This study aims to investigate the mechanism of Qingrun Decoction in alleviating hepatic insulin resistance in type 2 diabetes mellitus(T2DM) rats through the reprogramming of amino acid metabolism. A T2DM rat model was established by inducing insulin resistance through a high-fat diet combined with intraperitoneal injection of streptozotocin. The model rats were randomly divided into five groups: model group, high-, medium-, and low-dose Qingrun Decoction groups, and metformin group. A normal control group was also established. The rats in the normal and model groups received 10 mL·kg~(-1) distilled water daily by gavage. The metformin group received 150 mg·kg~(-1) metformin suspension by gavage, and the Qingrun Decoction groups received 11.2, 5.6, and 2.8 g·kg~(-1) Qingrun Decoction by gavage for 8 weeks. Blood lipid levels were measured in different groups of rats. Pathological damage in rat liver tissue was assessed by hematoxylin-eosin(HE) staining and oil red O staining. Transcriptome sequencing and untargeted metabolomics were performed on rat liver and serum samples, integrated with bioinformatics analyses. Key metabolites(branched-chain amino acids, BCAAs), amino acid transporters, amino acid metabolites, critical enzymes for amino acid metabolism, resistin, adiponectin(ADPN), and mammalian target of rapamycin(mTOR) pathway-related molecules were quantified using quantitative real-time polymerase chain reaction(qRT-PCR), Western blot, and enzyme-linked immunosorbent assay(ELISA). The results showed that compared with the normal group, the model group had significantly increased serum levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), and resistin and significantly decreased ADPN levels. Hepatocytes in the model group exhibited loose arrangement, significant lipid accumulation, fatty degeneration, and pronounced inflammatory cell infiltration. In liver tissue, the mRNA transcriptional levels of solute carrier family 7 member 2(Slc7a2), solute carrier family 38 member 2(Slc38a2), solute carrier family 38 member 4(Slc38a4), and arginase(ARG) were significantly downregulated, while the mRNA transcriptional levels of solute carrier family 1 member 4(Slc1a4), solute carrier family 16 member 1(Slc16a1), and methionine adenosyltransferase(MAT) were upregulated. Furthermore, the mRNA transcription and protein expression levels of branched-chain α-keto acid dehydrogenase E1α(BCKDHA) and DEP domain-containing mTOR-interacting protein(DEPTOR) were downregulated, while mRNA transcription and protein expression levels of mTOR, as well as ribosomal protein S6 kinase 1(S6K1), were upregulated. The levels of BCAAs and S-adenosyl-L-methionine(SAM) were elevated. The serum level of 6-hydroxymelatonin was significantly reduced, while imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid levels were significantly increased. Compared with the model group, Qingrun Decoction significantly reduced blood lipid and resistin levels while increasing ADPN levels. Hepatocytes had improved morphology with reduced inflammatory cells, and fatty degeneration and lipid deposition were alleviated. Differentially expressed genes and differential metabolites were mainly enriched in amino acid metabolic pathways. The expression levels of Slc7a2, Slc38a2, Slc38a4, and ARG in the liver tissue were significantly upregulated, while Slc1a4, Slc16a1, and MAT expression levels were significantly downregulated. BCKDHA and DEPTOR expression levels were upregulated, while mTOR and S6K1 expression levels were downregulated. Additionally, the levels of BCAAs and SAM were significantly decreased. The serum level of 6-hydroxymelatonin was increased, while those of imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid were decreased. In summary, Qingrun Decoction may improve amino acid metabolism reprogramming, inhibit mTOR pathway activation, alleviate insulin resistance in the liver, and mitigate pathological damage of liver tissue in T2DM rats by downregulating hepatic BCAAs and SAM and regulating key enzymes involved in amino acid metabolism, such as BCKDHA, ARG, and MAT, as well as amino acid metabolites and transporters.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Insulin Resistance ; Diabetes Mellitus, Type 2/genetics* ; Male ; Liver/drug effects* ; Amino Acids/metabolism* ; Rats, Sprague-Dawley ; Humans ; Metabolic Reprogramming

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

BACKGROUND: Quantitative flow ratio (QFR) holds significant value in guiding drug-coated balloon (DCB) treatment and enhancing outcomes. However, the predictive capability of post-angioplasty QFR for long-term clinical events in patients with de novo lesions who receive DCB treatment remains uncertain. The aim of this study was to explore the potential significance of post-angioplasty QFR measurements in predicting clinical outcomes in patients underwent DCB treatment for de novo lesions. METHODS: Patients who underwent DCB-only intervention for de novo lesions were enrolled. QFR was conducted after DCB treatment. The patients were then categorized based on post-angioplasty QFR. The primary endpoint was major adverse cardiac events (MACE), encompassing all-cause death, cardiovascular death, nonfatal myocardial infarction, stroke, and target vessel revascularization. RESULTS: A total of 553 patients with 561 lesions were included. The median follow-up period was 505 days, during which 66 (11.8%) MACEs occurred. Based on post-procedural QFR grouping, there were 259 cases in the high QFR group (QFR > 0.93) and 302 cases in the low QFR group (QFR ≤ 0.93). Kaplan-Meier analysis revealed a significantly higher cumulative incidence of MACE in the low QFR group (log-rank P = 0.004). The multivariate Cox proportional hazards model demonstrated a significant inverse correlation between QFR and the occurrence of MACEs (HR = 0.522, 95%CI: 0.289-0.942, P = 0.031). Landmark analysis indicated that high QFR had a significant reducing effect on the cumulative incidence of MACEs within 1 year (log-rank P = 0.016) and 1-5 years (log-rank P = 0.026). CONCLUSIONS In patients who underwent DCB-only treatment for de novo lesions, higher post-procedural QFR values (> 0.93) were identified as an independent protective factor against adverse prognosis.

Objective This research was performed to identify rodent-borne pathogens in Hekou Port,Yunnan Province.Methods Rodents were captured using cages and dissected to collect their lungs,liver,spleen,and other viscera.Eight pathogens,including Yersinia pestis,Leptospira,Bartonella,and Anaplasmataceae,were identified using polymerase chain reaction amplification.Amplified pathogen sequences from positive samples were sequenced,and BLAST homology searches were conducted using GenBank to confirm pathogen identities.A phylogenetic tree of the identified pathogens was constructed using the neighbor joining method.Results The total of 31 rodents,identified as Rattus tanezumi,R.norvegicus,and Mus musculus,were captured.Among these,R.tanezumi was the dominant species,accounting for 64.52％of the total.Two pathogens,Leptospira interrogans and Neoehrlichia mikurensis,were detected,with positivity rates of 9.68％and 29.03％,respectively.No other pathogens were detected.The overall positivity rate for rodent-borne pathogens was 35.48％.Conclusions The single 16S rRNA gene fragment is insufficient for the molecular identification of all Neoehrlichia species.Accurate species identification should be based on a combined analysis of multiple genes.The prevalence of rodent-borne pathogens in Hekou Port indicates the necessity for enhanced surveillance of rodent-borne diseases and implementation of additional prevention and control measures in border ports.

Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.

Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.

Objective:To investigate the correlation between serum Chemerin and nerve growth associated protein (GAP) -43 levels and hyperhomocysteinemia (HHcy) in acute ischemic stroke.Methods:The clinical data of 149 patients with acute ischemic stroke admitted to the Sun Simiao Hospital of Beijing University of Traditional Chinese Medicine from March 2021 to May 2023 were retrospectively analyzed, and the patients were divided into observation group (97 cases) and control group (52 cases) according to whether they were combined with HHcy. Observation group patients were divided into mild group ( n=29), moderate group ( n=38) and severe group ( n=30) according to the severity of the disease. The serum Chemerin and GAP-43 levels of the observation group and the control group were compared, and the serum Chemerin and GAP-43 levels of the observation group with different severity of disease were compared, and the correlation between the serum Chemerin and GAP-43 levels and the severity of acute ischemic stroke patients with HHcy was analyzed. The influencing factors of poor prognosis in patients with acute ischemic stroke complicated with HHcy were analyzed, and receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of serum Chemerin and GAP-43 for poor prognosis in patients with acute ischemic stroke complicated with HHcy. Results:The levels of Chemerin and GAP-43 in the observation group were higher than those in the control group (all P<0.05). Serum Chemerin and GAP-43 levels in the severe group were higher than those in the mild group and the moderate group (all P<0.05), and serum Chemerin and GAP-43 levels in the moderate group were higher than those in the mild group (all P<0.05). Pearson correlation analysis showed that serum Chemerin and GAP-3 levels were positively correlated with the severity of acute ischemic stroke patients with HHcy ( r=0.458, 0.497, all P<0.05). Among 97 patients with acute ischemic stroke complicated with HHcy, 19 had poor prognosis and 78 had good prognosis. In the poor prognosis group, the proportion of diabetes, the severity of the disease and the levels of blood glucose, C-reactive protein (CRP), vascular endothelial growth factor (VEGF) and malondialdehyde (MDA) were higher than those in the good prognosis group (all P<0.05), and the superoxide dismutase (SOD) was lower than those in the good prognosis group ( P<0.05). Logistic regression analysis showed that the severity of the disease, CRP, Chemerin and GAP-43 were the influential factors for the poor prognosis of acute ischemic stroke patients with HHcy (all P<0.05). ROC curve results showed that the area under the curve (AUC) of serum Chemerin and GAP-43 levels and their combination in predicting poor prognosis of acute ischemic stroke patients with HHcy were 0.799, 0.804 and 0.907, respectively, and the AUC of the combination was larger ( P<0.05). Conclusions:Serum Chemerin and GAP-43 levels are closely related to the severity and prognosis of acute ischemic stroke patients with HHcy, and their combined value is higher in predicting poor prognosis.

Objective To study the effects of dual-hemispheric transcranial direct current stimulation(Dual-tDCS)on upper limb motor function in chronic-phase stroke patients to provide theoretical references for neural mechanisms-based treatment of upper limb dysfunction.Methods Totally 24 chronic-phase stroke patients with upper limb motor dysfunction were selected from some hospital and divided into an experimental group(n=13)and a control group(n=11)the random number table.The control group was treated with tDCS pseudo-stimulation combined with conventional rehabilitation,while the experimental group was given with Dual-tDCS combined with conventional rehabilitation.The patient activities were assessed before and after treatment with Fugl-Meyer assessment upper limb scale(FMA-UL)and activities of daily living(ADL)scale.The changes of primary motor cortex(M1 area)and whole brain functional connectivity(FC)were compared before and after treatment.SPSS 24.0 statistical software was used for data analysis.Results After treatment,the two groups both had the FAM-UL and ADL scores increased significantly,and the experimental group had the scores statistically higher than those of the control group,and the differences were all statistically significant(P＜0.05).In the control group,the analysis on M1 area and whole brain FC after treatment indicated the FC decreased from M1 area at the unaffected side to midoccipital gyrus at the affected side and lingual gyrus and healthy angular gyrus at the unaffected side;there were no brain areas with changed FC found(P＜0.01).In the experimental group,the FC was lowered from M1 area at the unaffected side to cerebellum and cerebellar vermis at the unaffected side,while raised to precentral gyrus at the affected side(P＜0.01);the FC ascended from M1 area at the affected side to cerebellum and middle temporal gyrus at the affected side,while declined to precentral gyrus at the unaffected side(P＜0.01).Conclusion The neuromodulatory effect of Dual-tDCS on the brain improves FC in motor and non-motor-related brain areas in chronic-phase stroke patients,and may contribute to rehabilitation of upper limb motor dysfunction in chronic-phase stroke.[Chinese Medical Equipment Journal,2024,45(2):67-73]

Objective:To investigate the correlation between serum Chemerin and nerve growth associated protein (GAP) -43 levels and hyperhomocysteinemia (HHcy) in acute ischemic stroke.Methods:The clinical data of 149 patients with acute ischemic stroke admitted to the Sun Simiao Hospital of Beijing University of Traditional Chinese Medicine from March 2021 to May 2023 were retrospectively analyzed, and the patients were divided into observation group (97 cases) and control group (52 cases) according to whether they were combined with HHcy. Observation group patients were divided into mild group ( n=29), moderate group ( n=38) and severe group ( n=30) according to the severity of the disease. The serum Chemerin and GAP-43 levels of the observation group and the control group were compared, and the serum Chemerin and GAP-43 levels of the observation group with different severity of disease were compared, and the correlation between the serum Chemerin and GAP-43 levels and the severity of acute ischemic stroke patients with HHcy was analyzed. The influencing factors of poor prognosis in patients with acute ischemic stroke complicated with HHcy were analyzed, and receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of serum Chemerin and GAP-43 for poor prognosis in patients with acute ischemic stroke complicated with HHcy. Results:The levels of Chemerin and GAP-43 in the observation group were higher than those in the control group (all P<0.05). Serum Chemerin and GAP-43 levels in the severe group were higher than those in the mild group and the moderate group (all P<0.05), and serum Chemerin and GAP-43 levels in the moderate group were higher than those in the mild group (all P<0.05). Pearson correlation analysis showed that serum Chemerin and GAP-3 levels were positively correlated with the severity of acute ischemic stroke patients with HHcy ( r=0.458, 0.497, all P<0.05). Among 97 patients with acute ischemic stroke complicated with HHcy, 19 had poor prognosis and 78 had good prognosis. In the poor prognosis group, the proportion of diabetes, the severity of the disease and the levels of blood glucose, C-reactive protein (CRP), vascular endothelial growth factor (VEGF) and malondialdehyde (MDA) were higher than those in the good prognosis group (all P<0.05), and the superoxide dismutase (SOD) was lower than those in the good prognosis group ( P<0.05). Logistic regression analysis showed that the severity of the disease, CRP, Chemerin and GAP-43 were the influential factors for the poor prognosis of acute ischemic stroke patients with HHcy (all P<0.05). ROC curve results showed that the area under the curve (AUC) of serum Chemerin and GAP-43 levels and their combination in predicting poor prognosis of acute ischemic stroke patients with HHcy were 0.799, 0.804 and 0.907, respectively, and the AUC of the combination was larger ( P<0.05). Conclusions:Serum Chemerin and GAP-43 levels are closely related to the severity and prognosis of acute ischemic stroke patients with HHcy, and their combined value is higher in predicting poor prognosis.

Objective:The purpose of this study was to investigate the effect of voice therapy via telepractice on voice function in laryngopharyngeal reflux disease (LPRD) patients.Methods:The prospective study included 120 patients from January 2021 to July 2022 with dyspnea and LPRD diagnosed at the department of otolaryngology head and neck surgery of the First Hospital of Shanxi Medical University. These patients were then randomly divided into standard treatment group (group A), combined face-to-face voice therapy group (group B) and combined telepractice voice therapy group (group C). We collected and compared data on curative effect in patients with LPRD at the 8th week(Stage 1) and the 12th week of treatment(Stage 2) and the 6th week post-treatment(Stage 3). Statistical analysis was performed using SPSS 22.0.Results:One hundred and twenty patients with LPRD and dyspnea were included in the study (63 men, 57 women, 18-65 years old). At stage 1, there were statistically significant differences among the three groups in Voice Handicap Index(VHI), Reflux Symptom Index (RSI) and Reflux Finding Score(RFS) ( F=13.72, P<0.05; F=62.50, P<0.05; F=3.78, P<0.05). VHI and RSI in group B and C were significantly smaller than those in group A, VHI and RSI in group C were significantly smaller than those in group B, and RFS in group C was significantly smaller than that in group A and B. At stage 2, there were statistically significant differences between the three groups in Maximum Phonation Time(MPT), Dysphonia Severity Index(DSI), VHI, RSI and RFS( F=8.49, P<0.05; F=3.24, P<0.05; F=8.55, P<0.05; F=19.92, P<0.05; F=12.19, P<0.05). MPT and DSI in group B and C were significantly larger than those in group A. The scores of VHI, RSI and RFS in group B and C were significantly smaller than those in group A, and RFS in group C was significantly smaller than that in group B. At stage 3, there were statistically significant differences among the three groups in Jitter, MPT, DSI, VHI( F=3.19, P<0.05; F=19.37, P<0.05; F=43.56, P<0.05; F=11.05, P<0.05), and there were statistically significant differences among the three groups in RSI and RFS( F=25.58, P<0.05; F=11.82, P<0.05). MPT and DSI in group B and C were significantly larger than those in group A. The scores of VHI and RSI in group B and C were significantly smaller than those in group A, and RFS in group C was significantly smaller than those in group A and B. Conclusion:Telepractice can be used in patients with LPRD and dyspnea as an alternative to face-to-face voice therapy with better long-term outcomes.