Objective To compare the pharmacokinetics of crushed posaconazole enteric-coated tablets and oral suspension after intragastric administration in rabbits.Methods The experiment was designed in a randomized cross-over study.Six New Zealand rabbits were intragastrically administrated with crushed posaconazole enteric-coated tablets or suspension,and blood was collected at specific time points.The concentration of posaconazole in plasma was determined by high-performance liquid chromatography,and the pharmacokinetic parameters of both groups were calculated with DAS 2.0 software.Results The main pharmacokinetic parameters of posaconazole enteric-coated tablets and suspension were obtained as follows:AUC0-twere(40.03±5.04)and(49.92±16.09)μg·mL-1·h;AUC0-∞ were(44.00±4.50)and(51.10±16.80)μg·mL-1·h;t1/2 were(7.30±1.13)and(8.53±1.34)h;Cmrx were(3.12±0.57)and(2.78±0.60)μg·mL-1;apparent volume of distribution(Vd)were(2.40±0.34)and(2.59±0.76)L·kg-1;clearance rate(CL)were(0.23±0.02)and(0.22±0.08)L·h-1·kg.There were no statistic differences in AUC0-t,Cmax and Vd between posaconazole suspension and crushed enteric-coated tablets after intragastric administration(all P＞0.05).Conclusion There was no pharmacokinetic advantage for crushed enteric-coated tablets against oral suspension.

Objective To explore the difference in efficacy of metoprolol versus ivabradine in the treatment of postural orthostatic tachycardia syndrome(POTS)in the elderly after COVID-19 infection.Methods A total of 110 patients diagnosed with POTS at our department from Decem-ber 1,2022 to January 31,2023 were included.According to their drug regimen,they were divided into metoprolol group(62 patients)and ivabradine group(48 patients).On the 28th day of out-patient follow-up,the resting heart rate,heart rate of 10 min of standing,symptom disappearance rate,hospitalization rate,and mortality rate were compared between the two groups.Results On the 28th day of treatment,the resting heart rate and postural heart rate for 10 min were decreased in both groups when compared with the levels at initial diagnosis(P＜0.01).And there were no significant differences in the two types of heart rate between the two groups on the 28th day(71.0±7.0 vs 72.1±7.0,P=0.401;76.5±7.2 vs 77.4±7.6,P=0.573).No obvious differences were observed between the two groups in symptom disappearance rate,hospitalization rate,or mortality rate(88.7％vs 89.6％,3.2％vs2.1％,0％vs 0％,P＞0.05).Conclusion Metoprolol and ivabradine can effectively treat POTS in the elderly patients after COVID-19 infection.

Objective To investigate the dietary patterns of rural residents in the high-incidence areas of esophageal cancer (EC), and to explore the clustering and influencing factors of risk factors associated with high-incidence characteristics. Methods A special structured questionnaire was applied to conduct a face-to-face survey on the dietary patterns of rural residents in Yanting county of Sichuan Province from July to August 2021. Univariate and multivariate logistic regression models were used to analyze the influencing factors of risk factor clustering for EC. Results There were 838 valid questionnaires in this study. A total of 90.8% of rural residents used clean water such as tap water. In the past one year, the people who ate fruits and vegetables, soybean products, onions and garlic in high frequency accounted for 69.5%, 32.8% and 74.5%, respectively; the people who ate kimchi, pickled vegetables, sauerkraut, barbecue, hot food and mildew food in low frequency accounted for 59.2%, 79.6%, 68.2%, 90.3%, 80.9% and 90.3%, respectively. The clustering of risk factors for EC was found in 73.3% of residents, and the aggregation of two risk factors was the most common mode (28.2%), among which tumor history and preserved food was the main clustering pattern (4.6%). The logistic regression model revealed that the gender, age, marital status and occupation were independent influencing factors for the risk factors clustering of EC (P<0.05). Conclusion A majority of rural residents in high-incidence areas of EC in Yanting county have good eating habits, but the clustering of some risk factors is still at a high level. Gender, age, marital status, and occupation are influencing factors of the risk factors clustering of EC.

Objective:To understand the current status of pubertal sexual characteristics development of girls aged 6-18 years in Tongzhou District of Beijing and to compare the differences in sexual characteristics development among girls characterized as thin, normal, overweight, and obese.Methods:A cross-sectional survey was conducted among 2 844 girls aged 6-18 years in Tongzhou District of Beijing from September 2022 to July 2023. The developmental stages of breast and pubic hair were assessed on site, and menarche status was inquired. Weight and height were measured. The girls were subsequently characterized into thin, normal, overweight and obese groups. Basic information (including family and personal history) was obtained through questionnaires. Probit probability unit regression was applied to calculate the age of each Tanner stage of sexual characteristics development and the age of menarche. The χ 2 test was applied to compare the counting data between two or multiple groups. Results:A total of 2 844 girls were surveyed and 2 704 girls met the inclusion criteria, resulting in a valid response rate of 95.1%. Among these girls, 1 105 (40.9%) were aged 6-9 years, 1 053 (38.9%) were aged 10-13 years, and 546 (20.2%) were aged 14-18 years. The of height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and body mass index-for-age Z-score (BAZ) were 0.46(-0.23,1.16), 0.69(-0.16,1.67), and 0.67(-0.27,1.73) respectively. The prevalences of thin, overweight, and obesity were respectively 1.7% (45/2 704), 17.3% (467/2 704), and 19.9% (538/2 704), respectively. There were 45 girls in the thin group, 1 654 girls in the normal weight group, 1 005 girls in the overweight and obesity group. The age of Tanner stage breast 2 (B2), Tanner stage pubic hair 2 (P2), and menarche was 9.0 (95% CI 8.9-9.1), 10.5 (95% CI 10.4-10.6), and 11.4 (95% CI 11.3-1.5) years, respectively. The current status of breast and pubic hair maturity in girls with pubertal development shows that 64.6% (1 211/1 874) of these girls had breast development preceding pubic hair development, 32.4% (607/1 874) had concurrent breast and pubic hair development, and 3.0% (56/1 874) had pubic hairs development preceding breast development. The interval age between B2 and B5 was 4.7 (95% CI 4.6-4.8) years, between P2 and P5 was 4.5 (95% CI 4.4-4.6) years, and between B2 and menarche was 2.4 (95% CI 2.3-2.5) years. The ages of sexual characteristics development in overweight and obese groups were earlier than that in normal and thin groups. The ages of B2 in thin, normal, overweight, and obese groups were 10.0 (95% CI 9.5-10.6), 9.3 (95% CI 9.2-9.4), and 8.6 (95% CI 8.4-8.7) years, respectively. The age of menarche in thin, normal, overweight, and obese groups were 13.1 (95% CI 12.4-13.7), 11.6 (95% CI 11.4-11.7), and 11.1 (95% CI 11.0-11.2) years, respectively. The interval ages between B2 and B5 and between P2 and P5 was 4.5 and 4.1 years, respectively in the overweight and obese groups, and those in normal group and thin group was 4.7 and 4.5 years, 4.6 and 4.7 years, respectively. Conclusions:The ages of sexual characteristics development and menarche tend in Tongzhou District of Beijing to be earlier than that being reported of Beijing's survey 20 years ago. Girls characterized as overweight and obese not only start puberty at an earlier age than girls of normal weight, but also have a shorter developmental process.

Objective:To investigate the treatment strategy and prognostic factors of nasopharyngeal necrosis after the first radical radiotherapy for nasopharyngeal carcinoma.Methods:Clinical data of 1020 patients with nasopharyngeal carcinoma undergoing radical intensity-modulated radiotherapy in Jiangsu Cancer Hospital from January 2013 to January 2022 were retrospectively analyzed. Nasopharyngeal necrosis was confirmed by nasopharyngeal MRI, electronic nasopharyngoscopy and biopsy. Patients with nasopharyngeal necrosis were treated with electronic nasopharyngoscope irrigation debridement, combined with systemic anti-infection and nutritional support therapy. Kaplan-Meier method was used to calculate the survival, and Cox regression analysis was used to analyze the relationship between clinical factors and patients' survival.Results:Nasopharyngeal necrosis occurred in 20 cases of 1020 nasopharyngeal carcinoma patients after the first radical intensity-modulated radiotherapy, with an incidence rate of 1.96%. Odd smell and headache were common in nasopharyngeal necrosis patients. All patients had locally advanced nasopharyngeal carcinoma at initial treatment, including 2 (10%) cases of T 3 stage and 18 (90%) cases of T 4 stage. Nasopharyngeal necrosis occurred in the primary nasopharyngeal lesions. According to the stages of nasopharyngeal necrosis, there were 6 (30%) cases of stage I, 14 (70%) cases of stage II and no stage III. The occurrence time of nasopharyngeal necrosis was from 2 to 24 months after radiotherapy, and the median time was 5 months. All 16 cases of nasopharyngeal necrosis were cured clinically after debridement and irrigation under nasopharyngoscope, systemic anti-infection and symptomatic support treatment. Among them, 9 cases had no necrotic cavity and complete healing and 7 cases had residual necrotic cavity. Four patients died of massive nasopharyngeal hemorrhage or due to the inability to nasopharyngeal irrigation. The 5-year survival rates were 37.5% and 85.7% in patients with and without internal carotid artery involvement ( P=0.008), and 25.0% and 77.8% in patients with and without diabetes mellitus ( P=0.016). Univariate Cox regression analysis showed that necrotic lesions involving internal carotid artery ( HR=5.80, 95% CI=1.14-29.38, P=0.034) and diabetes mellitus ( HR=10.24, 95% CI=1.19-88.04, P=0.034) were the influencing factors of overall survival. Conclusions:Nasopharyngoscope irrigation debridement combined with anti-inflammation and nutritional support treatment are effective interventions for nasopharyngeal necrosis after the first radical intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma. The necrosis involving the internal carotid artery and diabetes mellitus are important factors affecting the survival of patients. Vascular invasion caused by vascular rupture is the main cause of death.

Abstract：Objective To optimize the production process of inactivated vaccine of Aeromonas veronii（AV）CA07 strain. Methods The fermentation culture process of AV CA07 strain liquid was determined through the optimization of the culture time（2～16 h），medium（optimized fermentation medium，LB medium and NB medium）and fermentation conditions（in⁃ oculation amount of 1%，5%，10% and 15%；ventilation rate of 2，4，6 and 8 L／min and fermentation time of 6，8，10 and 12 h）. The optimal inactivation process was determined through the comparison of the final concentration of formalde⁃ hyde solution（0. 10%，0. 20%，0. 30% and 0. 40%），inactivation temperature（28 and 37 ℃）and inactivation time（24， 48 and 72 h）. The large⁃scale production process of inactivated vaccine of AV CA07 strain in 500 L fermentor was estab⁃ lished and the prepared vaccines were tested for safety and immunogenicity. Results The optimal inoculation amount of AV CA07 strain was 5%，ventilation rate was 4 L／min and culture time was 10 ~ 12 h. The optimal inactivation condition was adding formaldehyde solution with final concentration of 0. 30% incubating at 37 ℃ for 24 h. The number of viable bacteria in the fermentation broth of AV CA07 strain prepared in 500 L fermentor was more than 8 × 109 CFU／mL. All crucian carps immunized with the inactivated vaccine by abdomen survived. After challenge，the relative immune protection rate was more than 90%. Conclusion AV CA07 strain inactivated vaccine prepared by optimized production process showed good safety and immunogenicity.

Objective: To explore the allergen map of patients with allergic diseases in northwest China, to investigate the distribution characteristics of serum specific Immunoglobulin E (sIgE) in different ages, genders, diseases and the sensitization patterns of allergens. Methods: This study is a cross-sectional study, a total of 1 161 patients with confirmed respiratory allergic diseases were selected retrospectively from outpatient or inpatient department of Gansu Provincial People's Hospital, Gansu Provincial Maternity and Child Care Hospital, General Hospital of Ningxia Medical University, Yinchuan Maternal and Child Health Care Hospital, Xijing Hospital, Air Force Military Medical University and Tumor Hospital of Inner Mongolia Autonomous Region from June 2019 to October 2022. HAIKE ALLEOS 2000 fluorescent magnetic particle chemiluminescence method was used to quantify their serum for 12 inhaled allergen-specific IgE. Chi square test or Fisher's exact test were used for comparison between count data groups (Bonferroni correction was used for further pairwise comparison in multiple groups, two-sided P<0.05/3=0.017 considered that the difference was statistically significant). Pearson correlation analysis was used for correlation of continuous numerical variables. Results: The positive detection rate of sIgE in 1 161 patients was 66.8%(776/1 161). The three highest positive rate of inhaled allergen were mugwort(599/1 161, 51.6%), French chrysanthemum(565/1 161, 48.7%) and dandelion(412/1 161, 35.5%). In different age groups, the highest positive rate of sIgE was 7-18 age group(379/513, 73.9%) while the lowest positive rate was 4-6 age group(222/370, 60.0%), the difference between groups was statistically significant(χ²=21.177, P<0.001). The sensitization peak of mugwort, French chrysanthemum, plantain, timothy, birch, dermatophagoides pteronyssinus, dermatophagoides farinae, cat epithelium, dog epithelium and German cockroach appeared in 7-18 age group. In different disease groups, the highest positive rate of sIgE was allergic rhinitis with asthma group (500/717, 69.7%) while the lowest positive rate was asthma group (76/144, 52.8%), the difference between groups was statistically significant(χ²=15.563, P<0.001). In different gender groups, the positive rate of sIgE in male (503/711, 70.7%) was higher than in female (273/450, 60.7%), the difference between groups was statistically significant(χ²=12.630, P<0.001). The multiple-sensitization rate was 86.9%(674/776) and the double-sensitization rate was 16.8%(130/776) in sIgE positive patients. Pearson correlation results showed that there was an extremely strong correlation between dandelion and French chrysanthemum(r=0.93,P<0.001). There was a strong correlation between mugwort and French chrysanthemum(r=0.64,P<0.001). In the co-sensitization analysis, the number of patients sensitized by mugwort, French chrysanthemum, dandelion, plantain and timothy accounted for 25.2%(170/674)of the total number of multiple sensitization. The number of patients sensitized by mugwort, French chrysanthemum and dandelion accounted for 58.3%(393/674)of the total number of multiple sensitization. The number of patients sensitized by mugwort, French chrysanthemum, dandelion and plantain accounted for 35.6%(240/674) of the total number of multiple sensitization. Conclusion: Mugwort, French chrysanthemum, dandelion are the major inhaled allergens in northwest China. The positive rate of sIgE was different in different ages, diseases and genders. The multiple-sensitization rate of allergen was high and there was a certain positive correlation between pollen allergen-specific IgE pairwise, suggesting that there may exist co-sensitization or cross-reactions among allergens.
Pregnancy ; Child ; Animals ; Dogs ; Female ; Humans ; Male ; Allergens ; Cross-Sectional Studies ; Retrospective Studies ; Respiratory System ; Asthma

Objective: To explore the allergen map of patients with allergic diseases in northwest China, to investigate the distribution characteristics of serum specific Immunoglobulin E (sIgE) in different ages, genders, diseases and the sensitization patterns of allergens. Methods: This study is a cross-sectional study, a total of 1 161 patients with confirmed respiratory allergic diseases were selected retrospectively from outpatient or inpatient department of Gansu Provincial People's Hospital, Gansu Provincial Maternity and Child Care Hospital, General Hospital of Ningxia Medical University, Yinchuan Maternal and Child Health Care Hospital, Xijing Hospital, Air Force Military Medical University and Tumor Hospital of Inner Mongolia Autonomous Region from June 2019 to October 2022. HAIKE ALLEOS 2000 fluorescent magnetic particle chemiluminescence method was used to quantify their serum for 12 inhaled allergen-specific IgE. Chi square test or Fisher's exact test were used for comparison between count data groups (Bonferroni correction was used for further pairwise comparison in multiple groups, two-sided P<0.05/3=0.017 considered that the difference was statistically significant). Pearson correlation analysis was used for correlation of continuous numerical variables. Results: The positive detection rate of sIgE in 1 161 patients was 66.8%(776/1 161). The three highest positive rate of inhaled allergen were mugwort(599/1 161, 51.6%), French chrysanthemum(565/1 161, 48.7%) and dandelion(412/1 161, 35.5%). In different age groups, the highest positive rate of sIgE was 7-18 age group(379/513, 73.9%) while the lowest positive rate was 4-6 age group(222/370, 60.0%), the difference between groups was statistically significant(χ²=21.177, P<0.001). The sensitization peak of mugwort, French chrysanthemum, plantain, timothy, birch, dermatophagoides pteronyssinus, dermatophagoides farinae, cat epithelium, dog epithelium and German cockroach appeared in 7-18 age group. In different disease groups, the highest positive rate of sIgE was allergic rhinitis with asthma group (500/717, 69.7%) while the lowest positive rate was asthma group (76/144, 52.8%), the difference between groups was statistically significant(χ²=15.563, P<0.001). In different gender groups, the positive rate of sIgE in male (503/711, 70.7%) was higher than in female (273/450, 60.7%), the difference between groups was statistically significant(χ²=12.630, P<0.001). The multiple-sensitization rate was 86.9%(674/776) and the double-sensitization rate was 16.8%(130/776) in sIgE positive patients. Pearson correlation results showed that there was an extremely strong correlation between dandelion and French chrysanthemum(r=0.93,P<0.001). There was a strong correlation between mugwort and French chrysanthemum(r=0.64,P<0.001). In the co-sensitization analysis, the number of patients sensitized by mugwort, French chrysanthemum, dandelion, plantain and timothy accounted for 25.2%(170/674)of the total number of multiple sensitization. The number of patients sensitized by mugwort, French chrysanthemum and dandelion accounted for 58.3%(393/674)of the total number of multiple sensitization. The number of patients sensitized by mugwort, French chrysanthemum, dandelion and plantain accounted for 35.6%(240/674) of the total number of multiple sensitization. Conclusion: Mugwort, French chrysanthemum, dandelion are the major inhaled allergens in northwest China. The positive rate of sIgE was different in different ages, diseases and genders. The multiple-sensitization rate of allergen was high and there was a certain positive correlation between pollen allergen-specific IgE pairwise, suggesting that there may exist co-sensitization or cross-reactions among allergens.
Pregnancy ; Child ; Animals ; Dogs ; Female ; Humans ; Male ; Allergens ; Cross-Sectional Studies ; Retrospective Studies ; Respiratory System ; Asthma

OBJECTIVE: To explore the transcriptional gene expression profile up-regulated in human macrophages stimulated by interferon-γ (IFN-γ) and the underlying intracellular signaling mechanisms. METHODS: RNA-seq was used to sequence and compare the differential gene expression profiles of human macrophage cell line U937 before and after IFN-γ stimulation, and the significantly up-regulated genes were screened out, which were verified by fluorescence-based real-time quantitative polymerase chain reaction (qPCR) in U937 and THP1 cell lines, respectively. JAK/STAT, MAPK/ERK and PI3K/AKT pathway inhibitors were added to simultaneously to the cultured U937 cells upon IFN-γ priming to detect their effects on the expressions of the up-regulated genes to explore the key regulatory mechanisms. RESULTS: RNA-seq and qPCR results showed that, the well-recognized chemokines CXCL9, CXCL10 and CXCL11, the APOL family including APOL1, APOL2, APOL3, APOL4, APOL6 and GBP family GBP1, GBP2, GBP3, GBP4 and GBP5 as well were significantly up-regulated in IFN-γ-stimulated U937 cells. JAK/STAT3 pathway inhibitor inhibited the upregulation of APOL1, APOL4, GBP1, GBP4 and GBP5 genes induced by IFN-γ, while MAPK/ERK pathway inhibitor inhibited the upregulation of CXCL10 gene. PI3K/AKT pathway inhibitor inhibited the upregulation of APOL1,APOL4, APOL6, GBP1 and GBP5 genes induced by IFN-γ, all three signal pathway inhibitors could inhibit the upregulation of CXCL9 gene, and none of them could inhibit the upregulation of APOL3 gene. CONCLUSION Upon IFN-γ stimulation, some family molecules of APOL and GBP in macrophages are significantly up-regulated, and PI3K/AKT, JAK/STAT3 and MAPK/ERK pathways have positive regulation on their expressions, respectively.
Apolipoprotein L1/pharmacology* ; Humans ; Interferon-gamma/pharmacology* ; Macrophages/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction

OBJECTIVE: To investigate the effect of Kangquan Recipe (, KQR) on bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) expression and its mechanism in rats with benign prostatic hyperplasia (BPH). METHODS: Forty-eight male Sprague-Dawley rats were divided into 6 groups using a random number table, with 8 in each group: the normal group (normal saline 10 mL/kg), the model group (normal saline 10 mL/kg), the finasteride group (0.5 mg/kg), the low-dose KQR group (3.5 g/kg), the middle-dose KQR group (7 g/kg), and the high-dose KQR group (14 g/kg). The 40 rats were subcutaneously injected with testosterone propionate after castration for 30 days to establish the BPH rat model except for those in the normal group. At the same time, the corresponding drugs were administered by gavage for 30 consecutive days. The effects of different doses of KQR on the protate wet weight, prostate volume and prostate index (PI) were observed. The changes in histopathology were monitored with hematoxylin-eosin staining. BAMBI protein and mRNA expression contents were determined by Western blot and quantitative real-time polymerase chain reaction, respectively. RESULTS: All doses of KQR could decrease prostatic epithelial tissue proliferation. Compared to the model group, the high and middle-dose KQR significantly reduced prostate wet weight, prostate volume and PI; increased BAMBI protein expression in the hypothalamus, pituitary and prostate tissue; all doses of KQR up-regulated BAMBI mRNA expression in serum, prostatic fluid and prostate tissue (P<0.05 or P<0.01). CONCLUSIONS KQR could inhibit the proliferation of rat prostatic tissue, promote BAMBI protein expression in the hypothalamic-pituitary-prostate of rats with BPH; and increase BAMBI mRNA expression in the blood, prostatic fluid and prostate tissue of rats with BPH, showing a dose-effect relationship. KQR can be used as a potential drug for the treatment of BPH.