BACKGROUND:Type 2 diabetes mellitus impairs renal function,and studies have shown that exercise interventions can protect the kidneys.Irisin can protect renal function in diabetic nephropathy patients by restoring autophagy through inhibition of the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway. OBJECTIVE:To explore whether exercise can restore autophagy and ameliorate renal injury by inhibiting over-activation of the renal PI3K/Akt/mTOR signaling pathway,as well as to analyze the differences in the effects of different modalities of exercise. METHODS:Six-week-old Sprague-Dawley rats were randomly divided into a blank control group(normal rats)and a diabetic group,and then the diabetic group was randomly divided into a diabetic model group,a moderate-intensity continuous exercise group,and a high-intensity intermittent exercise group after successful modeling using high-fat,high-sugar feeding plus intraperitoneal administration of low-dose 1%streptozotocin(30 mg/kg).The two exercise groups were subjected to 8 weeks of exercise intervention with different exercise intensities.The fasting blood glucose concentration was detected by glucose oxidase method,glycated hemoglobin levels was measured using a kit,serum insulin concentration was detected by Elisa method,and insulin resistance index was calculated.Gene expression of PI3K,AKT,mTOR,Beclin-1,podocin,and nephrin was detected by RT-PCR.Protein expression of mTOR and autophagy marker proteins LC3-1,LC3-2,and Beclin-1 was detected by western blot RESULTS AND CONCLUSION:Fasting blood glucose and glycosylated hemoglobin levels were highly significantly increased,insulin resistance levels were significantly increased,and insulin levels were significantly decreased in type 2 diabetic rats.Both exercises resulted in highly significant decreases in fasting blood glucose and glycosylated hemoglobin levels,significant decreases in insulin resistance levels and significant increases in insulin levels in type 2 diabetic rats.Insulin levels were significantly higher in the high-intensity intermittent exercise group compared with the moderate-intensity continuous exercise group.The expression of podocin and nephrind genes was significantly reduced in type 2 diabetic rats and two different forms of exercise significantly the gene expression.There was a further trend toward an increase in gene expression of podocyte-associated proteins in the moderate-intensity continuous exercise group compared with the high-intensity intermittent exercise group,but there was no significant difference.The mRNA and protein expression of PI3K,AKT and mTORC1 in kidney tissues of type 2 diabetic rats were significantly increased,and the expression of autophagy marker proteins Beclin-1 and LC3-2 and LC3-2/LC3-1 were significantly decreased.Both different forms of exercise significantly decreased the mRNA and protein expression of PI3K,AKT,and mTORC1,and significantly increased the autophagy marker proteins Beclin-1,LC3-2,and LC3-2/LC3-1 in renal tissues.Compared with the moderate-intensity continuous exercise group,there was a trend toward further decreases in mRNA expression of PI3K,AKT,and mTORC1 and protein expression of mTOR,and a trend toward further elevation of Beclin-1,LC3-2,and LC3-2/LC3-1 in the high-intensity intermittent exercise group,but only Beclin-1 showed a significant difference between groups.In summary,renal podocyte injury in type 2 diabetes mellitus with suppressed autophagy is closely related to aberrant activation of the PI3K/AKT/mTORC1 signaling pathway.Both moderate-intensity continuous exercise and high-intensity intermittent exercise can protect the diabetic kidney,reduce podocyte damage,and restore renal podocyte autophagy,which may be achieved by inhibiting the excessive activation of the PI3K/AKT/mTOR signaling pathway.High-intensity intermittent exercise shows a trend toward more favorable restoration of autophagy compared with moderate-intensity continuous exercise,but with a slight decrease in podocyte protein expression.

Objective To evaluate the acute toxicity and acute eye irritation of hydroquinone. Methods i) Acute toxicity test. Specific pathogen-free (SPF) Kunming mice were randomly divided into four dose groups, 10 mice per group with equal number of males and females. Hydroquinone was administered as a single exposure via oral gavage and intraperitoneal injection at doses of 0.00, 100.00, 250.00, and 500.00 mg/kg body weight. The mice were observed for 14 days. The toxic symptoms were recorded, and median lethal dose (LD₅₀) was calculated. ii) In vitro eye irritation test. Fertilized chicken embryos were randomly divided into four dose groups, with six embryos in each group. The chorioallantoic membrane (CAM) assay was used to evaluate the acute eye irritation potential of hydroquinone in vitro. iii) SPF Kunming mice were randomly divided into three doses groups, 10 mice per group with equal numbers of males and females. Hydroquinone was administered via tail vein injection at doses of 0.00, 25.00, and 50.00 mg/kg body weight. Blood alanine aminotransferase (ALT), aspartate aminotransferase (AST), methemoglobin (MetHb), and cholinesterase levels were measured using colorimetric methods after one hour exposure. Organ coefficients of the heart, liver, spleen, lungs, and kidneys in mice were calculated. Results i) Following oral administration of 500.00 mg/kg body weight hydroquinone, the mice rapidly developed severe toxic symptoms, including agitation, cyanosis of the lips, eye closure, and limb convulsions. Trunk rigidity and curling occurred within 15-60 mins, ended up with death. After intraperitoneal injection at 500.00 mg/kg body weight hydroquinone, toxic reactions occurred more rapidly, with all mice died within five mins. The LD₅₀ values for acute oral and intraperitoneal exposure were 356.64 and 275.90 mg/kg body weight, respectively. Female mice had higher LD₅₀ values for acute intraperitioneal exposure than males (316.58 vs 276.38 mg/kg body weight). ii) The in vitro eye irritation test results showed an irritation score of 3.05 at a dose of 100.00 mg/kg body weight, indicating mild eye irritation, accompanied by vascular congestion and edema in the embryos. iii) Tail vein injection results showed that mouse serum ALT activity increased with increasing hydroquinone doses (all P<0.05), and ALT activity was higher in males than in females (P<0.01). Serum AST activity of mice in the 25.00 and 50.00 mg/kg body weight groups was higher than that in the 0.00 mg/kg body weight group (both P<0.05). With increasing hydroquinone-exposed doses, whole bood MetHb levels increased and cholinesterase activity decreased in both male and female mice (both P<0.05). Male mice had higher MetHb levels than females at corresponding doses among 25.00 and 50.00 mg/kg body weight groups (all P<0.05). Serum cholinesterase levels in male mice were higher than that in females at corresponding doses among 0.00 and 25.00 mg/kg body weight groups (both P<0.05). As the hydroquinone exposure dose increased, the liver organ coefficients decreased in both female and male mice (both P<0.05). The liver organ coefficient in male mice at the 50.00 mg/kg body weight group was higher than that in female mice (P<0.05). Compared to mice of the same sex in the 25.00 mg/kg body weight group, the kidney organ coefficients decreased in both female and male mice in the 0.00 mg/kg body weight group (all P<0.05), and decreased in the 50.00 mg/kg body weight group (all P<0.05). The male mice had lower kidney organ coefficient than female mice at 25.00 mg/kg body weight group (P<0.05). Conclusion Hydroquinone is classified as a moderately toxic substance. Increasing exposure doses result in pronounced eye irritation and affect hepatic and renal functions of mice.

Objective To observe the value of machine learning(ML)models based on ultrasound radiomics for preoperatively distinguishing atypical parathyroid tumor(APT)/parathyroid carcinoma(PC)and parathyroid adenoma(PA).Methods Totally 330 primary hyperparathyroidism patients who underwent surgical treatments were retrospectively enrolled and categorized into APT/PC group(n=78)and PA group(n=252)according to surgical pathology and clinical follow-up results,also divided into training set(n=231)and test set(n=99)at the ratio of 7∶3.Based on preoperative ultrasound,545 radiomics features were extracted,and recursive feature elimination(RFE),Kruskal-Wallis or analysis of variance methods were used to screen the features,respectively.Support vector machine(SVM),linear discriminant analysis(LDA),least absolute shrinkage and selection operator logistic regression(LRLASSO),also random forest(RF)and decision tree(DT)algorithms were adopted to construct ML models for differentiating APT/PC and PA,respectively.Then the models were trained in training set,their performance were verified in test set,and a 5-fold cross-validation was adopted to screen out the better combinations.Results Compared with Kruskal-Wallis and analysis of variance methods,the distinguishing efficacy of SVM,LDA,LRLASSO,RF and DT models constructed based on features screened out using RFE method in training set(area under the curve[AUC]=0.870,0.878,0.850,0.847,1.000)and test set(AUC=0.856,0.842,0.827,0.847 and 0.704)were all relatively higher.In test set,the AUC of SVM,LDA,LRLASSO and RF models constructed based on the features screened out using RFE method(included 25,23,17 and 23 features)were all higher than that of DT model(8 features)(all P＜0.001).No significant difference of AUC was found between SVM,LRLASSO or RF models and LDA model(all P＞0.05).The AUC of SVM and RF models were higher than that of LRLASSO model(both P＜0.05),while of SVM and RF models were not significantly different(P＞0.05),indicating that SVM,LDA and RF models were better ones.Conclusion SVM,LDA,LRLASSO,RF and DT models based on ultrasound radiomics could effectively distinguish APT/PC and PA preoperatively,among which SVM,LDA and RF models had better diagnostic efficacy.

Objective To explore time-related changes in renal function,renal injury biomarkers,and renal pathology in rats entering a low-pressure and low-oxygen(LPLO)environment simulating moving from the plains to a plateau.Methods Thirty male Sprague-Dawley rats were divided randomly into five groups(n=6 rats per group).Rats in the Control group were placed outside the chamber under normal pressure and oxygen conditions.Rats in the experimental groups were placed in an LPLO chamber to simulate a plateau environment at 5000 m above sea level,and were maintained in the chamber for 3,7,14,and 28 days,respectively.Serum levels of creatinine(CRE),cystatin C(CysC),neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),and interleukin-18(IL-18)were measured as biomarkers of renal injury.Pathological changes in the kidney were observed by hematoxylin and eosin and periodic acid-Schiff staining,with quantitative assessment of the following parameters:average glomerular diameter,peritubular capillary(PTC)density per tubule,tubular injury score,and outer medulla(OM)congestion score.Results NGAL,KIM-1,CysC,and CRE were significantly increased in the experimental compared with the Control group(all P＜0.05).The average glomerulus diameter was significantly reduced in the LPLO 3 d group and significantly increased in the LPLO 14 d group(both P＜0.05).The peritubular capillary(PTC)/tubule ratio was significantly decreased.The renal tubular injury and OM congestion scores were significantly increased(both P＜0.05).Regression analysis showed that PTC/tubule was linearly negatively correlated with the LPLO duration,while CRE,CysC,and pathological indicators(mean glomerular diameter,OM congestion score,renal tubular injury score)were curvilinearly correlated with the duration of LPLO(all P＜0.05).Variables with a curvilinear correlation were analyzed using restricted cubic splines(RCS).Each curve exhibited an inverted-L shape,with inflection points on day 7,indicating that the rate of increase of all indicators was highest within the first 7 days of LPLO,and the rate of increase then slowed from 7 days to 28 days.Conclusions A simulated move from a plains to a plateau environment was associated with significant structural and functional renal damage,but the kidneys then showed a self-adaptive adjustment process towards the plateau environment.

Objective To preliminarily explore the potential efficacy of Xuesaitong Soft Capsule(XST)against post-stroke depression(PSD),and to investigate the material basis of XST's anti-PSD effect based on the metabolomics results to analyze its related pharmacokinetic(PK)characteristics and further analyze the pharmacodynamic(PD)equation of representative ingredients.Methods The initial evaluation of drug effica-cy was conducted by detecting the depressive-like behavior and neurotransmitter levels in rats.The Pearson correlation analysis was employed to analyze the correlation between the main metabolites regulated by XST and the saponin components entering the bloodstream.At various time points after drug administration,the blood concentration of ginsenoside Re and the concentration of norepinephrine(NE)in the serum of PSD rats were measured,and the compartment model was fitted accordingly.Furthermore,the liquid chromatography-mass spectrometry was utilized to determine the content of ginsenoside Re in the liver,spleen,kidney,prefron-tal cortex,hippocampus and striatum of PSD rats.Results Ginsenoside Re showed the optimal correlation by the Pearson correlation analysis.Based on its pharmacokinetic parameters,the pharmacodynamic equation with NE was E=160.462 × Ce/(38.663+Ce).The contents of ginsenoside Re in the liver,spleen,kidney,prefron-tal cortex,hippocampus and striatum of rats were(17.23+11.90),(19.05+5.67),(1.95+0.79),(70.13+6.75),(57.03+3.11),and(72.45+5.45)ng/g,respectively.Conclusion XST could improve the depressive-like behaviors in PSD rats by regulating the expression levels of neurotransmitter NE and 5-HT.Ginsenoside Re may be the pharmacodynamical material foundation for XST's preventative treatment of PSD.

ObjectiveTo investigate the therapeutic effects of direct-acting antiviral agents (DAAs) combined regimens for hepatitis C virus (HCV) patients in Dehong Prefecture, Yunnan Province from 2022 to 2024, to analyze the characteristics of treatment failure patients, so as to provide a basis for discovering more effective treatment regimens in the future. MethodsData on HCV prevention and treatment in Dehong Prefecture was extracted from the China Disease Control and Prevention Information System. A total of 617 patients with HCV antiviral therapy were included, and the differences in variable characteristics among patients with different genotypes were analyzed using comparative statistical tests, including basic socio-demographic characteristics, biochemical testing indicators, and information on previous treatment and current treatment. In addition, the cure rate of HCV patients with diverse characteristics was compared, and the potential causes of treatment failure were explored simultaneously. ResultsThe cure rate of HCV was 96.8%, and statistically significant differences were observed in aspartate transaminase (AST) and alanine transaminase (ALT) levels, previous antiviral therapy history and initial treatment regimens among patients with different HCV genotypes (all P<0.05). Among the multi-type combination regimens, the cure rate of sofosbuvir (SOF)-containing regimens was 97.00%, that of velpatasvir (VEL)-containing regimens was 95.45%, and the cure rate of other treatment regimens, including the regimens with ribavirin (RIB) intervention, was 93.10%. Among the patients with treatment failure, 45.00% had genotype 3, 40.00% had abnormal abdominal ultrasound results, and all presented with elevated baseline AST test levels. ConclusionThe clinical treatment of HCV patients should consider the differences in genotype and biochemical test results. DAAs combined regimens for HCV have achieved a high cure rate in Dehong Prefecture and are applicable to HCV patients with diverse clinical characteristics, providing research evidence for wider application.

Under the influence of long-term space flights and the confined space environment,it is very easy to induce space depression syndrome,mainly manifested as decreased emotional stability,sleep disorders,mental fatigue,etc.,which seriously affect the living conditions and working abilities of astronauts.The current treatment methods mainly focus on psychological support and drug intervention.Acupuncture has a good effect in treating depression.Therefore,starting from the TCM pathogenesis and modern medical pathogenesis of aerospace depression syndrome,we conducted literature retrieval from databases such as the Chinese Medical Classic,China National Knowledge Infrastructure(CNKI),Wanfang,VIP,PubMed,and Web of science.For the included literature,we adopted the stratified evidence scoring method and combined the TCM mechanism and modern medical mechanism of the effect of acupuncture.A prescription for acupuncture points was constructed to provide a basis for selecting acupuncture points for the prevention of aerospace depression syndrome through acupuncture.

Objective:To investigate the effect of intradialytic cerebral blood flow (CBF) fluctuation on cognitive decline in middle-aged and elderly maintenance hemodialysis (MHD) patients.Methods:It was a prospective cohort study. MHD patients aged ≥50 years from Beijing Shijitan Hospital were enrolled from January 2023 to June 2023. Middle cerebral artery mean flow velocity (MFV) was serially monitored via transcranial Doppler (TCD) during dialysis sessions. Cognitive function was assessed at baseline and after 12-month follow-up using standardized neuropsychological tests: montreal cognitive assessment (MoCA), auditory verbal learning test (AVLT 5), complex figure test (CFT), trail making test-B (TMT-B), Stroop color and word test (SCWT), and symbol digit modalities test (SDMT). ΔMFV was calculated as pre-to-post dialysis MFV difference. Multivariable linear regression was used to analyze the association of ΔMFV and cognition.Results:A total of 121 MHD patients were recruited with an age of (63.63±8.44) years. There were 97 males (80.2%), and the dialysis vintage was (55.08±54.73) months. Significant intradialytic MFV reductions were observed ( P<0.05). At 12 months, cognitive decline manifested in global cognition (MoCA), memory (CFT-memory), executive function (TMT-B, SCWT-C, SCWT-T), attention (SDMT), visuospatial ability (CFT-copy)(all P<0.05). Multivariable linear regression analysis revealed ΔMFV independently predicted declines in: MoCA ( B=0.066, 95% CI 0.018-0.113, P=0.007), AVLT5 ( B=0.050, 95% CI 0.004-0.097, P=0.035), TMT-B ( B=-1.955, 95% CI -3.453--0.457, P=0.011), SCWT-C ( B=0.298, 95% CI 0.112-0.484, P=0.002), SCWT-T ( B=-1.371, 95% CI -2.303--0.439, P=0.004). Conclusions:Hemodialysis induces acute CBF reductions detectable by TCD. Cumulative intradialytic CBF fluctuations may accelerate cognitive deterioration in middle-aged and elderly MHD populations, particularly affecting memory and executive domains.

Objective To compare the effects of desflurane inhalation anesthesia versus propofol total intravenous anesthesia on postoperative recovery quality in patients undergoing endoscopic transnasal pituitary adenoma resection,and to provide evidence-based recommendations for optimizing anesthetic management in this surgical population.Methods This single-center,prospective,randomized controlled trial enrolled 112 patients scheduled for endoscopic transnasal pituitary adenoma resection,who were randomly assigned to either the desflurane group(n=56)or the propofol group(n=56).The desflurane group received desflurane[0.7-1.0 minimum alveolar concentration(MAC)]combined with remifentanil for anesthesia maintenance,whereas the propofol group received propofol(4-6 mg·kg-1·h-1)with remifentanil.The primary outcome was defined as the time from discontinuation of anesthetics to achieving an Aldrete score of 9.Secondary outcomes included emergence time,extubation time,and incidences of postoperative agitation and vomiting.Results Patients receiving desflurane achieved an Aldrete score of 9 significantly faster than those in the propofol group(13.0 min vs 16.5 min,P=0.003).Similarly,both emergence time(14.0 min vs 16.5 min,P=0.009)and extubation time(13.0 min vs 16.5 min,P=0.003)were significantly shorter in the desflurane group.However,the desflurane group had higher incidences of postoperative agitation(17.9%vs 3.6%,P=0.015)and vomiting(19.6%vs 5.4%,P=0.022).No significant difference was observed in severe agitation rates or 24 h postoperative recovery quality[Quality of Recovery-15(QoR-15)scores]between groups.Conclusion Desflurane anesthesia significantly accelerates postoperative recovery in patients undergoing endoscopic transnasal pituitary adenoma resection,however,it may increase risks of mild agitation and vomiting.In clinical applications,it is necessary to balance recovery benefits against potential adverse effects,and take targeted prophylactic measures.

Objective:To explore drug detoxification motivation in methamphetamine-dependent female youth and its relationship with time perspective,perceived social support and emotion regulation strategies.Methods:To-tally 200 methamphetamine-dependent female youths under compulsory isolation were assessed with the Drug De-toxification Motivation Scale,Zimbardo Time Perspective Inventory-Chinese(ZTPI-C),Emotion Regulation Scale(ERS),and Perceived Social Support Scale(PSSS).Results:Multiple linear regression analysis showed that drug detoxification motivation scores were positively correlated with the scores of ERS reevaluation and expression inhi-bition,PSSS family support scores and level of education(β=0.24,0.16,0.20,0.16).Conclusion:Time perspec-tive,perceived social support and emotion regulation strategies are closely related to drug detoxification motivation in methamphetamine-dependent female youth.