Adverse drug reactions (ADRs) significantly impact clinical medication safety. The timely identification and prediction of ADRs rely on the efficient analysis of real-world data, such as electronic health records, social media, and spontaneous reporting databases. In recent years, the rapid advancement of artificial intelligence, particularly large language models, in natural language processing, causal reasoning, and complex data mining has provided new technological means for real-time ADRs monitoring and individualized prediction. This paper summarizes the latest research achievements in AI-driven ADRs monitoring. Focusing on diverse data sources, including structured databases and electronic health records, it elaborates on the advantages andchallenges of AI in ADRs event extraction, relationship identification, causal analysis, and risk prediction. The aim is to provide a theoretical reference for constructing more intelligent and efficient ADRs monitoring systems.

Objective:To analyze the pathogenic gene and prenatal diagnosis of a family with intellectual disability.Methods:Out of this family consisting of 17 members in three generations, four males had intellectual disability. The proband's elder sister (Ⅱ-7) visited Henan Provincial People's Hospital in Oct 2019 for genetic counseling at 8 weeks of gestation. After informed consent was obtained, peripheral blood samples of the family members were collected. The whole exome sequencing was performed on the genome DNA of the proband (Ⅱ-9, male) and his parents to screen the candidate variants for phenotype co-segregated analysis by Sanger sequencing. The expression vectors were constructed by homologous recombination and the splicing experiments were performed in vitro. Reverse transcription polymerase chain reaction, Sanger sequencing, and TA clone sequencing were used to analyze the effect of candidate variants on splicing. After the pathogenic variant was determined the proband's elder sister underwent prenatal diagnosis (Ⅲ-7) using goldeneyeTM20A genotyping system and Sanger sequencing. Results:A hemizygous synonymous variant of c.1302G>A (p. S434S) in DLG3 gene was found in the proband by whole exome sequencing, which was carried by his mother (Ⅰ-1) and co-segregated with the phenotype in other family patients. In vitro splicing experiment showed that c.1302G>A variant led to abnormal splicing of 88.24% transcripts, which further resulted in the reading frame shift and protein function impairment. The mutation was not detected in the fetus (Ⅲ-7), who was born alive later and showed no abnormal mental or behavioral development at the age of one and a half year and is still being followed up. Conclusions:The synonymous mutation c.1302G>A in DLG3 gene was the etiopathogenesis of X-linked intellectual disability in this family.

ObjectiveTo establish a neuroinflammation-based obesity and depression comorbidity （COM） model in mice and explore the pharmacodynamics and preliminary pharmacological mechanism of tripterine on COM mice. MethodC57BL/6J mice were randomly divided into a normal group （Chow）， a diet-induced obesity group （DIO）， and a COM group. The mice in the COM group were fed on a high-fat diet and chronically stressed with moist litter for 12 weeks to establish the COM model. C57BL/6J mice were randomly divided into a Chow group， a COM group， and a tumor necrosis factor-α（TNF-α） knock-down group. In the TNF-α knock-down group， TNF-α shRNA adeno-associated virus was injected into the amygdala through brain stereotaxis， and the expression of TNF-α in the amygdala was down-regulated. C57BL/6J mice were randomly divided into a Chow group， a DIO group， a DIO + low-dose tripterine group （0.5 mg·kg^-1）， a DIO + high-dose tripterine group （1.0 mg·kg^-1）， a COM group， a COM + low-dose tripterine group （0.5 mg·kg^-1）， and a COM + high-dose tripterine group （1.0 mg·kg^-1）. The body weight， food intake， glucose tolerance， white/brown fat ratio， serum total cholesterol （TC）， triglyceride （TG）， and high-/low-density lipoprotein cholesterol （HDL-C and LDL-C） content were recorded， and obesity of mice in each group was evaluated. Forced swimming test （FST）， tail suspension test （TST）， and open field test were used to evaluate the degree of depression of mice in each group. Immunofluorescence staining was used to detect the protein expression levels of neuropeptide Y， tryptophan hydroxylase 2 （TPH2）， and brain-derived neurotrophic factor （BDNF） in various brain nuclei of mice. Correlation analysis was used to detect the correlation of obesity and depression indexes. ResultThe comparison of the Chow group and the DIO group indicated that COM mice showed obesity and depression. To be specific， obesity was manifested as increased body weight and food intake （P<0.05， P<0.01）， as well as increased NPY expression in the central amygdala， and depression was manifested as prolonged immobility time in FST and TST （P<0.01）， and reduced TPH2-positive 5-hydroxytryptamine neurons in the dorsal raphe nucleus （DRN） and basolateral nucleus of the amygdala （BLA）. The down-regulation of TNF-α protein in BLA of COM mice shortened the immobility time in FST and TST （P<0.05， P<0.01）， increased TPH2/BDNF-positive neurons in BLA， and showed no significant changes in obesity. In DIO mice， the administration of 0.5 mg·kg^-1 tripterine for 9 days significantly decreased the 60 min blood glucose in glucose tolerance （P<0.01） and food intake （P<0.05）. In COM mice， 1.0 mg·kg^-1 tripterine was administered for 14 days to significantly decrease 30 min blood glucose in glucose tolerance （P<0.01）， and food intake （P<0.05）， and immobility time in TST （P<0.01）， increase TPH2-BDNF double-labeled cells in BLA and DRN， and reduce the area of TMEM119-stained cells. ConclusionThe model of obesity and depression comorbidity can be properly induced in mice under the condition of dual stress of energy environment. Tripterine can effectively interfere with obesity-depression comorbidity， and its mechanism may be related to the inhibition of central nervous system inflammation.

Objective:To evaluate the efficacy of medical cold patches in relieving burning pain and restoring skin homeostasis after hematoporphyrin monomethyl ether-based photodynamic therapy (HMME-PDT) for the treatment of port-wine stains.Methods:Forty patients with port-wine stains in the middle face, who met the inclusion and exclusion criteria, were collected from Department of Dermatology, the Seventh Medical Center of Chinese PLA General Hospital from November 2019 to April 2021, and randomly and equally divided into test group and control group. Patients in the test group received cold compress with medical cold patches at treatment sites for 1 hour immediately after HMME-PDT, and then once a day for 3 consecutive days, while those in the control group received no special treatment and experienced a spontaneous recovery. Pain numeric rating scale (NRS) scores were recorded immediately, 0.5, 1 and 12 hours after HMME-PDT. Skin surface temperature was measured 10 minutes before, and immediately, 30 minutes and 1 hour after HMME-PDT. Transepidermal water loss (TEWL) and water content of the stratum corneum (WCSC) were measured 10 minutes before, and immediately, 24, 48 and 72 hours after HMME-PDT. The scabbing rate was calculated at weeks 1, 2 and 3 after HMME-PDT. Two-way repeated measures analysis of variance was used for comparisons of observation indicators at different time points before and after treatment, and Bonferroni or Sidak′s test was used for comparisons between groups and within groups.Results:There were no significant differences in age, gender composition, TEWL or WCSC between the test group and control group before HMME-PDT (all P > 0.05) . Immediately after HMME-PDT, no significant difference in the NRS score was observed between the test group and control group (8.00 ± 1.17 vs. 8.20 ± 1.06, F = 0.30, P = 0.592) ; at 0.5 and 1 hour after HMME-PDT, the NRS score was significantly lower in the test group (6.25 ± 1.29, 4.80 ± 0.77, respectively) than in the control group (7.15 ± 0.99, 6.50 ± 0.69, respectively, both P < 0.05) . Immediately after HMME-PDT, the skin surface temperature in the test group and control group increased to 35.21 ± 1.333 ℃ and 35.64 ± 0.832 ℃, respectively, and there was no significant difference between the two groups ( P = 0.062) ; at 30 and 60 minutes after HMME-PDT, the skin surface temperature in the test group was 29.11 ± 1.59 ℃ and 32.46 ± 1.07 ℃ respectively, which were significantly lower than those in the control group (35.01 ± 0.91 ℃, 34.86 ± 0.74 ℃, F = 212.63, 100.20, respectively, both P < 0.001) . At 48 and 72 hours after HMME-PDT, the TEWL in the test group was 12.44 ± 0.67 g·h -1·m -2 and 10.85 ± 0.81 g·h -1·m -2 respectively, which were significantly lower than those in the control group (14.61 ± 0.34 g·h -1·m -2, 14.93 ± 0.24 g·h -1·m -2, F = 195.87, 520.54, respectively, both P < 0.001) , while the WCSC was significantly higher in the test group (57.83 ± 9.29 AU, 52.64 ± 8.09 AU, respectively) than in the control group (43.87 ± 4.82 AU, 38.68 ± 5.33 AU, F = 24.41, 49.22, respectively, both P < 0.001) . At 1 week after HMME-PDT, scab formation was observed in 3 cases in the test group, as well as in 6 cases in the control group, and there was no significant difference in the scabbing rate between the two groups ( P = 0.451) . Conclusion:The application of medical cold patches after HMME-PDT for the treatment of port-wine stains can reduce skin surface temperature, exert analgesic effects, shorten duration of postoperative pain, and promote the recovery of skin permeability barrier function.

Identification of significant biological relationships or patterns is central to many metagenomic studies.Methods that estimate association networks have been proposed for this pur-pose;however,they assume that associations are static,neglecting the fact that relationships in a microbial ecosystem may vary with changes in environmental factors(EFs),which can result in inaccurate estimations.Therefore,in this study,we propose a computational model,called the k-Lognormal-Dirichlet-Multinomial(kLDM)model,which estimates multiple association networks that correspond to specific environmental conditions,and simultaneously infers microbe-microbe and EF-microbe associations for each network.The effectiveness of the kLDM model was demonstrated on synthetic data,a colorectal cancer(CRC)dataset,the Tara Oceans dataset,and the American Gut Project dataset.The results revealed that the widely-used Spearman's rank correlation coefficient method performed much worse than the other methods,indicating the importance of separating samples by environmental conditions.Cancer fecal samples were then compared with cancer-free samples,and the estimation achieved by kLDM exhibited fewer associations among microbes but stronger associations between specific bacteria,especially five CRC-associated operational taxonomic units,indicating gut microbe translocation in cancer patients.Some EF-dependent associations were then found within a marine eukaryotic community.Finally,the gut microbial heterogeneity of inflammatory bowel disease patients was detected.These results demonstrate that kLDM can elucidate the complex associations within microbial ecosys-tems.The kLDM program,R,and Python scripts,together with all experimental datasets,are accessible at https://github.com/tinglab/kLDM.git.

Objective To induce fluconazole resistance in T.asahii by culture in medium containing increasing concentrations of fluconazole,and to evaluate the stability of the induced resistance.Methods Two T.asahii strains with a highest sensitivity to fluoconazole,including a clinical isolate CBS2479 (minumum inhibitory concentration (MIC) =0.25 μg/ml) and an environmental isolate CBS8904 (MIC =1.5 μg/ml),were selected from 11 T.asahii strains stored in the laboratory of the Department of Dermatology,General Hospital of Beijing Military Region.Both strains were respectively and serially subcultured in potato dextrose agar (PDA) medium containing growing concentrations of fluconazole (from 0.5 MIC to 256 μg/ml).E-test was performed to evaluate the susceptibility of T.asahii to fluconazole after each passage.To evaluate the stability of fluconazole resistance,the T.asahii isolates with induced resistance (MIC ＞ 256 μg/ml) were serially subcultured in drug-free PDA medium,and drug susceptibility assay was performed after each subculture.Results After serial culture in PDA medium containing fluconazole,high level of fluconazole resistance (MIC ＞ 256 μg/ml) developed in both of the fluconazole-susceptible T.asahii strains CBS2479 and CBS8904.The MIC value of fluconazole remained unchanged in the fluconazole-resistant strain CBS2479R,but gradually decreased to 64 μg/ml in the other resistant strain CBS8904R after 18-day culture in fluconazole-free PDA medium.Conclusions Fluconazole resistance can be induced in T.asahii strains from different origins by serial culture in medium containing growing concentrations of fluconazole,and the stability of the induced fluconazole resistance varies between strains of different origins.

Objective To observe the expression of decorin and its mRNA in the skin of normal mice and lesion of seleroderma mice to explore the possible role of decorin in the pathogenesis of scleroderma. Methods Scleroderma mice model induced by Bleomycin were developed and the expression of decorin in the scleroderma mice and normal control mice were determined by immunohistochemistry and RT-PCR. Comparisons between groups were performed with rank test and t test. Results According to the comparison of the histopathology of skin and lung and the skin collagen content between the model group and the control group, the construction of scleroderma model was successful. The results showed that the expression of decorin had no significant change in each group examined by immunohistochemistry, and the expression of decorin had high expression in normal control mice (0.60±0.15) and low expression in scleroderma mice (0.26±0.03) by RT-PCR. Conclusion The low expression of decorin is detected in scleroderma mice. It is suggested that this low expression maybe related to the high expression of TGF-β1 and TGF-β2 in scleroderma mice to neutralize or consume decorin.

ObjectiveTo study the Electrocardiogram (ECG) changes in AIDS patients at different age grades. MethodsThe ECG of 400 AIDS patients at different age were analyzed retrospectively. Results(①)The rate of abnormal ECG in the age group of 46 ～50 years was significantly higher than 11 ～ 15(P =0. 008) ,21 ～25( P = 0. 041 ),31 ～ 35 ( P = 0. 022 ),41 ～ 45 ( P = 0. 001 ) and 51 ～ 55 ( P = 0. 047 ) years groups respectively. (②)The rate of bradyarrhythmia in the age group of 46 ～ 50 years was significantly higher than 31 ～ 35 (U = 2. 44) ,36 -40( U = 2. 18 ) ,41 ～ 45 ( U = 2. 57 ) years groups ( P ＜ 0. 05 respectively. (③)The rate of left atrial and ventricular hypertrophy in 11 ～ 15 years group was significantly lower than the age groups older than 46 (except for 51 ～ 55years group) ;those aged ＞60 had higher atrial and ventricular hypertrophy rate than 36 ～40,41 ～45 and 51 ～55years groups ( P ＜ 0. 05 respectively). ConclusionsAIDS patients at all ages may present abnormal ECG, which is positively correlated with age.

OBJECTIVE To observe the significance of(1,3)-?-D-glucan in different humor samples on the rat model of systemic trichosporosis.METHODS Established the animal model with systemic infection of trichosporosis,to collect the bronchoalveolar lavage fluid(BALF),plasma and urine samples for determining,and checked with G-test,nested PCR and fungus culture.RESULTS In the earlier infection(10d),the sensitivity of G-test in the samples of plasma,BALF and urine were 80.00%,86.67%,and 6.67%,respectively,and had significant difference with control group.In the 30 plasma samples,the average sensitivity of G-test and nested-PCR blood fungus culture was 76.76%,68.85%,and 3.33%,respectively.With the statistical analysis,the sensitivity of G-test had significant deviation than fungus culture(P