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.

The endothelial glycocalyx(EG)is a polyglycoprotein complex present on the internal vascular surface,and its impairment is associated with the progression of multiple diseases,including atherosclerosis,stroke,sepsis,diabetes,kidney disease,hypertension,and lung edema.Therefore,glycocalyx health can be used as a biomarker to evaluate vascular health.Aging leads to dysfunctional changes in the glycocalyx;for example,its thickness decreases,and the genes of enzymes involved in its synthesis and digestion are dysregulated.As a natural barrier to the vascular system,age-related glycocalyx disruption is associated with vascular dysfunction,including impairment of vascular contraction and dilation,enhancement of permeability,dysregulation of inflammatory and immune reactions,and imbalance of anticoagulation and thrombin.From the perspective of'structure determines function'studies on the changing regularity of the thickness,components,microstructure,and mechanical properties of EG with aging and its relationship with vascular dysfunction are of great significance for the prevention,diagnosis,and treatment of atherosclerosis and other age-related cardiovascular diseases.

Objective To investigate the clinical and imaging characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease(MOGAD).Methods The clinical symptoms,MRI features,results of laboratory tests and clinical prognosis of 14 MOGAD patients who were hospitalized in our hospital from June 2016 to June 2022 were collected and retrospectively analyzed.Their clinical and imaging characteristics were summarized and discussed.Results Among the 14 enrolled patients,there were 10 males and 4 females,with a male to female ratio of 2.5∶1.Their age of first onset was＜18 years in 3 cases,18～45 years in 8 cases,and＞45 years in 3 cases.Optic neuritis(10/14,71.43％)was the most common clinical type,followed by encephalitis or meningoencephalitis(9/14,64.29％),brainstem encephalitis(5/14,35.71％)and myelitis(5/14,35.71％).Visual impairment(10/14,71.43％)was the most common clinical symptom,followed by headache in 8 cases(8/14,57.14％),fever in 6 cases(6/14,42.86％),dizziness in 6 cases(6/14,42.86％),parethesia in 5 cases(5/14,35.71％),and seizures,limb paralysis,sphincter dysfunction,ataxia,and vomit were all in 4 cases(4/14,28.57％).Four patients(4/14,28.57％)had a history of upper respiratory tract infection before MOGAD onset.There were 10 patients undergoing cerebrospinal fluid(CSF)test,and 8 of them had abnormal results,including 2 patients(2/10,20％)of increased pressure,8 patients(8/10,80％)of larger WBC count in CSF,and 5 patients(5/10,50％)of elevated total protein in CSF.MRI displayed multiple lesion involvement,and there were 7 cases(7/14,50.00％)in cortical/subcortical white matter,6 cases in brainstem(6/14,42.86％),5 cases in optic nerve(5/14,35.71％),4 cases in spinal cord(4/14,28.57％).The hippocampus,thalamus,basal ganglia,and paraventricular white matter were involved in 3 cases(3/14,21.43％),respectively,and the cerebellum and corpus callosum were in 2 cases(2/14,14.29％),respectively.MRI lesions demonstrated patchy hyperintensity on T2 WI and T2 FLAIR,with patchy,nodular and linear enhancement.Among the 10 patients undergoing visual evoked potential(VEP)test,abnormalities were detected in 9 cases(9/10,90％),and 8(8/10,80％)had bilateral visual pathway abnormalities.Eight patients(8/14,57.14％)experienced relapse and remission course.Both methylprednisolone pulse therapy and immunoglobulin modulation therapy were effective in the acute phase.Five patients with relapsed remission presented a significant reduction in recurrence after immunosuppressants.Conclusion MOGAD is manifested with various clinical features,with vision loss,headache,fever and dizziness more common.MRI lesions of MOGAD involve cerebral cortex,subcortical white matter,brainstem,and optic nerve,etc.Patchy hyperintesive signals are observed on T2WI and T2 FLAIR,and some lesions can be enhanced.Corticosteroid pulse therapy and immunoglobulin therapy show effective treatment in the acute phase,and immunosuppressants in the remission phase can reduce relapse.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

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.