OBJECTIVE: To investigate the load distribution on the more painful and less painful limbs in patients with mild-to-moderate and severe bilateral knee osteoarthritis (KOA) and explore the compensatory mechanisms in both limbs among bilateral KOA patients with different severity levels. METHODS: A total of 113 participants were enrolled between July 2022 and September 2023. This cohort comprised 43 patients with mild-to-moderate bilateral KOA (Kellgren-Lawrence grade 2-3), 43 patients with severe bilateral KOA (Kellgren-Lawrence grade 4), and 27 healthy volunteers (healthy control group). The visual analogue scale (VAS) score for pain, the Hospital for Special Surgery (HSS) score, passive knee range of motion (ROM), and hip-knee-ankle angle (HKA) were used to assess walking pain intensity, joint function, and lower limb alignment in KOA patients, respectively. Motion trajectories of reflective markers and ground reaction force data during walking were captured using a gait analysis system. Musculoskeletal modeling was then employed to calculate biomechanical parameters, including the peak knee adduction moment (KAM), KAM impulse, peak joint contact force (JCF), and peak medial/lateral contact forces (MCF/LCF). Statistical analyses were performed to compare differences in clinical and gait parameters between bilateral limbs. Additionally, one-dimensional statistical parametric mapping was utilized to analyze temporal gait data. RESULTS: Mild-to-moderate KOA patients showed the significantly higher HSS score (67.7±7.9) than severe KOA patients (51.9±8.9; t=8.747, P<0.001). The more painful limb in all KOA patients exhibited significantly greater HKA and higher VAS scores compared to the less painful limb ( P<0.05). While bilateral knee ROM did not differ significantly in mild-to-moderate KOA patients ( P>0.05), the severe KOA patients had significantly reduced ROM in the more painful limb versus the less painful limb ( P<0.05). Healthy controls showed no significant bilateral difference in any biomechanical parameters ( P>0.05). All KOA patients demonstrated longer stance time on the less painful limb ( P<0.05). Critically, severe KOA patients exhibited significantly higher peak KAM, KAM impulse, and peak MCF in the more painful limb ( P<0.05), while mild-to-moderate KOA patients showed the opposite pattern with lower peak KAM and KAM impulse in the more painful limb ( P<0.05) and a similar trend for peak MCF. CONCLUSION Patients with mild-to-moderate KOA effectively reduce load on the more painful limb through compensatory mechanisms in the less painful limb. Conversely, severe bilateral varus deformities in advanced KOA patients nullify compensatory capacity in the less painful limb, paradoxically increasing load on the more painful limb. This dichotomy necessitates personalized management strategies tailored to disease severity.
Humans ; Osteoarthritis, Knee/physiopathology* ; Range of Motion, Articular ; Male ; Female ; Middle Aged ; Biomechanical Phenomena ; Knee Joint/physiopathology* ; Pain Measurement ; Severity of Illness Index ; Aged ; Gait/physiology* ; Walking/physiology* ; Case-Control Studies ; Adult ; Weight-Bearing

Severe combined immunodeficiency (SCID) represents a group of genetically heterogeneous disorders characterized by mutations that lead to profound defects in both humoral and cellular immunity. Transplacental maternal engraftment (TME) is a frequently observed complication in SCID. While most cases of SCID with TME exhibit no substantial impact on disease progression, a subset of patients may encounter diagnostic delays or therapeutic challenges due to TME interference. Furthermore, TME may predispose these individuals to graft-versus-host disease (GVHD) prior to hematopoietic stem cell transplantation, thereby increasing diagnostic complexity and treatment risks. This review systematically examines the etiology and clinical manifestations of SCID associated with TME, analyzes its implications for disease management, and evaluates current detection methodologies. The synthesized evidence provides a theoretical foundation for future research and offers potential insights into the clinical diagnosis and management of SCID associated with TME.
Humans ; Severe Combined Immunodeficiency/diagnosis* ; Pregnancy ; Female ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Maternal-Fetal Exchange/immunology* ; Graft vs Host Disease/etiology* ; Animals ; Placenta/immunology*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

ObjectiveOur study seeks to investigate the connection between systemic immune inflammatory index and renal function， as well as to assess its predictive capacity for the deterioration of renal function in chronic kidney disease patients with non-dialysis. MethodsAdult non-dialyzing patients diagnosed with CKD were included. The computation of SII was calculated as the product of the peripheral blood neutrophil count （×10⁹/L） and platelet count （×10⁹/L）， divided by the lymphocyte count （×10⁹/L）. The logistic and Cox regression models were employed to scrutinize the linkage between SII levels and CKD. ResultsOut of the cohort， a significant portion of patients， numbering 244， which constitutes 17.2%， experienced progression of CKD. A notable upsurge in SII corresponded with an increased prevalence of advanced CKD and its progression， with significant difference. This trend was mirrored by a decline in the estimated glomerular filtration rate and hemoglobin levels， while serum creatinine， C-reactive protein， and lipoprotein（a） levels were on the rise. After adjusting for multiple variables， the natural logarithm of SII exhibited an independent association with advanced CKD ［OR=1.85 95% CI（1.46，2.35），P＜0.01］. Furthermore， Cox proportional hazards model analysis revealed that SII acted as an independent predictor for CKD progression ［adjusted HR= 1.35， 95% CI（1.09，1.67）， P＜ 0.01］. Subgroup analysis indicated a significant interaction among SII， gender， and hypertension concerning CKD progression. ConclusionOur findings underscore the robust relationship between SII and renal function， positioning SII as a potential forecaster for the progression of CKD.

Objective To observe effect of reconstructing physiological fulcrum in the treatment of elderly patients with intertrochanteric fracture of the femur. Methods Clinical materials of 40 elderly patients with osteoporotic intertrochanteric fracture of femur in the Tongling City People's Hospital from October 2020 to October 2022 were retrospectively analyzed. Among them, 20 patients treated with proximal femoral nail anti-rotation (PFNA) were assigned to the PFNA group, and 20 patients treated with proximal femoral bionic nail (PFBN) were assigned to the PFBN group. The operation time, intraoperative blood loss, length of hospital stay, postoperative rehabilitation, and incidence of complications were compared between the two groups. Results The postoperative weight-bearing time in the PFBN group was (8.50±1.99) days, which was significantly shorter than (20.15±4.87) days in the PFNA group (P<0.05). There were no significant differences in operation time, intraoperative blood loss, length of hospital stay, fracture healing time, excellent and good rate of fracture reduction quality, and excellent and good rate of Harris score between the PFBN group and the PFNA group (P>0.05). During the follow-up period of 10 to 14 months, no patients had complications such as wound infection, bone nonunion, implant failure, or deep venous thrombosis. Conclusion Both PFBN and PFNA can effectively treat elderly patients with osteoporotic intertrochanteric fracture of femur. However, patients treated with PFBN can take bed-off activities earlier, which is beneficial for postoperative rehabilitation, and the reason may be related to the double triangular stable structure reconstructed by PFBN.

Objective To investigate the effect of LAG-3 deficiency (LAG3^-/-) on natural killer (NK) cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis. Methods C57BL/6 mice, each weighing (20 ± 2) g, were divided into the LAG3^-/- and wild type (WT) groups, and each mouse in both groups was inoculated with 3 000 E. multilocularis protoscoleces via the hepatic portal vein. Mouse liver and spleen specimens were collected 12 weeks post-infection, sectioned and stained with sirius red, and the hepatic lesions and fibrosis were observed. Mouse hepatic and splenic lymphocytes were isolated, and flow cytometry was performed to detect the proportions of hepatic and splenic NK cells, the expression of CD44, CD25 and CD69 molecules on NK cell surface, and the secretion of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin (IL)-4, IL-10 and IL-17A. Results Sirius red staining showed widening of inflammatory cell bands and hyperplasia of fibrotic connective tissues around mouse hepatic lesions, as well as increased deposition of collagen fibers in the LAG3-/-group relative to the WT group. Flow cytometry revealed lower proportions of mouse hepatic (6.29% ± 1.06% vs. 11.91% ± 1.85%, P < 0.000 1) and splenic NK cells (4.44% ± 1.22% vs. 5.85% ± 1.10%, P > 0.05) in the LAG3^-/- group than in the WT group, and the mean fluorescence intensity of CD44 was higher on the surface of mouse hepatic NK cells in the LAG3^-/- group than in the WT group (t = −3.234, P < 0.01), while no significant differences were found in the mean fluorescence intensity of CD25 or CD69 on the surface of mouse hepaticNK cells between the LAG3^-/- and WT groups (both P values > 0.05). There were significant differences between the LAG3^-/- and WT groups in terms of the percentages of IFN-γ (t = −0.723, P > 0.05), TNF-α (t = −0.659, P > 0.05), IL-4 (t = −0.263, P > 0.05), IL-10 (t = −0.455, P > 0.05) or IL-17A secreted by mouse hepatic NK cells (t = 0.091, P > 0.05), and the percentage of IFN-γ secreted by mouse splenic NK cells was higher in the LAG3^-/- group than in the WT group (58.40% ± 1.64% vs. 50.40% ± 4.13%; t = −4.042, P < 0.01); however, there were no significant differences between the two groups in terms of the proportions of TNF-α (t = −1.902, P > 0.05), IL-4 (t = −1.333, P > 0.05), IL-10 (t = −1.356, P > 0.05) or IL-17A secreted by mouse splenic NK cells (t = 0.529, P > 0.05). Conclusions During the course of E. multilocularis infections, LAG3^-/- promotes high-level secretion of IFN-γ by splenic NK cells, which may participate in the reversal the immune function of NK cells, resulting in aggravation of hepatic fibrosis.

[摘 要] 目的：研究芳香烃受体（AHR）在乳腺癌中的表达及其对乳腺癌细胞增殖、凋亡和药物敏感性的调控机制。方法：通过GEPIA数据库数据分析乳腺癌组织及癌旁组织中AHR的表达水平，探讨其与患者生存期的关联。利用基因敲低和过表达技术构建AHR表达变化的乳腺癌细胞，采用CCK-8实验、细胞计数和流式细胞分析等方法评估AHR对细胞增殖、凋亡和药物敏感性的影响，通过免疫印迹法验证相关分子机制。此外，利用AHR激动剂6-甲酰基吲哚并[3,2-B]咔唑（FICZ）研究外源性激活AHR对乳腺癌细胞多柔比星（DOX）敏感性的影响。结果：GEPIA数据库数据分析结果显示，乳腺癌组织中AHR呈明显低表达（P < 0.05）；对155例乳腺癌患者的生存期进行统计分析也显示AHR低表达与不良预后呈正相关（P < 0.05）。敲低AHR促进细胞增殖（P < 0.05），过表达则能抑制其增殖（P < 0.05）并促进其凋亡（P < 0.05）。外源激活AHR能增强乳腺癌细胞对DOX的敏感性（P < 0.05）。AHR可与MYC基因启动子结合，抑制MYC表达（P < 0.05），从而影响乳腺癌的进展。结论：AHR在乳腺癌中通过调控MYC表达影响细胞增殖和凋亡，外源激活AHR可能成为提高乳腺癌细胞对DOX敏感性的治疗策略。

Objective To explore the risk factors of depression and anxiety in adult patients with epilepsy and their relationship with quality of life.Methods From May 2022 to January 2023,patients diagnosed with epilepsy(aged≥18 years)in the department of neurology of our hospital were collected.General demographic data and disease-related information were recorded.Quality of life,depression and anxiety scales were measured in all patients.SPSS26.0 software was used for multiple linear regression analysis,multiple ordered Logistic regression analysis,rank sum test,Pearson correlation analysis,etc.Results Among the 111 patients,49.5%had depression and 43.2%had anxiety.Depression score and anxiety score were correlated with attack type,attack frequency,quality of life and right temporal lobe,and there was a significant negative correlation between life quality score and anxiety and depression score(P<0.01).Seizure frequency,seizure type and right temporal lobe were common risk factors for depression and anxiety in patients with epilepsy(P<0.05).Conclusion Epileptic depression and anxiety were affected by seizure frequency and seizure type,and this bad mood further affected the quality of life of patients.No clear link has been found between the lateralization of seizures and the presence of depression and anxiety states,and further research is needed.