ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

Objective:To explore the dilemmas and demands encountered by enterostomal therapists in providing sexual education or guidance to young and middle-aged patients with enterostomy.Methods:From April to October 2022, purposive sampling was used to select 15 enterostomal therapists who received training at the International School of Stomatologists for semi-structured interviews. Colaizzi 7-step analysis method was used for data analysis.Results:Three themes were extracted, namely the "negative behavior" and "positive willingness" of enterostomal therapists, the multiple dilemmas in implementing sex education for young and middle-aged patients with enterostomy, and the demands for sexual education for young and middle-aged patients with enterostomy.Conclusions:Enterostomal therapists should actively pay attention to the sexual education for young and middle-aged patients with enterostomy, overcome multiple obstacles that affect the lack of sexual education for young and middle-aged patients with enterostomy, and persist in promoting sexual education for young and middle-aged patients with enterostomy in clinical practice, in order to improve the marital relationship and quality of marriage between patients and their spouses.

Objective To investigate the effect of chaizhu liwei decoction on gastrointestinal motility and p-NF-κBp65 pathway in functional dyspepsia(FD)rats with liver depression and spleen deficiency.Methods Sixty SD rats were random number table method divided into normal group(n=10)and model reserve group(n=50).The FD model of liver depression and spleen deficiency was repli-cated by compound factor stimulation in the model reserve group.After successful replication of the model,50 rats were random number table method divided into model group,traditional Chinese medicine high-dose,medium-dose and low-dose groups and domperidone group,with 10 rats in each group.Each group was given corresponding drugs by gavage,and the general state of rats was observed.The food intake,body mass,gastric emptying rate and intestinal propulsion rate were calculated.The levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in gastric antrum tissue of rats were detected by enzyme-linked immunosorbent assay(ELISA).Western blot and real-time quantitative polymerase chain reaction(RT-qPCR)were used to detect the expression of p-NF-κBp65 protein and p-NF-κBp65 mRNA in gastric antrum tissue of rats.HE staining was used to observe the morphology of gastric antrum.Results Compared with the normal group,the food intake,body mass,gastric emptying rate and intestinal propulsion rate of rats in the model group were decreased,and the levels of IL-6,TNF-α,p-NF-κBp65 protein expression and p-NF-κBp65 mRNA expres-sion in gastric antrum tissue were increased(P＜0.05).Compared with the model group,the food intake,body mass,gastric emptying rate and intestinal propulsion rate of rats in the traditional Chinese medicine groups and domperidone group were increased,and the levels of IL-6,TNF-α,p-NF-κBp65 protein expression and p-NF-κBp65 mRNA expression in gastric antrum tissue were decreased(P＜0.05).The levels of IL-6 and TNF-α in the traditional Chinese medicine high-dose group were lower than those in the domperi-done group(P＜0.05).The protein expression of p-NF-κBp65 in the traditional Chinese medicine high-dose and medium-dose groups was lower than that in the domperidone group(P＜0.05).Conclusion The mechanism of chaizhu liwei decoction in the treat-ment of FD with liver depression and spleen deficiency may be related to the reduction of IL-6,TNF-α levels,p-NF-κBp65 protein expression and p-NF-κBp65 mRNA expression in gastric antrum tissue of rats,and the improvement of gastrointestinal motility function.

Objective:Construct a combined detection model of miR-202-5p and interleukin-6 (IL-6) and explore its diagnostic value for acute myocardial infarction (AMI).Methods:Clinical data of 202 patients with coronary atherosclerotic heart disease (CHD) who were admitted to the Department of Cardiology and Emergency Department of Hebei People's Hospital from August 2020 to August 2022 were retrospectively analyzed, including 106 AMI patients and 96 non AMI patients. The clinical characteristics and blood levels of miR-202-5p and IL-6 were compared between the two groups, T-test was used for inter group comparison of measurement data that conforms to normal distribution, non parametric rank sum test was used for inter group comparison of measurement data that does not conform to normal distribution, and χ2 test was used for inter group comparison of count data. Binary Logistic regression model was used to determine the independent influencing factors of AMI, and a combined diagnostic model was constructed according to the analysis results, the diagnostic efficacy of miR-202-5p, IL-6 and combined detection for AMI was evaluated by ROC curve, and the clinical diagnostic effect was observed. Results:The expression levels of serum total cholesterol (4.40 (3.71, 5.00) mmol/L), low density lipoprotein cholesterol (2.99 (2.39,3.47) mmol/L), lipoprotein a (276.80 (182.58,390.13) mg/L), interleukin-4(IL-4)(2.69(2.29,3.16) μg/L), IL-6(89.82(68.26,107.16) μg/L) in AMI group were significantly higher than those of non-AMI group (4.04 (3.12, 4.73) mmol/L, 2.75 (2.15, 3.21) mmol/L, 213.45 (146.73, 348.80) mg/L, 2.46 (1.92, 3.01)] μg/L, 45.89 (32.38, 62.83) μg/L, while miR-202-5p(0.33 (0.27,0.38)) was lower than that in the non-AMI group (0.51 (0.36,0.68)), ( H values were 4 167.50, 4 234.00, 4 262.50, 4 228.00, 1 513.00, and 2 098.50, respectively; P values were 0.027, 0.040, 0.047, 0.038, <0.001, <0.001, respectively). Multivariate binary logistic regression analysis showed that high levels of IL-6 and low levels of miR-202-5p were independent risk factors for AMI. The joint diagnostic model of IL-6 and miR-202-5p was Logit (P)=-1.046-5.236 × miR-202-5p+0.051 × IL-6, with probability value P as the diagnostic indicator and P=0.45 as the diagnostic threshold. ROC curve results showed that the area under curve (AUC) of IL-6 and miR-202-5p were 0.851 and 0.794, respectively, while the AUC of the combined diagnosis model was 0.894, indicating that the diagnosis accuracy was higher than that of a single index. Compared with isolated detection, the sensitivity, specificity and Kappa value of the IL-6+miR-202-5p collaborative test for AMI prediction were increased, especially the diagnosis results were close to a high degree of agreement with the actual results ( Kappa=0.732). Conclusion:High levels of IL-6 and low levels of miR-202-5p are independent influencing factors for AMI, and the combined diagnosis model of the two has clinical application value.

Objective To evaluate the potential of miR-30a-5p as a novel indicator of acute myocardial infarction(AMI)and the underlying molecular mechanisms.Methods AMI-associated microRNAs(miRNAs)and mRNA microarray datasets were downloaded from the GEO database.Real-time fluorescence quantitative PCR(qRT-PCR)technique was used to detect the level of miRNAs in serum samples;automatic biochemistry was used to detect other biochemical indicators.Receiver operating characteristic(ROC)curve analysis and Spearson correlation analysis were performed to assess the value of miR-30a-5p as a diagnostic AMI marker.The target genes of miR-30a-5p were predicted with the R language multiMiR package,and the protein interaction network was constructed by the STRING database.The results were imported into Cytoscape 3.7.1 software to screen the pivotal genes of the network.The R language clusterProfiler package performed KEGG and GO analyses on the hub genes to explore the clinical significance of miR-30a-5p in AMI and its potential molecular mechanisms.Results Compared with the control group,miR-30a-5p was upregulated significantly in the serum of patients in the AMI group(P＜0.05);miR-30a-5p was positively correlated with the levels of CK-MB,CK,TnT,proBNP and CRP(rs=0.489,P＜0.001;rs=0.347,P＜0.001;rs=0.545,P＜0.001;rs=0.533,P＜0.001;rs=0.206,P＜0.05).The area under the ROC curve was 0.862,with sensitivity of 84.4％and specificity of 74.2％.A total of 780 differentially expressed genes(DEGs)were obtained from the two datasets.A total of 1 061 target genes of miR-30a-5p and 61 common genes were identified by taking the intersection set.Among the central genes of PPI,BCL6,FOSL2,JDP2,LYN,PDE4D,SOCS3 and SOX4 scored high and were closely associated with the occurrence of AMI.KEGG and GO enrichment analyses showed that miR-30a-5p might regulate JAK-STAT,NF-kappaB and Wnt signaling pathways,which were involved in inflammatory response,apoptosis,autophagy and post-infarction remodeling,and thus participated in the process of AMI.Conclusion Serum miR-30a-5p is up-regulated in the early stage of AMI,and the study on miR-30a-5p and its regulatory pathways can help with the diagnosis and treatment of myocardial infarction.

Objectives To investigate the regulatory role of miRNA-224-5p in hypoxia/reoxygenation(H/R)-induced H9c2 cardiomyocyte injury.Methods Plasma samples were collected from 160 patients with acute myocardial infarction and 80 healthy controls(HC)to measure miRNA-224-5p levels and other biochemical parameters.In cultured H9c2 cells with H/R injury,the effects of transfection with miR-224-5p mimics or a negative control sequence on cell viability,malondialdehyde(MDA)content,and superoxide dismutase 2(SOD2)and lactate dehydrogenase(LDH)activities were tested.Dual luciferase reporter gene assay was performed to verify the targeting relationship between miR-224-5p and PTEN.Bioinformatics methods were used to analyze the potential mechanisms of the target genes.The expression of miRNA-224-5p in the treated cells was detected with qRT-PCR,the protein expressions of PTEN,Bcl-2,Bax,cleaved caspase-3,SOD2,p-PI3K/PI3K,p-Akt/Ak and p-FoxO1/FoxO1 were determined using Western blotting,and cell apoptosis was analysed with flow cytometry.Results The levels of blood glucose,C-reactive protein,CK,CK-MB and cTnI were significantly higher in the AMI group compared with the HC group(P<0.05).The expression level of miR-224-5p was significantly lowered in patients with STEMI and NSTEMI and in H9c2 cells with H/R injury.The viability of H9c2 cells decreased time-dependently following H/R injury.PTEN was a target gene of miR-224-5p,and the PI3K/Akt pathway was the most significantly enriched pathway.H9c2 cells with H/R injury showed significantly decreased SOD2 activity,increased LDH activity and MDA content,increased cell apoptosis,decreased protein expression levels of p-PI3K,p-Akt,p-FoxO1,SOD2,and Bcl-2,and increased expressions of PTEN,Bax,and cleaved caspase-3.These changes were obviously attenuated by trasnfection of the cells with miR-224-5p mimics prior to H/R exposure.Conclusion MiR-224-5p overexpression upregulates the expression of the antioxidant gene SOD2 through the PI3K/Akt/FoxO1 axis to relieve H/R-induced oxidative stress and reduce apoptosis of H9c2 cells.

Objectives To investigate the regulatory role of miRNA-224-5p in hypoxia/reoxygenation(H/R)-induced H9c2 cardiomyocyte injury.Methods Plasma samples were collected from 160 patients with acute myocardial infarction and 80 healthy controls(HC)to measure miRNA-224-5p levels and other biochemical parameters.In cultured H9c2 cells with H/R injury,the effects of transfection with miR-224-5p mimics or a negative control sequence on cell viability,malondialdehyde(MDA)content,and superoxide dismutase 2(SOD2)and lactate dehydrogenase(LDH)activities were tested.Dual luciferase reporter gene assay was performed to verify the targeting relationship between miR-224-5p and PTEN.Bioinformatics methods were used to analyze the potential mechanisms of the target genes.The expression of miRNA-224-5p in the treated cells was detected with qRT-PCR,the protein expressions of PTEN,Bcl-2,Bax,cleaved caspase-3,SOD2,p-PI3K/PI3K,p-Akt/Ak and p-FoxO1/FoxO1 were determined using Western blotting,and cell apoptosis was analysed with flow cytometry.Results The levels of blood glucose,C-reactive protein,CK,CK-MB and cTnI were significantly higher in the AMI group compared with the HC group(P<0.05).The expression level of miR-224-5p was significantly lowered in patients with STEMI and NSTEMI and in H9c2 cells with H/R injury.The viability of H9c2 cells decreased time-dependently following H/R injury.PTEN was a target gene of miR-224-5p,and the PI3K/Akt pathway was the most significantly enriched pathway.H9c2 cells with H/R injury showed significantly decreased SOD2 activity,increased LDH activity and MDA content,increased cell apoptosis,decreased protein expression levels of p-PI3K,p-Akt,p-FoxO1,SOD2,and Bcl-2,and increased expressions of PTEN,Bax,and cleaved caspase-3.These changes were obviously attenuated by trasnfection of the cells with miR-224-5p mimics prior to H/R exposure.Conclusion MiR-224-5p overexpression upregulates the expression of the antioxidant gene SOD2 through the PI3K/Akt/FoxO1 axis to relieve H/R-induced oxidative stress and reduce apoptosis of H9c2 cells.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.

Objective:To evaluate the safety and efficacy of ciprofol and propofol for gynecological surgeries with general anesthesia through a meta-analysis.Methods:Electronic databases including PubMed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure, Wanfang Data, China Biomedical Literature Database, and China Science and Technology Journal Database were searched for randomized controlled trials comparing the safety and efficacy of ciprofol and propofol in gynecological surgeries with general anesthesia from inception to May 2023. Meta-analysis was performed using Revman 5.4 software.Results:Six randomized controlled trials were included, involving 741 patients, of which 371 received ciprofol and 370 received propofol. Compared with propofol group, the emergence time was significantly prolonged, the difference in mean arterial blood pressure, systolic blood pressure and diastolic blood pressure before and after anesthesia induction was decreased, and the incidence of injection pain, respiratory depression, body movement and hypotension was decreased in ciprofol group ( P<0.05). There were no significant differences between the two groups in terms of time of successful anesthesia induction, difference in BIS values and heart rate before and after anesthesia induction, and incidence of tachycardia, bradycardia and hypertension ( P>0.05). Conclusions:Ciprofol is comparable to propofol in terms of efficacy and has better safety than propofol when used in gynecologic surgeries with general anesthesia.