The plateau region is known for its unique environmental characteristics of low oxygen, low pressure, strong radiation, cold and dryness. Under the low oxygen environment, human physiological functions and drug metabolism are significantly affected. In order to gain a deeper understanding of drug metabolism in the plateau hypoxic environment and to guide the rational use of drugs in the plateau region, the effects of plateau hypoxia on drug metabolism were reviewed in this paper, which focused on changes in metabolic profiles, enzyme activity and expression, and probed the relevant mechanisms in depth.

The plateau region is known for its unique environmental characteristics of low oxygen, low pressure, strong radiation, cold and dryness. Under the low oxygen environment, human physiological functions and drug metabolism are significantly affected. In order to gain a deeper understanding of drug metabolism in the plateau hypoxic environment and to guide the rational use of drugs in the plateau region, the effects of plateau hypoxia on drug metabolism were reviewed in this paper, which focused on changes in metabolic profiles, enzyme activity and expression, and probed the relevant mechanisms in depth.

Objective: To explore the effects of personality and sleep quality with psychological distress of junior and senior high school stduents, so as to provide a reference basis for precise interventions of junior and senior high school students mental health. Methods: In October 2023, a convenience sampling method was used to select 9 034 students aged 12-17 from Shiyan City as the study subjects. The Pittsburgh Sleep Quality Index (PSQI) and Kessler Psychological Distress Scale (K10) were used to collect information on sleep quality and psychological distress of junior and senior high school stduents. Between group comparison was conducted by using t-test and Chi-square test. Generalized linear models were employed to analyze the interaction and joint effects of personality and sleep quality on psychological distress. Results: The generalized linear model analysis showed that the interaction between personality and sleep quality on psychological distress was statistically significant of junior and senior high school students(effect size=0.80, P <0.01). The general linear model analysis indicated that, after adjusting for variables such as age, gender, screen time, and daily sitting time with the extroverted and good sleep quality group as the reference, the introverted and poor sleep quality group had the largest mean difference in psychological distress scores (difference=0.51, P <0.05). When stratified by sleep quality, psychological distress scores were higher in the introverted and neutral personality groups with both poor and good sleep quality compared to the extroverted group (poor sleep quality: introverted difference=3.71, neutral difference=1.14; good sleep quality: introverted difference=2.23, neutral difference=0.57, all P < 0.05). When stratified by personality, psychological distress scores were higher in the poor sleep quality groups for introverted, neutral, and extroverted individuals compared to their good sleep quality counterparts (differences=8.66, 7.83, 7.34, all P < 0.05 ). Conclusions Personality and sleep quality have interactive and joint effects on psychological distress of junior and senior high school stduents. Personalized psychological interventions should be developed based on personality and sleep quality.

Objective To examine the association between epidemiological characteristics of hemorrhagic fever with renal syndrome (HFRS) and meteorological factors in Shenzhen City during the period from 2012 to 2019. Methods Average atmospheric pressure, average air temperature, average relative humidity, precipitation, wind speed, and sunshine duration were captured from Meteorological Bureau of Shenzhen City each month from 2012 to 2019. The average monthly rodent densities in Shenzhen City from 2012 to 2019 were acquired from the Vector Surveillance Management System of Guangdong Provincial Center for Disease Control and Prevention, and the monthly HFRS incidence was retrieved from Shenzhen Municipal Disease Surveillance System from 2012 to 2019. The correlation between meteorological factors and the monthly incidence of HFRS was examined us ing Spearman’s rank correlation in Shenzhen City, and the temporal trends in monthly HFRS incidence and the degrees of freedom for the rodent density were determined in Shenzhen City with a generalized additive model. The optimal lag time was identified using excess risk (ER) and its 95% confidence interval (CI), and univariate and multivariate models were fitted to evaluate the impact of meteorological factors on HFRS incidence in Shenzhen City. Results The median number of incident HFRS cases was 3.00 (interquartile range, 3.25) in Shenzhen City from 2012 to 2019, with an average air temperature of (23.44 ± 4.91) °C, average relative humidity of (76.05 ± 7.61)%, median precipitation of 4.10 (interquartile range, 6.83) mm, average wind speed of (1.97 ± 0.26) m/s, average sunshine duration of (5.17 ± 1.64) h, and median monthly rodent density of 1.74% (interquartile range, 2.52%). Spearman’s rank correlation analysis showed that the average air temperature positively correlated with average relative humidity (r_s = 0.420, P < 0.05), precipitation (r_s = 0.658, P < 0.05) and sunshine duration (r_s = 0.633, P < 0.05), and the atmospheric pressure negatively correlated with average air temperature (r_s = −0.925, P < 0.05), relative humidity (r_s = −0.614, P < 0.05), precipitation (r_s = −0.789, P < 0.05) and sunshine duration (r_s = −0.437, P < 0.05), while the average relative humidity correlated positively with precipitation (r_s = 0.724, P < 0.05) and negatively with sunshine duration (r_s = −0.218, P < 0.05). Univariate modeling analysis showed that the ERs and their 95% CI were 0.639% (0.540%, 0.737%) for average atmospheric pressure, −7.157% (−8.113%, −6.190%) for average air temperature, −3.603% (−4.219%, −2.985%) for average relative humidity, −5.889% (−7.085%, −4.669%) forprecipitation,21.881% (−5.149%, 56.612%) for average wind speed, and −13.877% (−16.641%, −11.022%) for sunshine duation (all P values < 0.05). Multivariate modeling analysis showed that in the ensemble model combining average atmospheric pressure and precipitation, the highest ER (6.686%) was caused by increased average atmospheric pressure, and the highest absolute ER values for average air temperature (6.615%), average relative humidity (3.107%) and precipitation (5.386%) were seen after adjustment only for sunshine duration (all P values < 0.05), while the highest absolute ER for sunshine duration (11.875%) was found after adjustment for precipitation (P < 0.05). Conclusions An increase in average air temperature, relative humidity, precipitation and sunshine duration resulted in a reduced incidence rate of HFRS in Shenzhen City from 2012 to 2019, and an increase in average atmospheric pressure increased the incidence of HFRS. Meteorological factors are important determinants affecting HFRS incidence in Shenzhen City.

Objective To map the genome-wide distribution profile of histone H3K27me3 modification in diffuse gastric cancer tissues,identify target genes regulated by H3K27me3,and primarily explore the potential mechanism of its modification reprogramming in the occurrence and development of the tumor.Methods Normal gastric mucosal tissues and diffuse gastric cancer tissues were harvested from the patients who underwent examinations or treatments in the departments of gastroenterology and gastrointestinal surgery of our medical center between 2021 and 2023.There were 14 patients in the normal group(6 males and 8 females,average age of 46 years)and 14 patients in the gastric cancer group(8 males and 6 females,average age of 63 years).Cleavage under target and tagmentation(CUT&Tag)technology was employed to capture genomic regions modified by H3K27me3,and analyze the reprogramming characteristics of these modifications.RNA sequencing data,data from high-throughput chromosome conformation capture(Hi-C)technology,and publicly available single-cell data were integrated to investigate the target genes regulated by the reprogramming of H3K27me3 modifications in diffuse gastric cancer cells.Results The quality of the CUT&Tag and RNA sequencing data met the standards required for subsequent analysis.Histone H3K27me3 modifications in normal gastric mucosa and diffuse gastric cancer tissues were primarily distributed in distal intergenic regions and intronic regions.In gastric cancer tissues,compared to normal tissues,there was significant reprogramming of H3K27me3 modifications,characterized by a marked reduction in overall H3K27me3 signal intensity.The loss of 2 912 H3K27me3 signal peaks might lead to the up-regulation of 822 tumor-associated genes.Among them,56 genes displayed the most significant up-regulation(fold change in signal intensity≥2,P<0.05),with notable enrichment in the mammalian target of rapamycin complex 1(mTORC1)signaling pathway.Specifically,the methionine transporter SLC7A5 and the cystine transporter SLC7A11 were found to have the highest expression levels in gastric cancer tissues.Single-cell data revealed that the abnormal overexpression of SLC7A11 in diffuse gastric cancer was primarily observed in tumor epithelial cells.Further validation using public data and immunohistochemical experiments confirmed the elevated expression of SLC7A11 in diffuse gastric cancer,which is associated with poor prognosis in gastric cancer patients.Conclusion The reprogramming of histone H3K27me3 modification is an important epigenetic characteristic in diffuse gastric cancer.Loss of H3K27me3 signal peaks may up-regulate the expression of SLC7A11 in diffuse gastric cancer cells,and thereby promote tumor progression.

Objective:To assess the efficacy and safety of Tacrolimus（TAC）in combination with glucocorticosteroid（GC）for treating IgA vasculitis nephritis（IgAVN）in children.Methods:A retrospective analysis was conducted on pediatric patients who were diagnosed with IgAVN from January 2015 to January 2022 in Children's Hospital of Hebei Province.The patients presented with nephrotic-range proteinuria or persistent urine protein（>0.5g/24 h）despite adequate glucocorticoid and other treatments in patients who do not reach massive proteinuria levels.They were treated with TAC combined with GC. The following laboratory parameters were obtained for outcome assessment: 24-hour urinary protein excretion, serum albumin, serum creatinine levels, and fasting blood glucose measurements. The efficacy and adverse reactions of TAC were summarized.Results:A total of 97 children (55 males and 42 females) were included. The average age of diagnosis of IgA vasculitis was (8.65±2.46) years, and 95.9% of the children developed renal involvement within 30 days after diagnosis. Pathological examination of renal puncture: 5 cases of grade Ⅱa, 2 cases of grade Ⅱb, 31 cases of grade Ⅲa, 57 cases of grade Ⅲb, and 2 cases of grade Ⅳb.Remission rate at 3 months was 96.9%（94/97）.Three patients failed to achieve clinical remission who were treaed with other immunosuppressants.After 1, 3, 6 and 12 months of TAC treatment, the urine protein levels of 94 children were lower than those before treatment, and the differences were statistically significant ( P < 0.05), showing a gradual downward trend. Serum albumin levels were higher than those before treatment, and the differences were statistically significant ( P < 0.05), showing a gradual upward trend.After 3 months and 6 months of TAC treatment, the serum creatinine and fasting blood glucose of the children increased. With the remission of the disease, TAC dosage decreased, the mean values of serum creatinine and fasting blood glucose decreased after 12 months of treatment.The average treatment time of TAC was (10.8±2.6) months, the average follow-up time was (3.33±1.56) years, and the longest follow-up time was 8 years. During the follow-up period, there were no serious adverse reactions such as gastrointestinal discomfort, liver function damage and severe infection. After stopping GC and TAC treatment, 80 children got sustained remission. Conclusion:The combination of TAC and GC has been proved to be effective in treating IgAVN in children.The overall effective rate is high,and clinical remission can be achieved quickly with relatively mild adverse reactions.

Objective:To compare the efficacy of intranasal nebulized remimazolam versus esketamine for preoperative sedation in pediatric patients.Methods:In this randomized double-blind controlled trial, 90 pediatric patients scheduled for elective surgery with general anesthesia at Fuyang People′s Hospital between October 2024 and January 2025, were divided into 3 groups ( n=30 each) using a simple randomization: remimazolam group (group R), esketamine group (group S) and normal saline group (group C). Group R received intranasal nebulization of remimazolam 1.5 mg/kg, group S received intranasal nebulization of esketamine 1 mg/kg, and group C received intranasal nebulization of normal saline 0.05 ml/kg. Primary outcome: The preoperative anxiety was assessed using the modified Yale Preoperative Anxiety Scale before intranasal drug administration (baseline), at 10 and 20 min after administration, and before anesthesia induction. Secondary outcomes included sedation level (Ramsay Sedation Scale score), satisfaction with intranasal administration acceptance, parental separation anxiety and mask acceptance, development of emergence agitation, emergence time, time of recovery from anesthesia, and nausea and vomiting and increased secretions. Results:Compared to group C, the incidence of anxiety was significantly decreased at 10 and 20 min after intranasal nebulization and before anesthesia induction, the level of sedation was deepened (to light sedation), and the satisfaction with intranasal administration acceptance was decreased in group R ( P<0.017), the incidence of anxiety was significantly decreased before anesthesia induction, the level of sedation was deepened (to deep sedation), and the satisfaction with intranasal administration acceptance was increased in group S ( P<0.017), and the satisfaction with parental separation anxiety and mask acceptance and anesthesiologists′ satisfaction were significantly increased in R and S groups( P<0.017). Compared to group R, the incidence of anxiety was significantly increased at 10 min after intranasal nebulization (7 cases [23%] versus 20 cases [67%]), the level of sedation was lighter at 10 min after intranasal nebulization, the level of sedation was deeper, and the satisfaction with intranasal administration acceptance was increased in group S ( P<0.017). Compared to groups C and R, the emergence time and time of recovery from anesthesia were significantly prolonged in group S ( P<0.017). There was no significant difference in the incidence of emergence agitation, nausea and vomiting and increased secretions or in parental satisfaction among three groups ( P>0.05). Conclusions:Both intranasal nebulized remimazolam and esketamine can produce good preoperative sedation in pediatric patients. Compared to esketamine, remimazolam provides a more appropriate level of sedation with a faster onset and does not prolong the recovery from anesthesia, making it more suitable for preoperative sedation in minor procedures.

Objective:To compare the efficacy of intranasal nebulized remimazolam versus esketamine for preoperative sedation in pediatric patients.Methods:In this randomized double-blind controlled trial, 90 pediatric patients scheduled for elective surgery with general anesthesia at Fuyang People′s Hospital between October 2024 and January 2025, were divided into 3 groups ( n=30 each) using a simple randomization: remimazolam group (group R), esketamine group (group S) and normal saline group (group C). Group R received intranasal nebulization of remimazolam 1.5 mg/kg, group S received intranasal nebulization of esketamine 1 mg/kg, and group C received intranasal nebulization of normal saline 0.05 ml/kg. Primary outcome: The preoperative anxiety was assessed using the modified Yale Preoperative Anxiety Scale before intranasal drug administration (baseline), at 10 and 20 min after administration, and before anesthesia induction. Secondary outcomes included sedation level (Ramsay Sedation Scale score), satisfaction with intranasal administration acceptance, parental separation anxiety and mask acceptance, development of emergence agitation, emergence time, time of recovery from anesthesia, and nausea and vomiting and increased secretions. Results:Compared to group C, the incidence of anxiety was significantly decreased at 10 and 20 min after intranasal nebulization and before anesthesia induction, the level of sedation was deepened (to light sedation), and the satisfaction with intranasal administration acceptance was decreased in group R ( P<0.017), the incidence of anxiety was significantly decreased before anesthesia induction, the level of sedation was deepened (to deep sedation), and the satisfaction with intranasal administration acceptance was increased in group S ( P<0.017), and the satisfaction with parental separation anxiety and mask acceptance and anesthesiologists′ satisfaction were significantly increased in R and S groups( P<0.017). Compared to group R, the incidence of anxiety was significantly increased at 10 min after intranasal nebulization (7 cases [23%] versus 20 cases [67%]), the level of sedation was lighter at 10 min after intranasal nebulization, the level of sedation was deeper, and the satisfaction with intranasal administration acceptance was increased in group S ( P<0.017). Compared to groups C and R, the emergence time and time of recovery from anesthesia were significantly prolonged in group S ( P<0.017). There was no significant difference in the incidence of emergence agitation, nausea and vomiting and increased secretions or in parental satisfaction among three groups ( P>0.05). Conclusions:Both intranasal nebulized remimazolam and esketamine can produce good preoperative sedation in pediatric patients. Compared to esketamine, remimazolam provides a more appropriate level of sedation with a faster onset and does not prolong the recovery from anesthesia, making it more suitable for preoperative sedation in minor procedures.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

Objective To investigate the epidemiological characteristics of dengue fever in Shenzhen City in 2024, so as to provide insights into formulation of the preventive and control measures for dengue fever. Methods The epidemiological data of dengue cases reported in Shenzhen City in 2024 were extracted from the China Disease Prevention and Control Information System and field epidemiological survey data of dengue fever in Shenzhen City, and the temporal, regional and population distributions of dengue fever cases, source of acquire dengue virus infections, disease diagnosis and treatment and outbreaks were analyzed. The dengue virus nucleic acid was tested and the serotypes of dengue virus were characterized using real-time quantitative reverse transcription PCR (RT-qPCR) assay, and the dengue virus gene was sequenced using next-generation sequencing (NGS). In addition, the surveillance on the density of Aedes albopictus was performed using Breteau index (BI) and mosquito oviposition index (MOI). Results A total of 1 735 dengue fever cases were reported in Shenzhen City in 2024, including 952 local cases and 783 imported cases. Most imported dengue fever cases acquired infections from eight cities of Foshan, Guangzhou, Zhongshan, Jiangmen, Dongguan, Zhaoqing, Huizhou, and Zhuhai in the Pearl River Delta region (664 cases, 84.8% of total imported cases) into Baoan, Longgang, and Nanshan districts. The epidemic exhibited an early onset and rapid progression, peaking during the period between September and November (1 632 cases, 94.1% of total cases), and dengue fever cases were distributed across 73 subdistricts in 10 districts, with most cases reported in densely populated central and western regions. The dengue fever cases had a male-to-female ratio of 1.9∶1.0, and a median age of 37 (21) years, with a higher median age among local cases than among imported cases [40 (20) years vs. 33(15) years; Z = -10.30, P < 0.05]. Housework, unemployment, workers, and business service were predominant occupations (1 405 cases, 81.0% of total cases), and there was a significant difference in the constituent ratio of occupations between local and imported cases (χ² = 92.30, P < 0.05). Among the 1 735 dengue fever cases, the median duration from onset to definitive diagnosis was 3.3 (2.9) days, and 1 686 cases (97.2%) were identified in healthcare facilities, with a low rate of hospitalization and isolation seen in 1 701 inpatients with available epidemiological data (485 cases, 28.5% of total inpatients). A total of 29 outbreaks of dengue fever occurred in Shenzhen City across 2024, which primarily in construction sites (27 outbreaks, 93.1% of total). Dengue virus type I was the dominant serotype causing dengue fever in Shenzhen City in 2024. Sequencing showed that the genomes of dengue virus from multiple dengue fever cases in Shenzhen City shared a high sequence homology with those from cities neighboring Shenzhen City, and there might be intra-city transmission of dengue virus among multiple construction sites in Shenzhen City. The Aedes albopictus density was significantly higher in Shenzhen City in 2024 than in 2023, peaking from May to September. The annual MOI values ranged from 0.9 to 14.0, and the BI values ranged from 0.6 to 6.0. Conclusions The overall epidemic of dengue fever was severe in Shenzhen City in 2024, which was greatly affected by case importation from neighboring cities, construction sites-centered local transmission, and the effectives of routine mosquito vector control was not satisfactory. Integrated dengue fever control measures should be implemented, focusing on regional joint prevention and control mechanisms, capacity building for mosquito vector control, addressing challenges in epidemic containment at construction sites, and strengthening case detection and management systems.