Objective To investigate the biological functions of the ERG3 gene in Candida albicans and its potential value in antifungal therapy. Methods The ERG3 null mutant was constructed by the CRISPR/Cas9 technology. Gas chromatography-mass spectrometry, microbroth dilution method, hyphal induction and mouse systemic infection models were carried out to evaluate sterol metabolism, drug susceptibility, hyphal formation ability and pathogenicity in C. albicans. Results The disruption of the ERG3 gene led to disordered sterol metabolism in C. albicans with a significant increased level of episterol, 14α-methylfecosterol and ergosta-7,22-dienol. The ERG3 null mutant exhibited significantly reduced susceptibility to antifungal azole and polyene drugs, which suggested that ERG3 involve in regulating drug resistance. Although the disruption of ERG3 inhibited hyphal growth and biofilm formation, it did not significantly alter the pathogenicity of the strain in a mouse model of systemic fungal infection. Conclusion The ERG3 gene was a key regulator in the ergosterol synthesis pathway in C. albicans. Its deletion induced multi-drug resistance by reshaping sterol metabolism, while pathogenicity maintenance depended on compensatory mechanisms. This study provided critical insights for developing antifungal drugs targeting sterol metabolism and overcoming drug resistance.

ObjectiveTo explore the possible mechanism of Chuanxiong （Rhizoma Chuanxiong） & Tianma （Rhizoma Gastrodiae） herbal pair in treating migraines based on AMP-activated protein kinase （AMPK）/transient receptor potential A1 channel （TRPA1） pathway. MethodsForty-eight healthy male SD rats were randomly divided into control group， model group， and Chuanxiong Tianma medication group， with 16 rats in each group. The control group and model group were given 10 ml/kg of normal saline by gavage， while the Chuanxiong Tianma medication group was given 0.675 g/kg of Chuanxiong Tianma herbal pair by gavage， once daily for 8 consecutive days in both groups. Migraime model was performed before the last administration， with subcutaneous injection of 10 ml/kg of normal saline in the control group， and subcutaneous injection of 10 ml/kg of nitroglycerin in the model group and Chuanxiong Tianma medication group. The Von Frey filament was used to measure the periorbital mechanical pain threshold of rats. The enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of calcitonin gene-related peptide （CGRP） in rat serum and cerebrospinal fluid. The nitric oxide （NO） assay kit was used to determine the NO level in serum and cerebrospinal fluid. RT-PCR was usedto detect the mRNA expression levels of immediate-early genes in the trigeminal ganglion of rats （c-Fos）， CGRP， transient receptor potential V1 channel （TRPV1）， AMPK alpha subunit （PRKAA）， and TRPA1. Immunofluorescence was used to detect the number of c-Fos-positive cells in the trigeminal cervical complex （TCC） and the protein expression levels of phosphorylated AMPK （pAMPK） and TRPA1 in the trigeminal ganglion. ResultsCompared to those in the control group， the mechanical stimulation threshold and pAMPK protein expression in the model group decreased， while the levels of CGRP and NO in serum， c-Fos， CGRP， TRPV1 and TRPA1 mRNA levels in the trigeminal ganglion， TRPA1 protein expression， and the number of c-Fos-positive cells in the TCC significantly increased （P＜0.05）. Compared to those in the model group， the mechanical stimulation threshold and pAMPK protein expression in the Chuanxiong Tianma medication group significantly increased， while the levels of CGRP and NO in serum， c-Fos， CGRP， TRPV1 and TRPA1 mRNA levels in the trigeminal ganglion， TRPA1 protein expression， and the number of c-Fos-positive cells in the TCC significantly decreased （P＜0.05）. ConclusionChuanxiong Tianma herbal pair may improve migraine symptoms by regulating the AMPK/TRPA1 pathway in the trigeminal ganglion and increasing the mechanical pain threshold.

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.

Objective To investigate the pathogenesis of superficial mycosis among naval trainees, and observe the efficacy of a novel antifungal drug. Methods A questionnaire survey was conducted on the onset, medication and recurrence of superficial fungal infection among the trainees from January, 2020 to July, 2020. At the same time, the new antifungal drug sulconazole nitrate spray was provided for treatment and the drug efficacy was observed. Results The participants generally lacked understanding and attention to superficial fungal infections. The incidence rate of superficial fungal infection was 52%, of which 76.2% of patients had recurrence of superficial fungal infection. The sulconazole nitrate spray showed great effect against these infections. Conclusion The trainees should understand the causes of superficial fungal infection through health education and seek medical treatment and medication in time. The cure rate of superficial fungal infections could only be improved through the collaborative management of the school, hospital, and trainees to reduce the impact of these infections on naval trainees’ work and life.

Objective To provide the reference resource for the safe clinical use of the compound of diphenhydramine hydrochloride and caffeine by observing its effects on the nervous system, cardiovascular system and respiratory system in experimental animals. Methods Single dose of the compound of diphenhydramine hydrochloride and caffeine was given to animals orally. The effects on climbing ability of mice and blood pressure, electrocardiogram, respiration rate and amplitude in beagle dogs were observed and recorded. Results With the dosage of the compound of diphenhydramine hydrochloride and caffeine (diphenhydramine hydrochloride / caffeine ratio is 1/2.4) at 51, 102, 204 mg/kg, there was no significant effect on the climbing ability in mice. With the dosages of 14.2, 28.3, 56.6 mg/kg for male Beagle dogs and 5.66, 14.2, 28.3 mg/kg for female Beagle dogs, no significant effects were observed in systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, ECG（P wave, R wave , T wave, QRS time, PR interval, QT interval）, respiratory rate and amplitude. Conclusion Under the experimental conditions, single oral dose of the compound of diphenhydramine hydrochloride and caffeine has no significant effect on the nervous system, cardiovascular system and respiratory system in experimental animals. Those results suggest that the compound of diphenhydramine hydrochloride and caffeine is a safe agent for clinical use.

Objective:To explore the predictive value of transvaginal ultrasound measurement of cervical length (CL) in the first and second trimester on spontaneous preterm birth in singleton pregnant women.Methods:This study retrospectively recruited 2 254 singleton pregnancies without severe comorbidities at Peking University First Hospital from January 2019 to June 2019. CL was measured for all subjects using transvaginal ultrasound in the first (11-13 +6 weeks) and second trimester (21-23 +6 weeks). Differences in CL between women with preterm (preterm group) and full-term delivery (full-term group) as well as the CL during the first and second trimester were compared. The independent risk factors for preterm birth and the predictive value of CL in the first and second trimester for spontaneous preterm birth were also explored. Fisher's exact test, t-test, χ2 test, and logistic regression analysis, etc, were adopted for statistical analysis. Results:(1) For the 2 254 subjects, CL measured in the first trimester and second trimester were (36.1±4.2) mm (22.4-52.6 mm) and (36.9±5.3) mm (2.9-59.7 mm), respectively. The incidence of short cervix in the first trimester and second trimester were 0.31% (7/2 254) and 1.46% (33/2 254), respectively. When CL was ≤25.0 mm ( OR=43.92, 95% CI:6.83-282.49) or >25.0-≤30.3 mm ( OR=6.59, 95% CI:1.97-22.0) in the first trimester, the risk of short cervix increased in the second trimester (both P<0.05). (2) The total incidence of preterm delivery was 3.06% (69/2 254). CL and the incidence of short cervix did not differ significantly in the first trimester between the preterm and full-term group [(35.2±4.5) and (36.1±4.1) mm, t=－1.78, P=0.076; 1.5% (1/69) and 0.3% (6/2 185), χ 2=2.98, P=0.084]. Compared with the full-term group, CL was shorter and the incidence of short cervix was higher in the second trimester in the preterm group [(33.6±6.7) vs (37.0±5.2) mm, t=－5.12;8.7% (6/69) vs 1.2% (27/2 185), χ 2=25.80, P<0.001]. (3) Multivariate regression analysis showed that age ≥35 years ( OR=2.05, 95% CI:1.22-3.46), history of spontaneous preterm birth ( OR=25.25, 95% CI:5.01-127.28), conception assisted by reproductive technology ( OR=10.39, 95% CI:2.39-50.33), and short cervix during the second trimester were independent risk factors for premature delivery. (4) There was no significant difference in the risk of preterm delivery when comparing to those with CL≤25.0 mm, >25.0-≤30.3 mm, >30.3-≤33.0 mm, >33.0-≤35.7 mm, >35.7-≤38.7 mm women with CL>38.7 mm during the first trimester (all P>0.05). The risk of premature delivery was relatively increased for those with CL≤25.0 mm,>25.0-≤29.5 mm, >29.5-≤33.6 mm, >33.6~≤36.8 mm, >36.8~≤40.1 mm during the second trimester compared to those with CL>40.1 mm [ OR (95% CI):17.64 (4.99-62.32), 6.89 (2.11-22.55), 3.58 (1.34-9.59), 4.04 (1.58-10.32), 3.34 (1.28-8.67), respectively , all P<0.05]. (5) When CL≤25.0 mm and ≤29.5 mm in the second trimester were used as the cut-off value, the prediction of preterm delivery was with a sensitivity of 8.70% and 17.39%, specificity of 98.80% and 95.29%, positive predictive value of 18.20% and 10.43%, negative predictive value of 97.16% and 97.34%, and the accuracy rate of 96.01% and 92.90%, respectively. Conclusions:There were no significant differences in CL and the incidence of short cervix during the first trimester among women with preterm or full-term delivery. CL in the first trimester is not an independent risk factor for preterm birth, but the risk of short cervix in the second trimester is increased when CL≤30.3 mm in the first trimester. The shorter the cervix during the second trimester, the greater the risk of preterm birth.

Objective To investigate the medication adherence of military academy students with superficial mycoses. Methods A 8-item Morisky medication adherence scale (MMAS) was modified into 7-item scale to evaluate the compliance of antifungal drugs in the sick students. The reliability and validity of the scale were analyzed. Results A total of 243 questionnaires were collected, of which 242 were valid questionnaires. 90.08% of the students took topical medication and 8.68% were treated both with topical and systematic combination. High, medium and low medication adherence rates as assessed by the modified MMAS were 9.09%, 23.97% and 66.94%, respectively. The reliability analysis showed that the internal consistency coefficient (Cronbach’s α ) was 0.781，and the adjusted Cronbach’s α was 0.790, indicating the high reliability of the scale. The KMO value was 0.798, and the Bartlett’s spherical test value was 440.866, P=0.000. One factor was extracted by exploratory factor analysis. The factor loadings of the items were all above 0.5. Therefore, the high convergent validity was good. Conclusion The modified MMAS has good reliability and validity and is applicable for the evaluation of medication compliance for superficial mycoses. In this study, the military students have a low level of medication adherence for superficial mycoses. Effective measures should be taken to help students strengthen their daily medication management and improve compliance.

Objective To investigate the effect from circumferential distribution angle of forwards wedge vortex generators on aerodynamic drag reduction during flow around a cylinder, so as to provide theoretical evidences for low drag sprint garment design. Methods Forwards wedge vortex generators were reconstructed based on the NIKE’s AeroBalde. Given that the individual parts of an athlete body can be treated as multiple cylinders with varied dimensions and positions, 48 forwards wedge vortex generators were distributed as four columns on windward side of the cylinder, which were symmetrical with the YOZ plane. When the air flowed through the cylinder at the speed of 32 km/h, large eddy simulation was carried out on the computational domains which were properly meshed with polyhedral mesh to investigate the drag force, flow filed and pressure distributions. Results It was effective for drag reduction of the cylinder induced by airflow when two columns of forwards wedge vortex generators were circumferential distributed in the range of 55°-75°and the circumferential internal angle between two columns was in the range of 10° or 15°. The pressure distribution on leeward side of the cylinder was apparently changed after surface modification, which minimized the pressure drag dominant in aerodynamic drag. The drag reduction mechanism was that micro-vortices were generated downstream after flow through the forwards wedge vortex generators, which resulted in an early transition to critical flow with low drag force. Conclusions Effective aerodynamic drag reduction is achieved if forwards wedge vortex generators are properly distributed. The research findings can provide guidance for wind tunnel test and low drag sprint garment design.