Background The job content of aircraft maintenance workers is complex, with high intensity and high requirements, and they are prone to work-related musculoskeletal disorders (WMSDs), but related research is relatively rare. Objective To investigate the positive rate of WMSDs among aircraft maintenance workers, evaluate ergonomic load, and analyze the risk factors of WMSDs. Methods We used a self-compiled questionnaire for WMSDs and the Quick Exposure Checklist (QEC) to investigate the basic situation, positive rate of WMSDs, and the ergonomic load of 2271 male maintenance workers in 6 departments of an aircraft maintenance company, including airline maintenance, overall overhaul, accessory/landing gear overhaul, engine overhaul, product customization, and power assist. We used a logistic regression model to analyze the risk factors of WMSDs in the neck, shoulder, hand/wrist, and lower back. Results The positive rate of WMSDs in the past 12 months was 70.4% (1598/2271) and the positive rate of WMSDs in different body parts ranged from 6.6% to 49.5%, with the top three parts of lower back, neck, and knee, respectively. There were statistically significant differences in the positive rate among different departments (P<0.05). The average QEC scores for neck, hand/wrist, and back (static) were moderate, while those for shoulder and back (dynamic) were high, and the body part specific positive rate of WMSDs increased with the increase of ergonomic load level. Working years (5-<10 years, ≥20 years), working with back flexed or twisted or side bent (moderately, excessively), high maximum force level exerted by one hand, and feeling difficult (sometimes, often) and stressful (moderately, very) while working were associated with higher risks of lower back pain (OR=1.486, 1.505; 2.151, 3.769; 1.637; 2.110, 2.407; 1.637, 1.794; P<0.05). Working years (15-<20 years, ≥20 years), working with head/neck bent or twisted (occasionally, continuously), feeling difficult (sometimes) and stressful (very) while working were associated with higher risks of neck pain (OR=1.731, 1.586; 3.732, 8.341; 1.633; 1.696; P<0.05). Working years (15-<20 years, ≥20 years), working with hands in a high position (at shoulder or above), very frequent shoulder/arm movements, feeling difficult (sometimes, often) and stressful (moderately, very) while working were associated with higher risks of shoulder pain (OR=1.587, 1.709; 1.299; 1.521; 1.643, 2.239; 1.659, 1.977; P<0.05). Working with wrist at deviated or bent angle, high repetition of similar movements, feeling difficult (sometimes, often) and stressful (moderately, very) while working were associated with higher risks of hand/wrist pain (OR=1.692; 1.670; 1.827, 2.884; 2.190, 2.625; P <0.05) . Physical exercise after work (≥3 times·week⁻¹) was associated with a lower risk of neck pain (OR=0.582, P<0.05). Shift workers were at a lower risk of shoulder pain and hand/wrist pain (OR=0.737 and 0.554, P<0.05). Conclusion The high positive rate of WMSDs symptoms among aircraft maintenance workers is related to individual, occupational ergonomic, and psychological factors, and active prevention and intervention should be taken.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

BACKGROUND:Currently,different methods of model establishment have been derived from different injury modes of spinal cord injury.Traditional physical injury modeling methods have their own advantages and disadvantages,and there is a lack of more effective and stable animal models of spinal cord injury. OBJECTIVE:To establish a reproducible,controllable,trauma-free,low-mortality,more stable,widely applicable,and short-term postoperative care rat model of spinal cord injury. METHODS:Forty Sprague-Dawley rats with similar body mass and ages were randomly divided into a control group and an improved group,with 20 rats in each group.Animal models of spinal cord injury in the control group were constructed using a clip model method,while the improved group used a modified ligation method based on the compression method to make the spinal cord injury models using suture ligation based on fenestration.Postoperative comparisons were made between the two groups,assessing urination behavior,hematuria,pyuria(infection rate),mortality,scoliosis rate and Basso-Beattie-Bresnahan locomotor rating scale scores at 1,3,5,and 7 days after modeling. RESULTS AND CONCLUSION:Compared with the conventional modeling method,the modified ligation method based on the compression method resulted in faster recovery of urination behavior,lower hematuria rate,lower infection rate,lower mortality rate,lower scoliosis rate,and more concentrated and stable Basso-Beattie-Bresnahan scores(all below 2 points within 1 week).This proves that the modified ligation method based on compression is more suitable for the establishment of spinal cord injury models in rats.

Objective: To investigate the current status of iron metabolism among apheresis donors in Guangzhou and analyze the improvement effects of health education on iron deficiency in frequent apheresis donors. Methods: Using a generalized linear mixed model (GLMM), a 180-day follow-up was conducted on 261 eligible apheresis donors at the Guangzhou Blood Center from January to July 2024. Hemoglobin (Hb), serum ferritin (SF), unsaturated iron-binding capacity (UIBC), total iron-binding capacity (TIBC), and transferrin saturation (TS) were selected as outcome variables. The effects of gender, age group, and number of donations within 180 days on these outcomes were analyzed and modeled. A general linear model (GLM) with repeated measures was applied to 55 donors who received health education interventions, comparing changes in Hb and iron metabolism-related indicators before and after follow-up and health education. Results: No significant difference in Hb levels was observed between first-time and regular apheresis donors, but SF levels were significantly higher in first-time donors (F=6.195, P<0.05). The GLMM revealed that female donors exhibited more significant reductions in Hb (T=-12.546) and SF (T=-5.829)(P<0.05 for both). Age group showed no interactive effects on Hb or SF changes. While number of donations within 180 days had no interactive effect on Hb, SF levels significantly decreased with increased number of donations (using ≥9 donations as the reference group; P<0.05 for all groups). After health education, Hb levels remained unchanged, but SF increased compared to pre-intervention levels (mean difference: -18.571, P<0.05), though a declining trend persisted compared to baseline (mean difference from baseline to post-intervention: 23.068,P<0.05). Conclusion: Female and number of donations are primary factors contributing to SF reduction in apheresis donors. Health education interventions promote SF recovery. Extending donation intervals and reinforcing iron deficiency-related health education may improve iron status in donors.

Objective To analyze the nonlinear relationship between hypothermic machine perfusion (HMP) parameters and delayed graft function (DGF) and optimize the construction of a predictive model for DGF. Methods The data of 923 recipients who underwent kidney transplantation from deceased donors were retrospectively analyzed. According to the occurrence of DGF, the recipients were divided into DGF group (n=823) and non-DGF group (n=100). Donor data, HMP parameters and recipient data were analyzed for both groups. The nonlinear relationship between HMP parameters and the occurrence of DGF was explored based on restricted cubic splines (RCS). Over-sampling, under-sampling and balanced sampling were used to address the imbalance in the proportion of DGF to construct logistic regression predictive models. The area under the curve (AUC) of each model was compared in the validation set, and a nomogram model was constructed. Results Donor BMI, cold ischemia time of the donor kidney, and HMP parameters (initial and final pressures, resistance, and perfusion time) were significantly different between the DGF and non-DGF groups (all P<0.05). The RCS analysis revealed a threshold-like nonlinear relationship between HMP parameters and the risk of DGF. Among the models constructed using different sampling methods, the balanced sampling model had the highest AUC. Using this model, a nomogram was constructed to stratify recipients based on risk scores. Recipients in the high-risk group had higher serum creatinine levels at 1, 6, and 12 months after kidney transplantation compared to those in the low-risk group (all P<0.05). Conclusions There is a nonlinear relationship between HMP parameters and the risk of DGF, and the threshold is helpful for organ quality assessment and monitoring of graft function after transplantation. The predictive model for DGF constructed on the base of balanced sampling algorithms helps perioperative decision-making and postoperative graft function monitoring of kidney transplantation.

[摘 要] 目的：探讨2',4'-二羟基查尔酮（D2）通过调控miR-7-5p诱导自噬，抑制结直肠癌细胞增殖、迁移及上皮间质转化（EMT）的分子机制。方法：选取结直肠癌细胞系HCT-15、SW620为研究对象，分别用不同浓度（0、12.5、25、50 µmol/L）的D2处理细胞，采用MTT法和平板克隆实验检测细胞增殖活力及克隆形成能力，划痕愈合实验及Transwell实验评估细胞迁移能力，WB法检测EMT相关蛋白、自噬相关蛋白及PI3K/AKT/mTOR信号通路蛋白的表达情况，免疫荧光染色法观察自噬小体的形成。基于TCGA数据库分析miR-7-5p在结直肠癌中的表达水平，并借助KEGG富集分析探究miR-7-5p与结直肠癌的关联。运用RT-qPCR检测miR-7-5p的表达量，同时采用慢病毒转染技术构建miR-7-5p稳定敲低或过表达的细胞系。结果：D2抑制结直肠癌细胞的增殖、迁移及EMT进程（P < 0.05或P < 0.01）。TCGA数据库分析及KEGG富集分析显示，miR-7-5p在结直肠癌中呈低表达，且与结直肠癌的发生有密切关联。12.5、25、50 µmol/L D2处理均可上调HCT-15、SW620细胞miR-7-5p的表达水平（均P < 0.01）。25 µmol/L D2处理组HCT-15、SW620细胞中 LC3、p-ULK1等自噬相关蛋白表达增加，而PI3K/AKT/mTOR信号通路受到抑制（均P < 0.05），细胞内自噬小体数量增加（均P < 0.01）；与D2单独处理组相比，经 D2处理的miR-7-5p敲减细胞中LC3、p-ULK表达量有所下降（P < 0.05或P < 0.01）。结论：D2通过调控miR-7-5p诱导自噬，抑制结直肠癌细胞的增殖、迁移及EMT进程，其机制可能与抑制PI3K/AKT/mTOR信号通路有关。

AIM:To investigate the effects of electroacupuncture at the Taiyang on refractive parameters and the expression of β-catenin and integrin β1 in the ciliary body of mice with form-deprivation myopia(FDM).METHODS:A total of 48 3-week-old healthy C57BL/6J mice were randomly divided into 4 groups: normal control(NC), FDM group, sham acupuncture(sham), and electroacupuncture at Taiyang acupoint(Taiyang), with 12 mice in each group. Mice in the FDM, sham, and Taiyang groups, wore translucent custom-made eye masks on the right eye to induce myopia. The Taiyang group received electroacupuncture stimulation at the Taiyang acupoint, while the sham group underwent non-penetrating stimulation with a blunt wooden stick. No intervention was performed on the NC group. Refraction and axial length were measured by infrared autorefractor and optical coherence tomography(OCT)before modeling and at 4 wk after modeling. The expression levels of β-catenin and integrin β1 in the ciliary body of mice at 4 wk after modeling were detected using quantitative real-time PCR(qPCR)and Western blotting(WB).RESULTS:After modeling for 4 wk, compared with the NC group, the FDM and sham groups showed significantly decreased refractive power(both P<0.05), elongated axial length(both P<0.05), and increased β-catenin and integrin β1 expression. Compared with the FDM and sham groups, the Taiyang group showed significantly increased refractive power(both P<0.05), shortened axial length(both P<0.05), and decreased β-catenin and integrin β1 expression.CONCLUSION:Electroacupuncture stimulation at the Taiyang acupoint effectively delayed the progression of myopia in FDM mice, and this effect may be partially mediated through modulating the expression of β-catenin and integrin β1 in the ciliary body.

OBJECTIVE To evaluate the efficacy and safety of ceftazidime/avibactam （CAZ/AVI） combined with amikacin （AMK） in the treatment of carbapenem-resistant Enterobacteriaceae （CRE） severe pneumonia. METHODS A retrospective cohort study was conducted on 240 patients diagnosed with severe pneumonia caused by CRE infection in the intensive care unit （ICU） of the Affiliated Hospital of Xuzhou Medical University from January 2022 to December 2024. The patients were divided into a combination group （CAZ/AVI combined with AMK， n＝136） and a control group （CAZ/AVI alone， n＝104）. The 28-day mortality rate， clinical efficacy，mechanical ventilation time， ICU stay， infectious markers [C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）， white blood cell count （WBC）， and neutrophil percentage （N%）]， Acute Physiology and Chronic Health Evaluation Ⅱ （APACHE Ⅱ） scores， and total incidence of adverse reactions were compared between two groups of patients. At the same time， subgroup analysis was conducted based on the severity of the condition， mechanical ventilation status， and baseline renal function. RESULTS The 28-day mortality rate of patients in the combination group was significantly lower than that in the control group （20.6% vs. 34.6%， P＝0.022）， and the clinical effective rate was significantly higher than that in the control group （80.1% vs. 65.4%， P＝0.004）. The mechanical ventilation time and ICU hospitalization time in the combination group were significantly shorter than those in the control group （[ 7.2±2.4） days vs. （10.4±3.6） days， （10.5±3.1） days vs. （13.7±3.8） days； P＜0.01].After 7 days of treatment， the CRP， PCT， IL-6， WBC， N% and APACHE Ⅱ scores of patients in the combination group significantly decreased compared to before treatment， and the decrease was significantly greater than that of the control group （P＜0.01）. There was no statistically significant difference in the total incidence of adverse reactions between the two groups of patients （11.8% vs. 13.5%， P＝0.690）. Subgroup analysis showed that among high-risk （APACHE Ⅱ score≥15） and mechanically ventilated patients， the 28-day mortality rate and weaning time of the combination group were significantly lower/ shorter than those of the control group （P＜0.05）， while there was no significant difference in the total incidence of adverse reactions between the combination group and the control group after dose adjustment in patients with chronic renal insufficiency （P＞0.05）. CONCLUSIONS The CAZ/AVI combined with AMK regimen has better anti-infective efficacy and good safety in patients with severe pneumonia caused by CRE infection compared to the CAZ/AVI regimen alone； the survival benefits of this joint regimen are more significant in high-risk and mechanically ventilated patients， with critically ill patients being the main beneficiaries.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

Biomolecular aggregation within cellular environments via liquid–liquid phase separation (LLPS) spontaneously forms droplet-like structures, which play pivotal roles in diverse biological processes. These structures are closely associated with a range of diseases, including neurodegenerative disorders, cancer and infectious diseases, highlighting the significance of understanding LLPS mechanisms for elucidating disease pathogenesis, and exploring potential therapeutic interventions. In this review, we delineate recent advancements in LLPS research, emphasizing its pathological relevance, therapeutic considerations, and the pivotal role of bioinformatic tools and databases in facilitating LLPS investigations. Additionally, we undertook a comprehensive analysis of bioinformatic resources dedicated to LLPS research in order to elucidate their functionality and applicability. By providing comprehensive insights into current LLPS-related bioinformatics resources, this review highlights its implications for human health and disease.