Objective To evaluate the efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors combined with high-intensity statins in the treatment of hypercholesterolemia. Methods A retrospective study was conducted on patients diagnosed with hypercholesterolemia at the First Affiliated Hospital of Zhengzhou University from June 2023 to December 2024. Patients were divided into an observation group (receiving alirocumab combined with atorvastatin) and a control group (receiving atorvastatin alone) based on their actual treatment regimens. The treatment period was 6 months. Primary outcome measures included lipid parameters such as low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), and lipoprotein (a), (Lp[a]); carotid ultrasound parameters such as intima-media thickness (IMT), plaque number, plaque area; and inflammatory markers including high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). Adverse reactions were also recorded. Results A total of 103 patients with hypercholesterolemia were included, with 53 in the observation group and 50 in the control group. After six months of treatment, the observation group demonstrated significantly greater reductions in LDL-C, total cholesterol (TC), triglyceride (TG), and apoB compared to the control group (P ＜ 0.05). The reduction in plaque count and plaque area were also significantly greater in the observation group than in the control group (P＝0.004). The reduction in TNF-α was also greater in the observation group (P＝0.006). There was no statistically significant difference in the incidence of adverse reactions between the two groups. Conclusions PCSK9 inhibitors combined with high-intensity statins can effectively reduce LDL-C levels, improve carotid atherosclerotic plaques and systemic inflammatory status in patients with hypercholesterolemia, and demonstrate good safety in real-world clinical settings.

Objective:To investigate the role of autophagy in the regulatory of phagocytosis in Vibrio vulnificus ( V. vulnificus)-infected murine macrophages. Methods:The expression of cellular autophagy-related proteins in PBS-treated and V. vulnificus-infected RAW264.7 and BMMφ cells was detected by Western blot. The co-localization of V. vulnificus-GFP and LC3Ⅱ protein in V. vulnificus-GFP-infected RAW264.7 and BMMφ cells were detected using confocal microscopy. The phagocytosis of V. vulnificus in V. vulnificus-GFP-infected RAW264.7 and BMMφ cells with or without autophagy inhibition using Bafilomycin A1 was detected by flow cytometry. Results:The up-regulated levels of Atg7, Atg12 and Atg16L1 proteins, increased LC3Ⅱ/actin ratio, as well as down-regulated p62 protein levels were significantly detected in V. vulnificus-infected RAW264.7 and BMMφ cells. The co-localization of V. vulnificus-GFP and LC3Ⅱ protein was clearly observed in V. vulnificus-GFP-infected RAW264.7 and BMMφ cells. Enhanced phagocytosis of V. vulnificus and increased autophagy were exhibited in V. vulnificus-GFP-infected RAW264.7 and BMMφ cells, while weakened phagocytosis, accumulation of Atg7, Atg12, Atg16L1, LC3Ⅱ and p62 protein levels, as well as blocking autophagy flux were detected in those cells within autophagy inhibition using Bafilomycin A1. Conclusion:Autophagy induced by V. vulnificus infection could promote phagocytosis of V. vulnificus in macrophages.

Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.

Objective To observe the clinical efficacy of electroacupuncture manipulation combined with massage therapy in the treatment of knee osteoarthritis,and to analyze the efficacy-value.Methods A total of 118 patients with knee osteoarthritis admitted to Kuitun Traditional Chinese Medicine Hospital of Xinjiang Production and Construction Corps from January 2023 to January 2024 were selected as research subjects and divided into electroacupuncture manipulation and massage group(n=60)and sodium hyaluronate group(n=58)by random number table methood.Electroacupuncture manipulation and massage group was treated 3 times a week for 3 weeks.Sodium hyaluronate group was injected with sodium hyaluronate injection in the joint cavity once a week for 3 weeks.Knee function scores and effective rate of two groups before and after treatment were observed,and the differences between two treatments were compared by using the health economics evaluation method.Results After comparing the patients before and after treatment,the knee function scores improved.There was significant difference of knee function scores after treatment between two groups(P＜0.05).There were significant difference of response rate and the incidence of adverse effects between two groups(P＜0.05).Sodium hyaluronate group had a better clinical efficacy-value than electroacupuncture manipulation and massage group.Conclusion Electroacupuncture manipulation and massage and sodium hyaluronate intra-articular injection can effectively improve joint pain and joint function in patients,and intra-articular injection of sodium hyaluronate has a higher incidence of adverse reactions.

Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.

Objective To observe the clinical efficacy of electroacupuncture manipulation combined with massage therapy in the treatment of knee osteoarthritis,and to analyze the efficacy-value.Methods A total of 118 patients with knee osteoarthritis admitted to Kuitun Traditional Chinese Medicine Hospital of Xinjiang Production and Construction Corps from January 2023 to January 2024 were selected as research subjects and divided into electroacupuncture manipulation and massage group(n=60)and sodium hyaluronate group(n=58)by random number table methood.Electroacupuncture manipulation and massage group was treated 3 times a week for 3 weeks.Sodium hyaluronate group was injected with sodium hyaluronate injection in the joint cavity once a week for 3 weeks.Knee function scores and effective rate of two groups before and after treatment were observed,and the differences between two treatments were compared by using the health economics evaluation method.Results After comparing the patients before and after treatment,the knee function scores improved.There was significant difference of knee function scores after treatment between two groups(P＜0.05).There were significant difference of response rate and the incidence of adverse effects between two groups(P＜0.05).Sodium hyaluronate group had a better clinical efficacy-value than electroacupuncture manipulation and massage group.Conclusion Electroacupuncture manipulation and massage and sodium hyaluronate intra-articular injection can effectively improve joint pain and joint function in patients,and intra-articular injection of sodium hyaluronate has a higher incidence of adverse reactions.

Objective:To investigate the role of autophagy in the regulatory of phagocytosis in Vibrio vulnificus ( V. vulnificus)-infected murine macrophages. Methods:The expression of cellular autophagy-related proteins in PBS-treated and V. vulnificus-infected RAW264.7 and BMMφ cells was detected by Western blot. The co-localization of V. vulnificus-GFP and LC3Ⅱ protein in V. vulnificus-GFP-infected RAW264.7 and BMMφ cells were detected using confocal microscopy. The phagocytosis of V. vulnificus in V. vulnificus-GFP-infected RAW264.7 and BMMφ cells with or without autophagy inhibition using Bafilomycin A1 was detected by flow cytometry. Results:The up-regulated levels of Atg7, Atg12 and Atg16L1 proteins, increased LC3Ⅱ/actin ratio, as well as down-regulated p62 protein levels were significantly detected in V. vulnificus-infected RAW264.7 and BMMφ cells. The co-localization of V. vulnificus-GFP and LC3Ⅱ protein was clearly observed in V. vulnificus-GFP-infected RAW264.7 and BMMφ cells. Enhanced phagocytosis of V. vulnificus and increased autophagy were exhibited in V. vulnificus-GFP-infected RAW264.7 and BMMφ cells, while weakened phagocytosis, accumulation of Atg7, Atg12, Atg16L1, LC3Ⅱ and p62 protein levels, as well as blocking autophagy flux were detected in those cells within autophagy inhibition using Bafilomycin A1. Conclusion:Autophagy induced by V. vulnificus infection could promote phagocytosis of V. vulnificus in macrophages.

ObjectiveTo explore the characteristics and major factors influencing mental health literacy (MHL) among non-graduating middle school and high school students in Taizhou, Zhejiang Province, and to provide a reference for the promotion of mental health literacy among adolescents. MethodsFrom September to October 2023, a stratified random cluster sampling method was used to conduct a questionnaire survey among students from three classes each in non-graduating grades in four middle schools and four high schools in Taizhou, Zhejiang Province. The survey included basic demographic information, a Structured Mental Health Literacy Questionnaire (MHLQ), and other psychological scales [Educational Stress Scale for Adolescents (ESSA), Perceived Choice Single Scale (PC), Child Depression Inventory (CDI), Generalized Anxiety Disorder (GAD), The University of California at Los Angeles 3-item Loneliness Scale (UCLA-3) and Multidimensional Scale of Perceived Social Support (MSPSS)]. t-tests, chi-square tests, analysis of variance (ANOVA), and multiple linear regressions were applied for the statistical analysis of the data. ResultsThe mental health literacy average score of 2 094 students was (82.3±15.8) points, with a mean of (4.1±0.8) points. The dimension of belief in mental health rights had the highest score. There were significant differences in the mental health literacy score across different dimensions for students with different household registration, economic levels, academic performance, and father’s education level (P<0.001). Multiple linear regression analysis indicated that rural household registration, lower paternal education level, greater academic pressure, a weaker sense of control over one’s behavior, less social support, and symptoms of loneliness, depression, or anxiety were associated with poorer mental health literacy among the students. ConclusionThe mental health literacy of middle school and high school students in Taizhou is generally good, but there are differences among students with different characteristics. Targeted interventions should be carried out for students from rural areas, with poorer mental health, and less low social support to improve the overall mental health literacy of adolescents.

Artemisia argyi (A. argyi), a plant with a longstanding history as a raw material for traditional medicine and functional diets in Asia, has been used traditionally to bathe and soak feet for its disinfectant and itch-relieving properties. Despite its widespread use, scientific evidence validating the antifungal efficacy of A. argyi water extract (AAWE) against dermatophytes, particularly Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum, remains limited. This study aimed to substantiate the scientific basis of the folkloric use of A. argyi by evaluating the antifungal effects and the underlying molecular mechanisms of its active subfraction against dermatophytes. The results indicated that AAWE exhibited excellent antifungal effects against the three aforementioned dermatophyte species. The subfraction AAWE6, isolated using D101 macroporous resin, emerged as the most potent subfraction. The minimum inhibitory concentrations (MICs) of AAWE6 against T. rubrum, M. gypseum, and T. mentagrophytes were 312.5, 312.5, and 625 μg·mL^-1, respectively. Transmission electron microscopy (TEM) results and assays of enzymes linked to cell wall integrity and cell membrane function indicated that AAWE6 could penetrate the external protective barrier of T. rubrum, creating breaches ("small holes"), and disrupt the internal mitochondrial structure ("granary"). Furthermore, transcriptome data, quantitative real-time PCR (RT-qPCR), and biochemical assays corroborated the severe disruption of mitochondrial function, evidenced by inhibited tricarboxylic acid (TCA) cycle and energy metabolism. Additionally, chemical characterization and molecular docking analyses identified flavonoids, primarily eupatilin (131.16 ± 4.52 mg·g^-1) and jaceosidin (4.17 ± 0.18 mg·g^-1), as the active components of AAWE6. In conclusion, the subfraction AAWE6 from A. argyi exerts antifungal effects against dermatophytes by disrupting mitochondrial morphology and function. This research validates the traditional use of A. argyi and provides scientific support for its anti-dermatophytic applications, as recognized in the Chinese patent (No. ZL202111161301.9).
Antifungal Agents/chemistry* ; Arthrodermataceae ; Artemisia/chemistry* ; Molecular Docking Simulation ; Mitochondria ; Microbial Sensitivity Tests

ObjectiveTo understand the usage of antibiotics in outpatients in a county of Zhejiang Province from 2015 to 2020， so as to provide a basis for further standardizing the clinical application of antibiotics in this region. MethodsOutpatient records and prescription records of 146 public medical institutions from 2015 to 2020 were extracted from the electronic medical record data sharing platform system of medical institutions in a county of Zhejiang Province. The utilization rates and the number of types of antibiotics used in outpatient patients were described. According to the drug anatomy， therapeutic and chemical classification system （ATC）， clinical application classification and dosage form， the use status of different types of antibiotics was observed. The annual percentage change （APC） was used to analyze the time trend of antibiotic use. Among the antibiotic prescriptions in each year， the proportions of prescriptions aimed for different use reasons and patients were compared to analyze the changes in the structures of antibiotic prescriptions. ResultsDuring 2015‒2020， a total of 2 861 438 prescriptions were issued in146 primary public medical institutions in this county， including 314 642 prescriptions for antibiotics， and the overall utilization rate of antibiotics was 11%. The utilization rate of antibiotics showed a decreased trend across the years （from 14.23% in 2015 to 7.59% in 2020，APC=-11.51%， 95%CI=-0.01%‒-21.7%， t=-12.05， P<0.001） and an obvious seasonal variation character （higher in winter and spring， lower in summer and autumn）. Cefoxitin sodium for injection was the most used antibiotic in 2015， and cefuroxime was the most used antibiotic from 2015 to 2020， respectively. The utilization rates of cephalosporins （APC=-11.06%， 95%CI=0‒-20.89%， t=-22.233， P<0.001）， quinolones （APC=-9.74%， 95%CI=0‒-18.53%， t=-7.652， P=0.002）， macrolides （APC=-17.52%， 95%CI=0‒-17.52%， t=-3.626， P=0.022） and lincoamides （APC=-49.01%， 95%CI=0‒-74%， t=-3.35， P=0.029） showed a decreasing trend across the years. There were differences in the distribution of drug use reasons （χ²=9 458.427， P<0.001）， as well as the age （χ²=5 421.709， P<0.001） and sex （χ²=245.322， P<0.001） of patients. During the observation period， 50.69% of antibiotic prescriptions were used to treat respiratory diseases， with the highest proportion of 57.67% in 2015 and the lowest proportion of 34.93% in 2020. 58.37% of patients were aged 50‒70 years， with a decreasing proportion of patients under 50 years （17.83% in 2015， 6.64% in 2020） and an increasing proportion of patients over 70 years （24.1% in 2015， 38.41% in 2020）. ConclusionThe utilization rate of antibiotics used in outpatients from primary public medical institutions in a county of Zhejiang Province shows a decreasing trend across the years， but higher than that of secondary and above hospitals in China， and also higher than that of primary medical institutions in economically-developed areas. The management and monitoring of the clinical use of antibiotics in the county should be actively strengthened.