The auxin/indole-3-acetic acid (Aux/IAA) gene family is an important regulator for plant growth hormone signaling, involved in plant growth, development, as well as response to environmental stresses. In the present study, we identified SmIAA7 which is potentially associated with Salvia miltiorrhiza leaf development through comparatively analyzed the transcriptome data from different pinnate leaves. SmIAA7 was successfully isolated from S. miltiorrhiza using the specific primers. Then subsequent bioinformatic analysis, prokaryotic expression and purification, subcellular localization, and induction expression analysis under auxin and abiotic stress were performed. The full-length of SmIAA7 contained an ORF of 684 bp encoding a protein of 227 amino acid with a molecular weight of 25.3 kD. Conserved domain analysis showed that SmIAA7 contains the conserved Aux_IAA domain (pfam02309). Sequence analysis and phylogenetic tree analysis results indicated SmIAA7 was phylogenetically close to IAA7 and IAA14 from other plants, suggesting SmIAA7 involved in plant growth and development as well as response to environmental stresses. The prokaryotic expression vector pET28a-SmIAA7 was constructed and SmIAA7 recombinant protein was successfully expressed in E. coli Rosetta (DE3) strain. Subcellular localization experiment demonstrated that SmIAA7 localized in the nucleus of plant cells. Real-time fluorescence quantitative PCR results showed that the expression level of SmIAA7 was upregulated in response to auxin. Drought, low temperature, and salt stress significantly increased the transcript level of SmIAA7 gene. This study lays a foundation for further elucidating the role of SmIAA7 in leaf development, signal transduction, and stress defense in S. miltiorrhiza.

Objective To observe the clinical efficacy of FANG's scalp acupuncture combined with timing auricular point pressing therapy in the treatment of insomnia patients with maintenance hemodialysis(MHD).Methods A total of 70 patients with insomnia on MHD were randomly divided into observation group and control group,with 35 patients in each group.Both groups were given conventional treatment,the control group was given oral use of Estazolam Tablets on the basis of conventional treatment,and the observation group was given FANG's scalp acupuncture combined with timing auricular point pressing therapy.Both groups were treated for a total of 4 weeks of treatment.After 1 month of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the Pittsburgh Sleep Quality Index(PSQI)score and the Kidney Disease Quality of Life Short Form(KDQOL-SF)score,as well as the scores of the Hamilton Depression Scale(HAMD)and the Hamilton Anxiety Scale(HAMA),were observed in the patients of the two groups before and after treatment.The changes in hemoglobin(Hb),serum creatinine(Scr),and blood urea nitrogen(BUN)levels were compared before and after treatment between the two groups,and the safety of the two groups was evaluated.Results(1)After treatment,the PSQI and KDQOL-SF scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving PSQI and KDQOL-SF scores,and the difference was statistically significant(P＜0.05).(2)After treatment,the HAMD and HAMA scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving HAMD and HAMA scores,and the differences were statistically significant(P＜0.05).(3)After treatment,the Hb,Scr,BUN levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving Hb,Scr,BUN levels,and the differences were all statistically significant(P＜0.05).(4)The total effective rate was 77.14%(27/35)in the observation group and 62.86%(22/35)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(5)Comparison of the incidence of adverse reactions in the two groups of patients,the difference was not statistically significant(P＞0.05).Conclusion FANG's scalp acupuncture combined with timing auricular point pressing therapy in the treatment of insomnia patients with MHD can effectively improve the sleep quality of patients and alleviate anxiety and depression,so as to improve the quality of life of patients,with remarkable efficacy.

Objective To evaluate the bioequivalence of oral sidenafil citrate tablets manufactured(100 mg)test preparations and reference preparations in healthy subjects under fasting and fed conditions.Methods Using a single-dose,randomized,open-lable,two-period,two-way crossover design,36 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test 100 mg with 7-day washout period.Plasma concentration of sidenafil and N-demethylsildenafil was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The pharmacokinetic parameters were calculated by Analyst 1.6.3(AB Scie)using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The main pharmacokinetic parameters of sidenafil after a single oral dose of sidenafil citrate tablets under fasting condition for test and reference were as follows:Cmax were(494.69±230.94)and(558.78±289.83)ng·mL-1,AUC0-t were(1 336.21±509.78)and(1 410.82±625.99)h·ng·mL-1,AUC0-were(1 366.49±512.16)and(1 441.84±628.04)h·ng·mL-1,respectively.The main pharmacokinetic parameters of sidenafil under fed condition for T and R were as follows:Cmax were(381.89±126.53)and(432.47±175.91)ng·mL-1,AUC0-t were(1 366.34±366.99)and(1 412.76±420.37)h·ng·mL-1,AUC0-were(1 403.28±375.32)and(1 454.13±429.87)h·ng·mL-1,respectively.The results demonstrated the bioequivalence of sidenafil citrate tablets between T and R.The incidence of adverse events in fasting and fed tests were 33.33％and 25.00％,respectively.No serious adverse event was reported.Conclusion The test and reference formulation of sidenafil citrate tablets were equivalent and was safe.

Objective Pancreatic cancer(PC)is a malignant tumor of the digestive tract that is difficult to diagnose early,easily metastasizes and relapses,and resistant to conventional chemotherapy.PC is a very difficult disease to treat.The key regulatory factors of PC resistance,such as epithelial-mesenchymal transition phenotypic cells,tumor stem cells,and miRNAs,have been reviewed in the past few years,and some new regulatory factors have been discovered as supplements.This review mainly focuses on the characteristics and properties of the key regulatory factors of PC chemotherapy resistance including long noncoding RNAs,nuclear factor KB and exosomes,drug resistance mechanisms,and treatment related strategies,and future treatment directions were predicted.

Objective To investigate the bioequivalence of gliclazide sustained-release tablets in Chinese healthy subjects.Methods The study was designed using a single-center,open,randomized,single-dose,two-cycle,two-sequence administration method;subjects were orally administered the test/reference preparation 30 mg on an fasting or fed conditions,with self-cross-dosing.The concentration of gliclazide in human plasma was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS)method.The main pharmacokinetic parameters of gliclazide(Cmax,AUC0-t and AUC0-∞)were analyzed by non-atrioventricular model of WinNonlin.Result In the fasting study,24 subjects were recruited and 22 completed the study.The main pharmacokinetic parameters of gliclazide sustained-release tablets test preparation and reference preparation in the fasting group were as follows:Cmax were(862.48±294.48)and(902.96±259.09)ng·mL-1;AUC0-t were(2.60 × 104±8 930.46)and(2.50 ×104±7 573.42)h·ng-1·mL-1;AUC0-∞ were(3.00 × 104±1.43 × 104)and(2.68 × 104±7 085.99)h·ng·mL-1.In the fed study,twenty-four subjects were enrolled and 23 completed the study.The main pharmacokinetic parameters of gliclazide sustained-release tablets test preparation and reference preparation in fed group:Cmax were(1 531.74±273.49)and(1 510.87±241.08)ng·mL-1;AUC0-t were(2.78 ×104±9 565.89)and(2.76 ×104±9 821.43)h·ng·mL-1;AUC0-∞ were(3.02 ×104±1.24 ×104)and(3.02 × 104±1.30 × 104)h·ng·mL-1 h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of Cmax,AUC0-t,AUC0-∞ for the test preparation and reference preparation gliclazide sustained-release tablets were all between 80％and 125％.Conclusion The test and the reference preparation of gliclazide sustained-release tablets are bioequivalent in Chinese healthy subjects.

Objective To investigate the protective effect of moxifloxacin(Moxi)on Mycoplasma pneumoniae pneumonia by down-regulating long non-coding RNA growth inhibition specific gene(lncRNA GAS5)through non-receptor protein tyrosine kinase(JAK)/signaling and transcriptional activator protein(STAT)signaling pathways.Methods BALB/c mice were randomly divided into control group,model group,experimental group and combined group.Mice in model group,experimental group and combined group were treated with nasal drops of Mycoplasma pneumoniae fluid to establish Mycoplasma pneumoniae pneumonia model.By intraperitoneal injection of the experimental group and the combined group of 100 mg·kg-1 moxifloxacin treatment;on the basis,the overexpressed plasmid pc-GAS5 was injected into the tail vein of the combined group.The control group and model group were injected with the same amount of 0.9％NaCl intraperitoneally.The serum levels of interleukin-1 β(IL-1β)and IL-6 were detected by enzyme-linked immunosorbent assay(ELISA);the serum levels of superoxide dismutase(SOD)were detected by biochemical method;and the expression of lncRNA GAS5 in lung tissue was detected by real-time fluorescence quantitative polymerase chain reaction;the protein expression levels of B-cell lymphoma-2(Bcl-2),JAK2 and STAT3 in mouse lung were detected by Western blot.Results The serum IL-1 β content in control group,model group and experimental group were(64.03±14.19),(254.85±63.79)and(157.46±42.93)pg·mL-1,respectively;IL-6 contents were(22.61±5.01),(184.14±39.50)and(132.64±25.47)pg·mL-1;SOD activities were(50.38±11.75),(28.17±6.71)and(37.67±8.09)U·mL-1,respectively;the relative expression levels of lncRNA GAS5 in lung tissues were 1.00±0.16,3.78±0.69 and 2.41±0.54,respectively.The relative expression levels of Bcl-2 protein in control group,model group,experimental group and combined group were 1.00±0.17,0.65±0.14,0.82±0.16 and 0.62±0.13,respectively;phospherylated JAK2/JAK2 ratios were 1.00±0.20,4.98±1.01,2.13±0.52 and 4.21±0.92,respectively;phospherylated STAT3/STAT3 ratios were 1.00±0.18,3.77±0.78,2.65±0.64 and 3.49±0.75,respectively.Compared with the control group,the above indexes in the model group had statistical significance(P＜0.05,P＜0.001).The above indexes in the experimental group were statistically significant compared with those in the model group(P＜0.05,P＜0.01,P＜0.001).There were significant differences between combined group and experimental group(P＜0.05,P＜0.001).Conclusion Moxifloxacin can effectively improve the lung tissue morphology of mice with Mycoplasma pneumoniae pneumonia,regulate the levels of inflammatory factors and oxidative stress damage,and affect apoptosis and JAK/STAT pathway protein expression by down-regulating lncRNA GAS5.

Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannan-binding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with RAP. Methods Recombinant plasmids were used to evaluate the assay sensitivity.Common blood influenza bacteria were used for the specific detection.Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)assays.Kappa analysis was used to evaluate the consistency between the two assays. Results The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial species.The M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05). Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objective:To understand the incidence of diabetes and influencing factors, the trend of FPG change and risk for mortality in HIV-infected individuals after antiretroviral therapy (ART) in Dehong Dai and Jingpo Autonomous Prefecture (Dehong).Methods:The HIV/AIDS treatment database was collected from China Information System for Disease Control and Prevention. This retrospective cohort study was conducted in HIV-infected individuals with access to ART in Dehong during 2004-2020.The Cox proportional hazard regression model was used to analyze the incidence density of diabetes, the influencing factors and risk for mortality in HIV-infected individuals with access to ART, mixed linear effects model was used to analyze the trend of FPG change and predict FPG in those with different glucose metabolic status at baseline survey. Statistical analysis was performed using software SAS 9.4.Results:A total of 8 763 HIV-infected individuals were included, in whom 8 432 (96.2%) had no diabetes, 331 had diabetes. The incidence density of diabetes was 2.31/1 000 person years. Multivariate Cox proportional hazard regression analysis revealed that 30- 59 years old, BMI ≥24.0 kg/m 2, Efavirenz (EFV) based initial treatment regimen and impaired fasting glucose (IFG) at baseline survey were significantly and positively associated with incidence of diabetes. Mixed effect model revealed that FPG was positively correlated with the duration of ART, age and baseline FPG. Suffering from diabetes was a risk factor for mortality in HIV-infected individuals both at baseline survey and during follow-up. Conclusions:The risk for diabetes increased in HIV-infected individuals who were 30-59 years old, baseline BMI ≥24.0 kg/m 2, received EFV based initial treatment, and IFG in HIV-infected individuals after antiretroviral therapy in Dehong, 2004-2020. It is important to pay close attention to their blood glucose, and patients with high blood glucose should receive treatment as early as possible.

AIM To study the neoflavonoids from Dalbergia cochinchinensis Pierre ex Laness and their anti-hypoxia/reoxygenation injury activities on H9c2 myocardial cells.METHODS The 70%ethanol extract from D.cochinchinensis was isolated and purified by silica gel,Sephadex LH-20 and reverse-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The CCK-8 method was used to detect their activities on H9c2 cells and protective effects on hypoxia-reoxygenation injury of H9c2 cells,and their structure-activity relationship was analyzed.RESULTS Twelve compounds were isolated and identified as latifolin(1),5-O-methyllatifolin(2),mimosifoliol(3),5-O-methydalbergiphenol(4),dalbergiphenol(5),cearoin(6),2,4-dihydroxy-5-methoxy-benzophenone(7),2-hydroxy-4,5-dimethoxybenzophenone(8),melannoin(9),2,2′,5-trihydroxy-4-methoxybenzophenone(10),dalbergin(11),4-methoxydalbergione(12).The dalbergiphenols and dalbergins had little toxicity to H9c2 cells,and dalbergiphenols had strong activity against hypoxia-reoxygenation injury of H9c2 cells.CONCLUSION Compound 8 is a new natural product.Compounds 4,9 are isolated from this plant for the first time.Dalbergiphenols may be the main neoflavonoids against hypoxia-reoxygenation injury of H9c2 cells.