Pulmonary hypertension (PH) is a progressive and fatal disease. The dysfunction of pulmonary artery endothelial cells (PAECs) is one of its important pathogenic factors. PAECs are monolayer flat epithelial cells, which play an important role in maintaining pulmonary vascular homeostasis. Studies have found that PAECs show damage and apoptosis at the early stage of PH development, while PAECs show anti-apoptotic characteristics at the late stage of PH development. The transition of PAECs into mesenchymal cells induced by hypoxic and inflammatory factors is also involved in the pathogenesis of PH. Carcinoid metabolism and mitochondrial dysfunction, bone mor- phogenic type 2 receptor mutation, epigenetic changes and inflammation of PAECs are the main pathogenesis of pulmonary vascular endothelial dysfunction in PH patients. New therapeutic measures targeting PAECs dysfunction are expected to play an important role in the treatment of PH in the future.

Objective To evaluate the effects of high-fat diet on the pharmacokinetics of metronidazole in Chinese healthy adult subjects.Methods This program is designed according to a single-center,randomized,open,single-dose trial.Forty-seven healthy subjects were assigned to receive single dose of metronidazole tablets 200 mg in either fasting and high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of metronidazole in plasma were determined by high performance liquid chromatography-mass spectromentry.Results The main pharmacokinetic parameters of metronidazole in fasting state and high-fat diet state were as follows:Cmax were(4 799.13±1 195.32)and(4 044.17±773.98)ng·mL-1;tmax were 1.00 and 2.25 h;t1/2 were(9.11±1.73)and(9.37±1.79)h;AUC0_t were(5.59±1.19)x 104 and(5.51±1.18)x 104 ng·mL-1·h;AUC0_∞ were(5.79±1.33)x 104 and(5.74±1.32)× 104 ng·mL-1·h.Compared to the fasting state,the tmaxof the drug taken after a high fat diet was delayed by 1.25 h(P＜0.01),Cmax,AUC0_t,AUC0-∞ were less or decreased in different degrees,but the effects were small(all P＞0.05).Conclusion High-fat diet has little effects on the pharmacokinetic parameters of metronidazole,which does not significantly change the degree of drug absorption,but can significantly delay the time to peak.

Objective To evaluate the bioequivalence of metronidazole tablet and reference formulation in Chinese healthy subjects.Methods A single-dose,two-cycle,randomized,open,self-crossover trial was designed with 48 healthy subjects randomly assigned to fasting or postprandial group.For each group,a single oral dose of metronidazole tablet(200 mg)or a reference preparation(200 mg)per cycle were enrolled.The concentration of metronidazole in plasma was measured by high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).The non-compartmental model was applied to calculate the pharmacokinetic parameters for bioequivalence analysis via SAS 9.3 software.Results The main pharmacokinetic parameters of test and reference metronidazole tablets in the fasting group were as follows,the Cmax were(4 855.00±1 383.97)and(4 799.13±1 195.32)ng·h·mL-1;the AUC0-t were(54 834.68±12 697.88)and(55 931.35±11 935.28)ng·h·mL-1;the AUC0-∞ were(56 778.09±13 937.76)and(57 922.83±13 260.54)ng·h·mL-1;the Tmax were respectively 1.17 and 1.00 h;t1/2 were(8.99±1.76)and(9.11±1.73)h,respectively.The ratio of the geometric mean and its 90％confidence intervals(CI)of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.As for postprandial conditions,the main pharmacokinetic parameters of test and reference metronidazole tablets were as follows,the Cmax were(4 057.08±655.08)and(4 044.17±773.98)ng·h·mL-1;the AUC0-t were(55 956.42±12 228.12)and(55 121.04±11 784.55)ng·h·mL-1;the AUC0-∞ were(58 212.83±13 820.00)and(57 350.38±13 229.46)ng·h·mL-1;the Tmax were 2.50 and 2.25 h;the t1/2 were(9.37±1.68)and(9.37±1.79)h,respectively.The ratio of the geometric mean and 90％CI of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.Conclusion The two preparations were bioequivalent to Chinese healthy adult volunteers under both fasting and fed conditions.

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Objective:To investigate the outcome of epicanthoplasty combined with double eyelidplasty in different aesthetic forms of double eyelids (inner type and outer type) using Z-epicanthoplasty and inverted L method.Methods:The clinical data of patients with single eyelids and epicanthus were retrospectively analyzed from November 2021 to October 2022 in Gaoxin Hospital of the First Affiliated Hospital of Nanchang University. Patients were divided into inner type group and outer type group based on their aesthetic requirements for inner double eyelids. Both groups underwent Z-epicanthoplasty or inverted L method for epicanthus correction. Postoperative follow-up was conducted to observe the incision healing, complications, and postoperative effects of the two groups. The correction effects [ineffective, effective, and markedly effective, with the effective rate calculated as (the number of markedly effective cases + the number of effective cases)/total number of cases × 100%], scar scores, and patient satisfaction scores were collected for more than 12 months after surgery. Independent sample t-test was used for the scar scores and patient satisfaction scores, and chi-square test was used for the epicanthus correction effects. P<0.05 indicated a statistically significant difference. Results:A total of 76 patients were included. Among them, 41 patients in the inner type group (4 males and 37 females, with an average age of 22.3 years, ranging from 18 to 28 years) underwent 19 cases of Z-epicanthoplasty and 22 cases of inverted L method; 35 patients in the outer type group (3 males and 32 females, with an average age of 24.2 years, ranging from 19 to 30 years) underwent 20 cases of Z-epicanthoplasty and 15 cases of inverted L method. After 12 to 16 months of follow-up, with an average of 14 months, all incisions in both groups healed in the first stage, with no significant scar hyperplasia or other complications. Most of the double eyelid shapes are natural after the surgery, and the correction of epicanthus is obvious. Comparison of the treatment efficacy between Z-epicanthoplasty and inverted L method showed no significant difference [94.87% (37/39) vs. 94.59% (35/37), P>0.05]. In the inner type group, the postoperative scar score of the inverted L method was lower than that of the Z-epicanthoplasty [(6.81±0.66) vs. (7.31±0.88)], and the satisfaction score was better than that of the Z-epicanthoplasty [(0.86±0.63) vs. (1.73±0.65)], with statistically significant differences (both P<0.05). In the outer type group, the scar score of the inverted L method was higher than that of the Z-epicanthoplasty [(7.66±0.89) vs. (7.00±0.64)], and the satisfaction score was worse than that of the Z-epicanthoplasty [(1.80±0.86) vs. (1.00±0.56)], with statistically significant differences (both P<0.05). Conclusion:For patients requiring inner type aesthetic form of medial double eyelids, inverted L method can achieve less postoperative scars and higher postoperative satisfaction compared with Z-epicanthoplasty. For patients requiring "outer type" aesthetic form, Z-epicanthoplasty can achieve less postoperative scars and higher postoperative satisfaction compared with inverted L method.

Objective:Based on the health ecological model, this paper systematically explores the influencing factors of mild cognitive impairment among the elderly herders in Nanshan pastoral area of Xinjiang, and provides the basis for local medical institutions to formulate prevention and control strategies for mild cognitive impairment among the elderly herders.Methods:A total of 1 145 valid questionnaires were collected, all of them were permanent herdsmen aged over 60 years in Nanshan pastoral area of Xinjiang were selected from June 2022 to February 2023 by stratified cluster random sampling method in a cross-sectional survey. Under the guidance of health ecological model, the research variables were included from five dimensions: physiology, psychology, behavioral lifestyle, social network and medical and health environment, and questionnaires were conducted. SPSS 23.0 was used for chi-square test and binary Logistic regression to analyze the influencing factors of mild cognitive impairment in elderly herders.Results:There were 564 males and 581 females with age of (70.84 ± 5.69) years old in the study. The prevalence rate of mild cognitive impairment among elderly herdsmen in Nanshan pastoral area of Xinjiang was 36.1%(413/1 145). Binary Logistic regression analysis showed that: personal monthly income (1 000-2 999 yuan)( OR = 0.583, 95% CI 0.366 - 0.926, P<0.05), education level (junior high school and above)( OR = 0.479, 95% CI 0.315 - 0.728, P<0.01) were the protective factors for mild cognitive impairment among the elderly herdsmen in Nanshan pastoral area. Hypertension ( OR = 1.842, 95% CI 1.256 - 2.702, P<0.01), dyslipidemia ( OR = 1.449, 95% CI 1.069 - 1.964, P<0.05) and chronic pain ( OR = 1.549, 95% CI 1.082 - 2.216, P<0.05) were the risk factors of mild cognitive impairment in elderly herders in Nanshan pastoral area. Conclusions:The prevalence rate of mild cognitive impairment among elderly herders in Nanshan pastoral area of Xinjiang is high, so it is necessary to carry out mild cognitive impairment screening as soon as possible, especially focusing on people suffering from hypertension, dyslipidemia and chronic pain, and making intervention plans to delay the occurrence and development of mild cognitive impairment and improve the quality of life of elderly herders.

Objective:To investigate the incidence and influencing factors of allergic reactions to cephalosporins.Methods:A cross-sectional study of 29 medical institutions in Zhejiang Province was conducted from April 2021 to June 2021.The incidence of allergic reactions to cephalosporins was investigated,and the influencing factors of cephalosporin-induced allergic reactions were analyzed by Poisson regression.Results:A total of 56 155 patients were included in this study.The total incidence of allergic reactions to cephalosporin was 1.67‰,the highest incidence of anaphylaxis occurred for ceftizoxime(4.27‰),followed by ceftriaxone(3.49‰)and cefotaxime(2.40‰).There was no significant difference in the incidence of allergic reactions between patients with negative skin tests and those without skin tests(1.75％o vs.1.63‰,RR=1.07,95％CI:0.70-1.63,P＞0.05).Poisson regression showed that body mass index(BMI)＜18.5 kg/m2(RR=2.43,95％CI:1.23-4.82,P＜0.05)and history of β-lactam antibiotics allergy(RR=33.88,95％CI:1.47-781.12,P＜0.05)increased cephalosporin-induced anaphylaxis.Compared with cefuroxime,the risk of allergic reactions was increased for ceftriaxone(RR=3.08,95％CI:1.70-5.59,P＜0.01),ceftazidime(RR=1.89,95％CI:1.03-3.47,P＜0.05),and ceftizoxime(RR=3.74,95％CI:1.64-8.50,P＜0.01).Conclusions:Lower BMI and history of β-lactam antibiotics allergy increase the risk of cephalosporin allergic reactions.The routine skin test may not reduce the occurrence of allergic reactions to cephalosporins. This study has been registered at Chinese Clinical Trial Registry(ChiCTR2200064314).

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To investigate the outcome of epicanthoplasty combined with double eyelidplasty in different aesthetic forms of double eyelids (inner type and outer type) using Z-epicanthoplasty and inverted L method.Methods:The clinical data of patients with single eyelids and epicanthus were retrospectively analyzed from November 2021 to October 2022 in Gaoxin Hospital of the First Affiliated Hospital of Nanchang University. Patients were divided into inner type group and outer type group based on their aesthetic requirements for inner double eyelids. Both groups underwent Z-epicanthoplasty or inverted L method for epicanthus correction. Postoperative follow-up was conducted to observe the incision healing, complications, and postoperative effects of the two groups. The correction effects [ineffective, effective, and markedly effective, with the effective rate calculated as (the number of markedly effective cases + the number of effective cases)/total number of cases × 100%], scar scores, and patient satisfaction scores were collected for more than 12 months after surgery. Independent sample t-test was used for the scar scores and patient satisfaction scores, and chi-square test was used for the epicanthus correction effects. P<0.05 indicated a statistically significant difference. Results:A total of 76 patients were included. Among them, 41 patients in the inner type group (4 males and 37 females, with an average age of 22.3 years, ranging from 18 to 28 years) underwent 19 cases of Z-epicanthoplasty and 22 cases of inverted L method; 35 patients in the outer type group (3 males and 32 females, with an average age of 24.2 years, ranging from 19 to 30 years) underwent 20 cases of Z-epicanthoplasty and 15 cases of inverted L method. After 12 to 16 months of follow-up, with an average of 14 months, all incisions in both groups healed in the first stage, with no significant scar hyperplasia or other complications. Most of the double eyelid shapes are natural after the surgery, and the correction of epicanthus is obvious. Comparison of the treatment efficacy between Z-epicanthoplasty and inverted L method showed no significant difference [94.87% (37/39) vs. 94.59% (35/37), P>0.05]. In the inner type group, the postoperative scar score of the inverted L method was lower than that of the Z-epicanthoplasty [(6.81±0.66) vs. (7.31±0.88)], and the satisfaction score was better than that of the Z-epicanthoplasty [(0.86±0.63) vs. (1.73±0.65)], with statistically significant differences (both P<0.05). In the outer type group, the scar score of the inverted L method was higher than that of the Z-epicanthoplasty [(7.66±0.89) vs. (7.00±0.64)], and the satisfaction score was worse than that of the Z-epicanthoplasty [(1.80±0.86) vs. (1.00±0.56)], with statistically significant differences (both P<0.05). Conclusion:For patients requiring inner type aesthetic form of medial double eyelids, inverted L method can achieve less postoperative scars and higher postoperative satisfaction compared with Z-epicanthoplasty. For patients requiring "outer type" aesthetic form, Z-epicanthoplasty can achieve less postoperative scars and higher postoperative satisfaction compared with inverted L method.

We aim to evaluate prostate health index as an additional risk-stratification tool in patients with Prostate Imaging Reporting and Data System score 3 lesions on multiparametric magnetic resonance imaging. Men with biochemical or clinical suspicion of having prostate cancer who underwent multiparametric magnetic resonance imaging in two tertiary centers (Queen Mary Hospital and Princess Margaret Hospital, Hong Kong, China) between January 2017 and June 2022 were included. Ultrasound-magnetic resonance imaging fusion biopsies were performed after prostate health index testing. Those who only had Prostate Imaging Reporting and Data System score 3 lesions were further stratified into four prostate health index risk groups and the cancer detection rates were analyzed. Out of the 747 patients, 47.3% had Prostate Imaging Reporting and Data System score 3 lesions only. The detection rate of clinically significant prostate cancer in this group was 15.0%. The cancer detection rates of clinically significant prostate cancer had statistically significant differences: 5.3% in prostate health index <25.0, 7.4% in prostate health index 25.0-34.9, 17.9% in prostate health index 35.0-54.9, and 52.6% in prostate health index ≥55.0 (P < 0.01). Among the patients, 26.9% could have avoided a biopsy with a prostate health index <25.0, at the expense of a 5.3% risk of missing clinically significant prostate cancer. Prostate health index could be used as an additional risk stratification tool for patients with Prostate Imaging Reporting and Data System score 3 lesions. Biopsies could be avoided in patients with low prostate health index, with a small risk of missing clinically significant prostate cancer.