Background Work-related musculoskeletal disorders (WMSDs) are one of the major occupational health problems faced by bus drivers and should receive special attention. Objective To explore the associations of weekly working hours and sleep quality with neck and lower back WMSDs among bus drivers, as well as assess the potential mediating role of sleep quality. Methods From June to December 2022, we recruited bus drivers from 5 subsidiaries of the Shenzhen Bus Group by convenient sampling method. Demographic characteristics, lifestyles, and work-related features of the bus drivers were collected through a questionnaire survey. The Pittsburgh Sleep Quality Index (PSQI) scale and the Musculoskeletal Disorders Survey Questionnaire were used to assess sleep quality and WMSDs respectively. Logistic regression models were applied to analyze the associations of weekly working hours and sleep quality with WMSDs in neck and lower back. Furthermore, mediation analysis was performed to investigate the role of sleep quality in the associations between weekly work hours and neck and lower back WMSDs. Results A total of 1792 valid questionnaires were collected, with a response rate of 95.07%. Among these, 89.3% of the bus drivers worked more than 40 h per week, and the positive rate of poor sleep quality was 28.2%. The overall positive rate of WMSDs within one year before the survey was 69.12%. Among different body regions, the leading positive rates were identified in neck and lower back regions, at 55.92% and 53.68%, respectively. The logistic regression model showed that compared to the bus drivers with weekly work hours ≤40 h, those weekly worked (40~48] h (OR=1.43, 95%CI: 1.02, 2.01; OR=1.65, 95%CI: 1.17, 2.34), (48~56] h (OR=2.69, 95%CI: 1.89, 3.83; OR=2.30, 95%CI: 1.62, 3.29) and ＞56 h (OR=2.63, 95%CI: 1.86, 3.74; OR=3.23, 95%CI: 2.27, 4.62) had significantly increased risk of WMSDs in neck and lower back. Additionally, when compared to those with good sleep quality, bus drivers with poor sleep quality had higher risks of both neck and lower back WMSDs (OR=4.08, 95%CI: 3.20, 5.23; OR=4.15, 95%CI: 3.26, 5.30, respectively). Further mediation analysis indicated that sleep quality partially mediated the associations between weekly working hours and both neck and lower back WMSDs, with 36.15% and 33.68% as the respective proportion of mediation. Conclusion The positive rate of WMSDs is high among bus drivers, and the most common WMSDs occur in neck and lower back. Long working hours and poor sleep quality are significantly associated with increased risks of neck and lower back WMSDs. Sleep quality may mediate the associations of weekly working hours with neck and lower back WMSDs.

OBJECTIVE To evaluate the cost-effectiveness of iruplinalkib for ALK-positive non-small cell lung cancer （NSCLC） patients who had not previously received ALK-tyrosine kinase inhibitors （TKIs） from the perspective of the Chinese healthcare system. METHODS Based on the INSPIRE clinical trial， a three-health state partitioned survival model was developed to simulate the progression of disease， with model cycle of 3 weeks and a life-year time range of 15 years； the discount rate was 5%. For the treatment of ALK-positive advanced NSCLC， total cost， quality-adjusted life year （QALY）， and incremental cost- effectiveness ratio （ICER） were compared between iruplinalkib and crizotinib； using 1-3 times China’s per capita gross domestic product （GDP） （89 358-268 074 yuan） in 2023 as the willingness-to-pay （WTP） threshold， the cost-effectiveness of two regimens were compared. The sensitivity analysis and scenario analysis （altering the distribution of survival curves， utility values） were conducted to assess model robustness. RESULTS Compared with the crizotinib regimen， the ICER for the iruplinalkib regimen was 194 412.74 yuan/QALY， which was below the WTP threshold of three times China’s per capita GDP in 2023 yuan）. The results under the scenario of altering the survival curve distribution were consistent with the base case analysis. However， after increasing the utility value of the disease progression state， the ICER exceeded the WTP threshold， and iruplinalkib no longer had a cost-effective advantage. The results of the one-way sensitivity analysis indicated that the cost of iruplinalkib and the utility values of disease progression states had a significant impact on the ICER. The probabilistic sensitivity analysis confirmed the robustness of the base case analysis results. CONCLUSIONS From the perspective of China’s healthcare system， compared with crizotinib regimen， the therapy with iruplinalkib is cost-effective for ALK-positive NSCLC patients who have not previously received ALK-TKIs.

Objective: To investigate the characteristics and risk factors of an outbreak of acute hemorrhagic conjunctivitis (AHC) in a boarding middle school in Guangdong Province, in order to provide a scientific evidence for effective prevention and control of campus AHC outbreaks. Methods: From September 1st to 28th 2023, case identification was conducted among 559 students and 60 faculty members using standardized definition. Descriptive analysis was conducted on the three distrubution patterns of the outbreak. Questionnaires were designed, and a case-control study was adopted to analyze the possible risk factors of the disease transmission. The propensity score matching (PSM) method was used to control the difference of baseline data. Results: A total of 269 cases of AHC were identified, with an attack rate of 43.46%. The pathogen was confirmed as Coxsackie virus A24 variant (CA24v). Among these, 264 cases were students (attack rate of 47.23%) and 5 were staff (attack rate of 8.33%). A total of 153 pairs of PSM were successfully matched. After PSM matching, there were no statistically significant differences in gender, grade and class between the case group and the control group ( χ 2=0.12, 5.41, 11.24, P >0.05). The results of multivariate Logistic regression analysis showed that middle school students whose towels contacted with others ( OR =1.81), and direct contact with other AHC cases recently ( OR =4.89) were more likely to have AHC; while wearing glasses ( OR =0.43) and frequent use of hand sanitizer ( OR = 0.37 ) were less likely to have AHC ( P <0.05). Conclusion The outbreak of AHC is caused by CA24v, demonstrating rapid spread and extensive impact within the school setting.

OBJECTIVE: To explore the integrated traditional Chinese and Western medicine treatment plan for ankylosing spondylitis complicated with lower cervical spine fracture and dislocation, adopt the treatment plan of preoperative continuous traction, intraoperative prizing reduction combined with anterior long-segment plate-screw and posterior short-segment pedicle screw-rod system internal fixation, and evaluate its surgical efficacy and clinical application value. METHODS: From June 2018 to September 2022, 7 male patients with ankylosing spondylitis complicated with lower cervical spine fractures were admitted, aged 43 to 65 years old. Among them, there was 1 case of C_3,4 fracture, 1 case of C_4,5 fracture, 1 case of C_6,7 fracture, and 4 cases of C_5,6 fracture, all of which were fracture and dislocation. All patients received preoperative continuous skull traction, and intraoperative prizing reduction combined with anterior long-segment plate-screw and posterior short-segment pedicle screw-rod system internal fixation. The Neck Disability Index (NDI), Japanese Orthopedic Association (JOA) score, and Frankel scale were used to evaluate the neurological function and quality of life before and after surgery. The visual analogue scale (VAS) was used to evaluate neck and limb pain. The operation time, blood loss, hospital stay, and surgery-related complications were recorded. RESULTS: All 7 patients were followed up for 6 to 24 months after surgery. The operation time of the 7 patients ranged from 300 to 480 minutes, the blood loss ranged from 300 to 1000 ml, and the hospital stay ranged from 8 to 25 days. The preoperative NDI of the 7 patients ranged from 25% to 42%, which decreased to 12% to 30% at 1 week after surgery and 5% to 25% at the last follow-up. The preoperative JOA score ranged from 8 to 13 points, which increased to 12 to 15 points at 1 week after surgery and 13 to 16 points at the last follow-up. The preoperative VAS ranged from 6 to 8 points, which decreased to 2 to 4 points at 1 week after surgery and 0 to 3 points at the last follow-up. Regarding the Frankel grade of neurological function, 2 patients were grade C before surgery and recovered to grade D at the last follow-up after surgery, and the remaining patients recovered to grade E at the last follow-up after surgery. There were 3 cases of pressure ulcers, including 1 case of intraoperative pressure ulcer, 1 case of cervical cerebrospinal fluid leakage, 1 case of screw loosening, and 1 case of aggravated fracture dislocation due to preoperative traction. CONCLUSION Preoperative cervical traction combined with intraoperative prizing reduction and anterior long-segment plate combined with posterior short-segment pedicle screw internal fixation provides a safe and effective surgical option for ankylosing spondylitis complicated with lower cervical spine fracture and dislocation, which can minimize surgical trauma and improve clinical efficacy. However, this study has a small sample size and a short follow-up time for some patients, so further verification with large-sample and long-term follow-up data is still needed.
Humans ; Male ; Adult ; Middle Aged ; Fracture Fixation, Internal/methods* ; Spondylitis, Ankylosing/surgery* ; Cervical Vertebrae/surgery* ; Spinal Fractures/surgery* ; Traction ; Aged ; Joint Dislocations/surgery*

OBJECTIVE: To establish venetoclax-resistant acute myeloid leukemia (AML) cell lines, assess the sensitivity of venetoclax-resistant cell lines to the BCL-2 protein family, and investigate their resistance mechanisms. METHODS: CCK-8 method was used to screen AML cell lines (MV4-11, MOLM13, OCI-AML2) that were relatively sensitive to venetoclax. Low concentrations of venetoclax continuously induced drug-resistance development in the cell lines. Changes in cell viability and apoptosis rate before and after resistance development were measured using the CCK-8 method and flow cytometry. BH3 profiling assay was performed to anayze the transform of mitochondrion-dependent apoptosis pathway as well as the sensitivity of resistant cell lines to BCL-2 family proteins and small molecule inhibitors. Real-time fluorescence quantitative PCR (RT-qPCR) was utilized to examine changes in the expression levels of BCL-2 protein family members in both venetoclax-resistant cell lines and multidrug-resistant patients. RESULTS: Venetoclax-resistant cell lines of MV4-11, MOLM13, and OCI-AML2 were successfully established, with IC₅₀ values exceeding 10-fold. Under the same concentration of venetoclax, the apoptosis rate of resistant cells decreased significantly (P < 0.05). BH3 profiling assay revealed that the drug-resistant cell lines showed increased sensitivity to many pro-apoptotic proteins (such as BIM,BID and NOXA). RT-qPCR showed significantly upregulated MCL1 and downregulated NOXA1 were detected in drug-resistant cell lines. Expression changes in MCL1 and NOXA1 in venetoclax-resistant patients were consistent with our established drug-resistant cell line results. CONCLUSION The venetoclax-resistant AML cell lines were successfully established through continuous induction with low concentrations of venetoclax. The venetoclax resistance resulted in alterations in the mitochondrial apoptosis pathway of the cells and an increased sensitivity of cells to pro-apoptotic proteins BIM, BID, and NOXA, which may be associated with the upregulation of MCL1 expression and downregulation of NOXA1 expression in the drug-resistant cells.
Humans ; Sulfonamides/pharmacology* ; Drug Resistance, Neoplasm ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology* ; Leukemia, Myeloid, Acute/pathology* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis ; Antineoplastic Agents/pharmacology*

Cancer is the result of evolving crosstalk between neoplastic cell and its immune microenvironment. In recent years, immune therapeutics targeting T lymphocytes, such as immune checkpoint blockade (ICB) and CAR-T, have made significant progress in cancer treatment and validated targeting immune cells as a promising approach to fight human cancers. However, responsiveness to the current immune therapeutic agents is limited to only a small proportion of solid cancer patients. As major components of most solid tumors, myeloid cells played critical roles in regulating the initiation and sustentation of adaptive immunity, thus determining tumor progression as well as therapeutic responses. In this review, we discuss emerging data on the diverse functions of myeloid cells in tumor progression through their direct effects or interactions with other immune cells. We explain how different metabolic reprogramming impacts the characteristics and functions of tumor myeloid cells, and discuss recent progress in revealing different mechanisms-chemotaxis, proliferation, survival, and alternative sources-involved in the infiltration and accumulation of myeloid cells within tumors. Further understanding of the function and regulation of myeloid cells is important for the development of novel strategies for therapeutic exploitation in cancer.
Humans ; Tumor Microenvironment/immunology* ; Myeloid Cells/immunology* ; Neoplasms/therapy* ; Animals

Objective To investigate the feasibility and early efficacy of transapical transcatheter aortic valve replacement (TAVR) combined with transcatheter mitral valve edge-to-edge repair (TEER) in patients with high-risk aortic valve lesions combined with severe mitral regurgitation. Methods The clinical data of patients who underwent "one-stop" transapical TAVR+TEER in our hospital from August 2022 to October 2023 were retrospectively analyzed. Results Five patients were collected, including 3 males and 2 females with a mean age of 66.6±1.8 years. Four patients had aortic valve insufficiency combined with mitral regurgitation and one had aortic valve stenosis and insufficiency combined with mitral regurgitation. All patients successfully completed transapical TAVR+TEER, and the immediate postoperative echocardiographic results revealed that none of them had more than mild perivalvular leakage and mitral regurgitation, and the prosthetic valves were in good position and function. At 1 week postoperatively, echocardiographic results showed 5 patients with no displacement of the prosthetic valve, detachment of the mitral clip, or damage to the leaflets. At 1 month postoperatively, cardiac function was improved to varying degrees in 4 patients, and 1 patient died of multiorgan failure. At 2 months postoperatively, 1 patient died of cerebrovascular accident, and at 3 months postoperatively the echocardiographic results of the remaining 3 patients revealed that there was no more than mild perivalvular leakage or mitral regurgitation, and the patients' postoperative cardiac function and daily life ability were significantly improved. Conclusion In high-risk aortic valve lesions combined with severe mitral regurgitation, "one-stop" transapical TAVR+TEER is feasible with favorable early efficacy and safety.

OBJECTIVE To investigate the improvement effects of sinomenine （Sin） on non-alcoholic steatohepatitis （NASH） and its potential mechanism. METHODS Male C57BL/6J mice were randomly divided into standard chow diet （SCD） group， high- fat diet （HFD） group， Sin low-dose group （Sin-L group， 50 mg/kg）， and Sin high-dose group （Sin-H group， 100 mg/kg）， with 6 mice in each group. The mice of SCD groups were fed with SCD， and other groups were given HFD for consecutive 24 weeks to establish NASH model. Since 17th week， the mice in each drug group were given corresponding drug solutions intragastrically， once a day， for 8 consecutive weeks. After the last medication， the body weight and liver weight of mice were determined， and liver indexes were calculated. The contents of total cholesterol （TC） and triglyceride （TG） in liver tissue， the serum contents of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， interleukin-1β （IL-1β） and IL-18 were all determined. Hepatic steatosis and fibrosis were observed， and hepatic lipid droplets were located. The expressions of IL-18 and IL-1β mRNA， inflammation-related proteins （IL-1β， cleaved-IL-1β）， fibrosis-related proteins [collagen Ⅰ （Col-Ⅰ）， α-smooth muscle actin （α-SMA）， connective tissue growth factor （CTGF）]， and pathway-related protein [adenosine monophosphate-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， Yes-associated protein （YAP）， phosphorylated YAP （p-YAP）] were all determined. HepG2 human liver cancer cells were selected as subjects and divided into control group， oleic acid （OA） group， Sin 50 μmol/L group， Sin 100 μmol/L group， OA+Sin 50 μmol/L group and OA+Sin 100 μmol/L group. After 24 hours of treatment， the accumulation of lipid droplets was observed， and the expressions of pathway-related proteins were detected.RESULTS Compared to HFD group， hepatic steatosis， zengcheng@gdpu.edu.cn fibrotic lesions and lipid droplet accumulation were all alleviated in Sin groups； body weight， liver weight， liver indexes， the contents of AST， ALT， IL-1β， IL-18 in serum and TG， TC in liver tissue， the mRNA expressions of IL-1β and IL-18， and the expressions of cleaved-IL-1β and fibrosis-related proteins all decreased significantly （P＜0.01）； the protein expression of IL-1β， and the phosphorylation levels of AMPK and YAP proteins significantly increased （P＜0.01）. Compared with OA group， the lipid droplet accumulation of cells in OA+Sin groups significantly decreased， while the phosphorylation levels of AMPK and YAP proteins significantly increased （P＜0.05）. CONCLUSIONS Sin can ameliorate the inflammation， lipid deposition and fibrosis of liver tissue in mice， the mechanism of which may be associated with activating the AMPK signaling pathway and promoting YAP phosphorylation.

{L-End}Objective To investigate the prevalence of neck and waist work-related musculoskeletal disorders (WMSDs) and its relationship with occupational stress among express delivery workers. {L-End}Methods A total of 437 express delivery workers in Shenzhen City were selected as the research subjects using convenient sampling method. The prevalence of neck and waist WMSDs and the level of occupational stress were investigated by the Musculoskeletal Disorder Questionnaire and Work Content Questionnaire. {L-End}Results The prevalences of neck and waist WMSDs among the workers in the past year were 47.6% (208/437) and 60.2% (263/437), respectively. The detection rate of occupatioonal stress was 51.5%(225/437). The prevalences of neck and waist WMSDs among the workers of the occupational stress group were higher than that in the non-occupational stress group (51.9% vs 42.6%, 66.4% vs 53.0%, both P<0.01). The results of multivariate logistic regression analysis showed that the risk of neck WMSDs was higher in workers with weekly working hours >40 hours, workers with poor working posture, and workers with occupational stress compared with workers with weekly working hours ≤40 hours, workers without poor working posture, and workers without occupational stress, respectively (all P<0.05). The risk of waist WMSDs was higher in workers without weekly exercise, workers with poor working posture, and workers with occupational stress compared with workers with weekly exercise, workers without poor working posture, and workers without occupational stress, respectively (all P<0.05). {L-End}Conclusion The prevalence of neck and waist WMSDs, which may be influenced by occupational stress and poor working postures, is relatively high among express delivery workers.