ObjectiveTo investigate the effect of linalool against acute liver injury induced by aflatoxin B₁（AFB₁） in rats and explore its protective mechanism. MethodTwenty male SPF SD rats were randomly divided into three groups： Control （n=6）， AFB₁ （n=7）， and linalool （n=7） groups. Linalool solution （200 mg·kg^-1） was administered preventatively for 14 days， while the control and AFB₁ groups intragastrically received an equivalent volume of double distilled water. After preventative administration of linalool， AFB₁ solution （1 mg·kg^-1， dissolved in saline） was intraperitoneally injected for two consecutive days to induce acute liver injury in rats. Samples were collected and processed 14 days after model establishment. Pathological changes in liver tissue of rats were observed using Hematoxylin-eosin（HE） staining and Masson staining. Biochemical detection was performed to measure the levels of alanine transaminase（ALT）， aspartate transaminase（AST）， γ-glutamyl transferase（GGT）， lactate dehydrogenase（LDH）， alkaline phosphatase（ALP）， total bilirubin（TBil）， direct bilirubin（DBil）， indirect bilirubin（IBil）， malondialdehyde（MDA）， superoxidedismutase（SOD）， catalase（CAT） ， glutathione（GSH）， Fe³⁺， and Fe²⁺ in the liver tissue. Western blot was adopted to assess protein expression levels of nuclear factor-erythroid 2-related factor 2（Nrf2） and heme oxygenase-1（HO-1）. Molecular docking was performed to verify the binding between linalool and key proteins of the Nrf2/HO-1 signaling pathway. Molecular dynamics techniques were used to confirm the stability and affinity of linalool binding with key proteins of the Nrf2/HO-1 signaling pathway. ResultPathological results showed that compared to that in the AFB₁ group， the liver structure in the linalool group tended to be normal， with a significant decrease in blue collagen fibers. The linalool group exhibited significantly reduced levels of ALT， AST， GGT， LDH， ALP， TBil， DBil， and IBil （P<0.01）， Fe³⁺ and Fe²⁺ content， and oxidative stress marker MDA （P<0.01）. The levels of antioxidants SOD， CAT， and GSH significantly increased （P<0.01）. Molecular docking showed a molecular docking energy between linalool and Nrf2 and HO-1 targets of -5.495 6 and -5.199 4 kcal·mol^-1（1 cal≈4.186 J）， respectively. Molecular dynamics results indicated strong affinity in the binding of linalool with Nrf2 and HO-1. Western blot revealed a significant increase in Nrf2 protein expression （P<0.05） and a decrease in HO-1 protein expression （P<0.01） in the linalool group. ConclusionLinalool may protect against AFB₁-induced acute liver injury by modulating the Nrf2/HO-1 ferroptosis signaling pathway to inhibit liver cell ferroptosis and regulate hepatic oxidative stress levels.

Harmine(HM)is a type of β-Carboline alkaloid abundant in nature and has many biological effects.In recent years.Studies have found that HM had a significant positive effect on Alzheimer's disease(AD)both in vivo and in vitro.Its mechanism may be related to the reduction of abnormal deposition of β-amyloid protein(Aβ),excessive phosphorylation of Tau protein,regulation of the cholinergic system,antioxidant stress,and antineuritis.This article reviews the research progress on the improvement effect and mechanism of HM in AD in order to provide an experimental basis for the clinical application of HM and the development of drugs in the area of AD the prevention and treatment.

Objective To explore the efficacy of semaglutide in the treatment of type 2 diabetes mellitus(T2DM)com-bined with non-alcoholic fatty liver disease(NAFLD)and its effect on oxidative stress and inflammatory factors.Methods Totally 80 patients with T2DM accompanied by NAFLD admitted to the First Affiliated Hospital of Xinxiang Medical University from July 2021 to December 2022 were selected and randomly assigned to the observation group and the control group,with 40 patients in each group.Patients in the control group were treated with pioglitazone metformin and dapagliflozin,while patients in the observation group were treated with pioglitazone metformin,dapagliflozin,and semaglutide.The levels of glycated hemoglobin(HbA1c),fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPG),body mass,body mass index(BMI),waist circumference,alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(GGT),controlled attenuation parameter(CAP),liver stiffness measurement(LSM),malondialdehyde(MDA),glutathione peroxidase(GSH-PX),lipid peroxide(LPO),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10)before and after the treatment were compared.Results After 24 weeks of treatment,the overall response rate(ORR)in the observation group and control group was 92.5％(37/40)and 72.5％(29/40),respectively;and the ORR in the observation group was significantly higher than that in the control group(x2=5.541,P＜0.05).Before treatment,there was no statistically significant difference in the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,GSH-PX,LPO,TNF-α,IL-6,and IL-10 of patients between the 2 groups(P＞0.05);after 24 weeks of treatment,the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,LPO,TNF-α,IL-6,and IL-10 were significantly lower than before treatment,while GSH-PX was significantly higher than before treatment(P＜0.05);after 24 weeks of treatment,the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,LPO,TNF-α,IL-6,and IL-10 of patients in the observation group were significantly lower than those in the control group,and GSH-PX was significantly higher than that in the control group(P＜0.05).The incidence of adverse reactions in the observation group and the control group during the treatment period was 17.5％(7/40)and 12.5％(5/40),respectively;and the difference in the incidence of adverse reactions between the two groups was not statistically significant(P＞0.05).Conclusion Semaglutide significantly downregulates the levels of FBG,2hPG and HbA1c in patients with T2DM combined with NAFLD and reduces the body mass,waist circumference,liver enzyme level,hepatic fat content,hepatic fibrosis,oxidative stress,and inflammatory indicators.

Objective To explore the therapeutic effects of different doses of radioactive iodine-131 on patients with hyperthyroidism.Methods A total of 574 patients with hyperthyroidism treated in the First Affiliated Hospital of Xinxiang Medical University from April 2020 to April 2023 were sampled for this study and were divided evenly into the observation group and the control group by a random number table,with 287 patients in each group.The control group was treated with high-dose radioactive iodine-131(＞10-15 mCi),while the observation group was provided with low-dose radioactive iodine-131(5-10 mCi).The therapeutic effects were estimated six months after treatment.Data of the two groups of patients before treatment and 3 and 6 months after treatment were compared,including the levels of thyroid hormone(FT4),free triiodothyronine(FT3),and thyroid-stimulating hormone(TSH),which were measured through the fluorescence immunochromatography of serum(obtained by centrifugation of 3 mL fasting venous blood),and the tumor necrosis factor-α(TNF-α),transforming growth factor-β1(TGF-β1),interleukin-6(IL-6),and IL-1,which were measured through the enzyme-linked immunosorbent assay of serum.The salivary gland uptake index and salivary gland secretion index of the patients before treatment and 3 and 6 months after treatment were measured through radionuclide imaging.The incidence of adverse reactions during treatment was documen-ted.The incidence of hypothyroidism in both groups was evaluated 6 months after treatment.Results The total effective rate of the observation group and the control group was 83.27％(234/281)and 92.88％(261/281),respectively,and that of the observation group was significantly higher(x2=12.353,P＜0.05).The FT4,FT3,and TSH levels of the two groups before treatment showed no statistical discrepancy(P＞0.05).According to data collected 3 and 6 months after treatment,FT4 and FT3 levels of both groups significantly decreased,while TSH increased(P＜0.05)compared to corresponding pre-treatment levels;FT4 and FT3 levels of both groups observed 6 months after treatment were significantly lower than those observed 3 months before,in contrast to the growing TSH trend(P＜0.05).At 3 and 6 months after treatment,FT4 and FT3 levels of the observation group were significantly lower than those of the control group,while TSH levels were significantly higher(P＜0.05).The salivary gland uptake index and salivary gland secretion index between the two groups before treatment showed no statistical discrepancy(P＞0.05).At 3 and 6 months after treatment,such indexes of both groups obviously decreased(P＜0.05).However,those observed 6 months after treatment were higher than three months before(P＜0.05).At 3 months after treatment,the salivary gland uptake index and salivary gland secretion index of the observation group were notably higher than the control group(P＜0.05);at 6 months after treatment,no statistical discrepancy was observed between the two groups in terms of the two indexes(P＞0.05).Before treatment,there was no statistical difference in TNF-α,TGF-β1,IL-6,and IL-1 levels between the two groups(P＞0.05).At 3 and 6 months after treatment,the TNF-α,TGF-β1,IL-6,and IL-1 levels of both groups decreased significantly from pre-treatment levels(P＜0.05),and the data observed 6 months after treatment were still lower than those observed 3 months after treatment(P＜0.05).At 3 months after treatment,the TNF-α,TGF-β1,IL-6,and IL-1 levels of the observation group were significantly lower than those of the control group(P＜0.05);at 6 months after treatment,no statistical difference was observed between the two groups(P＞0.05).The incidence of adverse reactions during treatment in the control group and the observation group was 16.38％(47/287)and 8.01％(23/287),respectively,and that of the observation group was significantly lower than the other group(x2=8.457,P＜0.05).At 6 months after treatment,the incidence of hypothyroidism in the control group and the observation group was 12.46％(35/281)and 3.56％(10/281),respectively,and that of the observation group was significantly lower than that in the control group(x2=15.098,P＜0.05).Conclusion Low doses of radioactive iodine-131 work better in the treatment of hyperthyroidism and can effectively alleviate inflammation and salivary gland dysfunction,with less risk of inducing hypothyroidism and adverse reactions.

Objective To develope a clinical decision support system(CDSS)on insulin titration and validate its effectiveness and safety.Methods Eighty patients with type 2 diabetes mellitus treated at the Department of Endocrinology of the First Affiliated Hospital of Xinxiang Medical University from January 2021 to July 2023,who had difficulty in achieving glycemic control on the basis of lifestyle interventions and oral hypoglycemic drug treatments,were selected for the study.The patients were divided into the observation group and the control group using a random number table,with 40 cases in each group.Patients in both groups received oral metformin extended-release tablets,subcutaneous insulin degludec before bedtime,and subcutaneous aspartate insulin injection before three meals for glycemic control.Patients in the observation group were given insulin titration using the CDSS,and patients in the control group were given insulin titration using the conventional method.The retrospective continuous glucose monitoring system was used to monitor time in range(TIR)for glucose,mean amplitude of glycemic excursion(MAGE),mean blood glucose(MBG),standard deviation of blood glucose(SDBG),and the coefficient of variation(CV)of blood glucose.Fasting blood glucose(FBG),2-hour postprandial glucose(2hPG),length of hospitalization,time to achieve standard blood glucose control,and incidence of hypoglycemia of patients were recorded before and after treatment in the two groups.Results There was no significant difference in FBG and 2hPG of patients between the two groups before treat-ment(P＞0.05).The FBG and 2hPG levels of patients in the two groups were significantly lower than those before treatment(P＜0.05).The FBG and 2hPG levels of patients in the observation group were significantly lower than those in the control group after treatment(P＜0.05).TIR of patients in the observation group was significantly higher than that in the control group,while MAGE,MBG,SDBG,and CV were significantly lower than those in the control group after treatment(P＜0.05).The length of hospitalization was 9.0(7.3,10.0)days and 11.0(8.3,12.0)days of patients in the observation group and control group,respectively;and the length of hospitalization of patients in the control group was significantly longer than that in the observation group(Z=-2.408,P＜0.05).The time required to achieve glycemic control was 6.5(5.0,8.8)days and 7.5(6.0,10.0)days of patients in the observation group and control group,respectively;and the time required to achieve glycemic control of patients in the control group was significantly longer than that in the observation group(Z=-2.019,P＜0.05).The incidence of hypoglycemia of patients in the observation group and control group was 20.0％(8/40),12.5％(5/40),respectively;there was no significant difference in the incidence of hypoglycemia between the observation group and the control group(x2=0.827,P＞0.05).Conclusion Compared with the conventional titration of insulin,the application of CDSS can provide decision support during the implementation of a basal-meal insulin regimen,which can lead to more effective glycemic control,improved glucose TIR,reduced glycemic fluctuations,shorter time required for patients to achieve glycemic control,and shorter hospital stays without increasing the risk of hypoglycemia.

This study was performed to evaluate the role and mechanism of Ephedra aqueous extract in alleviating lung injury of rats with Streptococcus pneumoniae pneumonia via regulating reactive oxygen species(ROS)/NOD-like receptor protein 3(NLRP3)/caspase-1 pathway.Male SD rats were randomly divided into control group,model group,Ephedra aqueous extract(100 mg/kg,200 mg/kg,400 mg/kg)groups,solvent control group(110 ml/kg DMSO),model+solvent group,high-dose Ephedra aqueous extract+solvent group,and high-dose Ephedra aqueous extract+trimethylamine N-oxide(TMAO,110 mg/kg)group.Pneumonia model was established by instilling Streptococcus pneumoniae solution into the trachea.After 24 hours of modeling,each group was given medication by gavage for 10 consecutive days.24 hours after the last gastric lavage,pathological changes in lung tissue and the contents of interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α)in serum and bronchoalveolar lavage fluid(BALF)were detected;and the contents of malondialdehyde(MDA),superoxide dismutase(SOD),the activity of ROS and the expression levels of NLRP3,Caspase-1,GSDMD-N in lung tissue were detected.The model group rats demonstrated pathological changes in lung injury including thickening of alveolar septa and infiltration of inflammatory cells,as well as the contents of IL-1β,IL-6,TNF-α in BALF and serum,the content of MDA,the activity of ROS,the expression levels of NLRP3,Caspase-1 and GSDMD-N in lung tissue were higher than those of the control group,while the SOD content in lung tissue was lower than that of the control group(P<0.05).The lung injury of the low,medium,and high dose Ephedra aqueous extract groups were reduced,and the contents of IL-1β,IL-6,TNF-α in BALF and serum,the content of MDA,the activity of ROS,the expression levels of NLRP3,Caspase-1 and GSDMD-N in lung tissue were lower than that of the model group,while the SOD content in lung tissue was higher than that of the model group(P<0.05).The lung injury of rats in the high-dose ephedra aqueous extract+TMAO group worsened,the contents of IL-1β,IL-6,TNF-α in BALF and serum,the content of MDA,the activity of ROS,the expression levels of NLRP3,Caspase-1 and GSDMD-N in lung tissue were higher than those of the high-dose Ephedra aqueous extract+solvent group,while the SOD content in lung tissue was lower than that of the high-dose Ephedra aqueous extract+solvent group(P<0.05).In conclusion,Ephedra aqueous extract alleviates the lung injury of rats with Streptococcus pneumoniae pneumonia via inhibiting the inflammatory response,oxidative stress and pyroptosis mediated by ROS/NLRP3/Caspase-1 pathway.

Objective To investigate the clinical therapeutic effect of Chaishi fever particles on patients with epidemic encephalitis B and to study the machanism of anti-inflammatory.Methods One hundred and twenty one patients with epidemic encephalitis B admitted to the Second Clinical Medical College of Henan University of Chinese Medicine from January 2014 to May 2017 were enrolled, and they were divided into a routine treatment group (60 cases) and a traditional Chinese medicine (TCM) treatment group (61 cases) by random number table. The patients in routine treatment group were given symptomatic support and comprehensive treatment for 15 days, while those in the TCM treatment group were given as that of routine group with the addition of Chaishi fever particles 8 g, 4 times every day, orally taken for consecutive 15 days. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL-1β, IL-10) in the serum of two groups were determined by enzyme-linked immunosorbent assay (ELISA), and the clinical therapeutic effect, complications and sequelae in two groups after treatment were observed.Results Compared with the routine treatment group, after treatment the time of body temperature recovering normal (days: 5.8±1.2 vs. 7.5±1.7), the coma time (days: 5.5±1.3 vs. 6.8±1.6), the remission time of convulsion (days: 5.2±1.4 vs. 6.5±1.5), and the length of stay in hospital (days: 22.6±1.9 vs. 25.2±1.8 ) were significantly shorter in TCM treatment group (P < 0.05). After treatment, the levels of serum tumor TNF-α and IL-1β were decreased, IL-10 was increased in both groups, moreover, compared with the routine treatment group, the changes were more obvious in TCM treatment group [TNF-α (μg/L): 11.4±3.6 vs. 14.6±3.5, IL-1β (μg/L): 22.3±6.2 vs. 26.2±5.6, IL-10 (μg/L): 225.2±19.2 vs. 186.2±21.5, allP < 0.05]. In addition, compared with the routine treatment group, the total effective rate was higher [98.3% (60/61) vs. 90.0% (54/60),P < 0.05], and the incidence of sequelae was lower [1.64% (1/61) vs. 13.3% (8/60),P < 0.05] in TCM treatment group.Conclusion The Chaishi fever particles can effectively treat the patients with epidemic encephalitis B and the action is related to the inhibition of inflammatory reaction.

Objective To investigate the changes of visual acuity,fundus changes,and serum vitamin D concentration in diabetic retinopathy patients treated with metformin,and to evaluate its clinical efficacy.Methods Totally 80 cases (160 eyes) patients with background diabetic retinopathy were included in the study,and were divided into observation group (metformin + Pancreatic Kininogenase Enteric-coated Tablets) and control group (Pancreatic Kininogenase Enteric-coated Tablets) according to the different treatment methods used for 3 months.Fundus fluorescein angiography was used to evaluate the improvement of the fundus lesions.The serum levels of vitamin D were measured with electrochemiluminescence immunoassay (ECLIA).Results After 3 months of treatment,serum vitamin D concentration of the observation group increased,and the differences were statistically significant (P ＜ 0.05) when compared to before treatment.However,3 months after treatment,serum vitamin D levels of the control group increased slightly,but the difference was not statistically significant (P ＞ 0.05).The total effective rate of fundus improvement in the observation group and the control group was 70％ and 55％,respectively.There was significant difference between the two groups in the improvement of fundus (P ＜ O.05).Conclusions Metformin has an adjunctive effect on background diabetic retinopathy,and the increase of serum vitamin D may be one of the mechanisms of metformin in improving diabetic retinopathy.

Objective:To explore the cognition of undergraduates on advance directives in a medical universi -ty, and to analyze the affect factors on cognition status of advance directives .Method: Total 594 undergraduates were selected by stratified cluster random sampling and this study conducted a face to face interview using self -de-signed questionnaire .Results: The cognitive status on advance directives was poor .This study found the inde-pendent variables of the gender , religion, the self-reported health, the average monthly living expenditure , the survival time and quality choice and the type of health insurance were the effect factors (P<0.05).Conclusion:the undergraduates′cognitive status on advance directives was poor in this medical university , and we need adopt relevant measures to improve the cognitive of undergraduates on advance directives .

OBJECTIVETo explore the application of Monte Carlo simulation in optimizing and adjusting the reimbursement scheme with regard to the New Rural Cooperative Medical System (NCMS) to scientific steering practice. Optimization of the reimbursement scheme in rural areas of China was also studied.

METHODSA multi-stage sampling household survey was conducted in Sihui county, with 4 433 rural residents from 1 179 households from 13 towns in Guangdong province surveyed by self-designed questionnaire. Probit Regression Model was applied in fitting data and then estimating the own-price elasticity and cross elasticity of healthcare demand for both outpatients and inpatients. Monte Carlo simulation model was constructed to estimate the reimbursement effects of various alternative reimbursement schemes, by replicated simulation for one thousand times and each sampling on five hundred households. In this way, optimization of the implemented reimbursement scheme in Sihui county was conducted.

RESULTSOwn-priced elasticity of demands for outpatient visit, inpatient visit in the township hospital center, secondary hospital and tertiary hospital were -0.174, -0.264, -0.675 and -0.429, respectively. Outpatient demand was affected by the per-visit price of township hospital center and secondary hospital. The cross-priced elasticity of demands for outpatient visit appeared to be 0.125 and 0.150. The reimbursement effects of Scheme B7 showed that the efficiency of NCMS fund was 17.85% , the reimbursement ratio for healthcare was 25.63%, and the decreased percentages of poverty caused by illness was 18.25%, more than 9.37%, from the implemented scheme A. So the implemented scheme was in need for optimization.

CONCLUSIONMonte Carlo simulation technique was applicable to simulate the effects of the optimized alternative reimbursement scheme of NCMS and it provided a new idea and method to optimize and adjust the reimbursement scheme.

Adolescent ; Adult ; China ; Female ; Humans ; Insurance, Health, Reimbursement ; economics ; Male ; Middle Aged ; Monte Carlo Method ; Rural Population ; statistics & numerical data ; Young Adult