Over the past two decades, genome-wide association study(GWAS) has identified numerous genetic variants and loci associated with heritable diseases. With the gradual maturation and saturation of GWAS methodologies, transcriptome-wide association study(TWAS) offers a novel perspective by linkinggenetic phenotypes to gene expression levels. By integrating TWAS with other multi-omics analyses, researchers can gain a deeper understanding of heritable diseases. This article provides an overview of recent groundbreaking and representative TWAS methods and tools, analyzes their strengths and limitations, and discusses future trends in TWAS development.

Based on LI Gao's theory of "heavy obstruction" and "blockage of the nine orifices"， this paper proposes the pathological concept of "heavy obstruction and orifice blockage". It is suggested that the core pathogenesis of functional constipation （FC） lies in simultaneous sinking of spleen and lung， together with accumulation and obstruction of dampness and turbidity， resulting in impaired movement of intestinal qi. Within this framework， spleen deficiency with sinking of dampness is considered as the primary pathological mechanism of outlet obstructive constipation （OOC）， while sinking of lung qi is regarded as the key mechanism underlying slow transit constipation （STC）. When both pathological mechanisms coexist， mixed constipation （MC） develops. Guided by this theory， FC is classified into three patterns for syndrome-based treatment. OOC is treated by promoting bowel movement， descending turbid pathogens， and opening the orifices to restore function， with self-formulated Shengxian Tongqiao Decoction （升陷通窍汤）. STC is treated by diffusing lung qi， regulating spleen function， raising sinking qi， and promoting transportation， with self-formulated Xuanfei Yunpi Decoction （宣肺运脾汤）. MC is treated by regulating lung and spleen function， simultaneously raising clear qi and descending turbidity， with self-formulated Xuanyun Tongqiao Decoction （宣运通窍汤）. In clinical practice， modifications should be made according to accompanying syndromes and individual conditions.

Based on LI Gao's theory of "heavy obstruction" and "blockage of the nine orifices"， this paper proposes the pathological concept of "heavy obstruction and orifice blockage". It is suggested that the core pathogenesis of functional constipation （FC） lies in simultaneous sinking of spleen and lung， together with accumulation and obstruction of dampness and turbidity， resulting in impaired movement of intestinal qi. Within this framework， spleen deficiency with sinking of dampness is considered as the primary pathological mechanism of outlet obstructive constipation （OOC）， while sinking of lung qi is regarded as the key mechanism underlying slow transit constipation （STC）. When both pathological mechanisms coexist， mixed constipation （MC） develops. Guided by this theory， FC is classified into three patterns for syndrome-based treatment. OOC is treated by promoting bowel movement， descending turbid pathogens， and opening the orifices to restore function， with self-formulated Shengxian Tongqiao Decoction （升陷通窍汤）. STC is treated by diffusing lung qi， regulating spleen function， raising sinking qi， and promoting transportation， with self-formulated Xuanfei Yunpi Decoction （宣肺运脾汤）. MC is treated by regulating lung and spleen function， simultaneously raising clear qi and descending turbidity， with self-formulated Xuanyun Tongqiao Decoction （宣运通窍汤）. In clinical practice， modifications should be made according to accompanying syndromes and individual conditions.

Objective To explore the relationship between pathogenic microorganism types,age and season in 2 188 children with respiratory tract infections.Methods A total of 2 188 children with respiratory tract in-fections admitted to the Department of Pediatrics,962 Hospital,Joint Logistic Support Force of PLA from June 2023 to May 2024 were selected as the study subjects.Targeted next generation sequencing(tNGS)tech-nology was used to detect 107 common pathogenic microorganism in children with respiratory tract infections,including Haemophilus influenzae,rhinovirus,Moraxella catarrhalis,Mycoplasma pneumoniae,Staphylococcus aureus,Streptococcus pneumoniae,human parainfluenza virus,human respiratory syncytial virus,etc.The re-spiratory tract infection situation and epidemiological characteristics of children in Harbin were analyzed.Re-sults Among 2 188 pediatric patients,98.5%(2 156/2 188)tested positive for pathogenic microorganism,with Haemophilus influenzae accounting for the highest proportion of 33.5%(732/2 188),followed by rhino-virus of 25.0%(547/2 188)and Moraxella catarrhalis of 24.8%(543/2 188).The positive rates of Hae-mophilus influenzae and human adenovirus in male children were higher than those in female children(P<0.05),while there were no statistically significant differences in the positive positive rates of other pathogenic microorganism between male and female children(P>0.05).Except for human adenovirus and influenza A virus,which showed no statistically significant differences in positive rates among different age groups(P>0.05),there were statistically significant differences in the positive rates of other pathogenic microorganism a-mong different age groups(P<0.05).The positive rates of pathogenic microorganism in preschool children were relatively high.There were no statistically significant differences in the positive rates of Streptococcus and Staphylococcus aureus in different seasons(P>0.05),while there were statistically significant differences in the positive rates of other pathogenic microorganism in different seasons(P<0.05).The positive rates of Haemophilus influenzae,Streptococcus pneumoniae,human metapneumovirus,human parainfluenza virus and SARS-Cov-2 were the highest in summer(P<0.05).Conclusion 2 188 children with respiratory tract infec-tions were mainly caused by pathogenic microorganism such as Haemophilus influenzae,rhinovirus,and Moraxella catarrhalis,etc.Preschool children is a susceptible group,and the prevalence of pathogenic microor-ganism varies seasonally.In clinical practice,relevant prevention and control measures should be developed based on this characteristic to reduce the incidence of diseases.

Acute ischemic stroke is the most common type of stroke, characterized by high mortality, disability, and recurrence rates. Intravenous thrombolysis is the core treatment method. Among them, alteplase is effective as the standard drug, but it has limitations such as narrow time window, high risk of bleeding, and the need for continuous infusion. The new generation of improved drug tenecteplase has the advantages of single intravenous injection and higher fibrin specificity, making it a potential alternative drug to alteplase. In addition, endovascular therapy compensates for the low recanalization rate of large vessel occlusion on the basis of intravenous thrombolysis. This article reviews the clinical progress of teneplase in the treatment of acute ischemic stroke, aiming to provide reference for optimizing the treatment plan of acute ischemic stroke.

Objective To investigate the correlation between changes in physiological indicators and altitude,age,and sex among ethnic Tibetan college students living in Xizang on long-term basis upon their first ever visit to a low-altitude region,thereby providing health guidance for long-term residents of high-altitude regions when they visit low-altitude environments for the first time.Methods A cluster random sampling method was used to select 170 healthy first-year college students of Tibetan ethnicity(85 males and 85 females),from Xizang Minzu University.The participants did not have any respiratory,circulatory,or nervous system diseases,nor any family history of such conditions.Based on their responses to questionnaires and the monitoring data of their physiological indicators,an analysis was conducted to assess the incidence and duration of deacclimatization symptoms among these Tibetan college students during the first month after their arrival at a low-altitude region.In addition,the R programming language and the SPSS software were used to analyze the correlation between changes in blood pressure,heart rate,and body weight and the participants'age,sex,and the altitude of their long-term residence in Xizang before and after their arrival at a low-altitude region.Results Statistical analysis revealed that Tibetan college students experienced deacclimatization symptoms within the first week of their first ever visit to a low-altitude region,primarily characterized by dizziness,fatigue,and drowsiness.The incidence was 41.9％among female students and 22.5％among male students.Furthermore,after arriving at low-altitude region,the participants experience an initial decrease followed by a recovery in both blood pressure and heart rate.They gained an average of 1.5 kg in body mass compared with their initial measurements upon arrival in a low-altitude region.Significant differences in blood pressure,heart rate,and body mass were observed among Tibetan students of different sexes and altitudes of their long-term residence in Xizang after their arrival in a low-altitude region.Conclusion After arriving at a low-altitude region,Tibetan college students exhibit marked changes in physiological indicators,showing strong correlations between systolic blood pressure,body mass,etc.,and sex,altitude,and other parameters.

Objective:To explore the relationship between maternal rejection and internet addiction in college students, as well as the chain mediating role of rejection sensitivity and adaptability.Methods:From March to May 2024, a total of 1 119 college students were surveyed using the short-form Egna Minnen av Barndoms Uppforstran for Chinese(s-EMBU-C), internet addiction test(IAT), rejection sensitivity questionnaire(RSQ), and the China college student adjustment scale(CCSAS).SPSS 26.0 statistical software was used for independent sample t-test, one-way ANOVA, Pearson product moment correlation, and multiple linear regression analysis, and PROCESS 4.0 macro program was used for chain mediation analysis. Results:(1)Maternal rejection (11.19±2.97) was positively correlated with internet addiction (44.89±9.74)( r=0.60, P<0.01) and rejection sensitivity (102.93±55.63)( r=0.63, P<0.01), while negatively correlated with adaptability (200.19±14.18)( r=-0.56, P<0.01) among college students. Rejection sensitivity was positively correlated with internet addiction ( r=0.75, P<0.01) and negatively correlated with adaptability ( r=-0.76, P<0.01). Adaptability was negatively correlated with internet addiction ( r=-0.68, P<0.01). (2)Maternal rejection had a significant direct effect on internet addiction among college students (effect value=0.193, 95% CI=0.145-0.241), accounting for 32.06%(0.193/0.602) of the total effect. Rejection sensitivity mediated the relationship between maternal rejection and internet addiction (effect value=0.290, 95% CI=0.232-0.357), accounting for 48.17%(0.290/0.602) of the total effect. Adaptability also mediated this relationship (effect value=0.028, 95% CI=0.009-0.053), accounting for 4.65%(0.028/0.602) of the total effect. Additionally, there was a chain mediation effect of rejection sensitivity and adaptability on the relationship between maternal rejection and internet addiction (effect value=0.091, 95% CI=0.052-0.130), accounting for 15.12%(0.091/0.602) of the total effect. Conclusion:Maternal rejection can directly influence internet addiction in college students, and it can also indirectly influence internet addiction through the independent mediating effects of rejection sensitivity and adaptability, as well as through the chain mediating effects of both rejection sensitivity and adaptability.

Objective:To explore the impact of the stimulator of interferon genes(STING)-interferon regulatory factor 3(IRF3)pathway on the senescence of rapid pacing HL-1 myocytes.Methods:HL-1 cells were divided into five groups: the control group(HL-1 cells without any treatment), pacing group(HL-1 cells paced for 48 hours), STING siRNA group(HL-1 cells paced for 48 hours and transfected with STING siRNA), NC siRNA group(HL-1 cells paced for 48 hours and transfected with NC siRNA), and H151 inhibitor group(HL-1 cells paced for 48 hours with the addition of 1 μmol/L STING inhibitor H151). Mitochondrial membrane potential was assessed in control and pacing group cells, and mitochondrial MitoTracker and TFAM co-localization staining was performed on these cells.Cellular senescence was evaluated using β-galactosidase staining in each group, and the positive rate of cellular senescence was observed and calculated.Western blotting was employed to detect the expression levels of STING, IRF3, P-IRF3, P16, P21, and P53 proteins in all groups.Immunofluorescence was utilized to examine the expression distribution of STING and P21 across the various groups.ELISA was performed to measure the concentrations of interleukin(IL)-1β, IL-6, and IL-8 in the cell supernatants from each group as part of the senescence-associated secretory phenotype(SASP).Results:Compared with the control group, the ratio of mitochondrial JC-1 multimer to monomer was significantly decreased in the pacing group( t=16.42, P<0.05), the co-localization of mitochondrial MitoTracker and TFAM in the cells was significantly weakened, the proportion of cells with positive cellular senescence-associated β-galactosidase staining significantly increased in the pacing group, the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 proteins were significantly elevated in the pacing group, and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants were markedly increased.Compared with the pacing group, the proportion of cells with positive cellular senescence-associated β-galactosidase staining decreased in the STING siRNA group and H151 inhibitor group ( F= 18.13, P<0.05), the expression levels of STING, P-IRF3/IRF3, P16, P21, and P53 were reduced in the STING siRNA group and H151 inhibitor group ( F=16.84, 26.56, 74.70, 31.80, 31.23, all P<0.05), and the concentrations of IL-1β, IL-6, and IL-8 in the cell supernatants decreased( F=197.80、1 339.00、1 308.00, all P<0.001). Conclusions:Rapid pacing of HL-1 cells can promote mtDNA release into the cytoplasm, activate the STING-IRF3 pathway, accelerate cellular senescence, and enhance the secretion of SASP.Inhibiting the expression of STING can delay the senescence induced by the rapid pacing of HL-1 cells and reduce SASP secretion.

Objective:To analyze the association between remnant cholesterol (RC) and the risk of atherosclerotic cardiovascular disease (ASCVD) in community population in Shanghai.Methods:Using baseline and follow-up data from the Shanghai Suburban Adult Cohort and Biobank, individuals with ASCVD (including coronary heart disease, stroke, myocardial infarction, and peripheral artery disease) at baseline were excluded. A Cox proportional hazards regression model was employed to analyze the relationship between RC and ASCVD risk and the association under different LDL-C levels.Results:A total of 57 281 participants were included, with a median follow-up of 5.61 person-years. During the follow-up, 1 436 ASCVD events (2.51%) were recorded. After adjusting for potential confounders, individuals with moderate ( HR=1.18, 95% CI: 1.03-1.36) or high RC levels ( HR=1.32, 95% CI: 1.15-1.51) had an increased risk of ASCVD. The association was stronger in participants younger than 60 years-old (interaction P=0.048). Participants with RC ≥0.97 mmol/L and LDL-C <3.40 mmol/L demonstrated a 19% ( HR=1.19, 95% CI: 1.06-1.35) increased risk of ASCVD. When RC ≥0.97 mmol/L and LDL-C ≥3.40 mmol/L, ASCVD risk increased by 42% ( HR=1.42, 95% CI: 1.21-1.67). Conclusions:Elevated RC increases ASCVD risk, regardless of LDL-C levels. RC can serve as a valuable predictor and intervention target for ASCVD.

We report the clinical course from birth to adolescence of a patient carrying a compound heterozygous variation in the ectonucleotide pyrophosphatase/phosphodiesterase family member 1(ENPP1) gene. The patient was diagnosed with generalized arterial calcification of infancy shortly after birth, and subsequently with autosomal recessive hypophosphatemic rickets type 2 at the age of 11 years. Following effective blood pressure control, treatment with neutral phosphate, calcitriol, and vitamin D was initiated. During follow-up, no progression of vascular calcification was observed. Through this case report and a review of relevant literature, we aim to enhance clinicians′ understanding of this rare condition.