OBJECTIVE To observe the clinical efficacy of Maitong Jun'an Decoction in treating coronary heart disease(CHD)angina of qi deficiency and blood stasis type,and preliminarily elucidate its possible mechanism of action through transcriptomics meth-ods.METHODS A total of 140 patients with CHD angina of qi deficiency and blood stasis type were included and randomly divided into a treatment group and a control group,with 70 cases in each group.During the treatment period,3 patients in the control group dropped out.The control group received basic Western medicine treatment for secondary prevention of CHD,while the treatment group received Maitong Jun'an Decoction in addition to the treatment in the control group.The treatment period for both groups was 8 weeks.Before and after treatment,the patients in both groups were evaluated for the TCM syndrome score,Canadian Cardiovascular Society(CCS)angina grading,Seattle angina questionnaire(SAQ)score,self-rating anxiety scale(SAS),self-rating depression scale(SDS)score,and adverse reactions.The peripheral blood of 9 patients before and after treatment was selected for transcriptomic sequencing based on the principle of gender,age,and disease duration matching.RESULTS After treatment,the TCM syndrome scores and total scores of the 2 groups were significantly reduced(P<0.01).The treatment group was better than the control group in improving chest pain,chest tightness,shortness of breath,fatigue and total score(P<0.05,P<0.01);the overall improvement rate of CCS angina grading in the treatment group was better than that in the control group(P<0.05);the SAQ,SAS and SDS scores of the 2 groups were significantly reduced before and after treatment(P<0.01),and the SAQ score of the treatment group was improved better than that of the control group(P<0.05,P<0.01).The transcriptomics results showed that there were 862 significantly different mR-NAs before and after treatment,including 509 up-regulated and 353 down-regulated.GO analysis showed that there were 666 biologi-cal processes in the differentially expressed mRNAs,mainly including viral gene expression,translation initiation,RNA catabolism,etc.There were 112 cell components,mainly including focal adhesion,ribosome subunit,nuclear spot,etc.There were 94 molecular functions,mainly including double-stranded RNA binding,cadherin binding,transcription co-regulatory factor activity,etc.KEGG analysis showed that the differentially expressed mRNAs enriched in 20 signaling pathways,mainly including glycerophospholipid me-tabolism pathway,AMPK signaling pathway,ribosome pathway,etc.CONCLUSION Maitong Jun'an Decoction can improve clini-cal symptoms in patients with CHD angina of qi deficiency and blood stasis type.Its mechanism of action is multi-target and multi pathway,mainly related to the regulation of glycerophospholipid metabolism pathway,AMPK signaling pathway,ribosome pathway.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

OBJECTIVE To study the differences in toxicity between intravenous(iv)administration and aqueous solution exposure of Dichroa alkali salt(DAS)in zebrafish.METHODS ① Well-devel-oped zebrafish larvae of 2 d post fertilization(2 dpf)were randomly divided into the normal control(no treatment),solvent control(saline,iv),and DAS groups(0.125,0.25,0.50,1.00 and 2.00 mg·kg-1,iv)before being observed for 3 consecutive days after administration.A heart rate of 0 was determined as death of zebrafish,and the mortality rate,maximum non-lethal dose(MNLD),and 10 percent lethal dose(LD10)were calculated.The incidence of venous sinus congestion,pericardial edema,slowing heart rate and blood flow of zebrafish in the 0.50 and 2.00 mg·kg-1 groups were observed and calculated by somatoscopic microscopy at 4 h after drug administration.Zebrafish larvae were iv given DAS at doses of 0.041,0.136,0.412,and 0.452 mg·kg-1 while the malformation phenotypes of zebrafish larvae development were observed under a stereomicroscope for 3 consecutive days,including pericardial edema,abnormal heart rate,slow blood flow,loss of circulation,eye abnormalities,brain malforma-tions,jaw abnormalities,loss/degeneration of the liver,delayed yolk sac absorption,intestinal abnormal-ities,abnormal body coloration,body edema,curvature of the trunk/tail/nodal cord and muscle degener-ation before the incidence was calculated.②Zebrafish larvae were randomly divided into a normal control group and DAS aqueous solution exposure groups at concentrations of 2.5,5.0,10.0,25.0,50.0,75.0,and 100.0 mg·L-1,observed for 3 d until the mortality rate,LD10,and MNLD were calculated.Zebrafish were exposed to DAS aqueous solutions at concentrations of 0.32,1.06,3.20,and 11.00 mg·L-1,and the malformation phenotypes of zebrafish larvae development were observed under a stereomicro-scope for 3 consecutive days to calculate the incidence.RESULTS ① The MNLD and LD10 of DAS iv administered to zebrafish larvae were 0.412 and 0.452 mg·kg-1,respectively.Compared with the solvent control group,4 h after DAS iv administration,the incidence of sinus congestion,slow heart rate and pericardial edema in the 0.50 and 2.00 mg·kg-1 groups significantly increased(P<0.05,P<0.01),so was the incidence of slow blood flow in the 2.00 mg·kg-1 group(P<0.01).The rate of delayed yolk sac absorption was significantly increased in the 0.041,0.136,0.412,and 0.452 mg·kg-1 groups(P<0.05,P<0.01),so was the mortality rate in the 0.452 mg·kg-1 group(P<0.05),with pericardial edema observed in the dead zebrafish.② The MNLD and LD10 of DAS aqueous solution exposure for zebrafish larvae were 3.20 and 11.00 mg·L-1,respectively.Compared with the normal control group,the incidence of decreased heart rate and slow blood flow was significantly increased in the 3.20 and 11.00 mg·L-1 groups(P<0.01),so was the incidence of significantly darkened intestines in the 1.06,3.20,and 11.00 mg·L-1 groups(P<0.01).The incidence of delayed yolk sac absorption was significantly increased in the 0.32,1.06,3.20,and 11.00 mg·L-1 groups(P<0.05,P<0.01),so was the incidence of trunk curvature and lower jaw malformation in the 11.00 mg·L-1 group(P<0.01).CONCLUSION The toxic phenotypes of DAS are different between iv administration and aqueous solution exposure in zebrafish larvae.DAS aqueous solution exposure can not only lead to slow heart rate,slow blood rheology,delayed yolk sac absorption and intestinal blackening,but also induce neurodevelopmental toxicity.However,iv adminis-tration can effectively ward off significant gastrointestinal damage and neurodevelopmental toxicity.

Objective:To evaluate the efficacy and safety of oral semaglutide versus sitagliptin in Chinese patients with type 2 diabetes mellitus(T2DM) inadequately controlled with metformin. Methods:The PIONEER 12 study was a phase Ⅲ clinical trial. Chinese patients were prospectively randomized to oral semaglutide(3mg, 7 mg, and 14 mg) or sitagliptin 100 mg. The primary endpoint was the change in HbA 1C from baseline to week 26, and the confirmatory secondary efficacy endpoint was the change in body weight from baseline to week 26. Results:Totally 1 084 Chinese participants(mean age 53 years, male 62.2%, mean duration of diabetes 5.5 years, HbA 1C 8.2%, and body weight 74.3 kg) were enrolled. The changes in HbA 1C at week 26 from baseline were -0.9%, -1.4%, and -1.6% for oral semaglutide 3 mg, 7 mg, and 14 mg, respectively, and -0.7% for sitagliptin. Compared to sitagliptin, oral semaglutide 3 mg, 7 mg, and 14 mg significantly reduced HbA 1C [estimated treatment difference(ETD), -0.2%(95% CI -0.4--0.0), -0.8%(95% CI -0.9--0.6), and -0.9%(95% CI -1.1--0.8), respectively; 3 mg, P=0.011, 7 mg and 14mg, P<0.001]. The estimated mean changes in body weight at week 26 from baseline were -1.1 kg, -2.5 kg, and -3.4 kg for oral semaglutide 3 mg, 7 mg, and 14 mg, respectively, and -0.4 kg for sitagliptin 100 mg. Compared with sitagliptin, oral semaglutide 3 mg, 7 mg, and 14 mg significantly reduced body weight [ETD, -0.8 kg(95% CI -1.3--0.2), -2.1 kg(95% CI -2.6--1.6), and -3.0 kg(95% CI -3.5--2.5), respectively; 3 mg, P=0.004, 7 mg and 14 mg, P<0.001]. The overall incidence of adverse events was similar across all treatment groups. The most common adverse events were gastrointestinal disorders, mostly mild or moderate in severity and transient in duration. Conclusions:Oral semaglutide resulted in significantly greater reduction in HbA 1C and body weight versus sitagliptin at week 26, with a favorable safety and tolerability profile in Chinese T2DM patients inadequately controlled with metformin.

Extracellular vesicles (EV) are highly heterogeneous nanoscale vesicles secreted by cells. They carry various bioactive molecules derived from the parent cells. EV are widely distributed in various body fluids, showing enormous potential in liquid biopsy and disease treatment. However, conventional flow cytometers face challenges in detecting single EV with a diameter smaller than 300 nm. The nano-flow cytometry (nFCM) developed based on Raleigh scattering and sheath-flow single-molecule fluorescence detection has successfully pushed the detection limit of EV to 40 nm. Through multi-parameter detection at the single-particle level, nFCM enables simultaneous analysis of particle size, particle concentration, and multiple biochemical properties of individual EV. nFCM can be applied to clinical diagnosis and therapeutics based on EV.

Purpose To preliminarily establish a predictive model for assessing preterm birth in the first trimester via clinical history and multiple ultrasound parameters.Materials and Methods This study included 200 women in the first trimester of pregnancy from 6 to 8 weeks in the Affiliated Renhe Hospital of Three Gorges University from September 2020 to September 2021,and their clinical history,two-dimensional imaging data and cervical elastography data were collected.Logistic regression analysis,screening and assignment were performed to initially establish a clinical prediction model for evaluating preterm birth during the first trimester.Results Finally,41 pregnant women developed preterm birth(preterm birth group),and 159 pregnant women did not develop preterm birth(term group).History of miscarriage,history of preterm birth,uterocervical angle(UCA),A,and A1 were the independent risk factors for preterm birth via univariate analysis,and multivariate analysis was carried out to obtain the formula:Logit(P)=1.495×abortion history+1.060×A1+0.795×UCA+1.354×A-14.951,which had a good fit via Hosmer-Lemeshow goodness-of-fit test,and the diagnostic efficiency was 96.9%.Conclusion The early pregnancy prediction model can effectively predict the occurrence of preterm birth in pregnant women with singleton pregnancy.

Objective: To investigate the status of hair loss and analyze the influencing factors among university students in Hangzhou City, so as to provide insights into the management of hair loss among university students. Methods: University students were recruited using a convenient sampling method from 4 universities in Hangzhou City in June 2021. The basic characteristics and life styles were collected using online questionnaire surveys. Self-reported hair loss was evaluated using the grading scales for loss of hair (Hamilton-Norwood scale for males and modified Ludwig scale for females), and factors affecting self-reported hair loss were identified among university students using the multivariable logistic regression model. Results: A total of 1 060 questionnaires were allocated, and 1 038 valid questionnaires were recovered, with an effective recovery rate of 97.92%. The respondents included 391 males ( 37.67% ) and 647 females ( 62.33% ), and 463 respondents ( 44.61% ) reported hair loss, including 431 students with mild hair loss ( 93.09% ). Multivariable logistic regression analysis showed that university students in their fourth or fifth years ( OR=1.721, 95%CI: 1.126-2.630 ), art specialty ( OR=0.411, 95%CI: 0.207-0.816 ), overweight or obesity (OR=1.685, 95%CI: 1.050-2.704), diet taste ( sweet: OR=2.131, 95%CI: 1.370-3.316; spicy: OR=1.510, 95%CI: 1.028-2.218; greasy: OR=3.023, 95%CI: 2.015-4.537 ), feeling nervous/anxious (occasionally: OR=1.891, 95%CI: 1.087-3.289; frequently: OR=2.487, 95%CI: 1.337-4.626 ), smoking ( occasionally: OR=1.906, 95%CI: 1.067-3.405; frequently: OR=1.983, 95%CI: 1.050-3.746), family history of hair loss ( OR=1.506, 95%CI: 1.075-2.110 ), perming/dyeing hair ( occasionally: OR=1.795, 95%CI: 1.280-2.517; frequently: OR=3.282, 95%CI: 1.736-6.204), self-perceived oily hair/scalp in the past three months (slightly increased: OR=1.980, 95%CI: 1.477-2.653; significantly increased: OR=5.347, 95%CI: 2.956-9.670) were factors affecting self-reported hair loss among university students. Conclusion The proportion of self-reported hair loss was 44.61% among university students in Hangzhou City, and hair loss was predominantly mild. A family history of hair loss, nervousness/anxiety, diet habits, smoking and frequency of perm/dyeing hair may affect hair loss among university students.

Objective     To explore the role of versican (VCAN) in ESCC prognosis based on bioinformatics data. Methods    First, three RNA microarray datasets of ESCC were downloaded from GEO database, which were then integrated and used to explore differentially expressed genes (DEGs). The subsequent analysis was conducted based on the results of these DEGs: (1) The STRING database was used to construct a protein-protein interaction (PPI) network;(2) molecular complex detection software was used to analyze the modules of the PPI network, of which the most significant modules were chosen, and hub genes were the genes included in the chosen modules; (3) high-throughput RNA sequencing data from TCGA and GTEx databases were used to verify the expression of these hub genes to confirm whether they were differentially expressed; (4) the survival curve analysis of confirmed DEGs was conducted to select genes that had significant influence on the survival of ESCC; (5) TIMER database was used to analyze the relationship between the gene expression of VCAN and the abundance of tumor-infiltrating immune cells (TIICs) and gene markers in these cells; (6) Targetscan and miRDB software were used to predict the miRNAs that could regulate VCAN, and Cytoscape software was used to construct the regulatory network. Results    A total of 630 DEGs and 32 hub genes were found, of which VCAN was an up-regulated DEG, and high expression of VCAN was significantly associated with poor prognosis of ESCC. Moreover, VCAN could also play a role in the immune microenvironment of ESCC, which was mainly manifested by a significant positive correlation between the abundance of VCAN and the abundance of M2 macrophages gene markers, some of which had been reported to be associated with poor prognosis of ESCC. Finally, we also found that VCAN could be regulated by 15 miRNAs in ESCC, some of which had been reported to be associated with ESCC prognosis. Conclusion    This study provides direct and indirect comprehensive evidence for the role of VCAN in ESCC prognosis. The direct evidence is that the survival curve shows that highly expressed VCAN is significantly associated with the poor prognosis of ESCC, and the indirect evidence is that VCAN is positively related to some markers which indicate poor prognosis in the ESCC immune microenvironment, and VCAN can be regulated by some prognostic miRNAs in ESCC.

Background: Antimicrobial peptides (AMPs) have been identified as promising compounds for consideration as novel antimicrobial agents. Objectives: This study analyzed the efficacy of cecropin B against Haemophilus parasuis isolates through scanning electron microscopy (SEM) and atomic force microscopy (AFM) experiments. Results: Cecropin B exhibited broad inhibition activity against 15 standard Haemophilus parasuis (HPS) strains and 5 of the clinical isolates had minimum inhibition concentrations (MICs) ranging from 2 to 16 μg/mL. Microelectrophoresis and hexadecane adsorption assays indicated that the more hydrophobic and the higher the isoelectric point (IEP) of the strain, the more sensitive it was to cecropin B. Through SEM, multiple blisters of various shapes and dents on the cell surface were observed. Protrusions and leakage were detected by AFM. Conclusions Based on the results, cecropin B could inhibit HPS via a pore-forming mechanism by interacting with the cytoplasmic membrane of bacteria. Moreover, as cecropin B concentration increased, the bacteria membrane was more seriously damaged. Thus, cecropin B could be developed as an effective anti-HPS agent for use in clinical applications.

Background: Antimicrobial peptides (AMPs) have been identified as promising compounds for consideration as novel antimicrobial agents. Objectives: This study analyzed the efficacy of cecropin B against Haemophilus parasuis isolates through scanning electron microscopy (SEM) and atomic force microscopy (AFM) experiments. Results: Cecropin B exhibited broad inhibition activity against 15 standard Haemophilus parasuis (HPS) strains and 5 of the clinical isolates had minimum inhibition concentrations (MICs) ranging from 2 to 16 μg/mL. Microelectrophoresis and hexadecane adsorption assays indicated that the more hydrophobic and the higher the isoelectric point (IEP) of the strain, the more sensitive it was to cecropin B. Through SEM, multiple blisters of various shapes and dents on the cell surface were observed. Protrusions and leakage were detected by AFM. Conclusions Based on the results, cecropin B could inhibit HPS via a pore-forming mechanism by interacting with the cytoplasmic membrane of bacteria. Moreover, as cecropin B concentration increased, the bacteria membrane was more seriously damaged. Thus, cecropin B could be developed as an effective anti-HPS agent for use in clinical applications.