Prosthesis loosening is the leading cause of postoperative revision in unicompartmental knee arthroplasty (UKA). The deviation of medial and lateral translational installation of the prosthesis during surgery is a common clinical phenomenon and an important factor in increasing the risk of prosthesis loosening. This study established a UKA finite element model and a bone-prosthesis fixation interface micromotion prediction model. The predicted medial contact force and joint motion of the knee joint from a patient-specific lower extremity musculoskeletal multibody dynamics model of UKA were used as boundary conditions. The effects of 9 femoral component medial and lateral translational installation deviations on the Von Mises stress of the proximal tibia, the contact stress, and the micro-motion of the bone prosthesis fixation interface were quantitatively studied. It was found that compared with the neutral position (a/A of 0.492), the lateral translational deviation of the femoral component significantly increased the tibial Von Mises stress and the bone-prosthesis fixation interface contact stress. The maximum Von Mises stress and the maximum contact stress of the fixation interface increased by 14.08% and 143.15%, respectively, when a/A was 0.361. The medial translational deviation of the femoral component significantly increased the bone-prosthesis fixation interface micro-motion. The maximum value of micromotion under the conditions of femoral neutral and medial translation deviation was in the range of 20-50 μm, which is suitable for osseointegration. Therefore, based on considerations such as the micromotion range suitable for osseointegration reported in the literature, the risk of reducing prosthesis loosening, and factors that may induce pain, it is recommended that clinicians control the mounting position of the femoral component during surgery within the safe range of 0-4 mm medial translation deviation.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Finite Element Analysis ; Biomechanical Phenomena ; Knee Prosthesis ; Tibia/surgery* ; Femur/surgery* ; Stress, Mechanical ; Prosthesis Failure ; Knee Joint/surgery* ; Prosthesis Design

Objective: To analyze the status and trends of the disease burden of periodontal disease among women of reproductive age (15-49 years) in China from 1990 to 2021, and to provide a reference for the development of periodontal disease prevention and control strategies for women of reproductive age. Methods: Using the global burden of disease (GBD) data from 1990 to 2021, this study investigated the periodontal disease burden among women of reproductive age, including prevalence, incidence, disability-adjusted life years (DALYs), DALY rates, and their corresponding standardized indicators. Joinpoint 5.2.0.0 software was used for time trend analysis of DALYs, age-specific DALY rates, and annual average percentage change (AAPC) values. A log-linear regression model was used to test trends for DALYs and DALY rates. Results: Compared with 1990, the prevalence and incidence of periodontal disease among Chinese women in 2021 increased by 45.67% (per 100,000 people) and 29.29% (per 100,000 people), respectively. The distribution of periodontal disease among women (15-49 years) showed a continuous and rapid upward trend, with the growth rate increasing rapidly with age. The number of cases increased the fastest in the 45-49 age group, and the prevalence increased the fastest in the 35-44 age group. The incidence of periodontal disease continued to rise with age, with the fastest increase in the 35-44 age group among women of reproductive age. The Joinpoint regression model results showed that periodontal disease led to an expanding trend in the disease burden among women of reproductive age in China, with an AAPC of DALYs = 1.20% and an AAPC of DALY rate = 1.25% (P<0.001). Conclusion The periodontal disease burden among Chinese women aged 15-49 years showed a gradually increasing trend from 1990 to 2021.

Most patients with pancreatic cancer are already in the locally advanced or metastatic stage at initial diagnosis. While systemic chemotherapy provides clinical benefits for those with mid-to-late-stage pancreatic cancer, its efficacy is often limited by patient tolerance. In response to the dual clinical demands of robust antitumor activity and high targeting specificity, antibody-drug conjugate (ADC) has emerged as a promising solution. By conjugating highly selective monoclonal antibodies with potent cytotoxic small-molecule drugs, ADC achieves precise tumor-targeting while minimizing damage to healthy tissues, which thereby improves treatment tolerance. However, due to the complex pathological features of pancreatic cancer, no ADC has yet been approved for clinical use for this disease. A comprehensive evaluation of factors including ADC-specific targets, payload selection, antibody-drug linkage strategies, drug delivery mechanisms, tissue distribution variability, and tumor heterogeneity will be crucial to advancing the clinical translation of ADC for pancreatic cancer treatment.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To evaluate the clinical efficacy and impact on quality of life of the biofeedback (BF) therapy combined with the Wenyang Yiqi Prescription and self-efficacy interventions in patients with functional defecation disorders (FDD).Methods:A prospective, randomized controlled trial design was employed. A total of 128 FDD patients were selected from the Pelvic Floor Center of the Department of Proctology, Suzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, between January 2021 and April 2023. These patients were randomly divided into two groups, with 64 cases in each group. Additionally, 41 historical control patients, who had received conventional BF training between June 2015 and January 2018 at the same center, were included for comparison. The historical control group received conventional BF therapy, the intervention group 1 combined BF therapy with self-efficacy interventions, and the intervention group 2 added the Wenyang Yiqi Prescription based on intervention group 1's treatment. All three groups underwent two treatment courses. Constipation symptom scores before and after treatment were performed; self-efficacy was assessed via the Self-Rated Abilities for Health Practices scale (SRAHP); health behaviors were evaluated using the Health-Promoting Lifestyle Profile (HPLP); anxiety and depression were evaluated through Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS); quality of life was measured through SF-36. Clinical efficacy was evaluated based on constipation symptom scores.Results:During the treatment period, seven patients dropped out due to personal reasons, leaving 61 patients in intervention group 1 and 60 patients in intervention group 2 for efficacy analysis.　The total effective rates were 80.32% (49/61) in intervention group 1, 83.33% (50/60) in intervention group 2, and 56.10% (23/41) in the historical control group. The total effective rates of both intervention groups were significantly higher than those in the historical control group ( χ2=7.06, 9.15; P=0.029, 0.010, respectively). After treatment, intervention group 2 showed significantly lower constipation-related straining scores [1 (1, 2) vs. 2 (1, 2), Z=-4.51] compared to intervention group 1 ( P<0.05). Additionally, intervention group 2 had lower scores for straining [1 (1, 2) vs. 2 (1, 2), Z=-3.15] and defecation time [1 (0, 1) vs. 1 (1, 2), Z=-3.13] compared to the historical control group ( P<0.05). Psychological comfort efficacy (19.13 ± 2.51 vs. 16.98 ± 1.86, t=5.36), health responsibility efficacy (23.63 ± 4.69 vs. 22.59 ± 3.05, t=2.06), and overall SRAHP scores (75.98 ± 4.44 vs. 72.33 ± 5.16, t=4.17) were higher in intervention group 2 compared to intervention group 1 ( P<0.05). The HPLP scores (79.33 ± 11.13 vs. 72.80 ± 9.20, t=3.10) of intervention group 2 were higher than those of the historical control group ( P<0.05). Emotional functioning scores (75.98 ± 18.45 vs. 68.92 ± 20.58 and 68.55 ± 18.21, F=20.91) in intervention group 2 were higher than in both intervention group 1 and the historical control group ( P<0.05). Conclusion:The combination of the Wenyang Yiqi Prescription with BF therapy and self-efficacy interventions effectively improves the clinical symptoms and quality of life in FDD patients.

Objective:To systematically review the current registered clinical study schemes in China regarding the combination of TCM and targeted drug therapy for lung cancer; To analyze their strengths and weaknesses; To provide reference for future study.Methods:Chinese Clinical Trial Registry for clinical study schemes combining TCM with targeted drug therapy for lung cancer treatment was retrieved from the inception to July 10, 2024. The general characteristics, study types, intervention measures, and outcome indicators of existing schemes were systematically summarized and analyzed.Results:A total of 15 studies were included, with the earliest study registered in 2013. Registration locations were concentrated in Shanghai, Guangdong, Tianjin, and Zhejiang. Among them, 9 studies received funding from local, national finance, or hospitals; 13 studies passed ethical review, and 12 included informed consent. The design schemes included 10 randomized controlled studies, 1 cohort study, 1 interventional single-arm study, and 3 observational studies. 6 studies had a sample size smaller than 100 cases, and most were single-center trials. Intervention measures primarily involved the combination of Chinese patent medicine or TCM with targeted drugs, with evaluation indicators mainly focusing on clinical symptoms and laboratory indicators. The setting of outcome indicators lacked a unified standard.Conclusions:Since 2013, clinical studies combining TCM with targeted drug therapy for lung cancer have been relatively methodologically sound but face challenges such as small sample sizes and a certain degree of regional concentration, leading to relatively insufficient representativeness. The future direction for improvement lies in multi-center, large-sample, and well-designed clinical trials. It is also necessary to establish a standardized and normalized system for evaluating outcomes. Integrating basic research to clarify the mechanisms of TCM can provide a theoretical basis for the combination of TCM and targeted drugs, which is conducive to enhancing the rigor and scientific nature of clinical trial design and promoting the formation of high-level evidence-based medicine.

Objective To explore the correlation between the expression of microRNA-452(miR-452)and micro-RNA-221(miR-221)in peripheral blood and post-operative urinary sepsis after percutaneous nephrolithotripsy(PCNL).Methods From January 2019 to June 2023,92 patients with post-operative urinary sepsis after PCNL admitted to 909 Hospital of the Chinese People's Liberation Army Joint Logistic Support Force were regarded as the disease group,92 patients who underwent PCNL surgery during the same period without urinary sepsis were collect-ed as control group.RT-qPCR was applied to detect the expression of miR-452 and miR-221 in peripheral blood;Logistic regression was applied to analyze the influencing factors of urinary sepsis after PCNL surgery;Receiver op-erating characteristic(ROC)curve was applied to evaluate the diagnostic efficacy of peripheral blood miR-452 and miR-221 levels for post-operative urinary sepsis in PCNL patients.Results The time length of the surgical opera-tion in disease group was longer than that in the control group,and the level of miR-452 and miR-221 in peripheral blood,were higher than those in the control group(P＜0.05).Peripheral blood miR-452,miR-221,procalcitonin(PCT),C-reactive protein(CRP),neutrophil to lymphocyte ratio(NLR),urine routine and surgical time were all influence factors for post-operative urinary sepsis in PCNL(P＜0.05).The area under the curve(AUC)for the combined diagnosis of peripheral blood miR-452 and miR-221 in patients with urinary sepsis after PCNL surgery was 0.888,which was better than their individual detection(Zcombination-miR-452=2.005,Zcombination-miR-221=2.972,P=0.045,0.003),the sensitivity and specificity were 77.17%and 91.30%,respectively.Conclusions The change of miR-452 and miR-221 level in peripheral blood is closely related to urinary sepsis after PCNL.Combined testing has a high diagnostic efficacy for post-operative urinary sepsis after PCNL surgery.

Objective:To investigate the clinical value of neuroendoscopic resection in recurrent or residual sellar and clivus tumors and the prevention and treatment of operative complications.Methods:A retrospective study was performed. Clinical data of 49 patients with residual or recurrent sellar and clivus tumors after neuroendoscopic resection in Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University from November 2021 to October 2023 were collected; 45 patients were with pituitary adenoma, 3 were with craniopharyngioma, and 1 patient was with clivus chordoma; their surgical efficacy and complications were summarized and analyzed.Results:Total resection was achieved in 29 patients (59.2%), subtotal resection in 12 (24.5%), and partial resection in 8 (16.3%). Two patients (4.1%) had intraoperative internal carotid artery rupture and were given emergency laminar stenting, discharging with good recovery, but one of them left with unilateral motor nerve palsy. During 1-24 months of follow-up, 97.2% patients (35/36) had headache relief and visual acuity improvement, and no patient had permanent diabetes insipidus or cerebrospinal fluid rhinorrhea. Residual tumors increased in 3 patients (6.1%); no tumor recurrence after total resection was noted.Conclusion:Endoscopic resection of recurrent or residual sellar and clivus tumors is safe and effective; attention should be paid to the internal carotid artery during the operation.

ObjectiveThe mechanisms underlying therapeutic efficacies of Detumescence Analgesic Plaster was analyzed based on "effect-target" associations. MethodBased on CNKI and PubMed databases， the chemical components of Artemisia seed， bastard speedwell， and menthol in Detumescence Analgesic Plaster were collected. The capacity of transdermal absorption was predicted based on the Encyclopedia of Traditional Chinese Medicine （ETCM 2.0）. Golden Triangle of compounds with Accepted used for candidate target prediction based on the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP v2.0）according to the similarity of chemical structures. At the same time， the SoFDA data platform was employed to collect the symptoms related to the efficacy of Detumescence Analgesic Plaster and its related genes information. In addition， based on the interaction between the above-mentioned candidate targets and their efficacy-related genes， the "effect-target" interaction network of Detumescence Analgesic Plaster was constructed. The key targets by topological features calculation， and functional mining was carried out to explain the efficacy mechanism of Detumescence Analgesic Plaster. ResultA total of 165 candidate targets were obtained based on ETCM 2.0 and TCMIP v2.0 databases， and symptoms related to the efficacy of clearing heat， detumescence， and relieving pain， as well as 1 744 related genes were collected based on the SoFDA database. Network construction and analysis showed that the core effect targets of Detumescence Analgesic Plaster were mainly involved in regulating the "immune-inflammation" balance of the body and maintaining the homeostasis of material and energy metabolism， blood circulation， and nervous system functions， and they were closely related to the efficacy of this prescription in clearing heat， reducing detumescence， and relieving pain. Among them， the heat clearing group of Detumescence Analgesic Plaster had the functions of heat clearing， detoxifying， antibacteria， and anti-inflammation. The biological function of its key effect target group was related to correcting the imbalance of "immune-inflammation" induced by pathogens. The detumescence group of Detumescence Analgesic Plaster had the functions of reducing water and swelling and resolving hard lumps， and the biological function of its core effect target group was related to improving microcirculation disturbance. The pain relieving group of Detumescence Analgesic Plaster had the functions of removing stasis， promoting blood circulation， and relieving pain， and its core effect target group was related to correcting the nervous system and the disorder of material and energy metabolism. ConclusionThe heat clearing， swelling reducing， and pain relieving effects of Detumescence Analgesic Plaster may be closely related to its act on related candidate targets， so as to correct the imbalance of "nerve-immunity-vascular-axis"， regulate neuronal excitability and inflammatory response， and intervene in material and energy metabolism. The relevant research results lay a theoretical foundation for clarifying the advantages of Detumescence Analgesic Plaster and assisting its clinical precise positioning.