BACKGROUND:The exact pathogenesis of temporomandibular joint osteoarthritis is currently unclear.Traditional clinical treatment strategies for temporomandibular joint osteoarthritis are symptomatic treatments such as pain relief and reduction of inflammation,which can stop the progression of the disease to a certain degree but cannot reverse the destruction of the cartilage.Cartilage degeneration,as one of the most prominent pathologic features in the development of temporomandibular joint osteoarthritis,has been the subject of an increasing number of studies that focus on its pathogenesis.Consequently,we hope to provide an ideal radical solution for the regeneration of the temporomandibular joint.OBJECTIVE:To review the progress of research on cartilage degeneration in temporomandibular joint osteoarthritis.METHODS:The search terms were"temporomandibular joint osteoarthritis,degradation of cartilage matrix,synovitis,oxidative stress,chondrocyte hypertrophy,chondrocyte apoptosis,ferroptosis,autophagy,angiogenesis,extracellular vesicles"in Chinese and English.Literature search was conducted in PubMed database and CNKI,and the time limit for the search was from January 2004 to October 2024.Screening was performed by analyzing and reading the literature,and according to the inclusion and exclusion criteria,81 papers were finally included for review.RESULTS AND CONCLUSION:(1)Increased secretion of cartilage matrix degrading enzymes causes degradation of the cartilage matrix,leading to cartilage degeneration.(2)Synovitis promotes cartilage degeneration through macrophage M1-type polarization and production of inflammatory mediators.(3)Oxidative stress promotes cartilage degeneration by exacerbating the inflammatory response through overproduction of reactive oxygen species.(4)Chondrocyte phenotypic changes and death lead to the decrease of cartilage matrix synthesis,resulting in cartilage degeneration.(5)Blood vessels of subchondral bone penetrate the calcified cartilage layer to reach the superficial cartilage layer,which destroys the cartilage structure and leads to cartilage degeneration.(6)Bioactive substances carried by serum-derived extracellular vesicles in inflammatory states also promote cartilage degeneration in temporomandibular joint osteoarthritis.

Renal Fanconi syndrome (FS) is a rare renal manifestation of primary Sjögren's syndrome (pSS). This study aims to analyze the clinical and prognostic characteristics of patients with pSS-associated renal FS (pSS-FS) and provide insights for clinical management.

OBJECTIVE To evaluate the cost-effectiveness of cefiderocol versus best available therapy （BAT） or standard-of- care （SOC） for the treatment of confirmed or suspected carbapenem-resistant Gram-negative bacterial （CRGNB） serious infections from the perspective of the Chinese healthcare system， and to explore its reasonable pricing. METHODS A decision tree model was constructed based on data from two phase Ⅲ clinical trials （CREDIBLE-CR and GAME CHANGER） to simulate the cost- effectiveness of cefiderocol in two scenarios： salvage therapy for confirmed CRGNB infection （scenario 1） and empirical therapy for suspected CRGNB infection （scenario 2）. The primary outcome measure was the incremental cost-effectiveness ratio （ICER）. The willingness-to-pay （WTP） was set at 1 to 3 times China’s per capita GDP in 2024. To verify the robustness of the results， one- way and probabilistic sensitivity analyses were conducted， and based on these， a reasonable price range for cefiderocol in the Chinese market was explored. RESULTS The results for scenario 1 showed that the clinical cure rate in the cefiderocol group was higher than that in the BAT group （47.50% vs. 34.21%）， but its ICER was 415 065.03 yuan per cured case， exceeding three times China’s GDP per capita. Scenario 2 revealed that the ICER for cefiderocol relative to SOC was as high as 1 362 446.16 yuan per cured case， far exceeding the WTP. Sensitivity analysis indicated that the treatment duration and price of cefiderocol were key factors affecting its cost-effectiveness. In the two scenarios described above， the unit price of cefiderocol must fall below 683.47 and 242.00 yuan/g， respectively， to be considered cost-effective. CONCLUSIONS Based on the current market price， cefiderocol lacks sufficient cost-effectiveness for treating confirmed or suspected CRGNB serious infections within China’s healthcare system. To improve its accessibility， price negotiations or a tiered medical insurance payment strategy are required.

BACKGROUND:The exact pathogenesis of temporomandibular joint osteoarthritis is currently unclear.Traditional clinical treatment strategies for temporomandibular joint osteoarthritis are symptomatic treatments such as pain relief and reduction of inflammation,which can stop the progression of the disease to a certain degree but cannot reverse the destruction of the cartilage.Cartilage degeneration,as one of the most prominent pathologic features in the development of temporomandibular joint osteoarthritis,has been the subject of an increasing number of studies that focus on its pathogenesis.Consequently,we hope to provide an ideal radical solution for the regeneration of the temporomandibular joint.OBJECTIVE:To review the progress of research on cartilage degeneration in temporomandibular joint osteoarthritis.METHODS:The search terms were"temporomandibular joint osteoarthritis,degradation of cartilage matrix,synovitis,oxidative stress,chondrocyte hypertrophy,chondrocyte apoptosis,ferroptosis,autophagy,angiogenesis,extracellular vesicles"in Chinese and English.Literature search was conducted in PubMed database and CNKI,and the time limit for the search was from January 2004 to October 2024.Screening was performed by analyzing and reading the literature,and according to the inclusion and exclusion criteria,81 papers were finally included for review.RESULTS AND CONCLUSION:(1)Increased secretion of cartilage matrix degrading enzymes causes degradation of the cartilage matrix,leading to cartilage degeneration.(2)Synovitis promotes cartilage degeneration through macrophage M1-type polarization and production of inflammatory mediators.(3)Oxidative stress promotes cartilage degeneration by exacerbating the inflammatory response through overproduction of reactive oxygen species.(4)Chondrocyte phenotypic changes and death lead to the decrease of cartilage matrix synthesis,resulting in cartilage degeneration.(5)Blood vessels of subchondral bone penetrate the calcified cartilage layer to reach the superficial cartilage layer,which destroys the cartilage structure and leads to cartilage degeneration.(6)Bioactive substances carried by serum-derived extracellular vesicles in inflammatory states also promote cartilage degeneration in temporomandibular joint osteoarthritis.

ObjectiveTo investigate the associations of multiple glycolipid metabolic indicators and their cumulative abnormality burden with incident colorectal cancer risk in a general population-based prospective cohort, and to examine the mediating role of glycolipid metabolic abnormalities in the relationships between smoking, alcohol consumption, physical activity, and colorectal cancer incidence. MethodsA total of 17 897 eligible participants recruited from the Taizhou Cohort between 2011 and 2014 were included. Cox proportional hazards regression models were used to assess the associations of conventional and derived glycolipid indicators, as well as a glycolipid abnormality index constructed from total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and insulin, with incident colorectal cancer risk. Restricted cubic spline models were applied to evaluate dose-response relationships for major indicators. Receiver operating characteristic curves were generated to compare predictive performance across indicators. Mediation analyses were conducted to assess the mediating effects of the glycolipid abnormality index on the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence. ResultsDuring a median follow-up of 11.2 years, 102 incident colorectal cancer cases were identified, with an incidence density of 51.2 per 100 000 person-years. After adjustment for potential confounders, Cox proportional hazards regression analyses showed that decreased high-density lipoprotein cholesterol was associated with a 1.74-fold higher risk of colorectal cancer (HR=1.74, 95%CI: 1.03‒2.95), elevated low-density lipoprotein cholesterol was associated with a 1.78-fold higher risk (HR=1.78, 95%CI: 1.05‒3.02), and abnormal fasting plasma glucose was associated with a 1.86-fold higher risk (HR=1.86, 95%CI: 1.15‒3.02). Triglycerides and fasting plasma glucose showed an approximately linear increasing association with colorectal cancer risk in multivariable restricted cubic spline models. The glycolipid abnormality index showed a clear gradient association with colorectal cancer risk; participants with three or more abnormal indicators had a 3.08-fold higher risk than those without abnormalities (HR=3.08, 95%CI: 1.60‒5.92). The area under the curve was 0.795, higher than that of individual glycolipid indicators and other combined indices, and gender-stratified analyses showed generally consistent patterns. Glycolipid metabolic abnormalities partially mediated the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence, with mediation proportions of 8.33%, 9.45%, and 9.04%, respectively. ConclusionGlycolipid metabolic abnormalities are associated with an increased risk of incident colorectal cancer. The glycolipid abnormality index shows an increasing relationship with colorectal cancer risk and demonstrates better discrimination, and it partially mediates the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence in the overall population.

The plants of the genus Caragana Fabr. are desert plants of the Leguminosae family, which are widely used in traditional ethnomedicine, with the effects of nourishing Yin and nourishing blood, dispelling wind and removing dampness, clearing heat and detoxifying toxins. The anti-inflammatory effect of Caragana Fabr. has attracted much attention, the research on the related mechanism has made some progress, but it lacks systematic collation. By summarising the anti-inflammatory effects of the active ingredients of Caragana Fabr., the authors found that they have good anti-inflammatory activities on different inflammatory cell models in vitro, and have good improvement effects on rheumatoid arthritis, colitis, complex nephritis, and acute lung injury and other disease models. The anti-inflammatory effects of the active components of this genus mainly include the reduction of the levels of a variety of pro-inflammatory factors, and the signalling pathways involved mainly include TLR4/NF-κB, TLR4/MAPK, TLR4/NF-κB/IRF3, JAK/STAT-1, ERK/STAT-1 and so on. Therefore, the paper mainly reviews the research progress on the anti-inflammatory effects and mechanisms of the Caragana Fabr. plants and their active components according to disease types, with a view to providing reference for the in-depth study of their anti-inflammatory activities and the development of new products with related functions.

Fecal microbiota transplantation (FMT) technology originated in China during the Eastern Jin Dynasty and has rapidly developed over the past two decades, becoming a primary method for studying the causal relationship between gut microbiota and the occurrence and progression of diseases. At the same time, the therapeutic effects of FMT in the field of gastrointestinal diseases have gained widespread recognition and are gradually expanding into other disease areas. The FMT procedure is relatively complex, and there is currently no standardized method; its success is influenced by various factors, including the donor, recipient, processing of the fecal material, and the method of implantation. Given the increasingly recognized relationship between gut microbiota and various diseases, FMT has become a research hotspot in both scientific studies and clinical applications, achieving a series of significant advancements. To help researchers better understand this technology, this paper will outline the development history of FMT, summarize common operational methods in research and clinical settings, review its application progress, and look forward to future development directions.

BACKGROUND: Diabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot. METHODS: Datasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness. RESULTS: In total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm). CONCLUSIONS S100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.
Calgranulin B/therapeutic use* ; Diabetic Foot/metabolism* ; Humans ; Datasets as Topic ; Computational Biology ; Mice, Inbred C57BL ; Animals ; Mice ; Protein Interaction Maps ; Immunohistochemistry

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male