Objective:To evaluate the impact of prophylactic cranial irradiation (PCI) on the prognosis of patients with limited-stage small cell lung cancer (SCLC) in the era of widespread application of MRI.Methods:Clinical data were collected from an open-lable prospective clinical trial on thoracic radiotherapy target volumes for limited-stage SCLC conducted in Sun Yat-sen University Cancer Center and Zhejiang Cancer Hospital between June 2002 and January 2017. In this study, patients who achieved complete remission (CR) or partial remission (PR) after definitive chemoradiotherapy (CRT) were retrospectively analyzed. Stratified analysis was performed according to different clinical efficacies. Patients were divided into different groups according to whether PCI was conducted or not. Survival analysis of patients was carried out. Survival data were calculated by Kaplan-Meier method, and Cox proportional hazards model was applied for multivariate prognostic analysis.Results:Among 309 patients with limited-stage SCLC who received CRT, 133 patients achieved CR and 140 cases obtained PR. These 273 patients were enrolled in this study. Among 133 patients with CR, 29 of them did not receive PCI, and 89 (85.6%) of the remaining 104 patients receiving PCI underwent brain MRI to exclude brain metastasis (BM) before PCI. With a median follow-up time of 22.1 months, the cumulative BM rates were 18.3% and 37.9% in patients who received or did not receive PCI ( P=0.020). The median overall survival (OS) was 30.2 and 30.5 months, and the 1-, 3- and 5-year OS rates were 93.3%, 41.9%, 27.7% and 82.8%, 44.8%, 40.8%, respectively ( P=0.910). Multivariate analysis indicated that baseline Karnofsky performance status (KPS) = 90 was a favorable independent prognostic factor for OS in CR patients ( HR=0.93, 95% CI: 0.89-0.98, P=0.006). Among 140 patients achieving PR, 52 cases did not receive PCI and 80 (90.9%) of the remaining 88 patients received brain MRI before PCI. With a median follow-up time of 18.9 months, the cumulative BM rates were 10.2% and 44.2% ( P<0.001). The median OS was 26.0 and 18.0 months, and the 1-, 3-, and 5-year OS rates were 86.4%, 37.9%, 32.2% and 75.0%, 17.3%, 10.8%, respectively ( P=0.001). Baseline KPS = 90 ( HR=0.93, 95% CI: 0.89-0.97, P=0.001) and PCI ( HR=0.54, 95% CI: 0.36-0.80, P=0.002) were favorable prognostic factors for OS in PR patients. Conclusions:PCI significantly reduces the incidence of BM and prolongs the OS in patients with limited-stage SCLC who achieve PR after CRT, but it fails to significantly prolong the OS of CR patients.

Objective:To investigate the role of ubiquitin-specific protease 21 (USP21) in enterovirus group A type 71 (EV-A71) infection.Methods:Peripheral blood mononuclear cells (PBMC) were obtained from a cohort of 24 children infected with EV-A71 and 24 healthy children. Expression of USP21 was determined by real-time fluorescence quantitative PCR (qPCR). Additionally, the impact of USP21 overexpression or knockout on EV-A71 replication was evaluated using a combination of qPCR and western blot (WB) analysis. Furthermore, WB was employed to measure the levels of EV-A71 structural protein VP1, phosphorylated interferon regulatory factor 3 (IRF3) and other key molecules in the RIG-I-like receptor (RLR) signaling pathway. Co-immunoprecipitation (Co-IP) was utilized to investigate the effects of USP21 on the ubiquitin levels of EV-A71 nonstructural protein 2A protease (2A pro). Results:In comparison to healthy children, the expression of USP21 mRNA in PBMC of children infected with EV-A71 was notably elevated. The overexpression of USP21 significantly enhanced the cytopathic effects induced by EV-A71, upregulated levels of VP1 mRNA and protein, and facilitated EV-A71 replication, leading to a decrease in cell activity with increasing levels of USP21 transfection. Following the knockout of the USP21 gene, the VP1 mRNA levels were significantly declined in comparison to the control group. Furthermore, the overexpression of USP21 was found to have no impact on the transcriptional activity of EV-A71 2A pro. However, it was observed to enhance the expression of 2A pro protein, reduce the ubiquitination of 2A pro, suppress the protein levels of mitochondrial antiviral signaling protein (MAVS) and melanoma differentiation-associated gene 5 (MDA5), as well as decrease the phosphorylation of IRF3. Additionally, the induction of IFN-β mRNA by EV-A71 infection was downregulated. Conclusions:USP21 has been shown to enhance the replication of EV-A71 through the downregulation of 2A pro ubiquitination, suppression of MAVS and MDA5 protein expression, and inhibition of the interferon signaling pathway.

Objective:To investigate the role of ubiquitin-specific protease 21 (USP21) in enterovirus group A type 71 (EV-A71) infection.Methods:Peripheral blood mononuclear cells (PBMC) were obtained from a cohort of 24 children infected with EV-A71 and 24 healthy children. Expression of USP21 was determined by real-time fluorescence quantitative PCR (qPCR). Additionally, the impact of USP21 overexpression or knockout on EV-A71 replication was evaluated using a combination of qPCR and western blot (WB) analysis. Furthermore, WB was employed to measure the levels of EV-A71 structural protein VP1, phosphorylated interferon regulatory factor 3 (IRF3) and other key molecules in the RIG-I-like receptor (RLR) signaling pathway. Co-immunoprecipitation (Co-IP) was utilized to investigate the effects of USP21 on the ubiquitin levels of EV-A71 nonstructural protein 2A protease (2A pro). Results:In comparison to healthy children, the expression of USP21 mRNA in PBMC of children infected with EV-A71 was notably elevated. The overexpression of USP21 significantly enhanced the cytopathic effects induced by EV-A71, upregulated levels of VP1 mRNA and protein, and facilitated EV-A71 replication, leading to a decrease in cell activity with increasing levels of USP21 transfection. Following the knockout of the USP21 gene, the VP1 mRNA levels were significantly declined in comparison to the control group. Furthermore, the overexpression of USP21 was found to have no impact on the transcriptional activity of EV-A71 2A pro. However, it was observed to enhance the expression of 2A pro protein, reduce the ubiquitination of 2A pro, suppress the protein levels of mitochondrial antiviral signaling protein (MAVS) and melanoma differentiation-associated gene 5 (MDA5), as well as decrease the phosphorylation of IRF3. Additionally, the induction of IFN-β mRNA by EV-A71 infection was downregulated. Conclusions:USP21 has been shown to enhance the replication of EV-A71 through the downregulation of 2A pro ubiquitination, suppression of MAVS and MDA5 protein expression, and inhibition of the interferon signaling pathway.

Objective:To evaluate the impact of prophylactic cranial irradiation (PCI) on the prognosis of patients with limited-stage small cell lung cancer (SCLC) in the era of widespread application of MRI.Methods:Clinical data were collected from an open-lable prospective clinical trial on thoracic radiotherapy target volumes for limited-stage SCLC conducted in Sun Yat-sen University Cancer Center and Zhejiang Cancer Hospital between June 2002 and January 2017. In this study, patients who achieved complete remission (CR) or partial remission (PR) after definitive chemoradiotherapy (CRT) were retrospectively analyzed. Stratified analysis was performed according to different clinical efficacies. Patients were divided into different groups according to whether PCI was conducted or not. Survival analysis of patients was carried out. Survival data were calculated by Kaplan-Meier method, and Cox proportional hazards model was applied for multivariate prognostic analysis.Results:Among 309 patients with limited-stage SCLC who received CRT, 133 patients achieved CR and 140 cases obtained PR. These 273 patients were enrolled in this study. Among 133 patients with CR, 29 of them did not receive PCI, and 89 (85.6%) of the remaining 104 patients receiving PCI underwent brain MRI to exclude brain metastasis (BM) before PCI. With a median follow-up time of 22.1 months, the cumulative BM rates were 18.3% and 37.9% in patients who received or did not receive PCI ( P=0.020). The median overall survival (OS) was 30.2 and 30.5 months, and the 1-, 3- and 5-year OS rates were 93.3%, 41.9%, 27.7% and 82.8%, 44.8%, 40.8%, respectively ( P=0.910). Multivariate analysis indicated that baseline Karnofsky performance status (KPS) = 90 was a favorable independent prognostic factor for OS in CR patients ( HR=0.93, 95% CI: 0.89-0.98, P=0.006). Among 140 patients achieving PR, 52 cases did not receive PCI and 80 (90.9%) of the remaining 88 patients received brain MRI before PCI. With a median follow-up time of 18.9 months, the cumulative BM rates were 10.2% and 44.2% ( P<0.001). The median OS was 26.0 and 18.0 months, and the 1-, 3-, and 5-year OS rates were 86.4%, 37.9%, 32.2% and 75.0%, 17.3%, 10.8%, respectively ( P=0.001). Baseline KPS = 90 ( HR=0.93, 95% CI: 0.89-0.97, P=0.001) and PCI ( HR=0.54, 95% CI: 0.36-0.80, P=0.002) were favorable prognostic factors for OS in PR patients. Conclusions:PCI significantly reduces the incidence of BM and prolongs the OS in patients with limited-stage SCLC who achieve PR after CRT, but it fails to significantly prolong the OS of CR patients.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Objective:To evaluate the impact of orthopedic robotic assistance and conventional freehand methods on surgical strategies, the safety of pedicle screw placement, and clinical efficacy in patients with upper cervical spine diseases.Methods:From January 2017 to March 2023, a total of 63 cases with upper cervical spine disease, were divided into two groups based on the screw placement technique: the robot-assisted pedicle screw placement (RA) group (41 cases) and the conventional freehand pedicle screw placement (CF) group (22 cases), were retrospectively included. These patients in the RA and CF groups underwent two types of posterior cervical surgery, including occipitocervical fusion (9 cases and 8 cases) and fixation and fusion of atlantoaxial and distal vertebrae (32 cases and 14 cases). The outcome parameters, including the disease course, surgical time, intraoperative blood loss, fluoroscopy frequency, radiation dose, hospital stay, treatment costs, complications, the rate of the pedicle screw placement, accuracy of upper cervical pedicle screw placement, and the risk factors that possibly affected the accuracy were recorded and analyzed. Postoperative follow-up was conducted for at least 6 months, and the efficacy of patients was assessed using imaging parameters, ASIS classification, VAS, and JOA scores.Results:Both groups had no screw-related complications and no spinal cord or vertebral artery injuries. In the RA group, the pedicle screw placement rates for the patients with occipitocervical fusion, and fixation and fusion of atlantoaxial and distal vertebrae were 100% (48/48) and 89.6% (138/154), respectively, far exceeding the placement rate in the CF group 42.9% (18/42) and 78.3% (54/69) (χ 2=37.403, P<0.001; χ 2=5.128, P=0.024). The fluoroscopic exposure dose and operation time of the two types of surgical patients in the RA group were both higher than those in the CF group ( P<0.05). Compared with the CF group, the accuracy of C 1 screws in the RA group increased from 42% (11/26) to 80% (51/64), with statistical significance (χ 2=13.342, P=0.004); while the accuracy of C 2 screws improved from 77% (33/43) to 88% (63/72) with no statistical difference (χ 2=2.863, P=0.413). Non-parametric correlation analysis found a significant correlation between the accuracy of C 1 and C 2 pedicle screw placement and the order of guide wire insertion in the RA group ( r=0.580, P<0.001; r=0.369, P=0.001). Postoperatively, both groups showed significant differences in cervicomedullary angle (CMA), Chamberlain angle (CL), McGregor angle, Boogard angle, Bull angle, clivus-canal angle (CCA), occipitocervical (C 0-C 2) angle, posterior occipitocervical angle (POCA), C 2-C 7 angle, and anterior atlantodental interval (ADI) ( P<0.05). The ASIA classification improved to varying degrees for both groups postoperatively, but there were no statistically significant differences between preoperative, postoperative, and last follow-up evaluations. VAS and JOA scores significantly improved for both groups postoperatively and at the last follow-up ( P<0.05). Conclusion:Both orthopedic robotic-assisted and conventional freehand pedicle screw placement techniques achieved satisfactory therapeutic effects in the treatment of upper cervical spine diseases. The orthopedic robot can effectively ensure the accuracy of upper cervical pedicle screw placement, the increase placement rate of pedicle screws in the upper cervical spine, and reduce fluoroscopy exposure. However, it is necessary to avoid the vertebral displacement caused by the priority insertion of the guide needle, which may affect the accuracy of subsequent planning.

Objective To investigate the expression of lncRNA HOTAIR, HOTAIR, CRNDE and AFAP1-AS1 in lung cancer patients with bone metastasis (LCWBM), and to elucidate the diagnostic value of lncRNAs for LCWBM. Methods Serum was collected from 38 LCWBM patients and 38 lung cancer without bone metastasis (LCWOBM) patients. Questionnaires were used to collect basic information of patients. Fasting peripheral venous blood of patients was collected to separate serum. qRT-PCR was used to measure the expression levels of four serum lncRNAs, and their diagnostic value for LCWBM was analyzed. Results The expression of serum HOTAIR was decreased in LCWBM patients, compared with LCWOBM patients (P < 0.05); the AUC of serum HOTAIR diagnosing LCWBM was 0.722 (sensitivity was 70.0%, specificity was 81.3%). And the level of serum HOTTIP was significantly increased in LCWBM patients, compared with LCWOBM patients (P < 0.05); AUC of serum HOTTIP diagnosing LCWBM was 0.784 (sensitivity was 100.0%, specificity was 45.5%). The AUC of serum HOTAIR combined with HOTTIP diagnosing LCWBM was 0.818 (sensitivity, specificity, positive predictive value and negative predictive value were 87.5%, 72.7%, 70.0% and 88.9%, respectively). Conclusion Serum lncRNA HOTAIR and HOTTIP might be potential diagnostic biomarkers for bone metastases in lung cancer patients.

Oral medicine and deep brain stimulation are two main treatments for Parkinson′s disease (PD). But their long-term efficacies are decreasing, which limit the choice of patients in advanced stage. As a special way of sensory intervention, rhythmic cueing can improve gait parameters, reduce freezing of gait severity and improve gait-related mobility by activating the motor pathway directly, repairing internal clock, promoting internal dopamine release and improving cognitive function to maintain gait stability. Rhythmic auditory and visual cueing has a potential in PD treatment.

OBJECTIVE： To study the effects of curcumin on gemcitabine （GEM）-resistant pancreatic cancer SW1990 cells and its mechanism. METHODS： CCK8 assay was used to detect the effects of different concentrations of GEM （50， 100， 150， 200， 250 μmol/L） on the survival rate of SW1990 cells and GEM-resistant SW1990 cells （SW1991/GEM resistant cells）； half inhibitory concentration （IC50） and drug resistance multiple were calculated. CCK8 assay was performed to detect the effects of different concentrations of curcumin （1， 5， 10， 20， 40 μmol/L） on survival rate of SW1990/GEM resistant cells， and IC50 was calculated. CCK8 assay was used to detect the effects of curcumin 2.41 μmol/L combined with different concentrations of GEM （25， 50， 75， 100， 125 μmol/L） on the survival rate of SW1990 cells and SW1990/GEM resistant cells， and IC50 and drug resistance reversal fold of GEM were calculated. Flow cytometry was carried out to detect the cell cycle distribution and apoptosis rate of SW1990 after treated with GEM alone or curcumin （2.41 μmol/L） combined with GEM using IC50 of GEM as drug concentration. Western blot assay was used to the protein expression of FAS， AKT， p-AKT， PI3K， p-PI3K， Caspase-3， Bcl-2 and related X protein （Bax）. RT-PCR was used to detect mRNA expression. RESULTS： IC50 of GEM to SW1990 cells was 92 μmol/L. IC50 of GEM to SW1990/GEM resistant cells was 216 μmol/L， and drug resistance multiple SW1990 cells to GEM was 2.35. IC50 of curcumin to SW1990/GEM resistant cells was 9.2 μmol/L. Under 2.41 μmol/L curcumin， IC50 of GEM to SW1990 cells was 75  μmol/L， and IC50 of GEM to SW1990/GEM resistant cells was 98 μmol/L； drug resistance reversal multiple of SW1990/GEM resistant cells to GEM was 2.2. Compared with GEM alone， the apoptosis rate of SW1990 cells and SW1990/GEM resistant cells were increased significantly after curcumin combined with GEM （P＜0.05）， blocking at G0/G1 phase； the protein expression of FAS， p-AKT， p-PI3K and Bcl-2 and mRNA expression of FAS and Bcl-2 were decreased significantly  （P＜0.05）； the protein and mRNA expression of Bax      and Caspase-3 were increased significantly （P＜0.05）. CONCLUSIONS： Curcumin can reverse drug resistance of SW1990 cells to GEM， the mechanism of which may be associated with PI3K/AKT pathway.