[摘 要] 目的：探讨烯醇化酶1（ENO1）对胃癌细胞增殖、迁移及侵袭的影响及其分子机制。方法：通过WB法检测ENO1在人胃癌细胞HGC27、MKN-45、N-87、MGC803、BGC-823及人胃黏膜上皮细胞GES-1中的表达水平，利用CRISPR、过表达等基因编辑工具分别构建ENO1敲低及敲低—恢复表达细胞株，将MKN-45和BGC-823细胞分别分组为Ctrl组、ENO1 KD组、ENO1 KD-OE组。通过克隆形成实验、EdU染色、划痕实验、Transwell实验、流式细胞术检测敲低或敲低—恢复表达ENO1对胃癌细胞增殖、迁移、侵袭及凋亡的影响。构建胃癌细胞裸鼠移植瘤模型，通过小动物活体成像技术及肿瘤组织块测量观察ENO1对肿瘤生长的影响。在MKN-45细胞中通过RNA干扰技术沉默ENO1，利用RNA免疫共沉淀-转录组测序（RIP-Seq）结合生物信息学分析技术鉴定ENO1下游的靶基因，分析ENO1调控胃癌细胞增殖、迁移及侵袭的分子机制。结果：ENO1在胃癌细胞中表达水平均显著升高（P < 0.01或P < 0.001）。在MKN-45和BGC-823细胞中敲低ENO1可显著降低胃癌细胞的增殖、迁移、侵袭能力并促进细胞凋亡（P < 0.001或P < 0.000 1）；回复实验结果显示，恢复ENO1的表达后，胃癌细胞的增殖、迁移、侵袭能力均显著提高并减少细胞凋亡（P < 0.05或P < 0.01或P < 0.001或P < 0.000 1）。裸鼠荷瘤实验结果表明，敲低ENO1的表达可以显著抑制裸鼠移植瘤的生长（P < 0.000 1）。与ENO1蛋白具有相互作用的差异基因主要富集于RNA剪切相关通路，且ENO1蛋白与PKM基因具有相互作用，胃癌组织中ENO1与PKM2基因表达事呈正相关（r = 0.886）。结论：ENO1在胃癌细胞中呈高表达，其通过与PKM的前体mRNA相互作用影响PKM的RNA剪接过程，进而调控PKM2的表达水平并促进胃癌的进展。

Background Existing studies suggest that cadmium exposure is associated with the occurrence of cardiovascular disease (CVD), but the current epidemiological evidence is inconsistent. Objective To systematically evaluate the relationship between cadmium exposure and CVD through meta-analysis. Methods We systematically searched PubMed, Cochrane Library, Web of Science, CNKI, Wanfang and SinoMed databases to collect observational studies on the relationship between cadmium exposure and CVD in human population published until July 30, 2024. On the basis of following predetermined inclusion and exclusion criteria, the retrieved literature was systematically screened, and the basic information of the included research was extracted, including basic participant information, research outcomes, and data results. This study used the Newcastle-Ottawa Scale and a cross-sectional study evaluation protocol (11 items) recommended by the Quality of Health Care and Research Institutions of the United States for literature quality evaluation. Meta-analysis, subgroup analysis, sensitivity analysis, and assessment of publication bias of the data were conducted using Stata16.0 software. Result A total of 15 studies (18 datasets) were included, and the quality of all the studies was graded as medium or above. Among them, there were 10593 cases of CVD and 86801 controls. The results of meta-analysis showed that the standard mean difference (SMD) of the CVD case group was 0.44 and 95% confidence interval (95%CI) was (0.30, 0.58), and the cadmium exposure level of the CVD case group was higher than that of the control group (P<0.05). The subgroup analysis showed that the cadmium exposure levels in the CVD patients from the Americas (SMD=0.46, 95%CI: 0.29, 0.63) and Europe (SMD=0.14, 95%CI: 0.09, 0.19) were higher than those in the control group (P<0.05). The cadmium levels in blood (SMD=0.52, 95%CI: 0.31, 0.73) and urine (SMD=0.34, 95%CI: 0.16, 0.52) in the CVD case group were higher than those in the control group (P<0.05). In those cross-sectional studies (SMD=0.34, 95%CI: 0.23, 0.46), the cadmium exposure level in the CVD patients was higher than that in the control group (P<0.05). The sensitivity analysis showed robust meta-analysis results and the assessment of publication bias also showed no publication bias. Conclusion Cadmium exposure may increase the risk of cardiovascular disease after multiple studies were combined by meta analysis, suggesting that the scope and level of cadmium exposure in the population should be further controlled.

Objective: To examine the mediating effect of frailty on social isolation and cognitive function among the elderly. Methods: Demographic information, smoking, alcohol consumption and cognitive function of the elderly at ages of 60 years and older were collected from the China Health and Retirement Longitudinal Study 2020. Social isolation and frailty were evaluated using social isolation index and frailty index, respectively. The mediating effect of frailty on social isolation and cognitive function was analyzed using the Process program, and the significance of the mediating role was tested using the Bootstrap test. Results: A total of 2 822 individuals were enrolled, including 1 483 males (52.55%) and 1 339 females (47.45%). There were 2 497 (88.48%) and 325 (11.52%) individuals at ages of 60-<75 years and ≥75 years, respectively. The median cognitive function score was 14 (interquartile range, 16) points. There were 432 cases with social isolation (15.31%), with a median social isolation index of 10 (interquartile range, 5) points. The median frailty index was 0.11 (interquartile range, 0.15). There were 1 111 individuals without frailty, accounting for 39.37%; 1 214 individuals with pre-frailty, accounting for 43.02%; and 497 individuals with frailty, accounting for 17.61%. Mediating effect analysis showed that social isolation affected cognitive function directly and negatively with the effect value of -0.773 (95%CI: -0.899 to -0.647), and also affected cognitive function by frailty indirectly and negatively with the effect value of -0.147 (95%CI: -0.188 to -0.110), with the mediating effect contributed 15.98% of the total effect. Conclusion Frailty can directly or indirectly affect cognitive function among elderly through social isolation.

Cholesterol is an essential molecule for the biosynthesis of cell membranes and cell proliferation and differentiation， and the liver plays a central role in cholesterol metabolism and is responsible for the synthesis， uptake， secretion， and transport of cholesterol. The initial stages of cholesterol synthesis in the liver are particularly important， and abnormalities in such stages are closely associated with the progression of various liver diseases. Studies have shown that as a key rate-limiting enzyme in cholesterol biosynthesis， 3-hydroxy-3-methylglutaryl-coenzyme A reductase （HMGCR） has well-defined regulatory properties and has been confirmed as an important target for the regulation of various liver diseases. This article reviews the process of cholesterol metabolism， the degradation and regulatory mechanisms of HMGCR， and the application of inhibitors， as well as the role of HMGCR in liver diseases， in order to provide new insights for scientific research and the clinical prevention and treatment of liver diseases.

Background Air pollution has gradually become a major environmental and public health problem faced by countries around the world. Hazy weather not only affects the health of the population, but also poses a threat to social and public safety. China has successively promulgated policies such as the "Ten Articles on Atmosphere" and the Three-year action plan to fight air pollution, aiming to improve ambient air quality. It is clear that the Beijing-Tianjin-Hebei region has accomplished the set targets and improved air quality according to the environmental monitoring data of 2017. Objective To assess air quality improvements through the evaluation of the disease burden due to fine particulate matter (PM_2.5) pollution in Shijiazhuang City before and after the air quality improvement from 2014 to 2021, including fatalities and health economic losses attributed to PM_2.5 pollution. Methods Data on causes of death, PM_2.5 concentrations, the number of permanent residents at the end of the year, gross regional product, and disposable income per capita in urban areas of Shijiazhuang were collected from 2014 to 2021. Total, non-accidental, circulatory, and respiratory deaths due to PM_2.5 pollution were estimated by global exposure mortality models (GEMM). Health and economic losses due to selected diseases were calculated by value of statistical life (VOSL). Results During the study period, the average annual concentration of PM_2.5 in Shijiazhuang was highest in 2014, and began to decline year by year in 2017, but all exceeded the current national limit of the second level of ambient air quality standards (35 μg·m⁻³). The total deaths, non-accidental deaths, circulatory disease deaths, and respiratory disease deaths attributed to PM_2.5 pollution from 2014 to 2021 were 41326, 40246, 21792, and 5022, respectively; the associated health economic losses were 37.362, 36.369, 19.695, and 4.535 billion yuan, respectively. From the perspective of improved air quality, both the number of attributed deaths and health economic losses had declined in a volatile manner since 2017, with a significant decrease in 2019. If the average annual concentration of PM_2.5 reached the second-level limit of China's ambient air quality standard (35 μg·m⁻³), the total deaths, non-accidental deaths, and deaths from circulatory diseases and respiratory diseases due to PM_2.5 pollution would deducted by about 17000, 16000, 9000, and 2000, respectively; the corresponding health and economic losses would decreased by 15.201, 14.761, 7.959, and 1.859 billion yuan, respectively. If the average annual concentration of PM_2.5 reached the latest PM_2.5 air quality guidelines (5 μg·m⁻³) proposed by the World Health Organization, the total deaths, non-accidental deaths, circulatory disease deaths, and respiratory disease deaths due to PM_2.5 pollution would deducted by 36000, 35000, 19000, and 4000, respectively, and the corresponding health and economic losses would reduced by 32.673, 31.796, 17.211, and 3.969 billion yuan, respectively. Conclusion PM_2.5 pollution can lead to severe mortality burden and economic loss. Under the implementation of the State Council's "Ten Articles on Atmosphere" and the Three-year action plan to fight air pollution, Shijiazhuang's PM_2.5 concentration and health economic losses have been significantly reduced, and further control of PM_2.5 pollution can achieve greater health benefits and economic gains, affirming the positive results of local air pollution prevention work.

Objective To compare the clinical efficacy of anti-vascular endothelial growth factor(VEGF)combined with pars plana vitrectomy(PPV)treatment for patients with proliferative diabetic retinopathy(PDR)of different traditional Chinese medicine(TCM)syndrome types in the real world.Methods A prospective real-world study was performed in the 36 patients(involving 42 eyes)with PDR treated by anti-VEGF combined with PPV in the Department of Ophthalmology of the First Affiliated Hospital of Guangzhou University of Chinese Medicine from March 2019 to December 2019.According to the TCM syndrome manifestations,the patients were differentiated as qi-yin deficiency complicated with blood stasis obstructing collaterals type(15 cases,involving 18 eyes;shorten as qi-yin deficiency type),liver-kidney deficiency and ocular collaterals failing in the nourishment type(14 cases,involving 17 eyes;shorten as liver-kidney deficiency type),and yin-yang deficiency complicated with blood stasis and phlegm coagulation type(7 cases,involving 7 eyes;shorten as yin-yang deficiency type).The patients were treated with anti-VEGF therapy first and then received PPV after 5-7 days.Aqueous humor was sampled during anti-VEGF therapy and PPV.After treatment,the efficacy of PDR patients with different TCM syndromes was compared.Moreover,the patients were observed in the best corrected visual acuity(BCVA)of the affected eyes before surgery and 3 months after surgery,levels of cytokines in the aqueous humor before and after anti-VEGF treatment,macular central retinal thickness(CRT),area of the foveal avascular zone(FAZ),the blood density of macular center,inner ring,outer ring and intact macula 3 months after surgery,and the postoperative complications.Results(1)The difference of the therapeutic efficacy of PDR patients with various TCM syndrome types was statistically significant(P＜0.05).Among 3 syndrome types,the best efficacy was found in the qi-yin deficiency type,followed by liver-kidney deficiency type,and then yin-yang deficiency type,with the total efficacy rate being 88.89%(16/18),52.94%(9/17),and 42.86%(3/7),respectively.(2)Three months after surgery,the logarithmic value of minimum angle of resolution(LogMAR)for BCVA of patients with qi-yin deficiency type was significantly superior to that of patients with yin-yang deficiency type,with the difference being statistically significant(P＜0.05).After the anti-VEGF treatment,the levels of cytokines in the aqueous humor of the patients varied in the 3 syndrome types:vascular endothelial growth factor A(VEGF-A)level in the patients with the 3 syndrome types was significantly lower,placental growth factor(PLGF)and angiopoietin-like protein 4(ANGPTL4)levels in the patients with qi-yin deficiency type were higher,and interleukin 8(IL-8)level in the patients with liver-kidney deficiency type was higher than those before treatment,and the differences were statistically significant(P＜0.05 or P＜0.01).The blood density of macular outer ring and intact macula in the patients with qi-yin deficiency type and liver-kidney deficiency type was larger than that in the patients with yin-yang deficiency type,and the differences were statistically significant(P＜0.05).However,the differences of CRT,FAZ area,and blood density of macular center and inner ring among the 3 syndrome types were not statistically significant(P＞0.05).(3)The incidence of postoperative complications in the patients with yin-yang deficiency type was relatively high,but the difference among the 3 syndrome types was not statistically significant(P＞0.05).Conclusion In the real world,the best efficacy of anti-VEGF combined with PPV treatment in PDR patients with different TCM syndrome types can be achieved in the patients differentiated as qi-yin deficiency type,followed by liver-kidney deficiency type,and then yin-yang deficiency type.After anti-VEGF treatment,the levels of cytokines in the aqueous humor of the patients vary in the 3 syndrome types.Three months after the operation,the patients with qi-yin deficiency type and liver-kidney deficiency type have larger blood density of macular outer ring and intact macula,and exert good prognosis.

Methamphetamine(METH)is highly addictive and neurotoxic,which causes cognitive and memory dysfunction in abusers.The harm of METH lies not only in its own toxicity,but also in the high physical and mental dependence of drug addicts,often causing mental disorders and violent behavior,bringing great safety risks to society.Non-coding RNA(ncRNA)does not encode proteins and is an important factor in regulating gene expression at the post-transcriptional level.Studies have shown that ncRNA plays an important regulatory role in methamphetamine-induced addiction and neurotoxicity,but the specific mechanism is unclear.This article reviews the current research progress of ncRNA in regulating METH-induced addiction and neurotoxicity to provide a reference for ncRNA as a forensic identification index and potential therapeutic target for METH abusers.

Objective:To study the clinical and immunological features of two case of rare antisynthetase syndrome (ASS), so as to improve the level of diagnosis and treatment.Methods:Two cases with rare antisynthetase syndrome admitted to the First Affiliated Hospital of Zhengzhou University from July 2020 to August 2022 were collected.Results:The two rare ASS were anti-Zo antibody and anti-Ha antibody positive patients, both of which had interstitial lung disease (ILD) as the main clinical manifestation and positive anti-Ro52 antibody. Two rare antisynthetase autoantibodies manifested cytoplasmic ANA indirect immunofluorescence (IIF) staining pattern, but it is different from the cytoplasmic dense speckled pattern of several common ASS antibodies. After treatment with glucocorticoids and immunosuppressants, case 1 died of respiratory failure due to a long course of disease and late diagnosis, the lung lesions of case 2 improved significantly.Conclusion:When encountering the cytoplasmic ANA fluorescent pattern in ILD patients, especially with anti-Ro52 antibody, it is necessary to screen more myositis specific antibodies to rule out the possibility of rare ASS.

OBJECTIVE:Percutaneous sacroiliac screw internal fixation has become the main surgical procedure for the treatment of posterior pelvic ring fractures;however,the unassisted closure operation requires high operator experience and repeated fluoroscopy increases the radiation hazard for patients and medical personnel.This article compares the clinical efficacy of robot-assisted versus unassisted percutaneous sacroiliac screw placement for posterior pelvic ring fractures by meta-analysis. METHODS:Computer searches of CNKI,WanFang,VIP,CBM,PubMed,Embase,Cochrane Library and ClinicalTrials.gov were conducted from the time of database inception to December 2022.The literature on the clinical efficacy of robot-assisted versus freehand percutaneous sacroiliac screw placement in the treatment of posterior pelvic ring fractures was collected in and outside China.The data were independently screened and extracted by two investigators according to the inclusion and exclusion criteria,respectively.The quality of randomized controlled trials was evaluated using Cochrane risk assessment criteria.The quality of included cohort studies was assessed using the Newcastle-Ottawa Scale.Meta-analysis was performed using RevMan 5.4 software for inclusion metrics.Outcome metrics included operative time,intraoperative bleeding,fluoroscopy time,fluoroscopy frequency,number of holes drilled,Majeed postoperative function score,the excellent and good rates of Matta fracture reduction,the excellent and good rates of Gras screw position,fracture healing time and complications. RESULTS:(1)A total of 13 publications were included,2 were randomized controlled trials both referring to randomized methods,11 non-randomized controlled studies were evaluated for quality of literature according to the Newcastle-Ottawa Scale,1 scored 8,9 scored 7;and 1 scored 6;the quality of literature was good.A total of 748 patients were included,including 430 in the robot-assisted group and 318 in the freehand group.(2)The results of the meta-analysis showed that the operative time(MD=-28.30,95%CI:-40.20 to-16.40),intraoperative bleeding(MD=-6.36,95%CI:-10.06 to-2.66),intraoperative fluoroscopy time(MD=-12.13,95%CI:-19.54 to-4.72),intraoperative fluoroscopy frequency(MD=-17.39,95%CI:-29.00 to-5.78),number of intraoperative needle drillings(SMD=-9.50,95%CI:-14.27 to-4.73)and the excellent and good rates of Gras screw position(OR=8.65,95%Cl:3.26-22.92)in the robot-assisted group were significantly better than those in the freehand group(P<0.05).(3)In the robot-assisted group,the overall postoperative complication rate was significantly reduced(OR=0.10,95%Cl:0.02-0.48,P<0.05).(4)No significant difference was detected in fracture healing time(MD=-0.08,95%CI:-0.21,0.06),the excellent and good rates of Matta fracture repositioning rate(OR=2.06,95%Cl:0.97-4.39),and Majeed functional score(MD=0.91,95%CI:-0.31-2.13)between both groups(P>0.05). CONCLUSION:Compared with freehand sacroiliac joint nailing,robotic assistance shortens the operative time,reduces intraoperative bleeding,decreases radiation damage to patients and medical staff,improves the excellent and good rate of screw position,and reduces the overall incidence of postoperative complications in patients,but there was no significant improvement in fracture reduction quality,fracture healing time,and postoperative function.In the future,more large-sample,multicenter,and high-quality randomized controlled trials are still needed to verify.

The breakage pattern of unit particles during the production of oral solid dosage forms (OSD) is closely related to the quality of intermediate or final products. To accurately characterize the particles and study the evolution law of particle breakage, the Bonding model of the discrete element method (DEM) was used to investigate the breakage patterns of model parameters, particle shape and process conditions (loading mode and loading rate) on the dynamic breakage, force-time curve, breakage rate, maximum breakage size ratio and fracture strength of particles. The results showed that the particle breakage force was positively correlated with normal strength and bonded disk scale, negatively correlated with normal stiffness per unit area and tangential stiffness per unit area, and weakly correlated with tangential strength. The particle breakage rate was negatively correlated with the aspect ratio of the particles, and the maximum breakage size ratio was positively correlated with the aspect ratio of the particles; among the three loading modes, the breakage rate of compression breakage model was the largest, the breakage rate of shear breakage model was the second largest, and the breakage rate of wear breakage model was the smallest; the maximum breakage size ratio was positively correlated with the loading rate, the loading mode and the loading rate had no mutual influence on particle breakage rate, but had mutual influence on the maximum breakage size ratio. The research results will provide a theoretical basis for the shift of OSD from batch manufacturing to advanced manufacturing.