As the number of patients with compromised immune function increases and fungal resistance develops, so does the risk of contracting deadly fungi in humans. Both fungi and humans are eukaryotes, so identifying unique targets for antifungal drug development is difficult. In addition, the existing antifungal drugs are limited by toxicity, drug interaction and drug resistance in practical application, which leads to the increasing incidence and fatal rate of fungal infections. Therefore, it is urgent to develop new antifungal drugs. The semi-synthetic technology using microbial fermentation products from natural sources as lead compounds has become the most used method in structural modification of antifungal drugs due to its advantages of few reaction steps and easy operation. This paper will introduce the current status of natural antifungal drugs in clinical use, as well as the latest progress in the research and development of new semi-synthetic antifungal drugs, and summarize their mechanism of action, structural modifications, advantages and disadvantages, so as to provide reference for the subsequent development of new antifungal drugs.

Objective To analyze the prevalence status of cardiometabolic risk factor (CMRF) and its aggregation among workers engaged in new forms of employment. Methods A total of 5 429 new employment workers (including couriers, online food delivery workers, and ride hailing drivers) who underwent health medical examinations at a tertiary hospital in Beijing City were selected as the research subjects using the judgment sampling method. Data on waist circumference, blood pressure, blood glucose, and blood lipid levels were collected to analyze their CMRF [central obesity, elevated blood pressure, elevated blood glucose, elevated triglycerides, and reduced high-density lipoprotein cholesterol (HDL-C)] and their aggregation (with ≥ 2 of the above 5 risk factors) status. Results The detection rates of central obesity, elevated blood pressure, elevated blood glucose, elevated triglycerides, and reduced HDL-C were 61.2%, 38.2%, 29.5%, 40.9% and 22.6%, respectively. The detection rates of CMRF aggregation was 57.8%. The result of multivariable logistic regression analysis showed that male, age ≥45 years, smoking, overweight, and obesity were risk factors for CMRF aggregation (all P<0.05). Conclusion The detection rate of CMRF and its aggregation among workers with new forms of employment in Beijing City is relatively high. Targeted prevention and control efforts should be strengthened for high-risk populations, especially males, workers aged ≥45 years, smokers, and those who are overweight or obese.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

Objective To observe the effects of abdominal penetrating moxibustion combined with acupuncture at the"four chong points"on balance,walking function and trunk control in patients recovering from stroke.Methods Seventy-eight patients recovering from stroke were randomly divided into an observation group and a control group,with 39 patients in each group.The control group was given conventional rehabilitation exercises,while the observation group was given abdominal penetrating moxibustion combined with acupuncture at the"four chong points"on the basis of the control group.Both groups were treated for 2 consecutive months.After 2 months of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the Berg Scale score and the Timed Up and Go Test(TUGT)were observed before and after treatment.The changes in the National Institutes of Health Stroke Scale(NIHSS)scores were compared before and after treatment between the two groups.The Sheikh Trunk Control Scale scores were also evaluated.Results(1)The total effective rate of the observation group was 94.87%(37/39),and the total effective rate of the control group was 80.00%(31/39),and the efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the Berg scores of the patients in the two groups were significantly increased(P＜0.05),and the Berg scores of the observation group were higher than those of the control group,and the difference was statistically significant(P＜0.05).(3)After treatment,the TUGT time and NIHSS score of patients in the two groups were significantly improved(P＜0.05),and the TUGT time of the observation group was shorter than that of the control group,and the NIHSS score was lower than that of the control group,and the difference was statistically significant(P＜0.05).(4)After treatment,the Sheikh trunk control scores of the two groups were significantly increased(P＜0.05),and the Sheikh trunk control score of the observation group was higher than that of the control group,and the difference was statistically significant(P＜0.05).Conclusion Abdominal penetrating moxibustion method combined with acupuncture at the four chong points for the treatment of stroke recovery can effectively restore the patients'balance and walking function,improve the patients'trunk control ability,and the therapeutic effect is precise.

Objective:To investigate the impact of daily step count on glycemic outcomes in community residents with impaired glucose tolerance (IGT).Methods:This was a prospective cohort study, in October 2018, 204 residents who met the criteria of IGT were recruited in the Shijingshan District in Beijing. The subjects were tested for fasting blood glucose, oral glucose tolerance test 2-hour blood glucose (2hBG), glycated hemoglobin A 1c (HbA 1c), lipid profile, liver and kidney function, as well as measurements of height, weight and waist circumference. A dedicated mobile application was used to deliver prediabetes health knowledge monthly. Online guidance was provided to answer questions and daily step count was collected using the application. Three years later, a follow-up was conducted to assess the participants′ glycemic outcomes and other indexes, and a total of 142 participants completed the follow-up review. According to daily step count, the subjects were categorized into high step count group (42 cases,>7 000 steps daily), moderate step count group (54 cases, 5 000-7 000 steps daily), and low step count group (46 cases,<5 000 steps daily). Subjects were categorized into diabetes group (30 cases), prediabetes group (77 cases) and normal glucose tolerance group (35 cases) with glycemic outcomes. Independent sample t test was used to compare the differences in blood glucose, blood lipids, and step counts between the two groups. Kruskal-Wallis H test or one-way ANOVA was used to compare the differences in blood glucose, blood lipids, and step counts between multiple groups. The χ2 test was used to compare the differences in glycemic outcomes between multiple groups. Multivariate logistic regression analysis was used to assess the impact of daily step counts and body mass index on glycemic outcomes. Linear regression analysis was used to evaluate the relationship between daily step counts and 2 h BG. Results:A total of 142 participants completed the 3-year follow-up, including 43 males and 99 females, with a mean age of (60.15±5.67) years. At baseline, males had significantly higher body mass index, waist circumference, and fasting blood glucose when compared to those in females [(26.97±2.43) vs (24.89±2.93) kg/m 2, (92.68±7.75) vs (83.83±8.60) cm, (5.83±0.61) vs (5.62±0.52) mmol/L], the total cholesterol and HDL-C were also significantly lower in males than those in females [(5.10±1.16) vs (5.55±0.95) mmol/L, (1.35±0.34) vs (1.56±0.35) mmol/L] (all P<0.05). After 3-year follow-up, 21.1% (30/142) of IGT participants progressed to diabetes, with an annual conversion rate of approximately 7%. The normal glucose tolerance group showed significantly higher daily step counts when compared with the prediabetes and diabetes groups [(7 886±2 867) vs (5 981±2 655) vs (4 117±2 674) steps] ( H=31.778, P<0.001). Individuals with higher daily step counts exhibited lower body mass index, 2 h BG, and HbA 1c level when compared with those in the ones with moderate and low step counts [(24.26±3.09) vs (25.44±3.38) vs (26.26±3.59) kg/m 2, (7.50±1.71) vs (9.15±3.30) vs (11.19±3.84) mmol/L, 5.97%±0.46% vs 6.14%±0.99% vs 6.40%±0.96%] (all P<0.05). Higher step count was positively correlated with the reversal of prediabetes to normal blood glucose levels (moderate step count, OR=0.297, 95% CI: 0.109-0.804; low step count, OR=0.055, 95% CI: 0.010-0.287), lower daily step count correlated positively with prediabetes progressing to diabetes ( OR=4.857, 95% CI: 1.140-20.689) (all P<0.05). For every additional 1 000 steps per day, the 2 h BG decreased by 0.5 mmol/L. Conclusion:As daily step count increases, the glucose metabolism improves in IGT community residents. Higher daily step count is associated with reversal of IGT to normal glucose tolerance, while lower daily step count may be associated with the progression of IGT to diabetes.

AIM To explore the laws in accumulation of dry matter and medicinal ingredients of Isatis indigotica Fort.in Longdong area,and determine the best harvest time to obtain the high-quality and high-yield medicinal plant.METHODS The I.indigotica had its agronomic traits investigated regularly;the accumulation laws of its uridine,guanosine,(R,S)-geichan and adenosine measured by HPLC;and its comprehensive utilization value in different periods evaluated by grey correlation method.RESULTS There existed significant variations among the plant height,plant width,leaf length,leaf width,number of leaves,leaf weight,root length,root diameter,root weight,and the yields of uridine,guanosine,(R,S)-goitrin and adenosine at different growth stages,whose peak values appeared in different period.Additionally,there were also obvious differences in the aforementioned indexes levels among different strains.The highest weighted correlation degree of the comprehensive utilization value of Longde and 2008-6-2 on October 9,and of 2008-11 and 2016-2 on October 24.On the whole,the 2008-6-2 and 2016-2 were superior to 2008-11 and Longde.CONCLUSION It is suggested that the best harvest time of I.indigotica in Longdong area is in mid to late October.

Objective To understand the respiratory protection competency of staff in hospitals.Methods Staff from six hospitals of different levels and characteristics in Beijing were selected,including doctors,nurses,medical technicians,and servicers,to conduct knowledge assessment on respiratory protection competency.According to exposure risks of respiratory infectious diseases,based on actual cases and daily work scenarios,content of respira-tory protection competency assessment was designed from three aspects:identification of respiratory infectious di-seases,transmission routes and corresponding protection requirements,as well as correct selection and use of masks.The assessment included 6,6,and 8 knowledge points respectively,with 20 knowledge points in total,all of which were choice questions.For multiple-choice questions,full marks,partial marks,and no mark were given respective-ly if all options were correct,partial options were correct and without incorrect options,and partial options were correct but with incorrect options.Difficulty and discrimination analyses on question of each knowledge point was conducted based on classical test theory.Results The respiratory protection competency knowledge assessment for 326 staff members at different risk levels in 6 hospitals showed that concerning the 20 knowledge points,more than 60％participants got full marks for 6 points,while the proportion of full marks for other questions was relatively low.Less than 10％participants got full marks for the following 5 knowledge points:types of airborne diseases,types of droplet-borne diseases,conventional measures for the prevention and control of healthcare-associated infec-tion with respiratory infectious diseases,indications for wearing respirators,and indications for wearing medical protective masks.Among the 20 knowledge questions,5,1,and 14 questions were relatively easy,medium,and difficult,respectively;6,1,4,and 9 questions were with discrimination levels of ≥0.4,0.30-0.39,0.20-0.29,and ≤0.19,respectively.Conclusion There is still much room for hospital staff to improve their respiratory protection competency,especially in the recognition of diseases with different transmission routes and the indications for wearing different types of masks.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To study the role of sphingosine-1-phosphate(S1P)signal on the proliferation of breast cancer BT549 cells.Methods Cells were divided into control group and experimental group,experimental group were treated with 0.1,1.0,10.0 μmol·L-1 S1P receptor agonist SEW2871 for 72 h.Control group was cultured with 0.1％fetal bovine serum.Cell proliferation was detected by methyl thiazolyl tetrazolium(MTT)assay.Cell models of overexpressing S1P receptors in BT549 were divided into three groups:blank plasmid group(LUC),wild type S1P receptor overexpression group(WT),S1P receptor phosphorylation site mutation overexpression group(MUT);the proliferation ratio was detected by MTT,the number of cell clones was counted by colony formation experiment.S1P antagonist W146(10 μmol·L-1)and protein kinase(AKT)signaling inhibitor MK2206(90 nmol·L-1)were used to detect the role of S1P signaling in the proliferation of breast cancer cells.The expression of phosphorylate signal transducer and activator of transcription 3(p-STAT3),c-Myc proteins were detected by Western blot.Results The growth ratio of BT549 cells in control group and 0.1,1.0,10.0 μmol·L-1experimental groups were 1.00±0.03,1.13±0.06,1.06±0.10 and 1.07±0.03,0.1 μmol·L-1 SEW2871 promot the cell proliferation(P＜0.05).Compared between WT group,MUT group and LUC group,the growth rate and the number of clonal colonies were increased after overexpression of S1P receptor(all P＜0.05).The growth ratio of BT549 cells after treatment with W146 and MK2206 in the LUC group,WT group and MUT group were 1.25±0.12,1.31±0.03,1.43±0.14 and 0.87±0.15,0.77±0.03,0.88±0.02.Compared between MUT group,WT group and corresponding DMSO group,the differences were statistically significant(all P＜0.01).The number of cell clony formation number after treatment with W146 were 65.65±5.12,141.48±5.63 and 93.64±5.14;compared between MUT,WT group and corresponding DMSO group,the differences were statistically significant(all P＜0.05).The relative protein expression levels of p-STAT3 in LUC group,WT group and MUT group were 0.67±0.04,0.69±0.08 and 0.81±0.06,the relative protein expression levels of proto-oncogene c-Myc were 1.69±0.03,0.70±0.10 and 0.67±0.07,compared between WT group,MUT group and corresponding DMSO group,the difference was statistically significant(P＜0.05).Conclusion S1P signaling can promote proliferation in breast cancer BT549 cells,and the mechanism could be related to AKT and STAT3 signaling pathway.

Objective To observe the effect and safety of clindamycin phosphate gel combined with photodynamic therapy in the treatment of acne rosacea.Methods Patients with acne rosacea were divided into treatment group and control group by random number table method.The control group was treated with external application of clindamycin phosphate gel twice a day for 4 weeks.The treatment group was given 5-aminolevulinic acid photodynamic therapy on this basis,once a week for 4 weeks.The clinical efficacy of the two groups was evaluated.The erythema,papulopustule,demodex folliculorum and quality of life[dermatology life quality index(DLQI)]of the two groups were compared after 2 weeks and 4 weeks of treatment.The recurrence status was followed up and the safety of the treatment regimen was evaluated.Results There were 70 cases in treatment group and 70 cases in control group.The total clinical effective rate after 4 weeks of treatment in treatment group was 87.14％,which was higher than 72.86％in control group(P＜0.05).After 2 weeks of treatment,the erythema scores in treatment group and control group were(2.14±0.57)and(2.63±0.52)points;the papulopustule scores were(2.28±0.46)and(2.56±0.49)points;the total counts of demodex folliculorum of(2 mm ×2 mm)were 10.12±3.55 and 11.74±4.31;DLQI scores were(11.27±2.49)and(12.57±2.28)points.After 4 weeks of treatment,the erythema scores in treatment group and control group were(1.16±0.32)and(1.59±0.38)points;the papulopustule scores were(0.92±0.27)and(1.37±0.41)points;the total counts of demodex folliculorum of(2 mm ×2 mm)were 6.08±2.39 and 8.69±2.47;and the DLQI scores were(5.09±1.22)and(6.88±2.16)points,all with significant difference(all P＜0.05).During treatment,there was no statistical significance in the incidence of adverse drug reactions between treatment group and control group(28.57％vs 18.57％,P＞0.05).Follow-up to 3 months after the end of treatment,the recurrence rates in treatment group and control group were 4.29％and 14.29％,with statistical difference(P＜0.05).Conclusion Clindamycin phosphate gel combined with photodynamic therapy has an exact efficacy in the treatment of acne rosacea,and it has obvious advantages in relieving symptoms,improving demodex folliculorum infection and enhancing quality of life of patients,and it does not increase the incidence of adverse drug reactions.