Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

PI3Kγ and PI3Kδ have important regulatory roles in the immune system, and targeting these two subtypes helps to reshape the tumor microenvironment. PI3Kγ and PI3Kδ are potential targets for tumor immunotherapy. In this study, a series of new pyrazolopyrimidine derivatives were designed and synthesized on the basis of our previously reported PI3K inhibitors, resulting in the discovery of compound 16l as a potent and selective PI3Kγ/δ dual inhibitor. Compound 16l demonstrated strong biochemical potencies against PI3Kγ and PI3Kδ with IC₅₀ values of 0.11 and 0.79 nmol·L^-1. In cell-based assays, it potently inhibited the PI3Kγ and PI3Kδ mediated Akt S473 phosphorylation with EC₅₀ values of 3 and 7 nmol·L^-1. In vivo, compound 16l exhibited acceptable pharmacokinetic properties in Sprague-Dawley (SD) rats and suppressed the tumor growth in a MC38 syngeneic mouse model. The animal experiments were approved by the Animal Ethics Committee of Hefei Institutes of Physical Science, Chinese Academy of Sciences (approval number: DWLL-2000-06). In addition, no appreciable human ether-a-go-go-related gene (hERG) inhibition was observed for compound 16l even at 30 μmol·L^-1. These results suggested that compound 16l might be a potential research tool for studying the PI3Kγ/δ mediated signaling pathways.

A polymethionine(p-Met)-modified laser-induced graphene(LIG)electrode was constructed and integrated with portable electrochemical workstations and handheld computer to achieve on-site,simultaneous detection of azo dyes sunset yellow(SY)and tartrazine(Tz)in environmental water.Firstly,the sensor interface with the best electrical conductivity was obtained by optimizing the laser processing parameters,and then the electrochemical responses of SY and Tz were improved by electropolymerization of methionine on the surface of LIG.Finally,a portable electrochemical sensor platform was built by connecting p-Met/LIG,a small electrochemical workstation and a handheld computer application program.Differential pulse voltammetry(DPV)was used to determine these two dyes.SY showed a good linear relationship in the concentration range of 0.2-20 μmol/L and 20-100 μmol/L,the detection limit was as low as 0.001 μmol/L.Tz showed a good linear relationship in concentration range of 0.3-40 μmol/L and 40-100 μmol/L,and the detection limits was as low as 0.005 μmol/L.p-Met/LIG also had excellent anti-interference performance and reproducibility.The portable electrochemical platform was applied to real-time detection of real water samples,and the results showed that the platform was expected to be applied in field detection of SY and Tz in real environmental water bodies.

Objective:To study the changes in skeletal muscle and serum nutritional indicators during concurrent chemoradiotherapy in cervical cancer patients,and to evaluate their correlation with short-term efficacy and long-term prognosis. Methods:A retrospective analysis was conducted on 114 patients with cervical cancer who underwent radical concurrent chemoradiotherapy in the Department of Oncology,Nanjing Drum Tower Hospital from February 2019 to February 2023. All patients underwent a treatment regimen comprising external beam radiation (EBRT),internal radiation,and concurrent chemotherapy. Serum nutritional data of the patients were collected before radiotherapy,one week,two weeks and five weeks after the onset of radiotherapy. CT images of the patients at the time of simulation and about five weeks after the onset of radiotherapy were imported into the Pinnacle 39.10 planning system,and the skeletal muscle index (SMI) of the third lumbar vertebra (L3) were calculated for each patients. The changes of the serum nutritional indicators of the patients prior to and post EBRT were analyzed statistically. The patients are categorized into two groups according to the baseline SMI:a sarcopenic group consisting of 35 cases and a non-sarcopenic group comprising 79 cases. The therapeutic outcomes between the two groups were compared,and logistic analysis of the relevant factors affecting the occurrence of sarcopenia during radiotherapy was conducted. The survival curves were drawn using Kaplan-Meier method and disease-free survival (DFS) between the two groups was compared using Log Rank test. We used Cox univariate and multivariate regression analysis to identify prognostic factors related to DFS. Results:The serum nutritional indicators of the patient at one week,two weeks,and five weeks after the beginning of EBRT were significantly lower than those before radiotherapy (P<0.05). The SMI from the CT images of simulation at five weeks after the onset of radiotherapy was significantly lower than that before radiotherapy (P<0.001). There was a significant correlation between hemoglobin levels prior to radiotherapy and incidence of sarcopenia during radiotherapy (P=0.046). There was no significant difference in efficacy between the two groups at the end of EBRT (P>0.05). At the end of radiotherapy,the complete response (CR) rate of the non-sarcopenia group was significantly higher than that of the sarcopenia group (P=0.040). However,the objective response rate (ORR) and disease control rate (DCR) of both groups at the end of radiotherapy were 100％. The 2-year DFS of the sarcopenia group and the non-sarcopenia group were 66.7％ and 85.5％,respectively,and the difference was statistically significant (P=0.016). Only four patients died during the 2-year follow-up,so OS was not reached. Baseline SMI,serum squamous cell antigen levels prior to radiotherapy,and degree of bone marrow suppression were three independent prognostic factors affecting DFS in the patients. Conclusion:Cervical cancer patients experience significant nutritional loss during chemoradiotherapy,and baseline SMI is significantly correlated with short-term efficacy and long-term prognosis and can serve as a predictive marker for patients with cervical cancer receiving chemoradiotherapy.

Pogostemon cablin is a famous southern medicine.As the important raw material for modern medicine and industry,Pogostemon cablin becomes required with a large marketing demand.However,due to the serious continuous cropping obstacles in the growth process of Pogostemon cablin,the aggravation of diseases of Pogostemon cablin and the degradation of its quality arose.This paper outlined the ecological factors such as climate factors,soil factors and topographic factors suitable for the growth of Pogostemon cablin,analyzed the continuous cropping obstacles and diseases arising in the cultivation,reviewed the current ecological planting mode of Pogostemon cablin such as crop rotation,intercropping,relay-cropping and under-forest planting,and also made a comprehensive evaluation of the economic benefits,ecological benefits and social benefits of the ecological planting mode of Pogostemon cablin,aiming to provide a theoretical basis and a reference for the promotion of the ecological planting mode of Pogostemon cablin.

Objective To investigate the relationship between single nucleotide polymorphisms(SNPs)in the eNOS gene and genetic susceptibility to systemic lupus erythematosus(SLE)in Hainan.Methods Blood samples were collected from SLE patients(SLE group,n=214)and healthy controls(control group,n=214)from January 2020 to December 2022 at the First Affiliated Hospital of Hainan Medical College and Hainan Provincial People's Hospital.The bases of eNOS gene rs3918188,rs1799983 and rs1007311 loci in each group were detected by SNaPshot sequencing technology.Logistic regression was used to analyze the correlation between genotypes,alleles and gene models(dominant model,recessive model,and overdominant model)of the above 3 target loci of the eNOS gene and genetic susceptibility to SLE.Haplotype analysis was conducted using HaploView 4.2 software to investigate the relationship between haploid and genetic susceptibility to SLE at each site.Results The results of logistic regression analysis revealed that the CC genotype and the C allele at rs3918188 locus were risk factors for genetic susceptibility to SLE(CC vs.AA:OR=2.449,P<0.05;C vs.A:OR=2.133,P<0.001).In recessive model at rs3918188 locus,CC genotype carriers had an increased risk of SLE development compared with AA+AC genotype carriers(OR=2.774,P<0.001).In contrast,in overdominant model at this locus,AC genotype carriers had a decreased risk of SLE occurrence compared with AA+CC genotype carriers(OR=0.385,P<0.001).In addition,polymorphisms of rs1799983 and rs1007311 were not associated with susceptibility to SLE in genotype,allele type and the 3 genetic models(P>0.05).Haplotype analysis revealed a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene,but no significant correlation was found between haplotype and genetic susceptibility to SLE(P>0.05).Conclusion The CC genotype and C allele at rs3918188 locus of eNOS gene may be risk factors for SLE in Hainan,while the risk of SLE occurrence is reduced in carriers of AC genotype under the overdominant model.

Objective:To explore diagnostic value of echocardiography indexes for moderate-severe stenosis in CHD patients and their correlation with cardiac function class.Methods:A total of 90 CHD patients admitted to our hos-pital from Dec 2020 to Dec 2022 were selected as CHD group.According to NYHA classification,CHD group was divided into class Ⅰ～Ⅱ group(n=38)and class Ⅲ～Ⅳ group(n=52).The patients were divided into mild group(n=35)and moderate-severe group(n=55)according to Gensini score.In addition,90 healthy people who sim-ultaneously received physical examination in our hospital were enrolled as control group.LVEF,LVEDd and LVESd were measured in two groups by color ultrasound diagnostic instrument.Cardiac function indexes were com-pared between control group and CHD group,mild group and moderate-severe group,class Ⅰ～Ⅱ group and classⅢ～Ⅳ group.ROC curve was used to analyze the diagnostic value of above cardiac function indexes for moderate-severe stenosis in CHD patients.The correlation among LVEF,LVEDd,LVESd,different stenosis degree and NYHA class in CHD patients was analyzed by Spearman correlation analysis.Results:Compared with the control group,there was significant reduction in LVEF,and significant rise in LVEDd and LVESd in CHD group,P=0.001 all;compared with the mild group,there was significant reduction in LVEF[(45.31±5.08)％vs.(40.34±3.01)％],and significant rise in LVEDd[(53.92±5.09)mm vs.(61.68±4.79)mm]and LVESd[(52.72±4.72)mm vs.(58.06±3.50)mm]in moderate-severe group,P=0.001 all;compared with the class Ⅰ～Ⅱgroup,there was significant reduction in LVEF[(45.07±4.95)％vs.(40.23±3.06)％],and significant rise in LVEDd[(54.50±5.30)mm vs.(61.71±4.91)mm]and LVESd[(52.92±4.63)mm vs.(58.22±3.43)mm]in class Ⅲ～Ⅳ group,P=0.001 all.AUC of combined detection of LVEF,LVEDd and LVESd diagnosing moder-ate-severe stenosis in CHD was 0.909,which was significantly higher than those of single detections(0.733,0.787,0.789)(Z=2.925,2.125,2.043,P＜0.05 or＜0.01).Spearman correlation analysis showed a significant negative correlation between LVEF and NYHA class(r=-0.514),LVEDd and LVESd showed a significant posi-tive correlation with NYHA class(r=0.538,0.546,P=0.001 both),and it showed a significant positive correla-tion between different degrees of coronary stenosis and NYHA class in CHD patients(r=0.875,P=0.001).Con-clusion:The combined detection of LVEF,LVEDd and LVESd possesses high diagnostic value for moderate-se-vere stenosis in CHD patients,and it is significantly correlated with NYHA cardiac function class,which can be used as one of assessing methods for coronary stenosis severity in CHD patients.

Objective To understand the disease acceptance status and related factors in human immunodeficiency virus(HIV)-infected/acquired immunodeficiency syndrom(AIDS)patients,so as to guide the clinical development of intervention measures,and to provide empirical evidence for improving clinical outcomes.Methods Convenience sampling method was used to select 555 HIV-infected/AIDS patients who received treatment in the designated AIDS treatment clinic of a hospital.General data,disease acceptance,disease self-management efficacy and clinical out-comes(such as quality of life,CD4+T lymphocyte count and HIV viral load)of the studied subjects were collected.Results The average disease acceptance of HIV-infected/AIDS patients was(26.08±5.34)points.Multiple linear regression analysis showed that religious belief and self-management efficacy were related factors affecting the di-sease acceptance of patients(both P＜0.05),which could explain the 30.4％variation in disease acceptance of HIV-infected/AIDS patients,and the disease acceptance of patients was closely related to their quality of life(P＜0.001).Conclusion HIV-infected/AIDS patients have a moderate level of disease acceptance.Medical staff should fully consider patients'religious beliefs and self-management efficacy,so as to formulate targeted intervention mea-sures to improve patients'acceptance of disease,and further promote patients'quality of life.

Objective:To investigate the protective effect of endogenous ω-3 polyunsaturated fatty acid(PUFA)against cisplatin-induced myelosuppression and the mechanism of reducing apoptosis in bone marrow nucleated cells using mfat-1 transgenic mice.Methods:The experimental animals were divided into 4 groups:wild-type mice normal control group,mfat-1 transgenic mice normal control group,wild-type mice model group and mfat-1 transgenic mice model group.The mice in the model group were injected intraperitoneally with 7.5 mg/kg cisplatin on day 0 and day 7 to construct a myelosuppression model,while the mice in the normal control group were injected intraperitoneally with an equal amount of saline,and their status was observed and their body weight was measured daily.Peripheral blood was taken after 14 day for routine blood analysis,and the content and proportion of PUFA in peripheral blood were detected using gas chromatography.Bone marrow nucleated cells in the femur of mice were counted.The histopathological changes in bone marrow were observed by histopathological staining.The apoptosis of nucleated cells and the expression level changes of apoptosis-related genes in the bone marrow of mice were detected by flow cytometry and fluorescence quantitative PCR.Results:Compared with wild-type mice,mfat-1 transgenic mice showed significantly increased levels of ω-3 PUFA in peripheral blood and greater tolerance to cisplatin.Peripheral blood analysis showed that endogenous ω-3 PUFA promoted the recovery of leukocytes,erythrocytes,platelets and haemoglobin in peripheral blood of myelosuppressed mice.The results of HE staining showed that endogenous ω-3 PUFA significantly improved the structural damage of bone marrow tissue induced by cisplatin.Flow cytometry and PCR showed that,compared with wild-type mice model group,the apoptosis rate of bone marrow nucleated cells in mfat-1 transgenic mice was significantly reduced(P＜0.001),and the expression of anti-apoptotic genes Bcl-2 mRNA was significantly increased(P＜0.01),while the expressions of pro-apoptotic genes Bax and Bak mRNA were significantly reduced(P＜0.001,P＜0.05).Conclusion:Endogenous ω-3 PUFA can reduce cisplatin-induced apoptosis in bone marrow nucleated cells,increase the number of peripheral blood cells and exert a protective effect against cisplatin-induced myelosuppression by regulating the expression of apoptosis-related genes.

To enhance the clinical applicability of guidelines and provide more effective guidance for clinical practice, a clinical value assessment was conducted during the development of the World Federation of Acupuncture-Moxibustion Societies (WFAS) Clinical Practice Guideline of Acupuncture and Moxibustion for Migraine, which involved the evaluation of 59 acupuncture and moxibustion treatment protocols from randomized controlled trials (RCTs). This article introduced the methodology, content and results of the clinical value assessment of RCT-based acupuncture and moxibustion treatment protocols, which involved the integration of historical and contemporary medical evidence and expert consensus. It served as a methodological reference for the future development of acupuncture and moxibustion clinical practice guidelines.
Humans ; Moxibustion ; Acupuncture Therapy/methods* ; Acupuncture ; Clinical Protocols ; Migraine Disorders/therapy*