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。

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

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.

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.

BACKGROUND: Regulatory dendritic cell (DCreg) subset exhibits a unique capacity for inducing immune tolerance among the variety subsets of dendritic cells (DCs) within gut-associated lymphoid tissues (GALTs). Fms-like tyrosine kinase 3 ligand (FLT3L) is involved in the differentiation of DCregs and the subsequent expansion of regulatory T-cells (Tregs) mediated by DCregs, though the precise mechanism remains poorly understood. This study aimed to explore the expansion mechanism of Treg induced by DCreg and the role of FLT3L in this process. METHODS: DCregs were distinguished from other DC subsets isolated from GALTs of BALB/c mice through a mixed lymphocyte reaction assay. The functions and mechanisms by which FLT3L promoted Treg expansion via DCregs were investigated in vitro through co-culture experiments involving DCregs and either CD4 + CD25 - T-cells or CD4 + CD25 + T-cells. Additionally, an in vivo experiment was conducted using a dextran sulfate sodium (DSS)-induced colitis model in mice. RESULTS: CD103 + CD11b + DC exhibited DCreg-like functionality and was identified as DCreg for subsequent investigation. Analysis of Foxp3 + Treg percentages within a co-culture system of CD4 + CD25 - T-cells and DCregs, with or without FLT3L, demonstrated the involvement of the FLT3/FLT3L axis in driving the differentiation of precursor T-cells into Foxp3 + Tregs induced by DCregs. Cell migration and co-culture assays revealed that the FLT3/FLT3L axis enhanced DCreg migration toward Tregs via the Rho pathway. Additionally, it was observed that DCregs could promote Treg proliferation through the Notch pathway, as inhibition of Notch signaling by DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) suppressed Treg expansion within the co-culture system of DCregs and CD4 + T-cells or CD4 + CD25 + T-cells. Furthermore, the FLT3/FLT3L axis influenced JAG1 expression in DCregs, indirectly modulating Treg expansion. In vivo experiments further established that FLT3L promoted DCreg expansion and restored Treg balance in DSS-induced colitis models, thereby ameliorating colitis symptoms in mice. CONCLUSION The FLT3/FLT3L axis is integral to the maintenance of DCreg function in Treg expansion.
Animals ; T-Lymphocytes, Regulatory/immunology* ; Dendritic Cells/immunology* ; Mice ; Mice, Inbred BALB C ; Membrane Proteins/metabolism* ; Receptors, Notch/metabolism* ; Lymphoid Tissue/metabolism* ; Signal Transduction/physiology* ; Coculture Techniques ; Flow Cytometry

OBJECTIVE: To compare the short-term clinical efficacy and safety of closed reduction with Kirschner wire fixation versus open reduction with plate fixation for treating osteoporotic Colles' fractures in middle-aged and elderly patients. METHODS: Between January 2018 and January 2023, 119 patients with Colles fractures were retrospectively analyzed, including 39 males and 80 females, aged from 48 to 74 years old with an average of(60.58±6.71) years old. The time from injury to operation ranged 1 to 13 days with an average of (5.29±2.52) days. According to the surgical method, they were divided into Kirschner wire fixation group (Kirschner wire group) and plate internal fixation group (plate group). In Kirschner wire group, there were a total of 68 patients, comprising 21 males and 47 females. The average age was (61.15±6.24) years old, ranged from 49 to 74 years old. Among them, 41 cases involved the left side while 27 cases involved the right side. In the plate group, there were a total of 51 patients, including 18 males and 33 females. The average age was (59.78±5.71) years old ranged from 48 to 72 years old. Among them, there were 31 cases on the left side and 20 cases on the right side. The following parameters were recorded before and after the operation:operation time, intraoperative blood loss, hospitalization days, hospitalization expenses, postoperative complications, and radiographic parameters of distal radius (distal radius height, ulnar deviation angle, palmar tilt angle). The clinical efficacy was evaluated at 3 and 12 months after the operation using Gartland-Werley and disabilites of the arm shoulder and hand (DASH) scores. RESULTS: The patients in both groups were followed up for a duration from 12 to 19 months with an average of(13.32±2.02) months. The Kirschner wire group exhibited significantly shorter operation time compared to the plate group 27.91(13.00, 42.00) min vs 67.52(29.72, 105.32) min, Z=-8.74, P=0.00. Intraoperative blood loss was also significantly lower in the Kirschner wire group than in the plate group 3.24(1.08, 5.40) ml vs 21.91(17.38, 26.44) ml, Z=-9.31, P=0.00. Furthermore, patients in the Kirschner wire group had a shorter length of hospital stay compared to those in the plate group (8.38±2.63) days vs (11.40±2.78) days, t=-3.12, P=0.00. Additionally, hospitalization cost was significantly lower in the Kirschner wire group than in the plate group 10 111.29(6 738.98, 13 483.60) yuan vs 15 871.11(11 690.40, 20 051.82) yuan, Z=-5.62, P=0.00. The incidence of complications was 2 cases in the Kirschner wire group and 1 case in the plate group, with no statistically significant difference(P>0.05). At 3 months postoprative, the radial height of the Kirschner wire group was found to be significantly smaller than that of the plate group, with measurements of (11.45±1.69) mm and (12.11±1.78) mm respectively (t=-2.06, P=0.04). However, there were no statistically significant differences observed in ulnar deviation angle and palmar tilt angle between the two groups (P>0.05). The DASH score and Gartland-Werley score in the Kirschner group were significantly higher than those in the plate group at 3 months post-operation (19.10±9.89) vs (13.47±3.51), t=4.34, P=0.00;(11.15±3.61) vs (6.41±2.75), t=8.13, P=0.00). However, there was no significant difference between the two groups at 12 months post-operation (P>0.05). CONCLUSION Compared to plate internal fixation, closed reduction with Kirschner wire support fixation yields a slightly inferior recovery of radial height;however, there is no significant disparity in the functional score of the affected limb at 12 months post-operation. Nonetheless, this technique offers advantages such as shorter operation time, reduced intraoperative blood loss, decreased hospitalization duration, and lower cost.
Humans ; Female ; Male ; Middle Aged ; Aged ; Fracture Fixation, Internal/instrumentation* ; Bone Wires ; Bone Plates ; Retrospective Studies ; Colles' Fracture/surgery* ; Minimally Invasive Surgical Procedures/methods* ; Open Fracture Reduction/methods* ; Osteoporotic Fractures/surgery*

OBJECTIVE: To investigate the clinical effect of minimally invasive technique in the treatment of moderate and severe gluteal muscle contracture. METHODS: A retrospective study was conducted on 85 patients (170 sides) with bilateral gluteal muscle contracture admitted from January 2016 to December 2019. All patients were treated with minimally invasive release of tendon knife. There were 32 males and 53 females, ranging in age from 15 to 37 years old, with an average age of (22.3±6.3) years old. Operation time, intraoperative blood loss, incision length, first postoperative ambulation time, complication rate, recurrence rate, and Harris hip score (HHS) were analyzed and evaluated. RESULTS: The average follow-up time was (16.2±4.6) months, ranging from 12 to 30 months. The operation time ranged from 7 to 15 min, with an average of (10.2±3.1) min. Intraoperative blood loss ranged from 2 to 20 ml, with an average of (8.4±2.2) ml. The incision length ranged from 0.6 to 2.0 cm, with an average of (0.8±0.3) cm. The time to postoperative ambulation ranged from 12 to 28 h, with an average of (20.0±3.2) h. All patients achieved primary wound healing without sciatic nerve injury or recurrence. HHS hip function scores ranged from 90 to 98, with an average score of (96.2±1.4). Complications included intraoperative tendon blade tip fracture in two cases (removed under fluoroscopic guidance) and subcutaneous hematoma in three cases-two resolved with compression and one with open evacuation.. Twenty-nine patients exhibited transient swaying gait postoperatively, of which 24 patients returned to normal after 4 weeks and 5 patients returned to normal after 6 weeks. CONCLUSION Minimally invasive tendon blade release is a safe and effective technique for treating gluteal muscle contracture, offering minimal trauma, rapid recovery, and excellent cosmetic and functional outcomes. However, it exhibits a low risk of blade tip fracture and sciatic nerve injury, warranting experienced surgical handling.
Humans ; Male ; Female ; Adult ; Minimally Invasive Surgical Procedures/methods* ; Adolescent ; Retrospective Studies ; Buttocks/surgery* ; Young Adult ; Contracture/surgery* ; Tendons/surgery* ; Muscle, Skeletal/surgery*