BACKGROUND: Previous evidence showed that ambient air pollution and cardiovascular mortality are related. However, there is a lack of evidence towards the modification effect of long-term lifestyle on the association between short-term ambient air pollution and death from cardiovascular events. METHOD: A total of 14,609 death from major adverse cardiovascular events (MACE) were identified among the China Kadoorie Biobank participants from 2013 to 2018. Ambient air pollution exposure including particulate matter 2.5 (PM_2.5), SO₂, NO₂, CO, and O₃ from the same period were obtained from space-time model reconstructions based on remote sensing data. Case-crossover design and conditional logistic regression was applied to estimate the effect of short-term exposure to air pollutants on MACE mortality. RESULTS: We found MACE mortality was significantly associated with PM_2.5 (relative percent increase 2.91% per 10 µg/m³ increase, 95% CI 1.32-4.53), NO₂ (5.37% per 10 µg/m³ increase, 95% CI 1.56-9.33), SO₂ (6.82% per 10 µg/m³ increase, 95% CI 2.99-10.80), and CO (2.24% per 0.1 mg/m³ increase, 95% CI 1.02-3.48). Stratified analyses indicated that drinking was associated with elevated risk of MACE mortality with NO₂ and SO₂ exposure; physical inactivity was associated with higher risk of death from MACE when exposed to PM_2.5; and people who had balanced diet had lower risk of MACE mortality when exposed to CO and NO₂. CONCLUSIONS The study results showed that short-term exposure to ambient PM_2.5, NO₂, SO₂, and CO would aggravate the risk of cardiovascular mortality, yet healthy lifestyle conduct might mitigate such negative impact to some extent.
Humans ; Cardiovascular Diseases/epidemiology* ; China/epidemiology* ; Male ; Female ; Air Pollution/adverse effects* ; Middle Aged ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; Environmental Exposure/adverse effects* ; Life Style ; Aged ; Adult ; Risk Factors ; Cross-Over Studies ; East Asian People

Objective:To discuss the regulatory effect of berberine(BBR)on fatty acids in the human glioma T98G cells and its effect on the cell proliferation,migration,and invasion,and to clarify its potential mechanism.Methods:The T98G cells at logarithmic growth phase were divided into control group and different concentrations(25,50,and 100 mg·L-1)of BBR groups.Cell wound healing assay was used to detect the migration rates of the cells in various groups;Transwell chamber assay was used to detect the invasion rates of the cells in various groups.The T98G cells at logarithmic growth phase were divided into control group and 100 mg·L-1 BBR group,and Mass spectrometry was used to detect the fatty acid contents in the cells in two groups.The T98G cells at logarithmic growth phase were divided into control group and different concentrations(50,100,and 150 mg·L-1)of BBR groups;Western blotting method was used to detect the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(AKT),phosphorylated AKT(p-AKT),sterol regulatory element-binding protein 1(SREBP-1),and fatty acid synthase(FASN)in the cells in various groups.The expression of FASN was suppressed by gene silencing technology,and the T98G cells at logarithmic growth phase were divided into control group,shFASN1 group,and shFASN2 group.Western blotting method was used to detect the expression levels of FASN protein in the cells in various groups;clone formation assay was used to detect the clone formation of the cells in various groups;cell wound healing assay was used to detect the migration rates of the cells in various groups.Results:Compared with control group,the migration rates and invasion rates of the cells in different concentrations of BBR groups were decreased in a concentration-dependent manner(P<0.01),and the fatty acid content in the cells in 100 mg·L-1 BBR group was significantly decreased(P<0.01).Compared with control group,the expression levels of p-PI3K,p-AKT,SREBP-1,and FASN proteins in the cells in 150 mg·L-1 BBR group were significantly decreased(P<0.05 or P<0.01),and the expression level of SREBP-1 protein in the cells in 100 and 150 mg·L-1 BBR groups were significantly decreased(P<0.01).After suppression of FASN expression,compared with control group,the expression levels of FASN protein in the cells in shFASN1 and shFASN2 groups were significantly decreased(P<0.01),and the expression level of FASN protein in the cells in shFASN2 group was lower than that in shFASN1 group(P<0.05);compared with control group,the numbers of clone formation and migration rates of the cells in shFASN1 and shFASN2 groups were significantly decreased(P<0.01),and the migration rate of the cells in shFASN2 group was significantly lower than that in shFASN1 group(P<0.05).Conclusion:BBR interferes with fatty acid synthesis in the glioma T98G cells by reducing the expression of the PI3K/AKT/SREBP-1/FASN pathway related proteins,and decrease their migration and invasion capabilities.

AIM: To study the perception of first-order grating acuity and second-order spatial contrast sensitivity in patients with monocular anisometropia amblyopia.METHODS:A total of 715 children(715 eyes)diagnosed as monocular anisometropia amblyopia in our hospital from January 2018 to December 2022 were collected as amblyopia group, and 745 children(745 eyes)with normal corrected visual acuity were collected. The best corrected visual acuity(BCVA), first-order grating acuity and/or second-order spatial contrast sensitivity were measured, repectively. The perception ability of amblyopia patients to first-order grating acuity and second-order spatial contrast sensitivity were analyzed.RESULTS:There were significant differences between amblyopia group and normal control group in the perception of first-order grating acuity(11.58±6.10 vs. 20.27±3.47, P<0.001)and second-order spatial contrast sensitivity(0.33±0.16 vs 0.12±0.04, P<0.001). And there were significant differences between mild-to-moderate amblyopia and severe amblyopia patients in first-order grating acuity(12.10±6.23 vs. 8.13±3.70, P<0.001)and second-order spatial contrast sensitivity(0.32±0.16 vs. 0.37±0.17, P<0.05).CONCLUSION: The first-order and second-order visual pathway of the cerebral cortex in children with monocular anisometropia amblyopia have different degrees of damage. The injury of severe amblyopia is more serious than that of mild-to-moderate amblyopia.

AIM: To investigate the efficacy and safety of ZKY001 eye drops with different concentrations in the treatment of corneal epithelial defects(CED)after primary pterygium excision.METHODS: This was a multicenter, randomized, double-blinded, placebo-controlled phase II clinical trial. From March 15, 2022 to November 14, 2022, patients with primary pterygium who had undergone surgery were recruited from 12 tertiary hospitals across China. Using block randomization, 178 patients(178 eyes)were randomly assigned to 3 groups in a 1:1:1 ratio: 0.002% ZKY001 group(n=59), 0.004% ZKY001 group(n=59), and placebo group(n=60, receiving ZKY001 sham eye drops). Subjects in each group received 1 drop of the study drug 4 times per day for 4 d. The percentage of CED area recovery from baseline, the first complete healing time of CED area, the number of first complete healing cases of CED, and changes in visual analogue scale(VAS)scores for eye discomfort including eye pain, foreign body sensation, tearing and photophobia were observed.RESULTS: In terms of improvement in CED, there were no statistically significant differences among the three groups including the first healing time of CED, the percentage improvement in CED area compared to baseline, and the percentage of first healing cases at different follow-up visits(all P>0.05). Numerically, the first healing time of CED was shorter in the test groups compared to the placebo group(67.87±21.688 h for the 0.002% ZKY001 group, 61.48±22.091 h for the 0.004% ZKY001 group, and 68.85±20.851 h for the placebo group). On D1 morning, the percentage improvement in CED area compared to baseline was maximally different from the placebo group, and the numerical difference advantage was maintained at subsequent follow-up visits. The number of first healing cases in the CED area at different follow-up visits was higher in the test groups than the placebo group. In terms of improvement in ocular discomfort, the total VAS scores were lower in the test groups compared to the placebo group, mainly due to reductions in foreign body sensation and pain scores. At D3, the 0.004% ZKY001 group showed statistically significant improvement in foreign body sensation(P<0.017). In terms of safety, the overall incidence of adverse events was low(9.0%)and similar among groups.CONCLUSION: The use of ZKY001 eyedrops after primary pterygium surgery can safely improve the CED repair, and alleviate postoperative symptoms caused by CED.

Objective:To investigate the effect of preoperative radiotherapy on postoperative recurrence in central hepatocellular carcinoma patients treated by hepatectomy.Methods:A retrospective cohort study was conducted. Clinicopathological data of 142 patients with central hepatocellular carcinoma who underwent surgical treatment at the Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College from January 2016 to January 2019 were retrospectively collected. According to whether they received preoperative radiotherapy or not, the patients were divided into preoperative radiotherapy group (30 cases) and surgery-only group (112 cases). The main observation indexes were recurrence-free survival (RFS), intraoperative bleeding amount, operation time and the occurrence of postoperative complications. Kaplan-Meier method was used for survival analysis, and log-rank test was used for intergroup comparisons; the differences between the two groups for each factor were evaluated by standardized mean difference (SMD); Cox proportional hazards model was used to analyze the influencing factors of RFS in central hepatocellular carcinoma patients with hepatectomy. Propensity score matching (PSM), regression model-adjusted propensity score (CAPS) and inverse probability of treatment weighting (IPTW) methods were used to investigate the relationship between exposure factors and confounding variables and RFS. Sensitivity analysis was performed using E-value to assess the potential impact of unmeasured confounders on outcomes.Results:Men comprised 96.7% (29/30) and 87.5% (98/112) of the preoperative radiotherapy and surgery-only groups, with ages of (55±10) years old and (54±12) years old, respectively. Before matching by the PSM method, there were differences in gender, proportion of patients with hepatitis C, alanine aminotransferase, serum albumin, alpha-fetoprotein, satellite nodules by postoperative pathology, and number of tumors between the two groups (all SMD > 0.1). A total of 26 pairs of patients were successfully matched, and there was no difference in baseline characteristics between the preoperative radiotherapy group and the surgery-only group after matching (all SMD < 0.1). Univariate Cox regression analysis showed that preoperative radiotherapy, number of tumors, maximum diameter of tumor, and satellite nodules by postoperative pathology were the influencing factors of RFS (all P < 0.05); multivariate Cox regression analysis showed that preoperative radiotherapy was an independent protective factor of RFS in central hepatocellular carcinoma patients with hepatectomy ( HR = 0.55, 95% CI: 0.31-0.97, P = 0.038), and maximum diameter of tumor ( HR = 1.08, 95% CI: 1.02-1.15, P = 0.005) and satellite nodules by postoperative pathology ( HR = 1.97, 95% CI: 1.21-3.19, P = 0.006) were independent risk factors of RFS. Preoperative radiotherapy was associated with superior RFS in patients with central hepatocellular carcinoma (PSM, HR = 0.41, 95% CI: 0.20-0.86, P = 0.018; CAPS, HR = 0.42, 95% CI: 0.20-0.87, P = 0.019; IPTW, HR = 0.41, 95% CI: 0.22-0.76, P = 0.005). Before matching, the 1-, 3-, and 5-year postoperative RFS rates in the preoperative radiotherapy group were 77%, 56% and 45%, respectively, and the surgery-only group were 48%, 32% and 28%, respectively. RFS in the preoperative radiotherapy group was superior to that in the surgery-only group before and after matching ( χ2 = 5.65, P = 0.017; χ2 = 6.00, P = 0.014). The E-value for unmeasured confounders altering the conclusions was 2.39, suggesting reliable and stable results. After matching, intraoperative bleeding [ M ( Q1, Q3)] for patients in the preoperative radiotherapy group and the surgery-only group was 300 ml (125 ml, 600 ml) and 400 ml (200 ml, 600 ml), respectively ( U = 0.51, P = 0.611), and the proportions of patients with the operation time >180 min were 92.3% (24/26) and 84.6% (22/ 26), respectively ( χ2 = 0.75, P = 0.385), and the rates of mild postoperative complications were 100.0% (26/26) and 92.3% (24/26), respectively ( χ2 = 2.08, P = 0.149), the differences were not statistically significant. Conclusions:Preoperative radiotherapy for hepatectomy in patients with central hepatocellular carcinoma is safe and effective, and has the advantage of reducing postoperative recurrence.

AIM: To evaluate the efficacy of phacoemulsification with intraocular lens implantation(PEI)combined with goniosynechialysis(GSL)and goniotomy(GT)under direct vision with gonioscope in the treatment of advanced primary angle-closure glaucoma(PACG)combined with cataract.METHODS: Retrospective case series study. A total of 62 patients(65 eyes)with advanced PACG combined with cataract who were treated in the Second Hospital of Anhui Medical University from December 1, 2021 to March 31, 2023 were enrolled, and they were divided into two groups according to different surgical methods. The control group(32 cases, 33 eyes)received PEI+GSL, whereas the observation group(30 cases, 32 eyes)received PEI+GSL+GT. The intraocular pressure(IOP), best corrected visual acuity(BCVA)and the number of anti-glaucoma medications of the two groups before surgery and at 1 d, 1 wk, 1, 3, and 6 mo after surgery were evaluated. In addition, the visual field, cup-to-disc ratio(C/D), angle open range, anterior chamber depth, and average thickness of retinal nerve fiber layer(RNFL)were evaluated before and 6 mo after surgery.RESULTS: There were significant differences in IOP and lowering range of average IOP at 6 mo between the PEI+GSL+GT group(16.68±2.65, 11.12±8.53 mmHg)and the PEI+GSL group(18.71±2.51, 8.32±4.17 mmHg; P<0.05), and there was no difference in the rate of IOP reduction(44.57%±21.79% and 35.20%±17.94%, P>0.05). The number of anti-glaucoma medications, BCVA, anterior chamber depth, and angle closure range were improved in the two groups at 6 mo after operation(all P<0.01). The number of medication reductions and the range of angle opening at 6 mo after surgery in the PEI+GSL+GT group were significantly higher than those in the PEI+GSL group(P<0.05), and there was no difference in the other indicators between the two groups(all P>0.05). There was no difference in the mean deviation of visual field, C/D and average thickness of RNFL between the two groups at 6 mo after operation compared with those before operation(all P>0.05). The complete surgery success rate of the PEI+GSL+GT group was 81%(26/32), and the conditional success rate was 94%(30/32); while those rates of the PEI+GSL group were 58%(19/33)and 76%(25/33), respectively. There were statistical significance in the success rate of surgery between the two groups(complete success rate χ2=4.275, P=0.039; conditional success rate χ2=4.040, P=0.044). No vision-threatening complications and another surgery occurred in either group.CONCLUSION: The study showed that for patients with advanced PACG with cataract, PEI+GSL+GT is more effective than PEI+GSL.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Epidemiology and medical statistics are essential courses for undergraduate students majoring in clinical medicine. By studying the two courses, they can obtain the core skills for their future clinical practice. High-level medical schools both at home and abroad have accumulated successful experiences in curriculum, teaching methods and teaching models of the two disciplines. These colleges have also carried out the exploration of the curriculum reform centering on "organ systems integration". This paper summarizes the current status of epidemiology and medical statistics teaching and curriculum integration in representative medical schools both at home and abroad, and puts forward suggestions for deepening teaching reform and optimizing the curriculum system to provide reference for the integration of epidemiology and medical statistics curriculums for undergraduate students majoring in clinical medicine in China.

Objective To analyze the concentration and exposure of vancomycin in children with gram-positive coccal infection,and the corresponding clinical efficacy and safety to support rational use of vancomycin in children.Methods We prospectively collected the clinical and laboratory data of 87 children with gram-positive coccal infection in the Children's Hospital of Fudan University from January 2012 to March 2021.Therapeutic drug monitoring(TDM)was conducted for vancomycin simultaneously,to acquire the data of serum through concentration(Cmin),peak concentration(Cmax),the area under the drug concentration-time curve in a 24-h interval(AUC0-24h)and the ratio ofAUC0-24h to the minimum inhibitory concentration(AUC0-24h/MIC).Results The median(P25,P75)age of the children enrolled in this study was 3.60(1.20,20.00)months.The median dose of vancomycin was 39.23(30.00,46.51)mg/kg.The median serum Cmin was 3.30(1.50,7.10)mg/L.Cmin achieved the target(5-15 mg/L)in 23 cases(26.4％).The median AUC0-24h was 213(174,293)mg·h/L and the median AUC0-24h/MIC was 221(128,349).Adaily dose of above 60 mg/kg in children could achieve the median value of AUC0-24h and AUC0-24h/MIC greater than 400,and the corresponding median age was 28.50(6.85,36.00)months.Multivariate logistic analysis showed a good correlation between Cmin and AUC0-24h(P=0.002).At the end of treatment,the clinical efficacy rate was 85.1％(74/87)and the bacterial eradication rate was 95.4％(83/87).No renal injury occurred during the treatment.Conclusions In this study,the median daily dosage,Cmin and A UC0-24h/MIC of vancomycin were below the recommended range at home and abroad.However,good clinical and microbiological efficacy were achieved in children at low vancomycin exposure.The probability of target attainment(PTA)for A UC0-24h and AUC0-24h/MIC ≥400 increased when the daily dose of vancomycin was＞60 mg/kg(corresponding to the median age of 28.50 months)or Cmin ≥ 5 mg/L.