[摘 要] 目的：探讨IL-22通过STAT3信号轴损害NK细胞功能并促进膀胱癌细胞耐药的机制。方法：常规培养T24细胞，用梯度递增法构建耐药T24/顺铂（DDP）细胞。将细胞分为对照组（不处理）、DDP组、IL-22组、IL-22 + DDP组、IL-22 + anti-IL-22组、IL-22 + DDP + Stattic（STAT3抑制剂）组。qPCR法检测各组T24细胞中IL-22、cyclin D1、Bcl-2 mRNA的表达，WB法检测各组细胞中BAX、BCL2和p-STAT3的表达，CCK-8法检测各组细胞的增殖活性，流式细胞术检测各组细胞的凋亡，ELISA检测各组细胞上清液中乳酸脱氢酶（LDH）、TNF-α、IFN-γ、颗粒酶B（GzmB）和穿孔素（PRF）蛋白的水平。结果：T24/DDP细胞对DDP敏感性降低（P < 0.05）；其耐药相关基因P-糖蛋白（P-gp）、肺耐药蛋白（LRP)、多药耐药相关蛋白1（MRP1）和IL-22及其受体表达水平均明显升高（均P < 0.05），说明T24/DDP细胞构建成功。与对照组比较，DDP组T24细胞的增殖活力明显降低、凋亡率升高、BAX蛋白表达升高、BCL2表达下降（均P < 0.05）；与DDP组比较，IL-22 + DDP组T24细胞的增殖活明显升高、凋亡率明显下降、BAX蛋白表达降低、BCL2表达升高（均P < 0.05），表明IL-22通过调节BAX/Bcl-2的表达促进T24细胞对DDP耐药性。与对照组比较，IL-22组T24细胞总细胞和核中p-STAT3表达水平均明显升高（均P < 0.05）；与IL-22组比较，IL-22 + anti IL-22组T24细胞中 p-STAT3水平明显降低（P < 0.05），说明IL-22激活T24细胞中STAT3的磷酸化过程，并促进其转核。与对照组比较，DDP组T24与NK92细胞共培养上清液中LDH、TNF-α、IFN-γ、GzmB及PRF蛋白水平均明显升高（均P < 0.05），与DDP组比较，IL-22 + DDP组共培养上清液中上述蛋白水平均明显降低（均P < 0.05）；与对照组比较，IL-22组共培养上清液中LDH、TNF-α、IFN-γ、GzmB及PRF蛋白水平明显降低（均P < 0.05）；与IL-22组比较，IL-22 + Stattic组共培养上清液中上述蛋白水平均明显升高（均P < 0.05），说明IL-22可降低NK92细胞对T24细胞的毒性，STAT3抑制剂可逆转此作用。与DDP组比较，IL-22 + DDP组T24细胞增殖活力明显升高（P < 0.05）；与IL-22 + DDP组比较，IL-22 + DDP + Stattic组T24细胞增殖活力明显降低（P < 0.05）；与DDP组比较，IL-22 + DDP组T24细胞的凋亡率明显升高（P < 0.05）；与IL-22 + DDP组比较，IL-22 + DDP + Stattic组T24细胞的凋亡率明显升高（P < 0.05），说明IL-22调控STAT3影响T24细胞DDP耐药性及NK细胞免疫功能。结论： IL-22通过激活STAT3信号轴促进T24细胞的DDP耐药性，抑制NK细胞功能。

ObjectiveTo explore the effect of cluster scalp acupuncture combined with Taijiquan training on depressive symptom, motor function, activities of daily living, serum markers, as well as brain functional connectivity (FC) and network topological properties in patients with post-stroke depression (PSD). MethodsA total of 40 PSD patients in the Second Affiliated Hospital of Heilongjiang University of Chinese Medicine from September, 2022 to September, 2023 were enrolled and randomly divided into control group (n = 20) and experimental group (n = 20). The control group received cluster scalp acupuncture alone, while the experimental group underwent Taijiquan training in addition, for four weeks. They were assessed with Hamilton Depression Scale-17 (HAMD-17), Fugl-Meyer Assessment (FMA) and Barthel Index (BI) before and after treatment, while the serum levels of dopamine (DA), 5-hydroxytryptamine (5-HT), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected with enzyme-linked immunosorbent assay. Resting-state functional magnetic resonance imaging (rs-fMRI) was applied to assess brain FC, as well as the global efficiency (Eg) and small-world property (σ) of brain networks. ResultsThe scores of HAMD-17, FMA and BI improved in both groups (t > 2.922, P < 0.01) after treatment, and improved more in the experimental group than in the control group (t > 2.517, P < 0.05). The serum levels of DA and 5-HT increased in both groups (t > 2.637, P < 0.05), and increased more in the experimental group (t > 2.192, P < 0.05). The serum levels of IL-6 and TNF-α decreased in the experimental group after treatment (t > 4.059, P < 0.001), and they were less than those in the control group (t > 2.154, P < 0.05). FC between left middle frontal gyrus and right anterior cingulate gyrus, as well as between left hippocampus and right precuneus were higher in the experimental group than in the control group after treatment (t > 3.867, P < 0.001), while Eg and σ increased in both groups (t > 2.828, P < 0.05), and they were higher in the experimental group (t > 2.675, P < 0.05). ConclusionCombination of Taijiquan training is more effective on depressive symptoms, motor function and activities of daily living in PSD patients, which may be related to up-regulation of serum DA and 5-HT, reduction of inflammatory factors, enhancement of prefrontal-limbic system functional connectivity and optimization of brain network topological properties.

OBJECTIVE: To evaluate the short-term effectiveness of Ilizarov technique combined with steel needle internal fixation in treating Charcot neuroarthropathy (CN) of the foot and ankle. METHODS: Between June 2020 and December 2023, 12 patients with Eichenholtz stage Ⅲ CN of the foot and ankle were treated with Ilizarov technique and steel needle internal fixation. There were 9 males and 3 females with an average age of 48.6 years (range, 19-66 years). The disease duration ranged from 1 to 16 months (mean, 6.8 months). Ankle joint involvement predominated in 7 cases, while midfoot involvement occurred in 5 cases; 3 cases presented with skin ulceration and soft tissue infection. Preoperative American Orthopedic Foot and Ankle Society (AOFAS) score was 31.2±9.0, 36-Item Short-Form Health Survey (SF-36)-Physical Component Summary (PCS) score was 32.6±6.8, and Mental Component Summary (MCS) score was 47.8±8.4. Postoperative assessments included wound healing, regular X-ray film/CT evaluations of fusion status, and effectiveness via AOFAS and SF-36-PCS, MCS scores. RESULTS: All operations were successfully completed without neurovascular complication. Two patients experienced delayed wound healing requiring intervention, and the others achieved primary healing. All patients were followed up 15-43 months (mean, 23.3 months). Imaging confirmed successful joint fusion within 13-21 weeks (mean, 16.8 weeks). At last follow-up, the AOFAS score was 72.5±6.4, and the SF-36-PCS and MCS scores were 63.2±8.4 and 76.7±5.3, respectively, all of which improved compared to preoperative levels, with significant differences ( P<0.05). CONCLUSION Ilizarov technique combined with steel needle internal fixation effectively restores walking function and achieves satisfactory short-term effectiveness in CN of the foot and ankle.
Humans ; Middle Aged ; Male ; Female ; Adult ; Ilizarov Technique ; Arthropathy, Neurogenic/surgery* ; Aged ; Ankle Joint/surgery* ; Treatment Outcome ; Needles ; Fracture Fixation, Internal/instrumentation* ; Steel ; Young Adult ; Foot Joints/surgery*

OBJECTIVE: To compare the efficacy of percutaneous pedicle screw combined with unilateral nail placement combined with bone cement strengthening and bilateral nail placement in the treatment of osteoporotic thoracic and lumbar fractures. METHODS: A retrospective case-control study was used to analyze the clinical data of 78 patients with osteoporotic thoracic and lumbar fractures admitted from October 2017 to May 2019. According to the surgical method, it was divided into percutaneous pedicle screw combined with unilateral nail placement combined with unilateral bone cement strengthening group(bone cement group) and percutaneous pedicle screw combined with bilateral nail placement(screw group). In the bone cement group, 40 patients included 16 males and 24 females, with a mean age of (62.1±8.1) years old. In the screw group, 38 patients included 18 males and 20 females with a mean age of (65.1±9.3) years old. The operation time, intraoperative blood loss, length of hospital stay and postoperative complications were compared between two groups. The kyphosis Cobb angle, anterior edge height ratio, central height ratio and pain visual analogue score(VAS) were compared. RESULTS: All patients were followed up for 25 to 36 months. The operation time (70.1±17.3) min of the cement group was shorter than that of the screw group (78.6±18.2) min(P<0.05). There were no significant differences in intraoperative blood loss and length of hospital stay(P>0.05). The VAS in the cement group 1 year 1.5±0.5 and the latest follow-up 0.5±0.3 after operation were lower than 1 year 1.8±0.3 and the latest follow-up 0.8±0.4 in the screw group(P<0.05). The kyphosis Cobb angle, anterior edge height ratio, central height ratio in bone cement group, 1 year (6.2±1.2)°, (86.6±3.5)%, (91.1±2.5)%, the last follow-up (6.4±0.7)°, (85.5±3.3)%, (90.5±6.3)% were better than that of the screw group 1 year (6.8±1.4)°, (83.1±2.4)%, (89.9±3.4)% and the latest follow-up (7.1±1.1)°, (82.6±4.1)%, (87.6±5.9)%(P<0.05). There were 3 cases of bone cement leakage in the cement group, all of which had no clinical symptoms;and 2 cases of pedicle screws were extracted in the screw group, and the screws were removed at the last follow-up. CONCLUSION Percutaneous pedicle screw combined with unilateral nail placement combined with bone cement strengthening and bilateral nail placement in the treatment of osteoporotic thoracic and lumbar compression fractures in the elderly can achieve satisfactory efficacy and effectively relieve the pain of patients, but the former internal fixation system is more stable, and the long-term follow-up can effectively maintain the height of the anterior middle column and the correction of kyphosis deformity, and the incidence of chronic low back pain is lower.
Humans ; Male ; Female ; Aged ; Bone Cements ; Middle Aged ; Thoracic Vertebrae/surgery* ; Lumbar Vertebrae/surgery* ; Retrospective Studies ; Spinal Fractures/surgery* ; Osteoporotic Fractures/surgery* ; Case-Control Studies ; Bone Nails ; Pedicle Screws

G protein-coupled receptors (GPCRs) are significant drug targets, but their potential in cancer therapy remains underexplored. Conventional GPCR agonists or antagonists have shown limited effectiveness in cancer treatment, necessitating new GPCR-targeting strategies for more effective therapies. This study discovers that Yersinia pestis LcrV, a crucial linker protein for plague infection, acts as a biased agonist of a GPCR, the formyl peptide receptor 1 (FPR1). The LcrV protein induces unique conformational changes in FPR1, resulting in G proteins being activated in a distinctive state without subunit dissociation. This leads to a biased signaling profile characterized by cyclic adenosine monophosphate (cAMP) responses and β-arrestin2 recruitment, but not calcium mobilization. In FPR1-expressing triple-negative breast cancer (TNBC) cells, LcrV bi-directionally modulates intracellular signaling pathways, downregulating extracellular signal-regulated kinases (ERK1/2) and Akt pathways while upregulating Jun N-terminal kinase (JNK) and p38 pathways. This dual modulation results in cell cycle arrest and the inhibition of TNBC cell proliferation. In TNBC xenograft mouse models, long-term LcrV treatment inhibits tumor growth more effectively than a conventional FPR1 antagonist. Additionally, LcrV treatment reprograms tumor cells by reducing stemness-associated proteins OCT4 and c-MYC. Our findings highlight the potential of biased GPCR agonists as a novel GPCR-targeting strategy for cancer treatment.

Objective To analyze the influence path of medical students'professional identity on positive defensive medical behaviors and examine the mediating effect of medical risk perception between the two,aiming to provide theoretical support and practical reference for medical education to actively adapt to the demands of the medical and health system reform and promote the scientific guidance of positive defensive medical behaviors.Methods ln 2020,a questionnaire survey was conducted among medical students from four medical colleges in Heilongjiang Province using cluster sampling method,and data analysis was performed using SPSS 27.0 software.Results Medical students'professional identity showed a significant positive correlation with their positive defensive medical behavior(β=0.225,P＜0.001),with medical risk perception acting as a partial mediator(indirect effect accounting for 19%of the total effect).Professional identity(β=0.183,P＜0.001)and medical risk perception(β=0.195,P＜0.001)exerted direct positive effects on positive defensive medical behavior.Conclusion Medical students'professional identity drives them to adopt positive defensive medical behaviors by strengthening their sense of responsibility ethics and risk cognition ability,and medical risk perception is a key mediating variable in this process.Educational management should integrate policy-oriented clinical decision-making training and balance medical safety and efficiency through the collaborative mechanism of"professional identity-risk perception-behavioral practice".

Objective:To construct an artificial intelligence (AI)-based automatic grading model for neurological severity at acute phase of patients with traumatic cervical spinal cord injury (TCSCI) and evaluate its efficacy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 315 patients with TCSCI admitted to the Second Affiliated Hospital of Naval Medical University from January 2019 to December 2023, including 243 males and 72 females, aged 30-75 years [(57.6±7.0)years]. Injured segments involved C 1-C 4 in 143 patients and C 5-C 8 in 172. According to the American Spinal Injury Association (ASIA) scale, the injuries were classified as Grade A in 15 patients, Grade B in 53, Grade C in 74, and Grade D in 173. The patients were randomly divided into training group ( n=252) and test group ( n=63) with a ratio of 8∶2. The patients′ sensory and motor functions were assessed according to the ASIA scale within 48 hours after injury. The cervical spine MRI instance segmentation model was used to extract injury severity features of TCSCI patients in sagittal T2-weighted images. The grading model consisted of a two-layer cascade network. The first layer involved gradient boosting, Gaussian naive bayes, K-nearest neighbors, decision tree, random forest and support vector machine classifier. In the training group, the 6 machine learning models were trained separately. In the second layer, the performance of the six models was optimized to obtain the corresponding optimal grading models, so as to match the models with the best grading performance for each feature. In the test group, the performance of each model was evaluated by calculating accuracy, recall, precision, average precision, and F1 score. Results:A total of 138 clinical and imaging features were included to construct an automatic grading model for neurological severity of TCSCI patients at acute phase, comprising 132 clinical neurological features (including 56 light touch sensory scores, 56 pinprick sensory scores, and 20 key muscle scores) and 6 MRI imaging features. In the test group, the accuracy, recall, precision, average precision and F1 score of the six models, including gradient boosting, Gaussian naive bayes, K-nearest neighbors, decision tree, random forest and support vector machine classifier in the first layer of the automatic grading model for neurological severity at acute phase of TCSCI patients, in the overall grading of light touch, pinprick sensory and key muscle motor function were all above 0.86. In terms of the overall light touch function grading performance, the models with the highest accuracy, recall, precision, average precision, and F1 score were K-nearest neighbors (0.90), gradient boosting (0.99), Gaussian naive bayes (0.98), random forest (0.96), and gradient boosting (0.96), respectively. In terms of the overall pinprick sensory function grading performance, the models with the highest accuracy, recall, precision, average precision, and F1 score were gradient boosting (0.98), Gaussian naive bayes (0.98), gradient boosting (0.99), decision tree (0.99), and gradient boosting (0.95), respectively. In terms of the overall key muscle motor function grading performance, the models with the highest accuracy, recall, precision, average precision, and F1 score were K-nearest neighbors (0.97), gradient boosting and support vector machine classifier (0.97), decision tree (0.95), random forest (0.95), and support vector machine classifier (0.96), respectively. In terms of sensory function, gradient boosting had the highest number of superior performances in the overall light touch and pinprick sensory function grading. In terms of motor function, the support vector machine classifier had the highest number of superior performances in the overall key muscle motor function grading.Conclusion:The automatic grading model for neurological severity at acute phase of patients with TCSCI that is constructed based on machine learning models and two-layer cascade networks can achieve the optimization of the grading performance of each feature and exhibit a strong grading ability for the sensory and motor function severity.

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.

Objective:To understand the burden of chronic kidney disease (CKD) and its risk factors in Fujian Province during 1990-2019.Methods:Based on the Global Burden of Disease Study 2019, the incidence rate, mortality rate and disability-adjusted life years (DALYs) of CKD in Fujian from 1990 to 2019 were calculated. An age-period-cohort model was used to estimate the effects of age, period, and cohort on age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized DALY rate (ASDR) of CKD. Comparative risk assessment theory was used to calculate the potential attributable DALYs due to risk factors.Results:In 2019, the ASIR of CKD in Fujian exceeded the national average. The ASIR of CKD showed an increasing trend from 1990 to 2019, but the ASMR and ASDR of CKD exhibited decreasing trends during the same period. In 2019, the ASIR of CKD was higher in women than in men, while the ASMR and ASDR were higher in men than in women. Age-period-cohort analysis indicated that ASIR, ASMR, and ASDR of CKD increased with age. The period effect for ASIR decreased first before increase, while the period effect for ASMR and ASDR displayed fluctuating trends. The cohort effect showed an upward trajectory for ASIR, but a stable status before downward trajectories for ASMR and ASDR. Compared with 1990, except the increase in the ASDR of CKD attributed to high BMI and high temperatures, the ASDR of CKD attributed to other risk factors all showed decreases in 2019. However, the ASDR attributed to high sodium intake remained higher compared with the global average.Conclusion:The burden of CKD remains heavy in Fujian, and it is necessary to reduce the attributable risk factors, such as high sodium intake and high BMI, to address this problem.