Amyotrophic lateral sclerosis (ALS) is a chronic, progressive degenerative disease affecting both upper and lower motor neurons, primarily characterized by skeletal muscle weakness and atrophy. Notably, the same muscle group may exhibit asynchronous involvement. This study aims to investigate the involvement patterns of the orbicularis oculi (OOc) and orbicularis oris (OOr) in ALS patients, compare the findings with healthy controls (HCs) and myasthenia gravis (MG) patients, and explore the characteristics and clinical significance of facial muscle involvement in ALS.

Objective To construct and verify the risk profile model of surgically induced astigmatism(SIA)in elderly patients with diabetic catarac.Methods A total of 309 patients admitted to our hospital for phacoemulsification were selected as the study objects.Patients were divided into the SIA group(n=158)and the non-SIA group(n=151)according to whether SIA occurred after surgery.Multivariate Logistic regression analysis was used to analyze the factors influencing the occurrence of SIA in diabetic cataract patients,and the nomogram model of SIA in diabetic cataract patients was constructed.ROC curve,calibration curve and decision curve were used for evaluation and verification of the model.Results The patient age and the lens nucleus hardness level Ⅲ-Ⅳ,incision size≥3.00 mm,incision shape as trapezoidal transparent corneal incision,corneal incision length≥1.75 mm and horizontal diameter of the cornea were significantly higher in the SIA group than of the non-SIA group(P＜0.05).There were no significant differences in gender,body mass index(BMI),duration of diabetes,history of hypertension,history of cardiovascular disease,grading of diabetic retinopathy,axial length,anterior chamber depth,central corneal thickness,total corneal refractive power,astigmatism axis position and ultrasound phacoemulsification time between the two groups of patients(P＞0.05).Multivariate Logistic regression results showed that incision size,incision shape,corneal incision length and corneal horizontal diameter were the factors affecting the occurrence of SIA in diabetic cataract patients(P＜0.05).The R software was used to incorporate four influencing factors to generate a nomogram model that could be used to predict the occurrence of SIA in diabetic cataract patients.ROC curve analysis results showed that the area under the curve(AUC)value of this histogram to predict SIA in diabetic cataract patients was 0.810(95%CI=0.761-0.860).Hosmer-Lemeshow test and calibration curve analysis showed that the model fit well(χ2=11.142,P=0.194).The results of decision curve analysis showed that when the probability of high risk threshold 0.35-0.8,the clinical net benefit rate of the column graph model was greater than 0.Conclusion Incision size,incision shape,corneal incision length and corneal horizontal diameter are influential factors for the occurrence of SIA in patients with diabetic cataract.Based on the above influential factors,the columniogram model for predicting the occurrence risk of SIA in patients with diabetic cataract has good differentiation,accuracy and clinical applicability.

Purpose To analyze and compare the impact of incorporating molecular classification into the new FI-GO(2023)staging system for endometrial cancer(EC).Methods A retrospective analysis was conducted on 332 ca-ses of EC diagnosed and molecular subtyped by Department of Pathology Tianjin Central Hospital of Gynecology Obstet-rics in 2023.All cases were staged according to the FIGO(2023)staging criteria for EC.Results The median age of the 332 EC patients was 56 years(range:27-76 years).Molecular subtypes included 30 POLE mutation(POLE-mut),80 mismatch repair deficiency(MMRd),194 no specific molecular profile(NSMP),and 28 p53 abnormal(p53abn).Significant differences were observed among the four molecular subtypes regarding age,FIGO stage,patho-logical type,and lymph node metastasis rate(P＜0.05).However,no significant differences were found in the depth of myometrial invasion or lymphovascular space invasion.In the POLEmut group,19 cases(63.33％)were of non-ag-gressive histological types and 11(36.67％)were aggressive.After incorporating molecular subtyping,all 11 stage Ⅱ patients were downgraded to stage Ⅰ AmPOLEmut,increasing the proportion of stage Ⅰ patients from 62.07％to 100％.In the p53abn group,9 cases(32.14％)were non-aggressive and 19(67.86％)were aggressive.Molecular integra-tion led to the upstaging of 4 stage Ⅰ patients with myometrial invasion to stage Ⅱ Cmp53abn,increasing the proportion of stage Ⅱ patients from 34.61％to 50％.Conclusion Molecular subtypes p53abn and POLEmut are associated with distinct alterations in EC staging,specifically leading to tumor upstaging or downstaging.Our findings underscore the critical importance of comprehensive molecular subtyping in EC staging,as it refines prognostic risk stratification and provides valuable guidance for adjuvant treatment decisions.

OBJECTIVE To investigate the pharmacological efficacy and mechanism of action of Atractylenolide Ⅰ(Atr-Ⅰ)in inhibiting colorectal cancer.METHODS Among three active compounds of Atractylodes macrocephala,Atr-Ⅰ exhibited the highest anti-tumor potency by MTT assay.The optimal concentration of Atr-Ⅰ was determined.The effect of Atr-Ⅰ on LoVo cell prolifera-tion was assessed via a clonogenic assay,while its impact on apoptosis and cell cycle progression was evaluated using flow cytometry.The influence of Atr-Ⅰ on the migration and invasion of LoVo cell line was examined through wound healing and Transwell migration assays.Western blot analysis was performed to explore the effects and mechanisms of Atr-Ⅰ on proteins associated with mi-gration,proliferation,and epithelial-mesenchymal transition(EMT)in LoVo cells.The CT26 mouse subcutaneous tumor model was established,and histopathological analysis was conducted using hematoxylin-eosin(HE)staining.Western blot was also used to assess the effects of Atr-Ⅰ on EMT-related proteins in mouse tissues to elucidate underlying mechanisms.RESULTS Atr-Ⅰ significantly reduced colorectal cancer cell viability,with statistically significant differences between treatment and control groups(P<0.05,P<0.01).Atr-Ⅰ induced apoptosis in LoVo cells,with the treatment group showing significant differences compared to the control(P<0.05,P<0.01).Cell cycle analysis revealed that Atr-Ⅰ exerted anti-tumor effects by inducing G2/M phase arrest,with increased G2 phase cell numbers in the LoVo treatment group compared to the control(P<0.05).Wound healing and Transwell migration assays confirmed that Atr-Ⅰ significantly inhibited tumor cell migration and invasion(P<0.05,P<0.01).Western blot analysis demonstra-ted that Atr-Ⅰ specifically suppressed the expression of c-Myc and Bcl-2(P<0.05),as well as cell cycle-related proteins CDK1,Cyclin B1,and Cyclin D1(P<0.05),and angiogenesis-related proteins VEGF and MMP9(P<0.05).Additionally,Atr-Ⅰ down-regulated EMT-related protein N-cadherin and upregulated E-cadherin expression(P<0.05).It also reduced the expression of p-AKT and p-S6K1(P<0.05).CONCLUSION Atr-Ⅰ exhibits potent anti-tumor effects against colorectal cancer,potentially through modulation of the AKT/S6K1 signaling pathway.

Objective To construct and verify the risk profile model of surgically induced astigmatism(SIA)in elderly patients with diabetic catarac.Methods A total of 309 patients admitted to our hospital for phacoemulsification were selected as the study objects.Patients were divided into the SIA group(n=158)and the non-SIA group(n=151)according to whether SIA occurred after surgery.Multivariate Logistic regression analysis was used to analyze the factors influencing the occurrence of SIA in diabetic cataract patients,and the nomogram model of SIA in diabetic cataract patients was constructed.ROC curve,calibration curve and decision curve were used for evaluation and verification of the model.Results The patient age and the lens nucleus hardness level Ⅲ-Ⅳ,incision size≥3.00 mm,incision shape as trapezoidal transparent corneal incision,corneal incision length≥1.75 mm and horizontal diameter of the cornea were significantly higher in the SIA group than of the non-SIA group(P＜0.05).There were no significant differences in gender,body mass index(BMI),duration of diabetes,history of hypertension,history of cardiovascular disease,grading of diabetic retinopathy,axial length,anterior chamber depth,central corneal thickness,total corneal refractive power,astigmatism axis position and ultrasound phacoemulsification time between the two groups of patients(P＞0.05).Multivariate Logistic regression results showed that incision size,incision shape,corneal incision length and corneal horizontal diameter were the factors affecting the occurrence of SIA in diabetic cataract patients(P＜0.05).The R software was used to incorporate four influencing factors to generate a nomogram model that could be used to predict the occurrence of SIA in diabetic cataract patients.ROC curve analysis results showed that the area under the curve(AUC)value of this histogram to predict SIA in diabetic cataract patients was 0.810(95%CI=0.761-0.860).Hosmer-Lemeshow test and calibration curve analysis showed that the model fit well(χ2=11.142,P=0.194).The results of decision curve analysis showed that when the probability of high risk threshold 0.35-0.8,the clinical net benefit rate of the column graph model was greater than 0.Conclusion Incision size,incision shape,corneal incision length and corneal horizontal diameter are influential factors for the occurrence of SIA in patients with diabetic cataract.Based on the above influential factors,the columniogram model for predicting the occurrence risk of SIA in patients with diabetic cataract has good differentiation,accuracy and clinical applicability.

The "minimally-invasive and non-invasive diagnosis and treatment of the most important tumor in gynecology", which is an online + offline first-class undergraduate course in Chongqing, China, was used as an example to demonstrate how to explore the integration of medical specialty with humanistic spirit in the design and construction of courses for medical students, and to strengthen the early cultivation of medical humanistic spirit. Based on the concept of outcome-based education, innovative course content and teaching modes were designed to guide students to learn the history of focused ultrasound therapy technology, understand the concept of minimally-invasive and non-invasive medicine, and incorporate the literacy cultivation of "always having compassion". This study explored the importance of incorporating humanistic spirit into medical education and provides new ideas and concepts for the cultivation of physicians with humanity and compassion.

Objective:To investigate the influence and mechanism of extracellular vesicles (EVs) derived from human adipose-derived mesenchymal stem cells (hADMSCs), i.e. hADMSC-EVs on pyroptosis of human umbilical vein endothelial cells (HUVECs) induced by high glucose, with the aim of providing evidence for improving vascular function in diabetic wounds.Methods:This study was an experimental research. The umbilical cords from 5 women aged 25 to 40 years were collected who had normal vaginal delivery at the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Nanchang University from June to September in 2023, and HUVECs were isolated and successfully identified. Adipose tissue was obtained from 6 healthy women aged 25 to 35 years who underwent abdomen liposuction at the Department of Plastic Surgery of the above-mentioned hospital in the same period. After hADMSCs were isolated, hADMSC-EVs were extracted and successfully identified. The fourth passage of HUVECs were cultured in endothelial cell medium containing glucose in a molarity of 33 mmol/L and divided into phosphate buffered solution (PBS) group cultured with PBS, EV group cultured with hADMSC-EVs, and EV+LY294002 group cultured with hADMSC-EVs and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway inhibitor LY294002. Western blotting was used to detect the expressions of PI3K/Akt signaling pathway-related proteins PI3K and Akt, and pyroptosis-related proteins nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cysteinyl aspartate specific protease-1 (caspase-1), gasdermin D, interleukin-1β (IL-1β), and IL-18 of cells after 48 hours of culture. A cell counting kit-8 was used to test the proliferation levels of cells at 0 (immediately), 12, 24, 36, 48, 60, and 72 hours of culture. After 48 hours of culture, the cell scratch test was performed and the cell migration rates at 12 and 24 hours after scratching were calculated; the cell Transwell assay was conducted and the number of cells migrating in 24 hours was calculated; the cell tube formation experiment was performed, and the total length of tube formation and the number of branch nodes were measured and counted. The sample size was 3.Results:After 48 hours of culture, the protein expressions of PI3K and Akt of cells in EV group were significantly higher than those in PBS group ( P<0.05), and the protein expressions of PI3K and Akt of cells in EV+LY294002 group were significantly lower than those in EV group ( P<0.05). After 48 hours of culture, the protein expressions of NLRP3, caspase-1, gasdermin D, IL-1β, and IL-18 of cells in EV group were 0.54±0.08, 0.96±0.11, 0.525±0.061, 1.216±0.039, and 1.317±0.023, respectively, which were significantly lower than 2.32±0.11, 1.86±0.07, 1.256±0.113, 2.589±0.084, and 2.042±0.132 in PBS group ( P<0.05); the protein expressions of NLRP3, caspase-1, gasdermin D, IL-1β, and IL-18 of cells in EV+LY294002 group were 1.16±0.05, 1.37±0.06, 0.962±0.028, 1.834±0.017, and 1.803±0.065, respectively, which were significantly higher than those in EV group ( P<0.05). At 12, 24, 36, 48, 60, and 72 hours of culture, the proliferation levels of cells in EV group were significantly higher than those in PBS group ( P<0.05), and the proliferation levels of cells in EV+LY294002 group were significantly lower than those in EV group ( P<0.05). After 48 hours of culture, the cell migration rates at 12 and 24 hours after scratching in EV group were significantly higher than those in PBS group ( P<0.05), and the cell migration rates at 12 and 24 hours after scratching in EV+LY294002 group were significantly lower than those in EV group ( P<0.05); the number of cells migrating in 24 hours in EV group was significantly greater than that in PBS group ( P<0.05), and the number of cells migrating in 24 hours in EV+LY294002 group was significantly less than that in EV group ( P<0.05). After 48 hours of culture, compared with those in PBS group, the total length of tube formation of cells in EV group was significantly prolonged ( P<0.05), and the number of branch nodes was significantly increased ( P<0.05); compared with those in EV group, the total length of tube formation in EV+LY294002 group was significantly shortened ( P<0.05), and the number of branch nodes was significantly decreased ( P<0.05). Conclusions:hADMSC-EVs can inhibit the expression of pyroptosis-related proteins in HUVECs induced by high glucose through the PI3K/Akt signaling pathway and improve the proliferation, migration, and angiogenesis capabilities of HUVECs.

Objective:To explore the association between the use of tetracyclines during pregnancy and congenital malformations, with the aim of providing evidence-based guidance for the rational use of antibiotics during pregnancy.Methods:Data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Canada Vigilance Adverse Reaction (CVAR) database from January 2015 to September 2024 were collected. Five methods including Tree-based scan statistic (TreeScan), proportional reporting ratio (PRR), reporting odds ratio (ROR), the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard, and the Bayesian confidence propagation neural network (BCPNN) were used to detect signals of risk for congenital malformations in offspring following maternal use of tetracyclines during pregnancy. A signal that met the threshold criteria of all above 5 methods was considered as a risk signal. Based on population-based cohort of the drug exposures and adverse pregnancy outcomes (DEEP) data from January 2013 to December 2021 in Xiamen City, propensity score matching (PSM)-based Poisson regression was applied to evaluate the association between the first-trimester tetracyclines exposure and congenital malformations in offspring. Adjusted relative risk (a RR) and its 95% confidence interval ( CI) were calculated. Sensitivity analysis was conducted to validate the reliability of the results. Results:A total of 304 098 reports of adverse events during pregnancy were obtained from the FAERS and CVAR databases. Among them, 5 028 reports were related to tetracyclines, including 1 026 reports of congenital malformations in offspring, involving congenital malformations of musculoskeletal system, other digestive system, and other congenital malformations. Signal detection results suggested that tetracyclines may be a risk signal for above congenital malformations in offspring. The DEEP data included 411 936 pregnant women. After PSM, 240 pregnant women exposed to tetracyclines were included. The results showed no significant association between the first-trimester tetracyclines exposure and congenital malformations in offspring (a RR=0.75, 95% CI: 0.26-2.17), sensitivity analysis also showed no correlation. Conclusions:Data mining from the FAERS and CVAR databases suggests a potential association between tetracyclines use during pregnancy and congenital malformations in offspring. However, the DEEP data study shows no significant correlation.

Purpose To analyze and compare the impact of incorporating molecular classification into the new FI-GO(2023)staging system for endometrial cancer(EC).Methods A retrospective analysis was conducted on 332 ca-ses of EC diagnosed and molecular subtyped by Department of Pathology Tianjin Central Hospital of Gynecology Obstet-rics in 2023.All cases were staged according to the FIGO(2023)staging criteria for EC.Results The median age of the 332 EC patients was 56 years(range:27-76 years).Molecular subtypes included 30 POLE mutation(POLE-mut),80 mismatch repair deficiency(MMRd),194 no specific molecular profile(NSMP),and 28 p53 abnormal(p53abn).Significant differences were observed among the four molecular subtypes regarding age,FIGO stage,patho-logical type,and lymph node metastasis rate(P＜0.05).However,no significant differences were found in the depth of myometrial invasion or lymphovascular space invasion.In the POLEmut group,19 cases(63.33％)were of non-ag-gressive histological types and 11(36.67％)were aggressive.After incorporating molecular subtyping,all 11 stage Ⅱ patients were downgraded to stage Ⅰ AmPOLEmut,increasing the proportion of stage Ⅰ patients from 62.07％to 100％.In the p53abn group,9 cases(32.14％)were non-aggressive and 19(67.86％)were aggressive.Molecular integra-tion led to the upstaging of 4 stage Ⅰ patients with myometrial invasion to stage Ⅱ Cmp53abn,increasing the proportion of stage Ⅱ patients from 34.61％to 50％.Conclusion Molecular subtypes p53abn and POLEmut are associated with distinct alterations in EC staging,specifically leading to tumor upstaging or downstaging.Our findings underscore the critical importance of comprehensive molecular subtyping in EC staging,as it refines prognostic risk stratification and provides valuable guidance for adjuvant treatment decisions.

OBJECTIVE To investigate the pharmacological efficacy and mechanism of action of Atractylenolide Ⅰ(Atr-Ⅰ)in inhibiting colorectal cancer.METHODS Among three active compounds of Atractylodes macrocephala,Atr-Ⅰ exhibited the highest anti-tumor potency by MTT assay.The optimal concentration of Atr-Ⅰ was determined.The effect of Atr-Ⅰ on LoVo cell prolifera-tion was assessed via a clonogenic assay,while its impact on apoptosis and cell cycle progression was evaluated using flow cytometry.The influence of Atr-Ⅰ on the migration and invasion of LoVo cell line was examined through wound healing and Transwell migration assays.Western blot analysis was performed to explore the effects and mechanisms of Atr-Ⅰ on proteins associated with mi-gration,proliferation,and epithelial-mesenchymal transition(EMT)in LoVo cells.The CT26 mouse subcutaneous tumor model was established,and histopathological analysis was conducted using hematoxylin-eosin(HE)staining.Western blot was also used to assess the effects of Atr-Ⅰ on EMT-related proteins in mouse tissues to elucidate underlying mechanisms.RESULTS Atr-Ⅰ significantly reduced colorectal cancer cell viability,with statistically significant differences between treatment and control groups(P<0.05,P<0.01).Atr-Ⅰ induced apoptosis in LoVo cells,with the treatment group showing significant differences compared to the control(P<0.05,P<0.01).Cell cycle analysis revealed that Atr-Ⅰ exerted anti-tumor effects by inducing G2/M phase arrest,with increased G2 phase cell numbers in the LoVo treatment group compared to the control(P<0.05).Wound healing and Transwell migration assays confirmed that Atr-Ⅰ significantly inhibited tumor cell migration and invasion(P<0.05,P<0.01).Western blot analysis demonstra-ted that Atr-Ⅰ specifically suppressed the expression of c-Myc and Bcl-2(P<0.05),as well as cell cycle-related proteins CDK1,Cyclin B1,and Cyclin D1(P<0.05),and angiogenesis-related proteins VEGF and MMP9(P<0.05).Additionally,Atr-Ⅰ down-regulated EMT-related protein N-cadherin and upregulated E-cadherin expression(P<0.05).It also reduced the expression of p-AKT and p-S6K1(P<0.05).CONCLUSION Atr-Ⅰ exhibits potent anti-tumor effects against colorectal cancer,potentially through modulation of the AKT/S6K1 signaling pathway.