Background Air pollution remains a critical public health issue, with persistent exposure to air pollutants continuing to pose significant health risks. Currently, research investigating the association between air pollution and myocardial infarction mortality in Shenzhen remains inadequate. Objective To quantitatively assess the association between air pollutants and myocardial infarction mortality in residents. Methods Based on the mortality surveillance system of Shenzhen Center for Disease Control and Prevention, we conducted a time-stratified case-crossover study of 10089 permanent residents who died from myocardial infarction in Shenzhen between 2013 and 2022. Using residential address information, we obtained individual-level exposure data for air pollutants from the China High Air Pollutants dataset and meteorological factors from the China Meteorological Administration Land Data Assimilation System. A time-stratified case-crossover study design was employed to construct a conditional logistic regression model to assess the association between short-term exposure to air pollutants and myocardial infarction mortality. The exposure-response relationship was visualized, and a comprehensive health risk assessment was performed. Results This study included a total of 10 089 cases of myocardial infarction deaths in Shenzhen. The median [interquartile range (IQR)] concentrations of fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), carbon monoxide (CO), and ozone (O₃) in Shenzhen from 2013 to 2022 were 24.59 (20.19) μg·m⁻³, 42.85 (28.42) μg·m⁻³, 8.53 (3.39) μg·m⁻³, 29.47 (13.56) μg·m⁻³, 0.77 (0.27) mg·m⁻³, and 86.53 (51.39) μg·m⁻³, respectively. The moving average concentrations of PM_2.5 and PM₁₀ over the current day and the previous 2 days (lag02) showed the highest risk of myocardial infarction mortality, with an odds ratio (OR) and 95% confidence interval (95%CI) of 1.004 (1.001, 1.007) and 1.004 (1.002, 1.006), respectively. At lag05, SO₂ demonstrated the strongest association with the risk of myocardial infarction mortality, with an OR (95%CI) of 1.042 (1.019, 1.065). The exposure-response relationships of PM_2.5, PM₁₀, and SO₂ with myocardial infarction mortality were approximately linear, whereas NO₂ exhibited a nonlinear relationship. At lag05, the highest risk of myocardial infarction mortality associated with NO₂ exposure was observed when the NO₂ concentration was ≤21.92 μg·m⁻³, with an OR (95% CI) of 1.024 (1.003, 1.046). The health risk assessment indicated that, using the WHO Air Quality Guidelines as the reference, the local PM_2.5 and NO₂ exposure led to an excess mortality of 398 and 298 cases, respectively. The sensitivity analysis revealed that after adjusting for O₃ and restricting the study period to 2013—2019, the effect estimates for PM_2.5, PM₁₀, NO₂, and SO₂ on myocardial infarction mortality slightly increased. Conclusion Short-term exposure to air pollutants, including PM_2.5, PM₁₀, NO₂, and SO₂, could increase the risk of myocardial infarction mortality. This study provides important scientific evidence for environmental health risk assessment and environmental management in Shenzhen.

Objective To investigate the mechanism of inhibitory effect of mollugin on hepatocellular carcinoma based on the ferroptosis pathway.Methods HepG2 cells were cultured in vitro and divided into control group,mollugin low-(10 μmol/L),medium-(20 μmol/L),and high-dosage(40 μmol/L)groups based on the inhibitory concentration of 50%.The cell viability was detected by CCK-8 method,cytotoxicity was detected by LDH kit,and the ability of cell colony formation was observed by clone formation assay,the contents of GSH,MDA,ROS,SOD,superoxide,lipid peroxide and MMP were detected,the protein expression of ferroptosis suppressor protein 1(FSP1),GTP cyclohydrolase 1(GCH1),dihydroorotate dehydrogenase(DHODH)and glutathione peroxidase 4(GPX4)were detected by Western blot,the mRNA expression of FSP1,DHODH,GCH1 and GPX4 were detected using RT-qPCR.The effect of mollugin on cell viability and GSH,MDA contents of hepatocellular carcinoma cells were observed under overexpression and silencing of GPX4 by mollugin.Results The medium-and high-dose of mollugin could reduce the number of clone formation in HepG2 cells,decrease the GSH content and SOD activity of cells,increase the content of MDA,superoxide,lipid peroxides and ROS,and decreased MMP(P<0.001).The intervention of mollugin had no significant effect on the expressions of FSP1,GCH1,DHODH protein and mRNA in HepG2 cells,but could decrease the expression of GPX4 protein and mRNA(P<0.001).Overexpression and silencing experiments confirmed that GPX4 was the core target for the regulation of ferroptosis by mollugin.Conclusion Mollugin mainly exerts its anti-liver cancer effect by regulating GPX4 mediated ferroptosis.

Objective:To investigate the effect of Hounsfield Units (HU) at the upper instrumented vertebra (UIV) on postoperative proximal junctional kyphosis (PJK) after pelvic fixation with second sacral alar-iliac (S 2AI) screws in patients with degenerative spinal deformity. Methods:A total of 66 patients with degenerative spinal deformity who underwent pelvic fixation with S 2AI screws from August 2015 to April 2021 were retrospectively reviewed. The cohort included 4 males and 62 females, aged 61.9±7.3 years (range, 43-78 years), with a follow-up period of 18.4±14.3 months (range, 6-60 months). The prevalence of PJK was 26%. Patients were divided into two groups based on the occurrence of PJK during postoperative follow-up: the PJK group (17 cases) and the non-PJK group (49 cases). HU measurements were taken at the UIV, the vertebral body cephalad to the UIV (UIV+1), and the L 3 and L 4 vertebral bodies. The following sagittal radiographic parameters were measured: thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), PI minus LL (PI-LL), and sagittal vertical axis (SVA) at preoperative, postoperative, and final follow-up. General information and HU values of the two groups were compared, and Pearson correlation analysis was performed on HU values, bone mineral density (BMD), and T scores. Logistic regression analysis was used to explore the risk factors for PJK. Results:The HU values of L 3 and L 4 were significantly positively correlated with the BMD and T scores respectively ( r=0.530, P<0.001; r=0.537, P<0.001). Age, gender, follow-up time, fixation levels, bone mineral density (BMD) and T-score were not significantly different between PJK and non-PJK group. The average HU values of UIV and UIV+1 in PJK group was 104.3±32.9, whlie the average HU values of UIV and UIV+1 in non-PJK group was 133.7±29.5. The difference of HU between the two groups was statistically significant ( t=3.441, P=0.001). Logistic regression analysis showed that average HU values of UIV and UIV+1 [ OR=0.960, 95% CI(0.933, 0.987), P=0.004] and changes of lumbar lordosis [ OR=1.049, 95% CI(1.007, 1.092), P=0.023] were independent risk factors for PJK, with an optimal cutoff obtained by ROC that 106 for average HU values of UIV and UIV+1 and 22.5° for changes of LL. Conclusion:The average HU values of UIV and UIV+1 < 106 and changes of lumbar lordosis > 22.5° are independent risk factors for PJK after pelvic fixation with second sacralalar-iliac in patients with degenerative spinal deformity.

OBJECTIVE To observe the clinical efficacy of Maitong Jun'an Decoction in treating coronary heart disease(CHD)angina of qi deficiency and blood stasis type,and preliminarily elucidate its possible mechanism of action through transcriptomics meth-ods.METHODS A total of 140 patients with CHD angina of qi deficiency and blood stasis type were included and randomly divided into a treatment group and a control group,with 70 cases in each group.During the treatment period,3 patients in the control group dropped out.The control group received basic Western medicine treatment for secondary prevention of CHD,while the treatment group received Maitong Jun'an Decoction in addition to the treatment in the control group.The treatment period for both groups was 8 weeks.Before and after treatment,the patients in both groups were evaluated for the TCM syndrome score,Canadian Cardiovascular Society(CCS)angina grading,Seattle angina questionnaire(SAQ)score,self-rating anxiety scale(SAS),self-rating depression scale(SDS)score,and adverse reactions.The peripheral blood of 9 patients before and after treatment was selected for transcriptomic sequencing based on the principle of gender,age,and disease duration matching.RESULTS After treatment,the TCM syndrome scores and total scores of the 2 groups were significantly reduced(P<0.01).The treatment group was better than the control group in improving chest pain,chest tightness,shortness of breath,fatigue and total score(P<0.05,P<0.01);the overall improvement rate of CCS angina grading in the treatment group was better than that in the control group(P<0.05);the SAQ,SAS and SDS scores of the 2 groups were significantly reduced before and after treatment(P<0.01),and the SAQ score of the treatment group was improved better than that of the control group(P<0.05,P<0.01).The transcriptomics results showed that there were 862 significantly different mR-NAs before and after treatment,including 509 up-regulated and 353 down-regulated.GO analysis showed that there were 666 biologi-cal processes in the differentially expressed mRNAs,mainly including viral gene expression,translation initiation,RNA catabolism,etc.There were 112 cell components,mainly including focal adhesion,ribosome subunit,nuclear spot,etc.There were 94 molecular functions,mainly including double-stranded RNA binding,cadherin binding,transcription co-regulatory factor activity,etc.KEGG analysis showed that the differentially expressed mRNAs enriched in 20 signaling pathways,mainly including glycerophospholipid me-tabolism pathway,AMPK signaling pathway,ribosome pathway,etc.CONCLUSION Maitong Jun'an Decoction can improve clini-cal symptoms in patients with CHD angina of qi deficiency and blood stasis type.Its mechanism of action is multi-target and multi pathway,mainly related to the regulation of glycerophospholipid metabolism pathway,AMPK signaling pathway,ribosome pathway.

Objective·To investigate the effects of sennoside A(SA)on the formation of atherosclerotic plaque and the expression of 5-hydroxytryptamine(5-HT)and its receptor in mice with diabetes mellitus type 2(T2DM).Methods·Twelve mice with knocked-out apolipoprotein E gene were randomly divided into two groups,namely the model group and the model+SA group,with six mice in each group.Six C57BL/6J mice with the same genetic background were used as the control group.The control group was fed with normal diet,and the model group and the model+SA group were given intraperitoneal injection of streptozotocin(30 mg/kg)daily on the basis of high-fat diet to establish a model of T2DM.The model+SA group was given SA daily by gavage for 8 weeks,and the control group and the model group were given equal volume of distillation-distillation H2O by gavage.The body weight,fasting blood glucose(FBG)and 2-h postprandial blood glucose of mice were compared before and after modeling and treatment.The area of aortic plaque was observed by oil red O staining and hematoxylin-eosin(H-E)staining,and the level of 5-HT in serum and thoracic aorta was measured by ELISA kit.Western blotting was used to detect the expression of 5-hydroxytryptamine receptor 2B(HTR2B)and serotonin transporter(SERT)in thoracic aorta of mice.Results·Compared with the control group,the body weight,FBG and 2-h postprandial blood glucose in the model group increased,and glucose metabolism was disordered.The expression of HTR2B and SERT protein in thoracic aorta increased,while the concentration of 5-HT in thoracic aorta decreased.The serum 5-HT concentration increased(all P<0.05).After treatment with SA,compared with the model group,the body weight of the model+SA group decreased,and FBG and 2-h postprandial blood glucose were significantly improved.The area of aortic plaque and the expression of HTR2B and SERT protein in thoracic aorta significantly decreased,while the concentration of 5-HT increased.The serum 5-HT concentration decreased(all P<0.05).Conclusion·SA can reduce atherosclerotic plaque area in T2DM mice,which may be related to lowering blood glucose and inhibiting the expression of 5-HT and its receptor.

Radiotherapy is widely used in the management of advanced colorectal cancer (CRC). However, the clinical efficacy is limited by the safe irradiated dose. Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation. The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination (HR) DSB repair, and its functions may be affected by HERC2 or BAP1. Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes; however, the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn't been defined. Through activity-based profiling, we identified PT33 as an active entity for HR repair suppression. Subsequently, we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen. Mechanistically, pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction, interrupting HR repair. Consequently, PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo. Overall, these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain.

Objective:To analyze the association of pre-pregnancy body mass index (BMI) and gestational weight gain with macrosomia.Methods:In this retrospective cohort study, data of all puerperae and newborns in the Obstetrics Center of Peking Union Medical College Hospital from July 2020 to June 2021 were collected, including basic maternal information, pregnancy complications and neonatal conditions. A total of 2 422 pregnant women with full-term singleton live birth and their newborns were included in the analysis. The incidence of macrosomia (≥4 000 g) was calculated according to the birth weight of the newborns. Logistic regression and heat map were used to analyze the associations of pre-pregnancy BMI and gestational weight gain with macrosomia.Results:The incidence of macrosomia was 4.00% (97/2 422) in full-term singleton live birth newborns. Pre-pregnancy body weight, pre-pregnancy BMI, pre-pregnancy overweight/obesity rate, pre-delivery body weight, total weight gain during pregnancy, mean weekly weight gain during pregnancy, the proportion of excessive weight gain during pregnancy, duration of pregnancy, and the proportion of primiparity and education level of junior college or below were all significantly higher in the puerperae of the macrosomia group than those in the non-macrosomia group [(63.87±8.27) vs (58.14±7.86) kg, (23.33±2.97) vs (21.60±2.72) kg/m2, 35.1% vs 17.3%, (77.48±9.11) vs (70.02±8.79) kg, (13.61±4.56) vs (11.88±4.40) kg, (0.34±0.11) vs (0.30±0.11) kg, 58.8% vs 31.1%, (280.47±7.79) vs (276.14±7.83) d, 34.1% vs 23.7%, 18.6% vs 7.5%] (all P<0.05). Pre-pregnancy BMI ( OR=1.227, 95% CI: 1.145-1.314), mean weekly weight gain during the whole pregnancy ( OR=33.453, 95% CI: 5.172-217.947), duration of pregnancy ( OR=1.083, 95% CI: 1.055-1.112), primiparity ( OR=1.969, 95% CI: 1.232-3.101) and education level of junior college or below ( OR=2.525, 95% CI: 1.325-4.668) were all positively associated with occurrence of macrosomia (all P<0.05). The incidence of macrosomia increased with the pre-pregnancy body mass index and mean weekly weight gain during the whole pregnancy. Conclusions:High pre-pregnancy BMI and mean weekly weight gain during the whole pregnancy are associated with the increased risk of macrosomia. Appropriate weight management during pregnancy may help to reduce the incidence of adverse pregnancy outcomes.

Objective: To study the relationship between the single nucleotide polymorphism of HLA⁃A rs3132682 and the risk of liver cancer. Methods: The author selected 291 cases of liver cancer patients in Yanbian area as the experimental group and 272 healthy people as the control group. The genotypes and allele frequencies of the two loci were detected by MassARRAY SNPS mass spectrometry. Odds ratio (OR) and 95% confidence interval (CI) were calculated by unconditional logistic regression to evaluate the risk of liver cancer in patients with different genotypes. Results: There were G and C alleles in HLA⁃A rs3132682 locus , GG , GC and CC genotype. After adjusting for confounding factors in HLA⁃A rs3132682 locus , there was correlation between CC genotype and the risk of liver cancer compared with GG genotype (P < 0. 05) . Stratification analysis showed that compared with the population with CG + GG genotype , the Korean population with CC genotype increased the risk of liver cancer by 3. 331 times. Conclusion The single nucleotide polymorphism of HLA⁃A rs3132682 is correlated with the risk of liver cancer in Yanbian area.

OBJECTIVES: This study aimed to investigate the associations of obesity phenotypes with hypertension stages, phenotypes, and transitions among middle-aged and older Chinese. METHODS: Using the 2011-2015 waves of the China Health and Retirement Longitudinal Study, we conducted a cross-sectional analysis included 9,015 subjects and a longitudinal analysis included 4,961 subjects, with 4,872 having full data on the hypertension stage and 4,784 having full data on the hypertension phenotype. Based on body mass index and waist circumstance, subjects were categorized into 4 mutually exclusive obesity phenotypes: normal weight with no central obesity (NWNCO), abnormal weight with no central obesity (AWNCO), normal weight with central obesity (NWCO), and abnormal weight with central obesity (AWCO). Hypertension stages were classified into normotension, pre-hypertension, stage 1 hypertension, and stage 2 hypertension. Hypertension phenotypes were categorized as normotension, pre-hypertension, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH). The association between obesity phenotypes and hypertension was estimated by logistic regression. A comparison between different sexes was conducted by testing the interaction effect of sex. RESULTS: NWCO was associated with normal→stage 2 (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.11 to 3.42), maintained stage 1 (OR, 1.62; 95% CI, 1.14 to 2.29), and normal→ISH (OR, 1.39; 95% CI, 1.05 to 1.85). AWCO was associated with normal→stage 1 (OR, 1.75; 95% CI, 1.40 to 2.19), maintained stage 1 (OR, 2.77; 95% CI, 2.06 to 3.72), maintained stage 2 (OR, 2.80; 95% CI, 1.50 to 5.25), normal→ISH (OR, 1.56; 95% CI, 1.20 to 2.02), and normal→SDH (OR, 2.54; 95% CI, 1.72 to 3.75). An interaction effect of sex existed in the association between obesity phenotypes and hypertension stages. CONCLUSIONS This study highlights the importance of various obesity phenotypes and sex differences in hypertension progression. Tailored interventions for different obesity phenotypes may be warranted in hypertension management, taking into account sex-specific differences to improve outcomes.

Objective:To explore artificial intelligence technology and propose an algorithm for automatic identification of dicentric chromosomes to realize fast and high-throughput biodosimetry. In order to solve the time-consuming and laborious problem of manual analysis of dicentric chromosomes.Methods:Combining artificial intelligence technology and image processing technology, based on MATLAB software, algorithms like image preprocessing, threshold segmentation algorithm, binarization processing, area identification algorithm, convolutional neural network algorithm and double centripetal recognition algorithm were applied. A fuzzy membership function was defined to describe the degree of each chromosome belonging to a dicentric chromosome, and the discrimination threshold was set to realize the automatic identification of dicentric chromosomes.Results:Through the test on 1 471 chromosome images, compared with manual recognition, the detection rate of dicentric chromosomes cells of this algorithm reached 70.7%.Conclusions:This algorithm method carries out a preliminary study on the automatic identification of dicentric chromosomes with good result.