1.Neoadjuvant Sintilimab Combined with Gemcitabine and Cisplatin for Muscle-Invasive Bladder Cancer Patients Followed by Selective Bladder Sparing Surgery: A Phase 2 Trial
Zhou TONG ; Guanghou FU ; Feng ZHOU ; Xiaoyan LIU ; Xing XUE ; Hangyu ZHANG ; Yimin WANG ; Xudong ZHU ; Yang GAO ; Lulu LIU ; Xuanwen BAO ; Yi ZHENG ; Weijia FANG ; Peng ZHAO ; Baiye JIN
Cancer Research and Treatment 2026;58(2):581-590
Purpose:
This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery.
Materials and Methods:
Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety.
Results:
From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events.
Conclusion
Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.
2.Dimeric natural product panepocyclinol A inhibits STAT3 via di-covalent modification.
Li LI ; Yuezhou WANG ; Yiqiu WANG ; Xiaoyang LI ; Qihong DENG ; Fei GAO ; Wenhua LIAN ; Yunzhan LI ; Fu GUI ; Yanling WEI ; Su-Jie ZHU ; Cai-Hong YUN ; Lei ZHANG ; Zhiyu HU ; Qingyan XU ; Xiaobing WU ; Lanfen CHEN ; Dawang ZHOU ; Jianming ZHANG ; Fei XIA ; Xianming DENG
Acta Pharmaceutica Sinica B 2025;15(1):409-423
Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.
3.Metabolic reprogramming nanomedicine potentiates colon cancer sonodynamic immunotherapy by inhibiting the CD39/CD73/ADO pathway.
Yuanyuan ZHANG ; Weiwei JIN ; Zhichao DENG ; Bowen GAO ; Yuanyuan ZHU ; Junlong FU ; Chenxi XU ; Wenlong WANG ; Ting BAI ; Lianying JIAO ; Hao WU ; Mingxin ZHANG ; Mingzhen ZHANG
Acta Pharmaceutica Sinica B 2025;15(5):2655-2672
Sonodynamic therapy (SDT) can potentially induce immunogenic cell death in tumor cells, leading to the release of ATP, and facilitating the initiation of an immune response. Nevertheless, the enzymes CD39 and CD73 can swiftly convert ATP into immunosuppressive adenosine (ADO), resulting in an immunosuppressive tumor microenvironment (TME). This study introduced a nanomedicine (QD/POM1@NP@M) engineered to reprogram TME by modulating the CD39/CD73/ADO pathway. The nanomedicine encapsulated sonosensitizers silver sulfide quantum dots, and the CD39 inhibitor POM1, while also incorporating homologous tumor cell membranes to enhance targeting capabilities. This integrated approach, on the one hand, stimulates the release of ATP via SDT, thereby initiating the immune response. In addition, it reduced the accumulation of ADO by inhibiting CD39 activity, which ameliorated the immunosuppressive TME. Upon administration, the nanomedicine demonstrated substantial anti-tumor efficacy by facilitating the infiltration of anti-tumor immune cells, while reducing the immunosuppressive cells. This modulation effectively transformed the TME from an immunologically "cold" state to a "hot" state. Furthermore, combined with the checkpoint inhibitor α-PDL1, the nanomedicine augmented systemic anti-tumor immunity and promoted the establishment of long-term immune memory. This study provides an innovative strategy for combining non-invasive SDT and ATP-driven immunotherapy, offering new ideas for future cancer treatment.
4.Effectiveness and safety of augmentative plating technique in managing nonunion following intramedullary nailing of long bones in the lower extremity: A systematic review and meta-analysis.
Cong-Xiao FU ; Hao GAO ; Jun REN ; Hu WANG ; Shuai-Kun LU ; Guo-Liang WANG ; Zhen-Feng ZHU ; Yun-Yan LIU ; Wen LUO ; Yong ZHANG ; Yun-Fei ZHANG
Chinese Journal of Traumatology 2025;28(3):164-174
PURPOSE:
To methodically assess the effectiveness of augmentative plating (AP) and exchange nailing (EN) in managing nonunion following intramedullary nailing for long bone fractures of the lower extremity.
METHODS:
PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to gather clinical studies regarding the use of AP and EN techniques in the treatment of nonunion following intramedullary nailing of lower extremity long bones. The search was conducted up until May 2023. The original studies underwent an independent assessment of their quality, a process conducted utilizing the Newcastle-Ottawa scale. Data were retrieved from these studies, and meta-analysis was executed utilizing Review Manager 5.3.
RESULTS:
This meta-analysis included 8 studies involving 661 participants, with 305 in the AP group and 356 in the EN group. The results of the meta-analysis demonstrated that the AP group exhibited a higher rate of union (odds ratio: 8.61, 95% confidence intervals (CI): 4.12 - 17.99, p < 0.001), shorter union time (standardized mean difference (SMD): -1.08, 95% CI: -1.79 - -0.37, p = 0.003), reduced duration of the surgical procedure (SMD: -0.56, 95% CI: -0.93 - -0.19, p = 0.003), less bleeding (SMD: -1.5, 95% CI: -2.81 - -0.18, p = 0.03), and a lower incidence of complications (relative risk: -0.17, 95% CI: -0.27 - -0.06, p = 0.001). In the subgroup analysis, the time for union in the AP group in nonisthmal and isthmal nonunion of lower extremity long bones was shorter compared to the EN group (nonisthmal SMD: -1.94, 95% CI: -3.28 - -0.61, p < 0.001; isthmal SMD: -1.08, 95% CI: -1.64 - -0.52, p = 0.002).
CONCLUSION
In the treatment of nonunion in diaphyseal fractures of the long bones in the lower extremity, the AP approach is superior to EN, both intraoperatively (with reduced duration of the surgical procedure and diminished blood loss) and postoperatively (with an elevated union rate, shorter union time, and lower incidence of complications). Specifically, in the management of nonunion of lower extremity long bones with non-isthmal and isthmal intramedullary nails, AP demonstrated shorter union time in comparison to EN.
Humans
;
Bone Nails/adverse effects*
;
Bone Plates/adverse effects*
;
Femoral Fractures/surgery*
;
Fracture Fixation, Intramedullary/methods*
;
Fractures, Ununited/surgery*
;
Lower Extremity/injuries*
5.Methods for enhancing image quality of soft tissue regions in synthetic CT based on cone-beam CT.
Ziwei FU ; Yechen ZHU ; Zijian ZHANG ; Xin GAO
Journal of Biomedical Engineering 2025;42(1):113-122
Synthetic CT (sCT) generated from CBCT has proven effective in artifact reduction and CT number correction, facilitating precise radiation dose calculation. However, the quality of different regions in sCT images is severely imbalanced, with soft tissue region exhibiting notably inferior quality compared to others. To address this imbalance, we proposed a Multi-Task Attention Network (MuTA-Net) based on VGG-16, specifically focusing the enhancement of image quality in soft tissue region of sCT. First, we introduced a multi-task learning strategy that divides the sCT generation task into three sub-tasks: global image generation, soft tissue region generation and bone region segmentation. This approach ensured the quality of overall sCT image while enhancing the network's focus on feature extraction and generation for soft tissues region. The result of bone region segmentation task guided the fusion of sub-tasks results. Then, we designed an attention module to further optimize feature extraction capabilities of the network. Finally, by employing a results fusion module, the results of three sub-tasks were integrated, generating a high-quality sCT image. Experimental results on head and neck CBCT demonstrated that the sCT images generated by the proposed MuTA-Net exhibited a 12.52% reduction in mean absolute error in soft tissue region, compared to the best performance among the three comparative methods, including ResNet, U-Net, and U-Net++. It can be seen that MuTA-Net is suitable for high-quality sCT image generation and has potential application value in the field of CBCT guided adaptive radiation therapy.
Cone-Beam Computed Tomography/methods*
;
Humans
;
Image Processing, Computer-Assisted/methods*
;
Artifacts
;
Algorithms
;
Bone and Bones/diagnostic imaging*
;
Neural Networks, Computer
6.Risk factors for lymph node metastasis after RARP in high-risk prostate cancer patients and construction of a nomogram
Qi CAI ; Ziyan AN ; Zhoujie YE ; Jinpeng SHAO ; Kaipeng BI ; Zheng WANG ; Guanqiu CHEN ; Jie ZHU ; Guangfu CHEN ; Shaoxi NIU ; Baojun WANG ; Xin MA ; Jiangping GAO ; Weijun FU
Chinese Journal of Urology 2025;46(8):593-599
Objective:This study investigated the independent risk factors for lymph node metastasis(LNM)in high-risk prostate cancer(HRPCa)patients undergoing robot-assisted radical prostatectomy(RARP),and constructed a nomogram model based on clinical data to improve the accuracy and clinical practicality of preoperative prediction of LNM.Methods:A retrospective analysis was conducted on the clinical data of 218 HRPCa patients who received RARP treatment at the First Medical Center of the PLA General Hospital from January 2020 to March 2025 as the modeling group. The age of the modeling group was(66.91±6.94)years old. 75 cases(34.40%)had a history of smoking,and 48 cases(22.02%)had a history of drinking. There were a body mass index(BMI)of 25.55(23.58,27.00)kg/m 2,a total prostate-specific antigen(tPSA)of 20.59(10.42,30.61)ng/ml,a free prostate-specific antigen(fPSA)of 1.87(1.04,3.26)ng/ml,a prostate volume(PV)of(41.19±21.00)ml,a prostate-specific antigen density(PSAD)of 0.52(0.30,0.84)ng/ml 2. Among the patients,60 cases(27.52%)had a preoperative biopsy Gleason score >8,and the percentage of positive biopsy cores(PPBC)was 50%(31%,80%). Thirty-one patients(14.22%)were staged clinically as >T 2c. The diagnostic criteria for high-risk prostate cancer(HRPCa)were defined as meeting any one of the following:PSA >20 ng/ml,Gleason score on prostate biopsy ≥8,or clinical stage ≥T 3. Among the 218 patients in the modeling cohort,67 cases(30.73%)met two of the criteria,and 7 cases(3.21%)met all three criteria. All 218 patients underwent RARP,and based on postoperative pathology,they were divided into the LNM group and the non-LNM group. The relationship between the number of diagnostic criteria met and the occurrence of LNM was analyzed. An external validation cohort included 42 HRPCa patients who underwent RARP at the Third,Fifth Medical Centers of the PLA General Hospital between January 2023 and May 2025. Their mean age was(66.79±5.92)years. Eighteen patients(42.86%)had a smoking history,and nine(21.43%)had a history of alcohol consumption. The median BMI was 26.00(23.80,27.13)kg/m 2. The median tPSA level was 17.34(8.97,27.30)ng/ml. The median fPSA was 1.51(0.83,2.52)ng/ml,and the median PV was(35.57 ± 15.25)ml. The median PSAD was 0.57(0.23,0.87)ng/ml 2,and the median PPBC was 58%(36%,71%). Three patients(7.14%)had a clinical stage >T 2c,and 12 patients(28.57%)had a Gleason score >8 on preoperative biopsy. Univariate and multivariate binary logistic regression analyses were used to identify independent risk factors for LNM,and a nomogram model was constructed based on these factors. The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curves and calibration plots,and the model was validated in the external cohort. Result:According to postoperative pathology,45 patients were classified into the LNM group,and 173 into the non-LNM group. The probability of LNM increased proportionally with the number of diagnostic criteria met for HRPCa(meeting two criteria: OR = 4.762,95% CI 2.323-9.761, P < 0.01;meeting three criteria: OR = 10.667,95% CI 2.187-52.025, P=0.003). Binary logistic regression analysis revealed that age( OR=0.913,95% CI 0.859-0.971, P = 0.004),tPSA( OR=1.039,95% CI 1.018-1.061, P<0.01),PPBC( OR = 5.656,95% CI 1.101-29.056, P = 0.038),and clinical T stage(T 2c stage: OR=2.945,95% CI 0.888-9.769, P=0.077;>T 2c stage OR = 18.351,95% CI 4.790-70.306, P < 0.01)were independent risk factors for postoperative LNM in HRPCa patients after RARP. The ROC curve of the nomogram model based on these factors showed an area under the curve(AUC)of 0.853(95% CI 0.790-0.917). In the external validation cohort,the nomogram achieved an AUC of 0.743(95% CI 0.556-0.929). The calibration plots demonstrated good agreement between the predicted probabilities and actual observations. Conclusions:Age,tPSA,PPBC,and clinical T stage were independent predictors of postoperative LNM in HRPCa patients undergoing RARP. The greater the number of HRPCa diagnostic criteria met,the higher the likelihood of postoperative LNM. The nomogram developed in this study could effectively predict the risk of LNM in HRPCa patients after RARP.
7.Impacts of external fixation of different durations on rehabilitation outcomes after open repair of acute Achilles tendon rupture
Yuan CAO ; Xiuzhi LI ; Zengzhen CUI ; Yuliang FU ; Liangyu BAI ; Jixing FAN ; Tengjiao ZHU ; Gao SI ; Yang LYU ; Fang ZHOU
Chinese Journal of Trauma 2025;41(4):360-368
Objective:To compare the impacts of external fixation of different durations on rehabilitation outcomes after open repair of acute Achilles tendon rupture.Methods:A prospective cohort study was conducted to analyze the clinical data of patients with unilateral acute closed Achilles tendon rupture admitted to Peking University Third Hospital from August 2020 to August 2023. Patients were divided into Group A ( n=96), Group B ( n=347), Group C ( n=346), and Group D ( n=105) based on different postoperative immobilization durations (0, 2, 4 and 6 weeks, respectively). After all the patients received identical open repair procedure, Group A was rehabilitated immediately but the other groups were rehabilitated with the same protocol after removal of the external fixation. Four groups were compared in terms of recovery time of one-leg heel-rise height (OHRH), recovery time of light exercise (LE) in brisk walking and jogging and recovery time of range of motion (ROM). Visual analogue scale (VAS) scores were also compared at 2, 4, 6 and 8 weeks postoperatively. Achilles tendon total rupture score (ATRS) and American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores were evaluated at 6, 8, 10, 12, 14 and 16 weeks postoperatively. Complications were recorded. Results:A total of 894 patients including 869 males and 25 females were included, aged 18-60 years [(35.0±6.3)years]. All the patients were followed up for 14-25 months [(19.0±3.0)months]. The recovery time of OHRH in Group A and B was 12.0(12.0, 12.0)weeks and 12.0(10.0, 12.0)weeks, shorter than those in Group C [14.0(14.0, 16.0)weeks] and D [14.0(14.0, 14.0)weeks] ( P<0.05), with no significant difference between Group A and B ( P>0.05) and between Group C and D ( P>0.05). The recovery time of LE in Group A and B was 18.0(18.0, 18.0)weeks and 18.0(16.0, 18.0)weeks, shorter than those in Group C [20.0(20.0, 20.0)weeks] and D [20.0(20.0, 20.0)weeks] ( P<0.05), with no significant difference between Group A and B ( P>0.05) and between Group C and D ( P>0.05). The recovery time of ROM in Group A and B was 6.0(6.0, 6.0)weeks and 6.0(6.0, 6.0)weeks, shorter than those in Group C [8.0(8.0, 10.0)weeks] and D [10.0(10.0, 10.0)weeks)] ( P<0.05), with no significant difference between Group A and B, and between Group C and D ( P>0.05). At 2 weeks postoperatively, the VAS scores were 2.0(1.0, 2.0)points, 2.0(1.0, 2.0)points, and 2.0(1.5, 2.0)points in Group B, C and D, lower than 5.0(5.0, 5.0)points in Group A ( P<0.05), with no significant difference among Group B, C, and D ( P>0.05). At 4 weeks postoperatively, the VAS scores were 1.0(0, 1.0)points, 1.0(0, 1.0)points, and 1.0(0.5, 1.0)points in Group B, C and D, lower than 2.0(1.0, 2.0)points in Group A ( P<0.05), with no significant difference among Group B, C, and D ( P>0.05). At 6 weeks postoperatively, the VAS score was 0(0, 0)points in all the 4 groups, with no significant difference among them ( P>0.05). At 8 weeks postoperatively, the VAS score was 0(0, 0)points, with lower scores in Group A and B than those in Group C and D ( P<0.05) but with no significant difference between Group A and B and between Group C and D ( P>0.05). At 6 weeks postoperatively, the ATRS scores were 52.0(52.0, 53.8)points and 52.0(50.0, 53.0)points in Group A and B, higher than 41.0(38.0, 43.0)points and 19.0(18.0, 20.0)points in Group C and D ( P<0.05), with a higher score in Group C than that in Group D ( P<0.05) but with no significant difference between Group A and B ( P>0.05). At 8 weeks postoperatively, the ATRS scores were 66.0(66.0, 68.0)points in Group A, higher than 63.0(62.0, 64.0)points, 52.0(50.0, 53.0)points, and 39.0(37.0, 40.0)points in Group B, C and D ( P<0.05), with a higher score in Group B than those in Group C and D ( P<0.05) and a higher score in Group C than that in Group D ( P<0.05). At 10 weeks postoperatively, the ATRS score was 75.0(74.0, 76.0)points in Group B, higher than 69.0(69.0, 70.0)points, 72.0(66.0, 74.0)points, and 62.0(58.5, 63.0)points in Group A, C and D ( P<0.05), with higher scores in Group A and C than that in Group D ( P<0.05) but with no significant difference between Group A and C ( P>0.05). At 12 weeks postoperatively, the ATRS score was 84.0(82.0, 85.0)points in Group B, higher than 75.0(75.0, 77.0)points, 79.0(72.0, 81.0)points, and 72.0(71.0, 73.0)points in Group A, C and D ( P<0.05), with higher scores in Group A and C than that in Group D ( P<0.05) but with no significant difference between Group A and C ( P>0.05). At 14 weeks postoperatively, the ATRS score was 87.0(86.0, 87.0)points in Group B, higher than 82.0(82.0, 84.0)points, 83.0(80.0, 85.0)points, and 79.0(77.5, 80.0)points in Group A, C and D ( P<0.05), with higher scores in Group A and C than that in Group D ( P<0.05) but with no significant difference between Group A and C ( P>0.05). At 16 weeks postoperatively, the ATRS scores were 87.0(87.0, 88.0)points and 88.0(87.0, 88.0)points in Group A and B, higher than 86.0(85.0, 87.0)points and 84.0(83.0, 85.0)points in Group C and D ( P<0.05), with a higher score in Group C than that in Group D ( P<0.05) but with no significant difference between Group A and B ( P>0.05). At 6 weeks postoperatively, the AOFAS ankle-hindfoot scores were 94.0(94.0, 95.0)points and 95.0(94.0, 96.0)points in Group A and B, higher than 85.0(83.0, 86.0)points and 74.0(72.0, 75.0)points in Group C and D ( P<0.05), with a higher score in Group C than that in Group D ( P<0.05) but with no significant difference between Group A and B ( P>0.05). At 8 weeks postoperatively, the AOFAS ankle-hindfoot scores were 100.0(99.0, 100.0)points in Group B, higher than 94.0(94.0, 95.0)points, 92.0(90.0, 93.0)points, and 83.0(82.0, 84.0)points in Group A, C and D ( P<0.05), with a higher score in Group A than those in Group C and D ( P<0.05) and a higher score in Group C than that in Group D ( P<0.05). At 10 weeks postoperatively, the AOFAS ankle-hindfoot score was 100.0(100.0, 100.0)points in Group B, higher than 98.0(98.0, 98.0)points, 98.0(96.8, 99.0)points, and 96.0(95.0, 97.0)points in Group A, C and D, with higher scores in Group A and C than that in Group D ( P<0.05) but with no significant difference between Group A and C ( P>0.05). At 12 weeks postoperatively, the AOFAS ankle-hindfoot score was 100.0(100.0, 100.0)points in both Group A and B, with no significant difference between them ( P>0.05), which was higher than 100.0(98.0, 100.0)points and 99.0(98.0, 99.0)points in Group C and D ( P<0.05), with a higher score in Group C than that in Group D ( P<0.05). At 14 and 16 weeks postoperatively, AOFAS ankle-hindfoot score was 100.0(100.0, 100.0)points, with no significant difference among all the groups ( P>0.05). Superficial wound infection occurred in 12 patients [5.2%(5/96) in Group A, 0.6%(2/347) in Group B, 0.6%(2/346) in Group C and 2.9%(3/105) in Group D] ( P<0.01) while rerupture occurred in 16 [9.4%(9/96) in Group A, 1.2% (4/347) in Group B, 0.9%(3/105) in Group C, and 0 patient in Group D] ( P<0.01). Conclusion:For patients with unilateral acute Achilles tendon rupture, two weeks of postoperative external fixation after open repair can shorten the time of returning sports, alleviate pain, and promote functional recovery, without increasing the risk of complications.
8.Mechanotransduction proteins in intervertebral disc degeneration
Xilin GAO ; Si WU ; Chao ZHANG ; Liguo ZHU ; Bifeng FU ; Ping WANG
Chinese Journal of Tissue Engineering Research 2025;29(3):579-589
BACKGROUND:Recent research indicates that disc degeneration is closely related to abnormal stress load,and mechanotransduction proteins play a key role in it. OBJECTIVE:To investigate the role and mechanism of mechanotransduction proteins in the mechanotransduction process induced by abnormal mechanical stimulation in disc degeneration,and to summarize the current treatment strategies targeting mechanotransduction to delay intervertebral disc degeneration. METHODS:Using"intervertebral disc,nucleus pulposus,annulus fibrosus,cartilaginous endplate,cell,mechanics,signal transduction,protein,biomechanics"as Chinese search terms,and"intervertebral disc,nucleus pulposus,annulus fibrosus,cartilaginous endplate,cell,mechanical stimulation,signal transduction,protein,biomechanics"as English search terms,relevant literature in the PubMed and CNKI databases was searched.A total of 88 articles were ultimately included for review. RESULTS AND CONCLUSION:Disc cells can sense external mechanical stimulation through various mechanotransduction proteins and convert it into biological responses within the cells.These transduction proteins mainly include collagen proteins in the extracellular matrix,cell membrane surface receptors(such as integrins and ion channels),and cytoskeleton structural proteins.Their regulation of mechanotransduction processes primarily involves the activation of multiple pathways,such as the PI3K/AKT signaling pathway,nuclear factor-kB signaling pathway,and Ca2+/Calpain2/Caspase3 pathway.Mechanotransduction proteins play a key role in the mechanotransduction of disc cells.Abnormal expression of these proteins or resulting changes in the extracellular matrix environment can disrupt the mechanical balance of disc cells,leading to disc degeneration.In-depth study of the expression and regulatory mechanisms of mechanotransduction proteins in disc cells,and identification of key pathological links and therapeutic targets,is of significant importance for developing treatment strategies for disc degeneration.Current strategies to delay intervertebral disc degeneration by targeting mechanotransduction mainly include regulation of transduction proteins and improvement of the extracellular matrix.However,research in this area is still in its early stages.As research continues,new breakthroughs are expected in the regulation of disc degeneration by mechanotransduction proteins.
9.Needs for rehabilitation in China: Estimates based on the Global Burden of Disease Study 1990-2019.
Tian TIAN ; Lin ZHU ; Qingzhen FU ; Shiheng TAN ; Yukun CAO ; Ding ZHANG ; Mingxue WANG ; Ting ZHENG ; Lijing GAO ; Daria VOLONTOVICH ; Yongchen WANG ; Jinming ZHANG ; Zhimei JIANG ; Hongbin QIU ; Fan WANG ; Yashuang ZHAO
Chinese Medical Journal 2025;138(1):49-59
BACKGROUND:
As an essential part of health services, rehabilitation is of great significance to improve the health and quality of life of the whole population. Accelerating aging calls for a significant expansion of rehabilitation services in China, but rehabilitation needs remain unclear. We conducted the study to explore the rehabilitation needs in China and project the trend of rehabilitation needs from 2020 to 2034.
METHODS:
The data of health conditions that might potentially benefit from rehabilitation were obtained from Global Burden of Disease (GBD) study. Estimated annual percentage changes (EAPCs) were calculated to quantify the trends of the age-standardized rates. Projections of rehabilitation needs were made until 2034 using Bayesian age-period-cohort analysis (BAPC).
RESULTS:
Approximately 460 million persons (33.3% of the total population) need rehabilitation in China, contributing to 63 million years lived with disabilities (YLDs) in 2019. The number of prevalent cases that need rehabilitation increased from around 268 (95% uncertainty interval [UI]: 257-282) million in 1990 to almost 460 (95% UI: 443-479) million in 2019, representing an increase of 71.3%. The highest contribution to the need for rehabilitation was musculoskeletal disorders with about 322 (95% UI: 302-343) million persons in seven aggregate disease and injury categories, and hearing loss with over 95 (95% UI: 84-107) million people among 25 health conditions. Based on the projection results, there will be almost 636 million people (45% of the total population) needing rehabilitation services in China by 2034, representing an increase of 38.3%. The rehabilitation needs of neoplasms, cardiovascular diseases, and neurological disorders are expected to increase significantly from 2019 to 2034, with increases of 102.3%, 88.8% and 73.2%, respectively.
CONCLUSIONS
The need for rehabilitation in China substantially increased over the last 30 years. It is predicted that over two in five people will require rehabilitation by 2034, thus suggesting the need to develop rehabilitation services that meet individuals' rehabilitation needs.
Humans
;
China/epidemiology*
;
Global Burden of Disease
;
Female
;
Male
;
Musculoskeletal Diseases/epidemiology*
;
Rehabilitation/trends*
;
Quality of Life
;
Middle Aged
;
Aged
;
Bayes Theorem
10.Construction and optimization of automatic monitoring module for drug-induced movement disorders based on hospital information system data
Liqiang CUI ; Daihong GUO ; Man ZHU ; Tianlin WANG ; Ao GAO ; Anqi ZHAO ; An FU ; Jing XIAO
Adverse Drug Reactions Journal 2025;27(2):84-90
Objective:Based on the adverse drug event active surveillance and assessment system-Ⅱ (ADE-ASAS-Ⅱ) and the information of inpatients in the hospital information system (HIS), the automatic monitoring module of movement disorders was constructed and its application effect in the real-world study of drug-induced movement disorders (DIMDs) was explored.Methods:Literature reviews, case reports, spontaneous reports and medical records were collected, the keyword set was screened based on ADE-ASAS-Ⅱ system and text classification technology, and an automatic monitoring module was constructed. The information of hospitalized patients in Chinese PLA General Hospital (our hospital) was selected from October 10 to 16, 2022. The results of manual evaluation and the system alarm by the automatic monitoring module were compared, and the performance of the automatic monitoring module was evaluated and optimized through repeated machine learning. The medical record information of hospitalized patients who used sodium valproate throughout the year in our hospital in 2022 were collected, and the occurrence of movement disorders related to sodium valproate was analyzed using the automatic monitoring module.Results:A total of 4 918 hospitalized patients (146 with movement disorders) were collected, and the final setting conditions of the automatic monitoring module were determined, including inclusion criteria (43 text keywords, 3 diagnosis) and exclusion criteria (11 text and 20 document titles were omitted). Among the 1 138 hospitalized patients using sodium valproate in 2022, the incidence of DIMDs with tic and tremor as main clinical manifestations detected by automatic monitoring module was 1.67% (19/1 138).Conclusion:The automatic monitoring module of drug-induced movement disorders based on machine learning and manual evaluation can be applied to explore the occurrence characteristics of DIMDs in the real world, and provide information for pharmacovigilance in clinic.

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