Objective: To analyze the association between alcohol consumption and lumbar disc herniation (LDH), so as to provide a reference for the development of prevention and treatment strategies for LDH. Methods: From May to July 2022, permanent residents aged ≥18 years from eight counties (cities/districts) in Gansu Province were selected using a multistage stratified random sampling method. Data on basic characteristics, alcohol consumption in the past 30 days, hypertension, and diabetes mellitus were collected through questionnaire surveys. LDH was determined based on imaging findings, combined with disease history or clinical symptoms. Multivariable logistic regression model was used to analyze the association between alcohol consumption and LDH, with subgroup analyses conducted by gender, age, ethnicity, and altitude of residence. Propensity score matching (PSM) was utilized for sensitivity analysis. Results: A total of 4 545 individuals were surveyed. There were 2 026 (44.58%) males and 2 519 (55.42%) females. The mean age was (44.82±15.33) years. The study participants were predominantly of Han ethnicity, with 2 598 persons accounting for 57.17%. The altitude of residence was mainly above 3 500 m, with 1 941 persons accounting for 42.71%. There were 574 alcohol drinkers, accounting for 12.63%. LDH was detected in 1 035 cases, with a detection rate of 22.77%. Multivariable logistic regression analysis showed that after adjusting for gender, age, physical activity, and hypertension, compared to non-drinking residents, alcohol-consuming residents exhibited a 27.6% reduction in the risk of LDH (OR=0.724, 95%CI: 0.544-0.963). No significant interaction effects on LDH risk were observed between alcohol consumption and gender, age, ethnicity, or altitude of residence (all Pfor interaction >0.05). The results of the sensitivity analysis indicated that compared to non-drinking residents, alcohol-consuming residents exhibited a 38.8% reduction in the risk of LDH (OR=0.612, 95%CI: 0.382-0.976). Conclusion Alcohol consumption was statistically associated with a lower risk of LDH.

Bio-mineralization has emerged as a promising strategy to enhance vaccine immunogenicity. This study optimized the calcium phosphate (CaP) mineralization process of foot-and-mouth disease virus-like particles (FMD VLPs) to achieve high mineralization efficiency and scalability. Key parameters, including concentrations of Ca²⁺, HPO₄^2-, NaCl, and VLPs, as well as stirring speed, were systematically optimized. Stability of the scaled-up reaction system and immunogenicity of the mineralized vaccine were evaluated. Optimal conditions [25.50 mmol/L Ca(NO₃)₂, 15 mmol/L Na₂HPO₄, 300 mmol/L NaCl, 0.75 mg/mL VLPs, and 1 500 r/min] yielded CaP-mineralized VLPs (VLPs-CaP) with high mineralization efficiency, uniform morphology, and a favorable particle size. Scaling up the reaction by 25 folds maintained consistent mineralization efficiency and particle characteristics. Immunization in mice demonstrated that VLPs-CaP induced higher titers of specific antibodies and neutralizing antibodies than unmineralized VLPs (P < 0.05). Higher IgG2a/IgG1 ratio and enhanced IFN-γ secretion (P < 0.05) further indicated robust cellular immune responses. We establish a stable and scalable protocol for VLPs-CaP, providing a theoretical and technical foundation for developing high-efficacy VLPs-CaP vaccines.
Vaccines, Virus-Like Particle/immunology* ; Immunogenicity, Vaccine ; Calcium Phosphates/chemistry* ; Foot-and-Mouth Disease Virus ; Biomineralization ; Particle Size ; Animals ; Mice ; Antibodies, Neutralizing/blood* ; Antibodies, Viral/blood* ; Immunity, Cellular

Vaccination is a crucial strategy for the prevention and control of infectious diseases. Virus-like particles (VLPs), composed of structural proteins, have garnered significant attention as a novel type of vaccine due to their excellent safety and immunogenicity. However, similar to most vaccine antigens, VLPs exhibit insufficient thermal stability, which not only restricts the widespread application of vaccines but also increases the risk of vaccine inactivation. This study aims to enhance the stability and shelf life of VLPs derived from type A foot-and-mouth disease virus (FMDV) by employing vacuum freeze-drying technology. The optimal lyoprotectant formulation was determined through single-factor and combinatorial screening. Subsequently, the correlation between the immunogenicity of the freeze-dried vaccine and the content of FMDV VLPs was evaluated via a mouse model. The stability of FMDV VLPs before and after freeze-drying was further assessed by storing them at 4, 25, and 37 ℃ for varying time periods. Results indicated that the lyoprotectant formulation No.1, composed of 7.5% trehalose, 0.1% Tween 80, 50 mmol/L glycine, 1% sodium glutamate, and 3% polyvinylpyrrolidone (PVP), effectively preserved the content of FMDV VLPs during the vacuum freeze-drying process. The immunization trial in mice revealed that the levels of specific antibodies, immunoglobulin G1 (IgG1), interleukin-4 (IL-4), and neutralizing antibodies induced by freeze-dried FMDV VLPs were comparable to those induced by non-freeze-dried FMDV VLPs. The heat treatment results showed that the storage periods of freeze-dried FMDV VLPs at 4, 25, and 37 ℃ were significantly longer than those of non-freeze-dried FMDV VLPs. In conclusion, the selected lyoprotectant formulation effectively improved the stability of FMDV VLPs vaccines. This study provides valuable insights for enhancing the stability of novel subunit vaccines.
Freeze Drying/methods* ; Animals ; Foot-and-Mouth Disease Virus/immunology* ; Mice ; Vaccines, Virus-Like Particle/chemistry* ; Foot-and-Mouth Disease/immunology* ; Vacuum ; Drug Stability ; Mice, Inbred BALB C ; Viral Vaccines/immunology*

OBJECTIVE To analyze the effects of biapenem on the blood concentration of sodium valproate （VPA） in patients with severe infections. METHODS A retrospective collection of patient data was conducted， encompassing individuals admitted to our hospital from January 2021 to May 2024 who were treated with biapenem for severe infections and concurrently or sequentially administered VPA for the prevention or treatment of epilepsy. The effects of various factors on the blood concentration of VPA， including the combination of biapenem， the sequence of biapenem administration， the number of days of biapenem combination， the dosage of biapenem， and the time after biapenem discontinuation. RESULTS A total of 70 patients with 117 VPA blood concentration results were included in this study. When VPA was used alone， no statistically significant difference was observed in the steady-state blood concentrations of VPA between patients who received biapenem first and those who received it later （P＞ 0.05）. There was no statistically significant difference between the steady-state concentration of VPA in patients who received biapenem in combination for 1 to 3 days and those who did not receive the combination therapy （P＞0.05）. The steady-state concentration of VPA in patients not receiving biapenem combination therapy was significantly higher than that of the patients who received combination therapy for 4 to 7 days and more than 7 days （P＜0.001）. With the prolonged duration of combination therapy， the blood concentration of VPA gradually decreased （P＜0.001）. However， no statistically significant difference was observed between the group receiving combination therapy for more than 7 days and the group receiving it for 4 to 7 days （P＞ 0.05）. After 1 to 3 days of combination therapy， no statistically significant differences in VPA blood concentrations were observed among patients with different discontinuation times of biapenem （P＞0.05）. The blood concentration of VPA in patients who received combination therapy for more than 3 days was significantly lower than those who discontinued biapenem 4 to 7 days or more than 7 days after more than 3 days of combination therapy（P＜0.001）. There was no statistically significant difference in VPA blood concentrations between patients receiving a daily biapenem dose ＞1.0 g and those receiving a daily dose ＜1.0 g （P＞0.05）. CONCLUSIONS The concomitant administration of biapenem for 1-3 days has a minimal impact on the blood concentration of VPA. In patients receiving combination therapy for longer than 3 days， VPA blood concentrations return to baseline levels chouxiaoh@163.com within 4-7 days after biapenem discontinuation.

Objective To investigate the prognosis of patients with negative sentinel lymph nodes(SLN)after neoadjuvant chemotherapy(NAC)for breast cancer who are exempt from axillary lymph node dissection(ALND)and evaluate its safety in clinical treatment.Methods Clinical data of 2,163 patients initially diagnosed with breast cancer and having negative SLNs after NAC were se-lected from the SEER database from 2018 to 2021.Among them,373 patients underwent only SLN biopsy(SLNB group),and 1,790 patients underwent ALND(ALND group).Propensity score matching(PSM)was used to control for confounding factors,and the Kaplan-Meier method was em-ployed to analyze the overall survival rate.Univariate and multivariate Cox regression analyses were conducted to identify prognostic factors influencing the exemption from ALND in patients with negative SLNs after NAC for breast cancer.Results Before PSM,significant differences were observed be-tween the two groups in terms of clinical tumor stage,molecular subtype,estrogen receptor(ER)sta-tus,progesterone receptor(PR)status,human epidermal growth factor receptor 2(HER-2)status,efficacy of NAC,and breast surgery method(P＜0.05).After PSM,363 patients were included in each group.Univariate Cox regression analysis after PSM revealed that age,clinical tumor stage,and ER status were associated with overall survival(OS)of patients(P＜0.05).There was no sig-nificant difference in OS between patients who underwent SLNB and those who underwent ALND(P＞0.05).Multivariate Cox regression analysis indicated that age and clinical tumor stage were independent factors influencing OS in patients with negative SLNs after NAC.Survival curve analysis after PSM showed no statistically significant difference in overall survival rate between the SLNB and ALND groups(P=0.278).Conclusion Exemption from ALND in patients with negative SLNs af-ter NAC is feasible and does not affect the overall survival rate of patients.

Objective To investigate the mechanism of sanguinarine(SA)for alleviating ulcerative colitis(UC)induced by dextran sodium sulfate(DSS)in mice.Methods Male C57BL/6 mouse models of 3.5%DSS-induced UC were randomized for treatment with 1,5 and 10 mg/kg SA by gavage,400 mg/kg sulfasalazine by gavage,or 10 mg/kg SA combined with intraperitoneal injection of 30 mg/kg ML385(a Nrf2 inhibitor).The changes in intestinal inflammation was assessed by monitoring weight changes,disease activity index(DAI)score,colon length measurement,and HE staining.After the treatments,the colon tissues were collected for detection of malondialdehyde(MDA)content using colorimetry,mRNA expressions of inflammatory factors using RT-qPCR,and the expressions of Nrf2,HO-1,Keap-1,p-p65,p65,occludin,and ZO-1 proteins were detected using Western blotting.Results SA treatment obviously alleviated weight loss,colon length shortening and DAI score increase and ameliorated structural destruction of the colon glands and colonic crypts in mice with DSS-induced UC.SA intervention significantly decreased the levels of TNF-α,IL-1β and IL-6 mRNA and lowered ROS and MDA levels in the colon tissue of UC mice.The mouse models receiving SA treatment showed significantly increased expressions of Nrf2,HO-1,occludin and ZO-1 and lowered expressions of Keap-1 and P-P65 in the colon tissue without significant changes of p65 expression,and these changes were SA dose-dependent.Treatment with ML385 obviously attenuated the effect of high-dose SA for improving UC in the mouse models.Conclusion SA can improve UC-like enteritis in mice possibly by activating the Nrf2 pathway and inhibiting the NF-κB pathway in the colon tissue.

Objective To investigate the effect of sanguinarine(SAN)on proliferation and ferroptosis of colorectal cancer cells.Methods SW620 and HCT-116 cells treated with different concentrations of SAN were examined for cell viability changes using CCK8 assay to determine the IC50 of SAN in the two cells.The inhibitory effects of SAN on proliferation,invasion and migration of the cells were evaluated using colony-forming assay and Transwell assays.ROS production in the treated cells was analyzed with flow cytometry,and lipid peroxide production was assessed by detecting malondialdehyde(MDA)level.Glutathione(GSH)levels in the cells were detected,and Western blotting was used to detect the expressions of ferroptosis-related proteins STUB1 and GPX4.Results SAN significantly inhibited the proliferation,invasion and migration of SW620 and HCT-116 cells.SAN treatment significantly promoted ROS production,increased intracellular MDA level,and lowered GSH level in the two cells(P<0.05).Western blotting showed that SAN significantly upregulated the expression of STUB1 and down-regulated the expression of its downstream protein GPX4(P<0.05).Conclusion SAN induces ferroptosis in colorectal cancer cells by regulating STUB1/GPX4,which may serve as a new therapeutic target for colorectal cancer.

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.

Objective To investigate the mechanism of sanguinarine(SA)for alleviating ulcerative colitis(UC)induced by dextran sodium sulfate(DSS)in mice.Methods Male C57BL/6 mouse models of 3.5%DSS-induced UC were randomized for treatment with 1,5 and 10 mg/kg SA by gavage,400 mg/kg sulfasalazine by gavage,or 10 mg/kg SA combined with intraperitoneal injection of 30 mg/kg ML385(a Nrf2 inhibitor).The changes in intestinal inflammation was assessed by monitoring weight changes,disease activity index(DAI)score,colon length measurement,and HE staining.After the treatments,the colon tissues were collected for detection of malondialdehyde(MDA)content using colorimetry,mRNA expressions of inflammatory factors using RT-qPCR,and the expressions of Nrf2,HO-1,Keap-1,p-p65,p65,occludin,and ZO-1 proteins were detected using Western blotting.Results SA treatment obviously alleviated weight loss,colon length shortening and DAI score increase and ameliorated structural destruction of the colon glands and colonic crypts in mice with DSS-induced UC.SA intervention significantly decreased the levels of TNF-α,IL-1β and IL-6 mRNA and lowered ROS and MDA levels in the colon tissue of UC mice.The mouse models receiving SA treatment showed significantly increased expressions of Nrf2,HO-1,occludin and ZO-1 and lowered expressions of Keap-1 and P-P65 in the colon tissue without significant changes of p65 expression,and these changes were SA dose-dependent.Treatment with ML385 obviously attenuated the effect of high-dose SA for improving UC in the mouse models.Conclusion SA can improve UC-like enteritis in mice possibly by activating the Nrf2 pathway and inhibiting the NF-κB pathway in the colon tissue.