Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.

Objective To investigate the role of reactive oxygen species(ROS)and the extracellular signal-regulated kinase(ERK)/cAMP response element binding protein(CREB)signaling pathway in arsenic-induced apoptosis in HT-22 cells.Methods HT-22 cells were cultured in vitro and exposed to NaAsO2.The cells were divided into the following groups:control group,4,6,8,and 10 μmol/L NaAsO2 groups,NAC(5 mmol/L)group,and NAC(5 mmol/L)+NaAsO2(10 μmol/L)group.ROS levels were measured using a DCFH-DA assay.The expression of ERK/CREB signaling pathway-related and apoptosis-related proteins were analyzed by Western blotting.Apop-tosis rates were evaluated using flow cytometry.Results Compared with the control group,ROS levels in HT-22 cells significantly increased,while p-ERK protein level in the nucleus and p-CREB and Bcl-2 protein levels in the cells significantly decreased in the NaAsO2 only exposed groups(P＜0.05).Additionally,the apoptosis rate significantly increased in the 8 and 10 μmol/L NaAsO2 groups compared with the control group(P＜0.05).In the NAC+NaAsO2 group,ROS levels and the apoptosis rate significantly decreased while p-ERK protein level in the nucleus and p-CREB and Bcl-2 protein levels in the cells significantly increased compared with the 10 μmol/L NaAsO2 group(P＜0.05).Conclusion Arsenic exposure induces oxidative stress,inhibits the nuclear translocation of p-ERK,and dis-rupts the CREB signaling pathway,leading to apoptosis.

Objective:To summarize the best evidence for intense pulsed light therapy in dry eye.Methods:Literature on intense pulsed light therapy for dry eye was electronically retrieved from databases and websites, including the National Guideline Clearinghouse, Guidelines International Network, British Medical Journal (BMJ) Best Practice, UpToDate, Cochrane Library, PubMed, Web of Science, China National Knowledge Infrastructure, Wanfang Data, and China Biology Medicine disc. The search period was from database establishment to December 3, 2024. Two researchers independently conducted quality evaluation of the literature, and extracted and summarized the evidence.Results:A total of 22 articles were ultimately included, including four guidelines, seven expert consensus, and eleven systematic reviews. Twenty-seven piecesof evidence were summarized from six aspects of the mechanism of action, clinical indications, treatment protocols, operation and maintenance, therapeutic efficacy evaluation, adverse reactions, and precautions.Conclusions:The best evidence for intense pulsed light therapy in dry eye is evidence-based and scientific. Healthcare providers are advised to apply this evidence in conjunction with clinical context and patient preferences.

With the continuous increase in global obesity prevalence,the impact of obesity on reproduc-tive physiology has garnered widespread societal attention.As a metabolic disorder,obesity is typically accompanied by multiple abnormal physiological phenomena,such as excessive adipose accumulation and exacerbated inflammatory responses,which severely compromise the reproductive health of humans and animals.Reproductive damage induced by obesity involves a series of complex biochemical reactions and in vivo metabolic pathways,manifesting as impaired male sperm quality and female fertility.To better un-derstand the relationship between obesity and reproductive physiology,this review summarizes the repro-ductive injuries caused by obesity and their underlying mechanisms.In the obese state,conditions such as oxidative stress,insulin resistance,and hyperinsulinemia are induced,with adipokines(leptin,adi-ponectin,resistin,etc.)and inflammatory factors(TNF-α,IL-6,IL-1β,etc.)interacting synergisti-cally to affect the reproductive system.Oxidative stress activates the MAPK and NF-κB pathways,inter-fering with insulin signaling,while chronic inflammation leads to adipocyte secretory disorders and dis-rupts the hypothalamic-pituitary-gonadal regulatory axis.Studies have shown that obese males exhibit sig-nificantly decreased testosterone levels and impaired sperm quality,whereas obese females suffer from re-productive hormone imbalance,ovulation disorders,and polycystic ovary syndrome.This review discus-ses how obesity-induced metabolic disorders lead to impaired reproductive physiology in both males and females,along with the underlying mechanisms,providing a theoretical basis for the prevention and treat-ment of obesity-related reproductive disorders in the future.

Objective:To analyze the drug resistance status and related risk factors in elderly patients with pulmonary tuberculosis,and to construct and validate a drug resistance risk prediction model for elderly pulmonary tuberculosis patients,providing evidence for early clinical identification of high-risk populations.Methods:A retrospective study was conducted,consecutively enrolling 315 pulmonary tuberculosis patients aged ≥60 years from January 2019 to December 2021.Based on drug susceptibility test results,patients were divided into drug-resistant group(85 cases)and drug-sensitive group(230 cases).Data on demographic characteristics,clinical manifestations,comorbidities,imaging features,and previous treatment history were collected.Univariate and multivariate logistic regression analyses were performed to identify drug resistance-related factors,and a prediction model was constructed accordingly.The model was internally validated using the concordance index(C-index)and Bootstrap method.Results:Among 315 elderly pulmonary tuberculosis patients,the drug resistance rate was 26.98％,predominantly mono-resistance(48.24％)and multidrug-resistance(28.24％).Multivariate logistic regression analysis showed that previous anti-tuberculosis treatment history[OR=4.537,95％CI(1.962-10.498),P=0.005],diabetes mellitus[OR=3.286,95％CI(1.547-6.979),P=0.002],pulmonary cavitation[OR=4.158,95％CI(1.926-8.973),P＜0.001],pleural effusion[OR=2.563,95％CI(1.218-5.390),P=0.013],and tracheobronchial tuberculosis[OR=2.819,95％CI(1.352-5.876),P=0.006]were independent risk factors for drug resistance in elderly pulmonary tuberculosis.The prediction model constructed based on these factors had a C-index of 0.815(95％CI:0.762-0.868).Conclusion:The drug resistance rate is high among elderly pulmonary tuberculosis patients.Previous anti-tuberculosis treatment history,diabetes mellitus,pulmonary cavitation,pleural effusion,and tracheobronchial tuberculosis are independent risk factors for drug resistance in elderly pulmonary tuberculosis.The prediction model constructed based on these factors has good predictive value for identifying high-risk populations,which is helpful for early clinical intervention and individualized treatment strategy formulation.

Objective To explore the therapeutic effect of cornuside on diabetic retinopathy(DR)in rats and ana-lyze the acting mechanism of the reactive oxygen species(ROS)/thioredoxin interacting protein(TXNIP)/NOD-like recep-tor thermal protein domain associated protein 3(NLRP3)signaling pathway in this process.Methods A total of 56 suc-cessfully modeled DR rats were randomly divided into the model group,the cornuside 20 mg·kg-1 group,the cornuside 40 mg·kg-1 group,the calcium dobesilate 5.8 mg·kg-1 group,with 14 rats in each group;while,meanwhile another 14 healthy rats were selected as the control group.After the corresponding intervention of rats in each group,retinal tissue in-flammation,oxidative stress indicators,fasting blood glucose(FBG),and angiogenic factor levels were detected by the en-zyme-linked immunosorbent assay(ELISA).The hematoxylin-eosin(HE)staining and terminal deoxynucleotidyl transfer-ase dUTP nick end labeling(TUNEL)staining were used to observe retinal histopathology and retinal cell apoptosis,re-spectively.The mRNA expression of ROS,TXNIP,and NLRP3 in the retinal tissue was detected by the quantitative fluores-cence polymerase chain reaction(PCR).The apoptosis of retinal cells and the protein expression of the ROS/TXNIP/NL-RP3 signaling pathway were detected by Western blotting.Results Compared with the control group,the model group showed disordered arrangement of retinal cells and a significant decrease in the cell number,accompanied by nuclear con-densation and edema;interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),malondialdehyde(MDA),FBG,angiopoie-tin-1(Ang-1),vascular endothelial growth factor(VEGF),retinal cell apoptosis rate,ROS,and the mRNA and protein ex-pression levels of TXNIP and NLRP3 increased significantly,while superoxide dismutase(SOD)and B cell lymphoma-2(Bcl-2)protein expression levels decreased significantly(all P＜0.05).Compared with the model group,the arrangement of retinal cells in the cornuside 20 mg·kg-1 group,the cornuside 40 mg·kg-1 group,and the calcium dobesilate 5.8 mg·kg-1 group gradually became normal,the number of retinal cells increased,and the nuclear condensation and edema were relieved;IL-6,TNF-α,MDA,FBG,Ang-1,VEGF,retinal cell apoptosis rate,ROS,and the mRNA and protein expression level of TXNIP and NLRP3 decreased significantly,while the protein expression level of SOD and Bcl-2 increased signifi-cantly(all P＜0.05).In the intergroup comparison of the pathological damage of retinal tissue and the improvement degree of the above quantitative indexes in DR rats,the cornuside 40 mg·kg-1group was superior to the cornusin 20 mg·kg-1 group(all P＜0.05);the calcium dobesilate 5.8 mg·kg-1 group was superior to the cornusin 20 mg·kg-1 group,but infe-rior to the cornuside 40 mg·kg-1 group(all P＜0.05).Conclusion Cornuside can mitigate retinal inflammation,oxi-dative stress,and pathological damage in DR rats and inhibit blood glucose,retinal angiogenesis,and cell apoptosis.The acting mechanism of cornuside may be related to the inhibition of the ROS/TXNIP/NLRP3 signaling pathway.

Objective:To explore the effects of workload factors and social psychological factors on work-related musculoskeletal disorders (WMSDs) , construct a preventive decision-assisted ensemble learning model, and propose screening methods with clinical significance.Methods:In October 2022, 1071 workers from optoelectronic enterprises were selected as the research subjects by cluster sampling method. The general situation of workers, workload factors, social psychological factors and the occurrence of WMSDs were collected by using questionnaires. logistic regression, Extreme Gradient Boosting (XGBoost) , ensemble learning and classification chain model were adopted to explore the key factors influencing WMSDs, and the area under curve (AUC) was used to evaluate the model performance.Results:The incidence of WMSDs among workers in optoelectronic enterprises in the past year was 47.7% (511/1071) , among which the incidence of multi-site WMSDs was 54.4% (278/511) . logistic regression analysis showed that prolonged sitting, personnel shortage and forward neck tilt were risk factors for the occurrence of WMSDs in workers ( P<0.05) . XGBoost identified the key social psychological factors influencing WMSDs as low mood, mental tension, perceived happiness level, psychological calmness and tranquility. The integrated classification chain model based on the ordered label order had certain efficacy (AUC>0.7) when analyzing WMSDs at the neck, waist, shoulder, back, elbow and hip positions. Conclusion:Workload factors are the main risk factors for the occurrence of WMSDs among workers in optoelectronic enterprises, and social psychological factors also have potential influences. The construction of a classification chain model can accurately identify the occurrence of WMSDs in multiple parts. The alternating prevention strategy of workload factors and social psychological factors has important public health significance.

Objective:To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and 24-h urinary calcium excretion (24-h UCaE) and hypercalciuria in Chinese adults.Methods:This cross-sectional study was conducted from March 2022 to March 2023 in nine cities in China and included 1 239 residents. Demographic characteristics were collected through questionnaires and physical examinations, fasting blood samples were assessed for bone metabolism indicators, and 24-h urine samples were used to determine the 24-h UCaE. Multiple linear regression analysis was used to explore the relationship between serum 25(OH)D and 24-h UCaE and bone metabolism indexes. The relationship between serum 25(OH)D and hypercalciuria was analyzed using a multiple logistic regression model combined with restricted cubic spline modeling.Results:The mean participant age was (47.9±18.1) years, of which 453 (36.6%) were male. The percentages of vitamin D sufficiency, insufficiency, and deficiency were 7.6% (94/1 239), 29.0% (359/1 239), and 63.4% (786/1 239), respectively. The multiple linear regression model showed that after adjusting for the covariates the 24-h UCaE gradually increased with higher levels of 25(OH)D ( P overall <0.001, P nonlinear <0.001). The logistic regression analysis revealed that compared with the vitamin D deficient group, the OR for the prevalence of hypercalciuria in the vitamin D sufficient and vitamin D insufficient groups were 3.290 (95% CI 1.745 to 6.202) and 3.742 (95% CI 2.458 to 5.697), respectively. The results of the restricted cubic spline modeling showed a positive nonlinear relationship between 25(OH)D and the prevalence of hypercalciuria ( P overall <0.001, P nonlinear <0.001). The prevalence of hypercalciuria increased when 25(OH)D was >17.00 μg/L and peaked at 26.71 μg/L, after which there was a decreasing trend in the prevalence of hypercalciuria with increasing 25(OH)D. Conclusion:Associations between serum 25(OH)D levels and urinary calcium excretion and the prevalence of hypercalciuria were observed in the Chinese adult population.

Objective:To investigate the clinical characteristics, prevalent serum groups, and drug sensitivity test results of epidemic cerebrospinal meningitis in children in Shanghai area.Methods:The study was a retrospective case-control study. The children hospitalized for epidemic cerebrospinal meningitis in Children′s Hospital of Fudan University from January 2003 to December 2023 were enrolled. Clinical data were collected, including demographic characteristics, clinical manifestations, pathogen detection results, strain typing, and drug sensitivity test results.Results:A total of 77 children with confirmed epidemic cerebrospinal meningitis were hospitalized, including 50 males (64.94%) and 27 females (35.06%). The age was 24(8, 60) months, with 16 cases (20.78%) aged 0 to five months, nine cases (11.69%) aged six to 11 months, 21 cases (27.27%) aged 12 to 35 months, 16 cases (20.78%) aged three to five years, 13 cases (16.89%) aged six to 11 years, and two cases (2.60%) aged 12 years. The highest number of cases was in spring, with 36 cases (46.75%), followed by winter with 25 cases (32.47%). Thirty-three cases (42.86%) had vaccinated with meningococcal vaccine. The clinical symptoms included fever in all 77 cases (100.00%), skin petechiae and ecchymosis in 58 cases (75.32%), vomiting in 56 cases (72.73%), respiratory symptoms in 12 cases (15.58%), convulsions in 17 cases (22.08%), conscious disturbance in 24 cases (31.17%), shock in 38 cases (49.35%), circulatory failure in 13 cases (16.88%), and respiratory failure in seven cases (9.09%). Among the 77 children, fifty-seven cases (74.03%) were common type and 20 cases (25.97%) were fulminant type, with seven deaths (9.09%). Neisseria meningitidis (Nm) was detected in 55 cases (71.43%), with the positive rates of skin petechiae smear and cerebrospinal fluid smear of 23.26%(10/43) and 19.44%(14/72), respectively. The positive rates of cerebrospinal fluid culture and blood culture were 36.51%(23/63) and 31.51% (23/73), respectively. The positive rate of polymerase chain reaction detection was 79.17%(38/48). The serogroups were determined in the 38 Nm strains, including 18 cases (47.37%) of group B, 14 cases (36.84%) of group C, five cases (13.16%) of group A, and one case (2.63%) of group Y. Among the 29 Nm strains tested for antimicrobial susceptibility, one strain (3.45%) was resistant to penicillin, two strains (6.90%) were resistant to cefotaxime, 21 strains (72.41%) were resistant to ciprofloxacin, and 25 strains (86.21%) were resistant to sulfamethoxazole/trimethoprim. All strains were sensitive to ceftriaxone, azithromycin, meropenem, rifampicin, chloramphenicol, and minocycline. Conclusions:Epidemic cerebrospinal meningitis presents a low prevalence trend in children in Shanghai area. Infants and toddlers remain the major susceptible individuals. Nm has reduced sensitivity to penicillin, but remains sensitive to ceftriaxone. Ceftriaxone is recommended as the first-line choice for antibiotic therapy. The prevalent serogroups are Group B, Group C, Group A and Group Y in sequence. Immunization plan adjustment should be suggested. Vaccination covering the current epidemic serum population as early as possible should be recommended.