gavage every day. RESULTS: Resveratrol supplementation could reduce the plasma blood urea nitrogen content, creatine kinase activity, and malondialdehyde content in the skeletal muscle, increase the total superoxide dismutase activity in the skeletal muscle, and improve the fatigue state.Resveratrol supplementation could improve the activities of Ca2+ -Mg2+ -ATPase, Na+ -K+ -ATPase, succinate dehydrogenase, and citrate synthase in the skeletal muscle. Furthermore, resveratrol supplementation could up-regulate the sirtuin 1 (SIRT1)-proliferator-activated receptor gamma coactivator-1α (PGC-1α)-nuclear respiratory factor 1 pathway. CONCLUSIONS Resveratrol supplementation could promote mitochondrial biosynthesis via the SIRT1/PGC-1α pathway, increase the activity of the mitochondrial energy metabolismrelated enzymes, improve the antioxidant capacity of the body, and promote recovery from exercise-induced fatigue.

Substantial progress in the use of chemo-photodynamic nano-drug delivery systems (nano-DDS) for the treatment of the malignant breast cancer has been achieved. The inability to customize precise nanostructures, however, has limited the therapeutic efficacy of the prepared nano-DDS to date. Here, we report a structurally defined tandem-responsive chemo-photosensitive co-nanoassembly to eliminate primary breast tumor and prevent lung metastasis. This both-in-one co-nanoassembly is prepared by assembling a biocompatible photosensitive derivative (pheophorbide-diphenylalanine peptide, PPA-DA) with a hypoxia-activated camptothecin (CPT) prodrug [(4-nitrophenyl) formate camptothecin, N-CPT]. According to computational simulations, the co-assembly nanostructure is not the classical core-shell type, but consists of many small microphase regions. Upon exposure to a 660 nm laser, PPA-DA induce high levels of ROS production to effectively achieve the apoptosis of normoxic cancer cells. Subsequently, the hypoxia-activated N-CPT and CPT spatially penetrate deep into the hypoxic region of the tumor and suppress hypoxia-induced tumor metastasis. Benefiting from the rational design of the chemo-photodynamic both-in-one nano-DDS, these nanomedicines exhibit a promising potential in the inhibition of difficult-to-treat breast tumor metastasis in patients with breast cancer.

Objective:To explore the value of red blood cell distribution width (RDW) in evaluating the severity of patients infected with novel coronavirus Delta variant.Methods:A total of 28 patients infected with novel coronavirus Delta variant in designated hospital treated by the First Affiliated Hospital of Xi'an Jiaotong University medical team from December 2021 to January 2022 were enrolled (23 cases of common type, 4 severe and 1 critical cases). The detailed clinical data of patients was collected. Then, Pearson's correlation analysis was used to identify the blood examination indexes which affected the arterial partial pressure of oxygen (PaO 2) and arterial partial pressure of carbon dioxide (PaCO 2). According to the median standard deviation of red blood cell distribution width (RDW-SD, 42.5 fL), 28 patients were divided into low RDW-SD group (≤ 42.5 fL, 16 cases) and high RDW-SD group (> 42.5 fL, 12 cases), and the immune related indexes of the two groups were compared. Receiver operator characteristic curve (ROC) was drawn to evaluate the predictive value of RDW-SD on the severity of illness of coronavirus disease 2019 (COVID-19). Results:Correlation analysis showed that RDW-SD was the only index related to PaO 2 and PaCO 2 on the first day of admission, which was negative correlation with PaO 2 ( r = -0.379, P = 0.047) and positive correlation with PaCO 2 ( r = 0.509, P = 0.006). The results of effects of different clinical characteristics on RDW-SD level showed that there was no statistically significant difference in RDW-SD between groups with different clinical characteristics (including male/female, ≥ 65 years old/< 65 years old, having/without hypertension, having/without diabetes, smoking/not smoking, having/without hyperpyrexia, with/without fever for 3 days, with/without respiratory symptoms, with/without digestive symptoms). It was suggested that RDW-SD be relatively stable and not affected by the patient's baseline level. The percentage of B cells in low RDW-SD group was higher than that in high RDW-SD group (23.01±3.01 vs. 15.34±5.34, P < 0.05), immunoglobulin G (IgG) level in low RDW-SD group was lower than that in high RDW-SD group (g/L: 11.43±3.20 vs. 15.42±1.54, P < 0.05). The area under ROC curve (AUC) of RDW-SD in evaluating severe cases was 0.83 [95% confidence interval (95% CI) was 0.59-1.06], which was close to multilobularinltration, hypo-lymphocytosis, bacterial coinfection, smoking history, hyper-tension and age (MuL BSTA score; AUC = 0.82, 95% CI was 0.51-1.12) and better than British Thoracic Society's modified pneumonia score (CURB-65 score; AUC = 0.70, 95% CI was 0.50-0.91). Conclusion:RDW-SD has significant evaluative effect on the severity of COVID-19 patients with Delta variants.