BACKGROUND:Ferroptosis is a mode of programmed cell death distinct from apoptosis,necrosis,and other novel cellular deaths,which occurs mainly due to accumulated lipid peroxidation.Ferroptosis has been shown to be involved in the pathological process following subarachnoid hemorrhage.Baicalein,serving as an adept sequestered of iron,evinces its prowess by quelling lipid peroxidative cascades.Nonetheless,the enigma lingers as to whether baicalein possesses the capacity to ameliorate neuronal ferroptosis,elicited in the wake of early brain injury after subarachnoid hemorrhage. OBJECTIVE:To investigate the effect and mechanism of baicalein on neuronal ferroptosis after subarachnoid hemorrhage. METHODS:Primary neuronal cells were extracted from C57BL/6L fetal mice at 16-17 days of gestation.Hemoglobin was used to stimulate primary neuronal cells to simulate an in vitro subarachnoid hemorrhage model.The viability of primary neuronal cells treated with baicalein at concentrations of 5,15,25,50,and 100 μmol/L for 24 hours was detected by CCK-8 assay to determine the optimal concentration of baicalein.Primary neuronal cells were divided into control group,hemoglobin group,and hemoglobin+baicalein group.The levels of reactive oxygen species and malondialdehyde in cells were detected by kits.The mRNA expressions of ferroptosis-related markers PTGS2,SLC7A11,and glutathione peroxidase 4 were detected by RT-PCR.The primary neuronal cells were further divided into control group,SLC7A11 inhibitor Erastin group,hemoglobin group,hemoglobin+baicalein group,and hemoglobin+baicalein+Erastin group.The expression of the ferroptosis related markers SLC7A11 and glutathione peroxidase 4 was detected by western blot assay. RESULTS AND CONCLUSION:(1)Baicalein(25 μmol/L)was selected as the following experimental concentration.(2)Compared with the hemoglobin group,the level of malondialdehyde and the level of reactive oxygen species were significantly decreased(P<0.05)in the hemoglobin+baicalein group.(3)Compared with the hemoglobin group,the mRNA expression of PTGS2 significantly decreased,and the mRNA expression of SLC7A11 and glutathione peroxidase 4 significantly increased(P<0.000 1)in the hemoglobin+baicalein group.(4)SLC7A11 inhibitor Erastin could reverse the baicalin-improved ferroptosis effect to a certain extent(P<0.05).(5)The results showed that baicalein could alleviate the ferroptosis of neuronal cells after subarachnoid hemorrhage through the SLC7A11/GPX4 pathway.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Background As a pillar industry in China, the manufacturing sector has a high incidence of non-fatal occupational injuries. The factors influencing non-fatal occupational injuries in this industry are closely related at various levels, including individual, equipment, environment, and management, making the analysis of these influencing factors complex. Objective To identify influencing factors of non-fatal occupational injuries among manufacturing workers, providing a basis for targeted interventions and surveillance. Methods A total of 2243 frontline workers from cable and shipbuilding enterprises were selected as study subjects to investigate the incidence of non-fatal occupational injuries and collect information at four levels: individual, equipment, management, and environment in past 12 months. Data balancing was performed using resampling, and LASSO regression was used to select factors of non-fatal occupational injuries. The influence degree and type of variables were judged based on the magnitude of the estimated coefficients of each variable, where variables with estimated coefficients > 0 are risk factors, and those <0 are protective factors. The area under the receiver operating characteristic (ROC)curve (AUC) was used to test the performance of the model, with an AUC value > 0.7 indicating good model performance. Results Among the 2243 frontline workers, males accounted for 77.7% (1742 out of 2243), with the main age range being 40-49 years old, representing 29.5% (661 out of 2243), 82.7% of the workers (1854 out of 2243) were married, and 55.6% (1248 out of 2243) had a junior middle school education level. The average monthly income for 51.0% (1144 out of 2243) of the workers was between 5000 and 6999 Chinese Yuan. The incidence of non-fatal occupational injuries among the manufacturing workers was 8.4% (189/2243) in the past 12 months. Among the 22 factors associated with the occurrence of non-fatal occupational injuries (P<0.05), 10 were individual-level factors, including gender, smoking, alcohol consumption, colleague relationships, average exercise duration, job burnout, work fatigue, musculoskeletal disorders, cardiovascular diseases, and neurological and sensory organ diseases; 3 were equipment-level factors, including equipment operability, hazardous workpieces, and safety hazards; 5 were environmental-level factors, including low temperatures, special operations, noise, workspace size, and dirty and disorderly environment; and 4 were management-level factors, including daily working hours, weekly working days, overtime, and pre-job technical training. The AUC value of the LASSO regression model was 0.704 and the final model retained a total of 10 variables. Among them, there were 7 risk factors for non-fatal occupational injuries (coefficient > 0), including safety hazards, musculoskeletal disorders, dangerous workpieces, job burnout, dirty and disorderly environment, smoking, and male gender; and 3 protective factors (coefficient < 0), including pre-job technical training, good colleague relationship, and long working days per week. Conclusion Manufacturing enterprises need to focus on the incidence of non-fatal occupational injuries and conduct targeted interventions for non-fatal occupational injuries by controlling potential safety hazards, providing pre-job technical training, reducing dangerous workpieces, rectifying working environment, and reasonably arranging working hours.

Background Diseases severely affect the efficiency of workers. Comorbidity refers to the coexistence of two or more chronic diseases or health problems in the same individual. Previous studies have primarily focused on occupational injuries caused by environmental exposures, while the analysis of the epidemiological characteristics of self-reported diseases and occupational injuries among manufacturing workers has been insufficient. Objective To analyze the distribution of self-reported diseases and occupational injuries among manufacturing workers, the strength of correlation between different diseases, and common disease combinations, and to preliminarily explore the relationship between self-reported diseases and occupational injuries. Methods A cross-sectional survey was conducted to investigate the occupational injuries of 2382 workers in 2 manufacturing enterprises over the past year, and 2355 questionnaires were valid after cleaning. The questionnaire included three parts: basic information, occupational injury occurrence, and disease prevalence. The self-reported diseases diagnosed by physicians included musculoskeletal diseases, cardiovascular diseases, respiratory diseases, mental health problems, neurological and sensory organ diseases, digestive organ diseases, reproductive and urinary organ diseases, skin diseases, tumors, endocrine and metabolic system diseases, blood diseases and birth defects, a total of 11 types. Log-binomial model was used to calculate the prevalence ratio (PR) value of the association between different diseases, and UpSet diagram was used to present the disease combination pattern. Results In total, 40.2% (946/2355) of the study participants reported at least one disease, while 8.6% (203/2355), 5.2% (122/2355), and 5.9% (140/2355) reported having two, three, and four or more diseases, respectively. A higher prevalence was observed for musculoskeletal diseases, neurological and sensory organ diseases, digestive organ diseases, and skin diseases, which accounted for 18.0% (423/2355), 13.8% (324/2355), 9.3% (218/2355), and 9.1% (214/2355), respectively. Workers with musculoskeletal disorders, cardiovascular diseases, or neurological and sensory organ diseases reported significantly higher incidence of occupational injuries compared with workers without the corresponding diseases (P<0.001, P=0.041, and P=0.006, respectively). Musculoskeletal diseases were strongly associated with comorbidities of neurological and sensory organ diseases (PR values were 1.86 and 1.98, respectively), and the other patters were musculoskeletal diseases and digestive organ diseases (PR and OR values were 1.57 and 2.35, respectively), and musculoskeletal diseases and cardiovascular diseases (PR and OR values were 1.46 and 2.22, respectively). The largest binomial comorbidity group involved musculoskeletal diseases and neurological and sensory organ diseases, accounting for 5.4% (25/465) of the comorbid workers. Conclusion Among the self-reported diseases of manufacturing workers, musculoskeletal diseases, neurological and sensory organ diseases, digestive organ diseases, and skin diseases are more common. Musculoskeletal diseases and neurological and sensory organ diseases are the most common in all comorbidities. Musculoskeletal diseases, cardiovascular diseases, and neurological and sensory organ diseases are associated with occupational injuries. In the prevention and control of occupational injuries, joint prevention strategies targeting multiple diseases should be strengthened.

Natural killer cells(NK)are important innate immune cells that do not require prior antigen exposure and can directly recognize and attack virus-infected cells and tumor cells.The activation and effector functions of NK cells are regulated by a balance of signals delivered through their surface activating receptors and inhibitory re-ceptors,which bind to ligands on target cells to achieve cytotoxicity via"induced self"and"missing self"recogni-tion models.The killing mechanisms of NK cells primarily include release of cytotoxic granules such as perforin and granzymes to induce target cell lysis,death receptor-mediated apoptosis,secretion of various cytokines,chemokines and growth factors to coordinate with other immune cells in killing tumor cells,thereby generating secondary im-mune responses and antibody-dependent cellular cytotoxicity(ADCC).

Objective To compare the clinical efficacy and safety of transarterial chemoembolization(TACE)plus apatinib(Apa)and camrelizumab(Cam)and TACE plus Apa in treating CNLC stage Ⅲ hepatocellular carcinoma(HCC).Methods A total of 54 patients in Affiliated Yancheng No.1 People's Hospital,School of Medicine,Nanjing University with CNLC stage Ⅲ HCC were enrolled in this study.The patients were divided into triple treatment group(n=25,receiving TACE plus Apa and Cam)and dual treatment group(n=29,receiving TACE plus Apa).The overall survival(OS)and progression-free survival(PFS)were compared between the two groups.Univariate analysis and multivariate analysis were used to determine the independent influencing factors for OS and PFS.The target immunotherapy-related adverse reactions(TRAE)were analyzed.Results The median OS and PFS in the triple treatment group were 23.2 months and 10.9 months respectively,which were higher than 15.2 months and 5.8 months respectively in the dual treatment group(both P＜0.001).Multivariate analysis indicated that the therapeutic regimen and the type of portal vein tumor thrombosis(PVTT)were the independent factors affecting OS,while only the therapeutic regimen was the independent factor affecting PFS.The incidence of≥grade Ⅲ TRAE in the triple treatment group and the dual treatment group was 20％(5/25)and 17.2％(5/29)respectively,the difference between the two groups was not statistically significant(P＞0.05).Conclusion For the treatment of patients with CNLC stage Ⅲ HCC,TACE plus Apa and Cam is superior to TACE plus Apa in OS and PFS,and the type of PVTT and the therapeutic regimen are the independent prognostic factors associated with patient's survival.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

The clinical data of 2 pediatric patients with atypical hemolytic uremic syndrome (aHUS) who were admitted to the Department of Nephrology at the Children′s Hospital of Nanjing Medical University on July 2018 to June 2023 were retrospectively analyzed.Both patients had combined CFH and CD46 gene mutations.One patient, a 2-year-old boy, presented jaundice and darkened urine following mumps.The other patient, a 7-month-old girl and the younger sister of the boy, developed fever, cough, vomiting, and thrombocytopenia without any apparent cause.Laboratory tests revealed hemolytic anemia, thrombocytopenia, and acute kidney injury in both patients.The genetic test results revealed mutations in both CFH (c.3572C>T, p.Ser1191Leu) and CD46 genes (c.293C>T, p.Thr98Ile) in both patients.The patients′ mother is a heterozygous carrier of the CFH gene mutation, while their father is a heterozygous carrier of the CD46 gene mutation.Both parents exhibit normal phenotypes and are currently receiving regular infusions of Eculizumab.The pediatric aHUS caused by combined CFH and CD46 gene mutations is reported in this study for the first time in China.The clinical features of these patients are summarized and analyzed.

Objective To investigate the predictive value of serum lipoprotein-associated phospholipase A2(Lp-PLA2)and homocysteine(Hcy)combined with white matter hyperintensities(WMH)for cognitive impairment in patients with cerebral small vessel disease(CSVD).Methods A total of 240 patients with CSVD were selected.According to the Montreal Cognitive Assessment(MoCA)scale,all subjects were divided into the non-cognitive impairment group(MoCA≥26 points,120 cases)and the cognitive impairment group(MoCA＜26 points,120 cases).Paraventricular white matter high signal(PWMHs)and deep white matter high signal(DWMHs)were scored by Fazekas scale.The sum of the two parts was the total score,and the severity of DWMHs was graded by the score.The basic information,serum Lp-PLA2,Hcy level and severity of WMH were compared between the two groups.Logistic regression was applied to analyze influencing factors of cognitive impairment in CSVD patients.The predictive value of serum level of Lp-PLA2 and Hcy and WMH for cognitive impairment in CSVD patients was analyzed by receiver operating characteristic(ROC)curve.Results Compared with the non-cognitive impairment group,patients of the cognitive impairment group were older,had higher serum levels of Lp-PLA2 and Hcy,and had more severe of WMH(P＜0.05).Results of Logistic regression analysis showed that serum Lp-PLA2,Hcy levels and severity of WMH were influencing factors for cognitive impairment of patients with CSVD(P＜0.05).The results of ROC curve analysis showed that the area under the curve of serum Lp-PLA2,Hcy level combined with severity of WMH predicting cognitive impairment in patents with CSVD was 0.812,the sensitivity was 81.7%and the specificity was 71.7%(P＜0.05).Conclusion Patients with cognitive impairment caused by CSVD have higher serum levels of Lp-PLA2 and Hcy,and more severe WMH.The combination of the three has a relatively high predictive value for cognitive impairment in patents with CSVD.

Objective:To construct a shoulder and neck functional exercise program for patients undergoing endoscopic thyroidectomy by a gasless unilateral axillary approach and to explore its effectiveness.Methods:The first draft of the shoulder and neck functional exercise program for patients undergoing endoscopic thyroidectomy by a gasless unilateral axillary approach was constructed through literature review, and two rounds of expert consultation were conducted with 20 experts to determine the final draft of the program with the results of the pretest. A total of 98 patients who underwent endoscopic thyroidectomy by a gasless unilateral axillary approach in the Department of Thyroid Surgery of the First Affiliated Hospital of Zhengzhou University from September 2023 to January 2024 were selected for the study using the convenience sampling method. Patients from September to December 2023 were set up as control group and patients from October 2023 to January 2024 were set up as experimental group, with 49 patients in each group. Control group implemented routine nursing, and experimental group received the shoulder and neck functional exercise program developed in this study on the basis of control group. Constant-Murley Score score, occurrence of numbness in the chest wall access area, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire scores in cancer patients were compared between the two groups at one week, one month, and three months post-intervention.Results:In the two rounds of expert consultation, the effective questionnaire recovery rates were 85.00% (17/20) and 94.12% (16/17), and the coefficient of the expert familiarity was 0.938, the coefficient of basis of judgment was 0.891, and the coefficient of authority was 0.915. The coefficients of variation for the importance ratings of the entries in the second round of consultation were 0.096 to 0.190 and Kendall's harmony coefficient was 0.155 ( P<0.01). The shoulder and neck function exercise program for patients undergoing endoscopic thyroidectomy by a gasless unilateral axillary approach included three first-level items, five second-level items, and 13 third-level items. At one week post-intervention, the difference in occurrence of numbness in the chest wall access area was statistically significant in both groups ( P<0.05). At one month post-intervention, the differences in shoulder function scores, occurrence of numbness in the chest wall access area, and quality of life scores between the two groups were statistically significant (all P<0.05). At three months post-intervention, the differences in shoulder function scores and quality of life scores between the two groups were statistically significant (all P<0.05) . Conclusions:The shoulder and neck function exercise program for patients undergoing endoscopic thyroidectomy by a gasless unilateral axillary approach has certain scientific validity and feasibility, which can improve the shoulder and neck function of patients undergoing endoscopic thyroidectomy by axillary approach, reduce the numbness in the chest wall access area, and improve the quality of life of the patients in the postoperative period.