Metabolic changes are an important characteristic of vascular complications in diabetes. The accumulation of lactate in the microenvironment can promote vascular smooth muscle cell (VSMC) calcification in diabetes, although the specific mechanism remains to be fully elucidated. In this study, we explored the characteristics of lactylation in diabetic arterial calcification and the underlying molecular mechanism. We found that in high-glucose calcified VSMC, the overall lactylation level was significantly increased. Mass spectrometry analysis revealed a significant up-regulation of H3 histone lactylation. After site-specific point-mutation at K18 to simulate the delactylation modification, VSMC calcification was significantly reduced. Through a combination of H3K18la ChIP-seq, RNA-seq, H3K18la ChIP-qPCR, and point-mutation experiments, we confirmed that H3K18la can up-regulate CHI3L1. CHI3L1 knockout significantly alleviated VSMC osteogenic phenotype transformation and mouse arterial calcification. RNA-seq analysis of the downstream molecular signaling showed that CHI3L1 activates the IL-13-IL-13Ra2-JAK1-STAT3 pathway. Targeted inhibition of IL-13Ra2 reduced VSMC calcification. We conclude that in a diabetic calcification environment, the H3 histone K18 site undergoes lactylation modification in VSMCs, upregulating CHI3L1, which, in turn, regulates the IL-13-IL-13Ra2-JAK1-STAT3 signaling pathway, ultimately exacerbating arterial calcification. Our study elucidates the epigenetic mechanism by which lactate promotes arterial calcification in diabetes.

Our study aimed to develop and validate the Maladaptive Eating Behavior Questionnaire after Metabolic and Bariatric Surgery (MEBQMBS). Based on the conceptual framework of maladaptive eating behavior after metabolic and bariatric surgery (MBS), literature review, focus group discussion, and a pilot study, the initial questionnaire was developed. The questionnaire was administered to 457 patients who had undergone MBS at a tertiary hospital in Jiangsu Province, China. Its validity and reliability were evaluated using psychometric analyses. The initial questionnaire comprised 90 items. After stepwise removal of items with inadequate factor loadings, 53 items were retained, accounting for 69.54

Abstract Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis. Existing treatments for RA have serious side effects. Corosolic acid (CRA) is a natural pentacyclic triterpenoid compound with anti-inflammatory potential. However, the effect of CRA on inflammation, its possible mechanism of action, and potential therapeutic effect on RA are not well understood. This study explored the CRA mechanism of treatment action on RA by evaluating the NF-κB/PI3K/AKT signaling pathway in vitro and in vivo. In vitro, fibroblast like synovial cells (FLS) from collagen induced arthritis (CIA) rats were assessed. ELISA, western blot, and immunofluorescence techniques demonstrated CRA (6 µg/mL) to significantly inhibit FLS secretion of TNF-α, IL-1β, and IL-6, as well as downregulate the phosphorylation of NF-κB and PI3K/AKT pathways. Inhibition experiments demonstrated that NF-κB activation was upstream of PI3K/AKT activation. In vivo, after 21 days of oral administration of CRA (10 mg/kg) to CIA rats, the arthritis score, organ index, and serum inflammatory factor levels were significantly decreased. Histopathologic analysis and Micro-CT showed that CRA reduced synovial hyperplasia and bone erosion. These results indicated that CRA exerted anti-inflammatory effects by inhibition of the NF-κB/PI3K/AKT signaling pathway, providing a potential new treatment strategy for RA patients.

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease with limited therapeutic options, and current therapies are often associated with considerable adverse effects. Traditional Chinese medicinal plants such as Cirsium japonicum contain luteolin-7-O-rutinoside (lut-7-O-rutin), a flavonoid with reported anti-inflammatory activity.Aim of the studyLut-7-O-rutin is a flavonoid compound found in various medicinal plants. This study aimed to investigate the therapeutic effects of lut-7-O-rutin on RA and elucidate the underlying mechanisms using both in vitro and in vivo models, with a particular focus on the phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-κB (PI3K/AKT/NF-κB) and cell cycle signaling pathways.Materials and methodsIn vitro experiments, including ELISA, Western blotting, and immunofluorescence assays, were performed to evaluate the anti-inflammatory effects of lut-7-O-rutin on the IL-1β-induced inflammatory response in fibroblast-like synoviocytes (FLSs) derived from rat knee synovium. The effects of lut-7-O-rutin on the PI3K/AKT/NF-κB and cell cycle signaling pathways were also examined. In vivo experiments were conducted to assess the therapeutic effects of lut-7-O-rutin administered by gastric gavage in collagen-induced arthritis (CIA) rats.ResultsLut-7-O-rutin at 3.75 μg/mL significantly reduced the levels of TNF-α, IL-6, and COX-2 in IL-1β-induced FLSs. It also decreased the phosphorylation levels of key components of the PI3K/AKT/NF-κB signaling pathway, thereby attenuating inflammation. In addition, lut-7-O-rutin downregulated the expression of the cell cycle-associated proteins CDK4 and CCND and inhibited FLS proliferation. In vivo, 21 days of lut-7-O-rutin administration by gastric gavage resulted in a significant reduction in arthritis scores, organ indices, and serum inflammatory mediator levels in CIA rats. Histopathological analysis showed that lut-7-O-rutin alleviated synovial inflammation, synovial hyperplasia, and bone erosion. Immunohistochemistry (IHC) analysis further showed that lut-7-O-rutin significantly inhibited the expression of key proteins in the PI3K/AKT and cell cycle signaling pathways.ConclusionThese findings demonstrate that lut-7-O-rutin alleviates joint inflammation and synovial hyperplasia in RA may be mediated through inhibiting the PI3K/AKT/NF-κB signaling pathway and downregulating cell cycle-associated proteins, highlighting its potential as a therapeutic agent for RA.

Introduction: It was challenging to accurately measure the maladaptive eating behavior after bariatric surgery. Our study was aimed to develop and validate the Maladaptive Eating Behavior Questionnaire after Bariatric Surgery (MEBQBS). Methods: The initial questionnaire was developed through concept clarification, literature review, focus group discussion, and pilot study. Its reliability and validity were also examined in 457 patients after bariatric surgery. Results: The final 53-item MEBQBS comprised 8 factors, including emotional eating (negative emotion, positive emotion sub-domain), grazing behavior, food craving (positive outcome expectancy, emotional craving, preoccupation with food sub-domain), uncontrolled eating (cognition, behavior sub-domain). Exploratory factor analysis revealed a cumulative variance contribution rate of 69.54%. Confirmatory factor analysis revealed that the indices of c 2 /df, goodness-of fit index, normed fit index, incremental fit index, Tucker-Lewis index, confirmatory fit index and root mean-square error of approximation were 1.868, 0.804, 0.884, 0.943, 0.934, 0.942, and 0.050, indicating the model fit well. Additionally, significant correlations were observed between the total score of MEBQBS and the Three-Factor Eating Questionnaire-R21 ( P <0.05). The Cronbach's α and Guttman split-half coefficient of MEBQBS were 0.966 and 0.790, respectively. Conclusion: The MEBQBS is a valid and reliable instrument for identifying unhealthy eating behavior of patients after bariatric surgery, offering potential utility in evaluating the effect of tailored interventions.

BACKGROUND:Sleeve gastrectomy plus jejunojejunal bypass (SG + JJB) is increasingly accepted as a surgical treatment for severe obesity. However, data on the long-term results of this procedure are limited, and studies comparing it with other bariatric procedures are scarce. OBJECTIVES:The objective of this study was to compare 5-year outcomes following SG + JJB and Roux-en-Y gastric bypass (RYGB). SETTING:The study was conducted at University Hospital, P.R. China. METHODS:We compared all SG + JJB and RYGB cases handled at our institution between June 2015 and December 2018. We included 329 patients: 167 underwent SG + JJB, and 162 underwent RYGB. All patients completed assessments at presurgery and 5 years after surgery. The data were analyzed using the χ2 test and independent sample t test, with P < .05 denoting statistical significance. RESULTS:There was no statistically significant difference between the SG + JJB and RYGB groups in terms of weight loss or remission of most associated metabolic complications, such as hypertension, type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD), hyperuricemia, and obstructive sleep apnea syndrome (OSAS), although the remission rate of hyperlipidemia was higher in the RYGB group (P < .01). Compared with RYGB, SG + JJB results in lower incidences of dumping syndrome, cholelithiasis, anemia, and gastrointestinal dysfunction (P < .01), and a higher rate of gastroesophageal reflux disease (GERD) (P < .01). CONCLUSIONS:SG + JJB results in sustained weight loss and co-morbidity control after 5 years, yielding a low incidence of adverse events. Like RYGB, SG + JJB seems to be a safe and effective surgical procedure for treating obesity and related diseases.

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Metabolic changes are an important characteristic of vascular complications in diabetes. The accumulation of lactate in the microenvironment can promote VSMC calcification in diabetes, although the specific mechanism remains to be fully elucidated. Lactate participates in lactylation as a substrate and plays a role in many diseases. In this study, we explored the characteristics of lactylation in diabetic arterial calcification and the underlying molecular mechanism. We found that in high-glucose calcified VSMC, the overall lactylation level was significantly increased. Mass spectrometry analysis revealed significant upregulation of H3 histone lactylation. After site-specific point-mutation (lysine-to-arginine) at K18 to simulate the delactylation modification, VSMC calcification was significantly reduced. Through a combination of H3K18la ChIP-seq, RNA-seq, H3K18la ChIP-qPCR and point-mutation experiments, we confirmed that H3K18la can upregulate CHI3L1. We generated CHI3L1 knockdown VSMCs and constructed a mouse model of diabetic arterial calcification by knockout of the whole CHI3L1 gene. CHI3L1 knockout significantly alleviated VSMC osteogenic phenotype transformation and mouse arterial calcification. RNA-seq analysis of the downstream molecular signaling showed that CHI3L1 activates the IL-13-IL-13Ra2-JAK1-STAT3 pathway. Targeted inhibition of IL-13Ra2 reduced VSMC calcification. We conclude that in a diabetic calcification environment, the H3 histone K18 site undergoes lactylation modification in VSMCs, upregulating CHI3L1, which in turn regulates the IL-13-IL-13Ra2-JAK1-STAT3 signaling pathway, ultimately exacerbating arterial calcification. Our study elucidates the epigenetic mechanism by which lactate promotes arterial calcification in diabetes.Funding: This work was supported by the Changzhou Municipal Health Commission (CQ20210122), Project of Changzhou Medical Center of Nanjing Medical University (CZKYCMCB202209), and China Postdoctoral Science Foundation (2023M730372).Declaration of Interest: All authors declared that they have no conflict of interest.Ethical Approval: All in vivo experiments were approved by the Animal Care and Research Committee of Nanjing Medical University (China). All animal procedures were performed in accordance with the Guidelines of Animal Experiments from the Committee of Medical Ethics, the National Health Department of China (1998).

To explore whether Fengshi Liuhe Decoction (FLD) alleviates rheumatoid arthritis (RA) via the Fzd6/NF-κB signaling axis. We used real-time quantitative PCR (qPCR) and western blotting (WB) to determine the genes of the frizzled (Fzd) protein 1- Fzd protein 10 that are significantly differentially expressed between normal rat f fibroblast-like synoviocyte (FLS) and collagen II-induced arthritis (CIA) rat FLS. Next, we used enzyme-linked immunosorbent assay (ELISA) to evaluate the levels of inflammatory factors in cell culture supernatant to determine the ability of FLD to ameliorate RA. Finally, we employed WB to detect the key gene expression in protein levels of the Fzd6/NF-κB signaling axis among normal rat FLS, CIA rat FLS, and FLD-treated CIA rat FLS. Our results showed that Fzd6 expression was significantly higher in CIA rat FLS at both the mRNA and protein levels than in normal rat FLS. FLD was found to downregulate Fzd6 and inflammatory factors, including COX-2, IL-8, and TNF-α, at both the mRNA and protein levels. FLD was also found to downregulate the total protein levels of Fzd6 and the NF-κB signaling pathway key gene phosphorylation of p-p65/p65 and p-IκBα/IκBα. Moreover, FLD inhibited the nuclear translocation of NF-κB p65 in CIA rat FLS. FLD can alleviate inflammation of CIA rat FLS via the Fzd6/NF-κB signaling axis.

Introduction To explore if digital protractor could guide the anteversion of acetabular cup during primary THA and make it consistent with preoperative. Methods We retrospectively reviewed 172 cases of primary THA with direct anterior approach (DAA) over 2 years. The anteversion of acetabular cup were measured from computed tomography (CT) scan preoperative and de-identified plain radiographs postoperative by two blinded investigators who were not involved in the surgery. The effect of the digital protractor on the anteversion was determined using regression analysis. Results The mean anteversion for the THAs in digital protractor group was 15.5°and 21.4°in control group ( P < 0.01). The mean anteversion bias for the THAs in digital protractor group was 1.59° and 6.63° in control group ( P < 0.01).Regression analysis identified a 10.7% difference in anteversion due to the use of digital protractor ( P < 0.01), and THAs performed without digital protractor were six times more likely to result in anteversion of > 25°. The correlation coefficient for the interobserver reliability of the measurement of the two investigators was 0.94. Conclusion The digital protractor is a practical tool in the DAA for THA to determine the anteversion of the acetabular prosthesis.

目的 探讨基于云康复平台的全周期管理对减重患者手术效果的影响.方法 采用便利抽样法,选取2020年2月-2021年9月在南京医科大学第一附属医院行减重手术的125例患者为研究对象,采用随机数字表法,根据纳排及脱落标准分为对照组(61例)和观察组(64例).对照组予以常规健康宣教、治疗和随访;观察组患者在此基础上,应用云康复平台在手术全周期实施管理,干预时间为预约手术起至术后6个月.采用生物电阻抗法在基线和术后测量患者的身体成分指标,包括体重、BMI、体脂率和骨骼肌含量,收集手术相关指标包括:住院时间、住院费用、术后并发症和术前合并症缓解情况,以综合评估手术效果.结果 术后6个月时,观察组患者的体重、BMI、体脂率和骨骼肌含量相较于对照组均显著下降,差异有统计学意义(P＜0.05),住院时间和住院费用显著降低(P＜0.05),观察组合并症缓解情况均显著优于对照组(P＜0.05).结论 云康复平台的全周期管理能显著改善减重代谢手术患者的临床结局.

爱乔膝关节导航系统(I-join knee position assistive system,IKPAS)是一种便携式导航系统,可通过传感器技术在术中辅助医生进行精确地下肢力线的测量及截骨定位.相比传统的全膝关节置换手术,IKPAS可以通过内置的加速度计和陀螺仪提供个体化、精确化的测量数据,使得截骨更加准确和微创,从而获得更稳定的术后下肢力线及假体位置;同时,IKPAS不开髓,创伤小,使用便捷,可以有效减少术后并发症及翻修率.

A. sinensis polysaccharide (ASP), one of the effective components of A. sinensis, has been used to treat inflammatory diseases in China. However, its effect on rheumatoid arthritis (RA) is unknown. The purpose of this study was to explore the anti-inflammatory effects and mechanisms of ASP on RA using a rat model of collagen-induced arthritis (CIA). For evaluation of the therapeutic effects of ASP in vitro, the CIA model was used. Our study showed that ASP (100 and 200 mu g/mL) dose-dependently inhibited tumor necrosis factor (TNF)-alpha-induced (10 ng/mL) proliferation, migration, and invasion of fibroblast-like synovial (FLS) cells, promoted apoptosis, and arrested the cell cycle in G0/G1 phase (P < 0.05). In vivo, ASP increased body weight in CIA rats while decreasing paw swelling, arthritis score, and synovial tissue proliferation (P < 0.05). ASP also reduced the expression of pro-inflammatory cytokines (interleukin (IL) -6, IL-1 beta, inducible nitric oxide synthetase (iNOS), matrix metalloproteinase (MMP)-1 and MMP-3) (P < 0.05). ASP inhibited the phosphorylation of JAK2/STAT3 and MAPK signaling pathway components (P < 0.05) induced by TNF-alpha in CIA-FLS cells. Using JAK and p38 inhibitors, we found that JAK2/STAT3 might be an upstream pathway of MAPK. In conclusion, our study investigated the therapeutic effects of ASP in RA in vitro and in vivo. Our research suggests that ASP can inhibit the invasiveness and secretion of inflammatory cytokines of FLS cells in CIA rats via JAK2/STAT3 and MAPK signaling. Elucidation of the underlying mechanism will provide a theoretical basis for clinical application of ASP.

Purpose: Metabolic bariatric surgery (MBS) is increasingly accepted as a treatment for severely obese adolescents. However, its long-term efficacy and safety are not well characterized, particularly in the Eastern Asian population. We aimed to explore the long-term effects of MBS on Chinese adolescents with severe obesity.Methods: A total of 44 obese adolescents (<= 18 years old) underwent MBS at our institution from May 2011 to May 2017. A matched nonsurgical control group, including 43 patients, was recruited from lifestyle modification programs in the same period. All patients completed assessments at presurgery/baseline and five years after surgery. The data were collected and analyzed using the chi(2) test and an independent sample t-test.Results: Comparing the surgical and control groups revealed that the surgical patients showed significant weight loss and improvement in comorbidities, while the nonsurgical patients showed a trend of weight gain and increased comorbidities (p < .05). Furthermore, the surgical patients had a higher composite physical quality of life (as determined by the Short Form-36 questionnaire). On the other hand, the patients who underwent MBS had a higher risk of malnutrition.Discussion: Compared with nonsurgical patients, severely obese adolescents who undergo MBS exhibit more effective long-term weight loss, remission of comorbidities, and improved quality of life. Furthermore, more attention should be paid to helping adolescents avoid malnutrition after they undergo MBS.

BACKGROUND CONTEXT: In recent years, unilateral biportal endoscopic lumbar interbody fusion (ULIF) has been more and more favored by spinal surgeons because of its advantages of low trauma, rapid recovery, high fusion rate and fewer complications.PURPOSE: To compare the clinical effects of ULIF with those of conventional open posterior lumbar interbody fusion (PLIF).STUDY DESIGN: Prospective case control study.PATIENT SAMPLE: Twenty-seven patients treated by ULIF and thirty-three patients treated by PLIF.OUTCOME MEASURES: The preoperative baseline and surgical technique-related outcomes (mean operation time, blood loss during operation, postoperative drainage, and postoperative hospital stay) were compared between the two groups. The clinical status of the two groups before and after surgery were also compared: visual analogue scale (VAS) score of the legs and back, Japanese Orthopedic Association (JOA) score and Oswestry Disability Index (ODI). The clinical laboratory indexes of the two groups before and after the operation were compared: C-reactive protein (CRP), erythrocyte sedi-mentation rate (ESR), creatine phosphokinase (CPK), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), as well as the incidence of complications, such as dural tear, nerve root injury and infection.METHODS: Adult patients who underwent L3-S1 single level lumbar interbody fusion were included in the study. They were divided into a PLIF group and a ULIF group according to the type of surgery. This study comprised 60 cases: 27 cases in the ULIF group and thirty-three cases in the PLIF group.RESULTS: There was no significant difference in preoperative baseline between the two groups. The ULIF group experienced less blood loss, postoperative drainage and a shorter postoperative hospital stay than the PLIF group; however the ULIF group required a longer operation time than the PLIF group (p<.05). CRP, ESR, CPK, IL-6, and TNF-a levels of the PLIF group were all sig-nificantly higher than those of the ULIF group 5 days after surgery (p<.05). The improvements in the VAS scores for back pain, VAS scores for leg pain and JOA score in the ULIF group were all significantly better than those in the PLIF group at 5 days after surgery (p<.05). There was no sig-nificant difference in fusion rate at 6 months between the 2 groups (p>.05).CONCLUSIONS: This study showed that ULIF and PLIF were both effective surgical techniques for lumbar interbody fusion. However, ULIF caused less bleeding, reduced inflammatory reaction, less tissue damage and faster postoperative recovery compared with PLIF. Both long-term follow-up and larger clinical studies are needed to validate the clinical and radiological results of this surgery.(c) 2022 Elsevier Inc. All rights reserved.

目的 比较单侧双通道内镜技术(unilateral biportal endoscopy,UBE)和开放式椎板切除术(open laminectomy,OL)治疗腰椎管狭窄症(lumbar spinal stenosis,LSS)的安全性和有效性.方法 收集2020 年 7 月—2022 年 7 月在我院治疗的 69 例诊断为LSS的患者,其中 32 例接受UBE手术治疗,37 例接受OL手术治疗.比较UBE组和OL组患者的术前基线资料、术前和术后的临床和实验室指标、随访期间的临床疗效指标,以及并发症的发生率等.结果 两组手术方式的术前基线、平均手术时间、平均随访时间,差异无统计学意义(P>0.05).但是,UBE组患者的血红蛋白下降量、术后引流量、平均住院时间、术后实验室指标均显著低于OL组,两组差异有统计学意义(P<0.05).此外,UBE组术后第 3 天腰痛和腿痛的视觉模拟评分(visual analogue score,VAS)显著降低(P<0.05),术后 3 d和 1 个月日本骨科协会(Japanese Orthopedics Association,JOA)评分显著降低,以及术后 1 个月功能障碍指数(oswestry disability index,ODI)显著降低(P<0.05).术后 3 个月和 6 个月的VAS、JOA评分、ODI指数均无显著性差异(P>0.05).结论 这项研究表明两组手术方式都能获得满意的治疗效果;但是,UBE组具有诸多优势,包括减少组织损伤、术后炎症反应较轻、术后早期疼痛较轻、功能恢复较快,但两者远期临床疗效相近.

Mutations in MC4R are the most common genetic cause of obesity. In the reported Chinese morbid obesity cohort, 10 out of 59 harbor six MC4R variants, including Y35C, T53I, V103I, R165W, G233S, and C277X, among which V103I has a relatively high frequency, while other five variants are rare in the population. The prevalence of MC4R carriers in Chinese morbid obese patients (body mass index ≥ 45 kg m −2 ) is detected as 16.9% in this study. R165W and C277X are loss‐of‐function variants. The patient with R165W achieves excess weight loss (%EWL) as high as 20.6% and 50.3% at 1 and 8 months after surgery, respectively. G233S is reported for the first time in Asia obese population. The patient harboring G233S has a %EWL as 23.3% one month postsurgery. It is concluded that morbid obese patients with rare MC4R variants can benefit from metabolic surgery. More importantly, the choice of surgery procedure and MC4R variant should be taken into consideration for personalized treatment. In the future, a larger size cohort, accompanied with regular and longer follow‐up, would be helpful.

复发性腰椎间盘突出症是腰椎间盘突出症术后常见的并发症.后路椎间融合术能够彻底地摘除髓核组织,解除压迫,使黏连的神经根有效松解,融合手术同时可以通过使用cage撑开责任椎间隙,恢复腰椎生理曲度和椎间的高度,使得手术节段更符合生物力学要求,减缓腰椎退变的进程,有效改善患者的生存质量.

Despite recent advances, the poor outcomes in osteosarcoma suggest that novel therapeutic targets are needed. Karyopherin alpha 2 (KPNA2) has been identified as a novel oncogene in many cancers. However, the function of KPNA2 in osteosarcoma and its relative mechanisms remain unclear. Herein, we reported that KPNA2 was highly expressed in osteosarcoma, which contributed to poor survival of patients. Knockdown of KPNA2 significantly suppressed osteosarcoma growth and metastasis in vitro and in vivo. Hedgehog/GLI1 was identified as the key effector pathway of KPNA2 in the study. Mechanistically, KPNA2 acts as a nuclear–cytoplasmic shuttle vehicle to transport c-Myc into the nucleus, where c-Myc binds to the promoter of GLI1 to trigger its expression. Besides, c-Myc can also transcriptionally regulate the expression of KPNA2, thus providing a positive feedback effect to amplify the pro-cancer signal further. In summary, our study revealed that KPNA2 promoted the growth and metastasis of osteosarcoma in a c-Myc-dependent manner via the hedgehog/GLI1 signaling pathway. Targeting KPNA2/c-Myc/GLI1 signal axis might provide a potential therapeutic target for the treatment of osteosarcoma.