OBJECTIVE To confirm trigger items for adverse drug reaction （ADR） induced by bevacizumab， to identify and analyze the occurrence of related ADR， and to establish a predictive model for severe adverse reaction （SAR） caused by this drug. METHODS Based on the global trigger tool （GTT） theory， and referencing the GTT White Paper， drug package inserts and relevant literature， trigger items for bevacizumab-related ADR were confirmed using a single-round Delphi method. Utilizing these established items， electronic medical records of relevant patients at Guilin People’s Hospital from January 2020 to September 2024 were actively screened via the China Hospital Pharmacovigilance System. Pharmacists then identified and tallied the occurrence of bevacizumab-induced ADR. Data from patients with any positive trigger item served as the study subjects （divided into training and test sets at a ratio of 7∶3）， candidate feature variables were selected from 39 related variables using the Boruta algorithm， and the multivariable Logistic regression analysis was performed with the occurrence of SAR as the dependent variable. Based on these candidate features， Logistic Regression， Extreme Gradient Boosting， Light Gradient Boosting Machine， Random Forest， and Categorical Boosting models were constructed. Model performance was evaluated using metrics including the area under the curve （AUC） of receiver operating characteristic curve and recall rate. The Shapley Additive exPlanations （SHAP） method was applied to analyze and interpret the contribution of each variable. A nomogram was constructed based on the optimal model. RESULTS A total of 38 trigger items for active monitoring of bevacizumab-related ADR were determined， comprising 17 laboratory indicators， 13 clinical manifestations， and 8 intervention measures. In total， 483 patients with positive trigger items were included， and 318 patients with bevacizumab-induced ADR were identified， including 83 SARs. The positive predictive values for the trigger items and cases were 43.57% （708/1 625） and 63.84% （318/483）， respectively. Bevacizumab-induced ADR involved 7 systems/organs， with the hematological system being the most frequently involved （64.15%）. The Boruta algorithm selected 7 vari ables： serum potassium， hematocrit， albumin-to-globulin ratio， prealbumin， hypertension history， age and red blood cell count. Multivariable Logistic regression showed that elevated serum potassium levels were associated with a decreased risk of bevacizumab-induced SAR （OR＝0.234， P ＝0.002）， while a history of hypertension （OR＝2.642， P ＝0.006） and increased age （OR＝1.040， P ＝0.025） were associated with an increased risk. The Logistic Regression model demonstrated superior performance with higher AUC， F1 score and recall rate （0.761， 0.447， 0.607）， compared to other models. SHAP evaluation results indicated that variables such as serum potassium， hematocrit， and age ranked highest in importance. CONCLUSIONS Totally 38 trigger entries have been successfully identified for active screening of bevacizumab-related ADR. Elevated serum potassium levels are a protective factor against bevacizumab-induced SAR， whereas the hypertension history and increased age are risk factors. The Logistic Regression model is the optimal predictive model.

Separation and determination of chiral and achiral impurities in glimepiride tablets by supercritical fluid chromatography. Chiral and achiral impurities were separated on a ACQUITY UPC² Trefoil^TM CEL1 column (150 mm × 3.0 mm, 2.5 μm) maintained at 30 ℃ with the mobile phase containing a mixture of CO₂ and methanol-isopropanol (1∶1) at 1 mL·min^-1, and the detection wavelength was set at 228 nm. The back pressure was set at 13.8 MPa. The injection volume was 5 μL. In the chromatogram of the system suitability solution, the peaks elute in the following order: impurity Ⅳ, impurity Ⅴ, glimepiride, impurity Ⅲ, impurity Ⅰ and impurity Ⅱ. The six substances were separated successfully in 6 min using the proposed method with a resolution factor of 2.9, 1.6, 3.0, 2.0, 6.4. The impurity Ⅰ-Ⅴ detection limit (S/N = 3) was 0.17, 0.10, 0.06, 0.15, 0.10 μg·mL^-1, respectively. Good linear relationship was established between the peak response and the concentration in the range of 0.48-51.30 μg·mL^-1 for all impurities. The spiked recovery of impurity Ⅰ-Ⅴ was found to be acceptable for 99.9%, 98.9%, 102.1%, 100.1%, 96.3% (n = 9), respectively. The related substance and assay results of 11 sample batches are consistent with the results obtained using the HPLC method in the Chinese Pharmacopoeia. Compared to the two HPLC methods in the Chinese Pharmacopoeia, the established supercritical fluid chromatography method can simultaneously separate glimepiride and its 5 impurities in a single run, and it has the following advantages: simplified sample preparation, greatly reducing the volumes of organic solvents, environmentally friendly, high accuracy and good reproducibility. It can be employed for the quality control of the chiral and achiral impurities in glimepiride tablets.

Objective:To explore the expression and clinical significance of long non-coding RNA colorectal neoplasia differentially expressed (lncRNA CRNDE), microRNA-181a-5p (miR-181a-5p) and autophagy related 5 (ATG5) in the peripheral blood of patients with gouty arthritis (GA) patients.Methods:The clinical data, laboratory parameters and peripheral blood samples were collected from 40 patients with acute gout (AG), 40 patients with intermittent gout (IG) and 50 healthy subjects (HC). The expression levels of lncRNA CRNDE, miR-181a-5p and ATG5 mRNA were detected by real-time fluorescence quantification (RT-qPCR) and the expression level of ATG5 protein was detected by Western-blot. The expression levels of lncRNA CRNDE, miR-181a-5p, ATG5 mRNA were compared among the three groups and correlated with clinical indices, and a subject operating characteristic curve (ROC) was constructed to assess the value of lncRNA CRNDE, miR-181a-5p, ATG5 mRNA in the diagnosis of gout. Measurements conforming to normal distribution were analyzed using t test or ANOVA, data with non-normal distribution was analyzed using Mann-Whitney U test or Kruskal-Wallis H test, correlation analysis between variables was analyzed using Spearman's analysis, and the diagnostic value of each indicator was analyzed using ROC curve. Results:① The differences in the expression of lncRNA CRNDE, miR-181a-5p, and ATG5 mRNA between the three groups were statistically significant ( H=32.12, 57.73, 68.32, all P<0.001). Among them, lncRNA CRNDE expression level in the AG group was significantly higher than that in the IG group and healthy control group [61.95(11.39, 108.30)×10 -3, 25.71(15.40, 38.40)×10 -3, 13.80(3.97, 23.99)×10 -3; Z=-3.24, P=0.001; Z=-5.03, P<0.001], and the expression level of IG group was higher than that of healthy control group( Z=-3.56, P<0.001); miR-181a-5p and ATG5 mRNA expression levels in AG group were significantly lower than those in IG group and healthy control group [miR-181a-5p: 39.81(31.22, 69.38)×10 -3, 60.74(44.19, 90.35)×10 -3, 121.30(101.50, 316.90)×10 -3; Z=-3.01, P=0.030; Z=-6.93, P<0.001. ATG5 mRNA: 4.52(2.31, 26.63)×10 -3, 43.63(13.72, 102.70)×10 -3, 153.90(66.62, 365.80)×10 -3; Z=-5.47, -7.36, all P<0.001)], which were expressed at lower levels in the IG group than in the healthy controls ( Z=-5.25, -4.47, all P<0.001). The difference of ATG5 protein expression level among the three groups expressed was statistically significant ( F=6.24, P=0.030), and the AG group was higher than the healthy control group, and the difference was statistically significant [(0.96±0.13) vs.(0.61±0.04), t=4.25, P=0.013], but the difference between the IG group (0.78±0.15) and the AG group and the HC group was not statistically significant ( t=1.51, P=0.206; t=1.85, P=0138). ② Spearman correlation analysis showed that lncRNA CRNDE was negatively correlated with the expression levels of miR-181a-5p and ATG5 mRNA in gout patients ( r=-0.49, P<0.001; r=-0.35, P=0.002); miR-181a-5p was positively correlated with ATG5 mRNA expression levels ( r=0.64, P<0.001); lncRNA CRNDE expression level was positively correlated with ESR and WBC ( r=0.49, P<0.001; r=0.43, P=0.001); miR-181a-5p expression level was negatively correlated with ESR and WBC ( r=-0.29, P=0.009; r=-0.35, P=0.002), and ATG5 mRNA expression levels were negatively correlated with ESR, WBC, and GR ( r=-0.26, P=0.021; r=-0.26, P=0.024; r=-0.27, P=0.021). In the AG group lncRNA CRNDE was positively correlated with ESR and WBC ( r=0.36, P=0.022; r=0.36, P=0.026) and miR-181a-5p was negatively correlated with WBC ( r=-0.34, P=0.038) ③ ROC curve showed that the areas under ROC curve of lncRNA CRNDE, miR-181a-5p and ATG5 mRNA expression levels to predict gout were 0.764, 0.875 and 0.864, respectively. The area under ROC curve of gout predicted by the three combined was 0.928. Conclusion:lncRNA CRNDE, miR-181a-5p, and ATG5 may be involved in the pathoge-nesis of primary gouty arthritis, and are potential biological parameters for studying the pathogenesis of gout.

Humans ; Vitamins/therapeutic use* ; Iron, Dietary ; Diabetes Mellitus, Type 2 ; Nutrition Surveys ; Diet ; Vitamin A ; Vitamin K

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

[Abstract] Objective To explore the distribution situation of microRNA(miR) -30 gene single-nucleotide sites rs1192037A / T polymorphisms in Guangxi Zhuang population and compare its distribution differences with other populations and to analyze level of common blood lipid indexes in genotypes. Methods SNPscan was used to detect rs1192037A / T locus genotyping in 236 volunteers of Zhuang nationality in Guangxi. The genotypes and allele frequencies of rs1192037A / T locus genotyping in different genders and groups were analyzed. The levels of common blood lipids in the subjects were detected by roche automatic biochemical apparatus. Results Three genotypes of AA, AT and TT were found in rs1192037 A / T with the frequency distribution of 11. 0%, 38. 6% and 50. 4%, respectively. No significant differences in genotypes and alleles frequencies of rs1192037 A / T between different genders in Guangxi Zhuang population were observed (P > 0. 05) . However,there were significant differences in the genotype and allele frequency of miR-30 gene rs1192037 A / T in Guangxi Zhuang population compared with those of Europeans, Japanese, Africans, Mexicans and Indians published by HapMap (P<0. 05), and there were not significant difference in genotypes and allele frequencies in population of HCB and JTP (P>0. 05) . There were significant differences in the levels of TG among the 3 genotypes of rs1192037 A / T, and the TG levels of AT and TT genotypes were significantly higher than AA genotypes. Conclusion There are different degrees of rs1192037 A / T polymorphisms of miR-30 gene among Guangxi population and other ethnic populations and other regions. The polymorphism of rs1192037 A / T is related to the level of TG.

Objective: To understand the current situation and influencing factors of online psychological help seeking behavior among college students in Guangxi, China, so as to provide a scientific basis for improving the mental health of college students. Methods: From March to June 2022, a convenient sampling method was employed to select 2 239 university students from eight universities in Guangxi. The survey included the College Student Online Psychological Help Behavior Questionnaire, General Help Seeking Questionnaire (GHSQ), Attitudes Toward Seeking Professional Psychological Help Scale short Form (ATSPPH-SF), and the 10 item Kessler Psychological Distress Scale (Kessler10) to statistically analyze online psychological help seeking behavior and associated influencing factors. Results: The score of online psychological help seeking behavior among college students was ( 13.96± 5.20), and the scores of the three dimensions were as follows: online psychological self-help behavior (7.13± 2.95 ), online non-professional psychological help seeking behavior (4.28±2.19), online professional psychological help seeking behavior (2.54± 1.29 ). The factors influencing online psychological help seeking behavior were ranked as follows: mental health ( β = 0.32), CHSQ ( β =0.21), gender ( β =-0.09), ATSPPH-SF ( β =0.09) and registered residence ( β =0.08) ( P <0.05). Conclusion The online psychological help seeking behavior of college students in Guangxi is influenced by factors such as mental health. Seeking psychological help online has become a new form of support aimed at meeting the psychological health needs of college students, and constitutes an important supplement to offline psychological assistance. While there are similarities and differences between both modes, universities should pay attention to them.

Objective:To explore the expression and clinical significance of Janus protein tyrosine kinase/signal transducer and activator of transcription (JAK3/STAT5) signaling pathway in peripheral blood mononuclear cells (PBMCs) of patients with primary gouty arthritis (GA).Methods:Peripheral blood, clinical data and laboratory tests were collected from 50 patients with acute gout (AG), 50 patients with intermittent gout (IG) and 50 healthy controls (HC). Quantitative real-time-polymerase chain reaction (RT-qPCR) was used to detect mRNA expression level of JAK3/STAT5 related genes (JAK3, STAT5a, STAT5b). Enzyme linked immune sorbent assay (ELISA) was used to detect interleukin-2 (IL-2) concentration in subject′s plasma. Measurement data among the three groups that was in accordance with normal distribution was analyzed by one-way analysis of variance, pairwise comparisons using LSD, non-normal distribution data was analyzed by Mann-Whitney test or Kruskal-Wallis H test, and correlation analysis between variables was analyzed using Spearman correlation analysis. Results:① The mRNA expression levels of JAK3, STAT5a and STAT5b were significantly different among the three groups ( F=50.13, P<0.01; F=7.573, P=0.000 7; F=12.14, P<0.01), of which the JAK3 mRNA expression level in the HC group [(606±65)×10 -4] was significantly higher than that in the AG group [(103±13)×10 -4] and IG group [(114±24)×10 -4], and the difference was statistically significant (both P<0.01), while the STAT5a mRNA expression level in the AG group [(89±9)×10 -4] was significantly higher than that in the IG group [(59±4)×10 -4] and HC group [(61±4)×10 -4], and the difference was statistically significant ( P=0.002, P=0.003 9), and the expression level of STAT5b mRNA in HC group [(60±5)×10 -4] was significantly lower than that in AG group [(95±7)×10 -4] and IG group [(98±7)×10 -4], and the difference was statistically significant ( P=0.000 2, P<0.000 1). ② The difference of IL-2 concentration in plasma among the three groups was statistically significant ( F=22.87, P<0.01), and the serum IL-2 concentration in the AG group [(87.9±8.4) pg/ml] was significantly higher than that in the IG group [(32±4) pg/ml] and HC group [(44±4) pg/ml], and the difference was statistically significant (both P<0.01). ③ Spearman correlation analysis showed that the mRNA expression of STAT5a and STAT5b was positively correlated with the absolute value of neutrophils in patients with gout ( r=0.282, P<0.05; r=0.257, P<0.05). Conclusion:The IL-2/JAK3/STAT5 signaling pathway is involved in the occurrence and development of gout, suggesting that this pathway may play a key role in the pathogenesis of gout.

Objective:To detect the expression of interleukin 2 (IL-2)/Janus kinase 3/signal transduction and transcriptional activator 5 (JAK3/STAT5) signaling pathway in peripheral blood of patients with ankylosing spondylitis (AS) and explore its mechanism in the development and progression of AS.Methods:Clinical data, peripheral blood and laboratory tests of 30 patients with active AS (ASA), 30 patients with stable AS (ASS) and 50 healthy subjects (HC) were collected. The mRNA expression levels of JAK3, signal transduction and transcription activator 5a (STAT5a) and signal transduction and transcription activator 5b (STAT5b) were detected by quantitative real-time-polymerase chain reaction (RT-qPCR). The expression levels of JAK3, STAT5a and STAT5b proteins and phosphorylated proteins were detected by Western-blot. Plasma IL-2 concentration was determined by enzyme-linked immunosorbent assay (ELISA). Two independent samples t-test or one-way analysis of variance were used for measurement data consistent with normal distribution, LSD- t test was used for pairwise comparison between the three groups, Mann-Whitney U test or Kruskal-Wallis H test was used for non-normal distribution, χ2 test was used for correlation analysis of categorical variables. Spearman correlation analysis was used for correlation analysis between variables, and receiver operating characteristic (ROC) curve was used to evaluate the value of JAK3, STAT5a and STAT5b mRNA expression levels in monitoring AS activity. Results:① The mRNA expression levels of JAK3, STAT5a and STAT5b were significantly different among the three groups ( F=65.98, P<0.001; F=21.15, P<0.001; F=13.67, P<0.001). JAK3 mRNA expression in ASA group (2.5±0.9) was significantly higher than that in ASS group (1.1±0.4) and healthy subjects (1.0±0.5), the difference was statistically significant (both P<0.001). The mRNA expression level of STAT5a in ASA group (1.4±0.3) was significantly higher than that in ASS group (0.9±0.3) and healthy subjects group (1.0±0.3), the difference was statistically significant (both P<0.001). STAT5b mRNA expression level in ASA group (1.5±0.6) was significantly higher than that in ASS group (1.0±0.4) and healthy subjects (1.0±0.4), the difference was statistically significant (both P<0.001). The expression level of JAK3 mRNA in HLA-B27 positive group (1.9±1.0) was higher than that in HLA-B27 negative group (1.4±0.6), and the difference was statistically significant ( t=-2.22, P=0.032). The phosphorylation levels of JAK3, STAT5a and STAT5b showed statistically significant differences among the three groups ( F=91.56, P<0.001; F=25.15, P< 0.001; F=178.59, P<0.001). The phosphorylation level of JAK3 protein in ASA group (1.04±0.08) was significantly higher than that in ASS group (0.568±0.019) and healthy subjects (0.536±0.064), the difference was statistically significant (both P<0.001). The phosphorylation level of STAT5a protein in ASA group (1.166±0.096) was significantly higher than that in ASS group (0.923±0.018) and healthy subjects (0.911±0.017), the difference was statistically significant (both P<0.001). The phosphorylation level of STAT5b protein in ASA group (0.81±0.05) was significantly higher than that in ASS group (0.21±0.03) and healthy subjects (0.24± 0.07), the difference was statistically significant (both P<0.001). The difference of plasma IL-2 concentration among the three groups was statistically significant ( F=3.32, P=0.040). The IL-2 concentration in the ASA group [(110±40) pg/ml] was significantly higher than that in the ASS group [(89±40) pg/ml] and the healthy group [(88±39) pg/ml], the difference was statistically significant ( P=0.044, P=0.016). ② Spearman correlation analysis showed that STAT5a mRNA expression level was positively correlated with platelets in AS patients ( r=0.353, P=0.006). JAK3 mRNA expression level in ASA group was positively correlated with IL-2 concentration ( r=0.766, P<0.001), and negatively correlated with estimated glomerular filtration rate ( r=-0.485, P=0.007). STAT5a mRNA expression level was positively correlated with erythrocyte sedimentation rate ( r= 0.680, P<0.001), and STAT5b mRNA expression level was positively correlated with hypersensitive C-reactive protein (CRP) ( r=0.823, P<0.001). ③ The ROC curve showed that JAK3 mRNA expression level predicted the area under ROC curve (AUC) of ASA with a 95% CI of 0.920 (0.853, 0.987), sensitivity and specificity of 86.7% and 90.0%, respectively. STAT5a mRNA expression level predicted the AUC 95% CI of ASA was 0.874 (0.787, 0.961), and the sensitivity and specificity were 96.7% and 66.7%, respectively. STAT5b mRNA expression level predicted the AUC 95% CI of ASA was 0.749 (0.617, 0.881), and the sensitivity and specificity were 73.3% and 80.0%, respectively. Conclusion:This study suggests that IL-2/JAK3/STAT5 may be involved in the pathogenesis of AS, and JAK3 mRNA can be used as a biological indicator to monitor the activity of AS disease.

In this study, a novel oral drug delivery system based on linolenic acid-modified chitosan (CS-LA) micelle was developed to improve the oral bioavailability of doxorubicin (DOX), which was proven by its in vivo intestinal absorption in rats. The DOX-loaded CS-LA micelles (CS-LA@DOX) were prepared by the dialysis method. The synthesized micelle material was identified by proton nuclear magnetic resonance spectroscopy (¹H-NMR) and Fourier transform infrared spectroscopy (FT-IR). A series of the micelle properties, including particle size distribution, zeta potential, encapsulation efficiency (EE), drug loading (DL), micromorphology, polymorphy, and critical micelle concentration (CMC) were characterized or tested. The in vitro release of micelles was observed by the dialysis method, and the absorption-promoting effect of micelles was investigated by intestinal circulation experiments in rats. The animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Guilin Medical University. The results of ¹H-NMR and FT-IR showed that CS and LA were covalently bound via an amide linkage. The DOX encapsulated in the micelle core was in an amorphous state. The as-prepared micelles in the transmission electron microscope (TEM) image showed regular spherical shapes and uniform sizes with a series of excellent characteristics including (119.2 ± 2.1) nm of mean particle size [polymer dispersity index (PDI), 0.190 ± 0.08], +12.1 mV of zeta potential, (70.23 ± 0.74) % of EE, (8.77 ± 0.02) % of DL and 51.75 μg·mL^-1 of CMC. Compared with the reference, DOX hydrochloride, the proposed micelle drug delivery system showed an obvious sustained-release effect in vitro release; and enhanced drug absorption in the small intestine of rats.