Objective:To explore the relationship between BMI and levels of plasma amino acids and acylcarnitines in Chinese adults.Methods:Based on 2 182 individuals with targeted mass spectrometry metabolomic measurements from the first resurvey of the China Kadoorie Biobank, we assessed the linear and nonlinear associations between BMI and plasma levels of 20 amino acids and 40 acylcarnitines using linear regression models and restricted cubic spline models, and identified BMI-related metabolic pathways. We conducted one-sample Mendelian randomization (MR) with BMI genetic risk scores as the instrumental variable further to explore the potential causal relationships between BMI and 20 amino acids and 40 acylcarnitines, and tested for horizontal pleiotropy using the MR-Egger method.Results:Observational analyses found that BMI was associated with increased plasma levels of 3 branched-chain amino acids (isoleucine, leucine, and valine), 2 aromatic amino acids (phenylalanine and tyrosine), 3 other amino acids (cysteine, glutamate, lysine), and 7 acylcarnitines (C3, C4, C5, C10, C10:1, C14, and C16), and with decreased circulating levels of asparagine, serine, and glycine. Pathway analysis identified 7 BMI-related amino acids metabolic pathways (false discovery rate corrected all P<0.05), including branched-chain amino acids and aromatic amino acids biosynthesis, glutathione metabolism, etc. BMI showed a nonlinear relationship with leucine, valine, and threonine, and a linear relationship with other amino acids and acylcarnitines. One-sample MR analyses revealed that BMI was associated with elevated levels of tyrosine and 4 acylcarnitines [C5-DC(C6-OH), C5-M-DC, C12-DC, and C14], with tyrosine and acylcarnitine C14 positively correlated with BMI in both observational [the β values (95% CIs) were 0.057 (0.044-0.070) and 0.018 (0.005-0.032), respectively] and One-sample MR analyses [the β values (95% CIs) were 0.102 (0.035-0.169) and 0.104 (0.036-0.173), respectively]. The MR analyses of the current study satisfied the 3 core assumptions of instrumental variable. Conclusions:BMI was associated with circulating 11 amino acids and 7 acylcarnitines in Chinese adults, involving several pathways such as branched-chain amino acid and aromatic amino acid metabolism, fatty acid metabolism, and oxidative stress. There may be a causal relationship between BMI and tyrosine and acylcarnitine C14.

Kashin-Beck disease (KBD) is a chronic endemic bone and joint disease, with severe cases of short stature, joint deformities, and significantly reduced quality of life. Its etiology is currently unclear. Matrix metalloproteinases (MMPs) are endopeptidases that can degrade the extracellular matrix of articular cartilage cells, and are closely related to the occurrence and development of bone and joint diseases. At present, some scholars have found that MMPs can cause cartilage damage in KBD patients and promote the progression of KBD, but its specific mechanism of action is still unclear. This article reviews the research progress on the etiology of KBD, MMPs and its related genes, and their relationship with KBD cartilage injury both domestically and internationally. In order to provide theoretical support for in-depth research on the pathogenesis of KBD and to improve and update its treatment methods.

Objectives:To explore the effects of interatrial shunt on cardiac function and clinical prognosis of patients with heart failure with reduced ejection fraction(HFrEF). Methods:This study was a prospective single-arm study.From December 2021 to December 2022,15 consecutive patients with HFrEF from Beijing Anzhen Hospital were enrolled in this study.Interatrial shunt was performed with a D-Shant atrial shunt device.Right heart catheterization was performed before and immediately after device implantation,pulmonary capillary wedge pressure(PCWP),mean right atrial pressure(RAP),interatrial gradient pressure,mean pulmonary artery pressure,total pulmonary resistance(TPR),pulmonary vascular resistance(PVR),cardiac index(CI),and pulmonary/systemic blood flow ratio(Qp/Qs)were measured.Patients were followed-up for 12 months after procedure,changes in cardiac structure and function were evaluated by echocardiography.NYHA classification,6-minute walking distance(6MWD),and Kansas City cardiomyopathy questionnaire(KCCQ)were observed.All-cause mortality and rehospitalization for heart failure served as clinical endpoints. Results:Interatrial shunt procedure was successful in all patients.Compared with preoperative value,PCWP,interatrial gradient pressure,mean pulmonary artery pressure,and TPR were significantly decreased,while Qp/Qs was significantly increased immediately after procedure(all P<0.01).There were no significant changes in RAP,PVR,and CI post procedure(all P>0.05).There were no significant differences in shunt size,shunt velocity,and shunt pressure difference between postoperative immediately and at 12-months follow-up(all P>0.05).At 12 months,left ventricular ejection fraction was significantly higher than baseline level(P<0.05),and there were no significant changes in right atrial diameter and right ventricular fractional area change(both P>0.05).Compared with preoperative status,NYHA classification was improved,KCCQ score was increased,and the number of patients with 6MWD>450 m was increased at 12 months(all P<0.05).N-terminal pro-B-type natriuretic peptide value was significantly decreased at 12 months(P<0.05).No patient died during the 12-months follow-up period,and there were no device-related adverse events.Two patients experienced hospital readmission for heart failure. Conclusions:Implantation of interatrial shunt device could effectively improve hemodynamic parameters in patients with HFrEF and is related to significantly improved cardiac function at 12-months follow-up.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin’s lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton’s tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies.

BACKGROUND: Evidence on the relations of the American Heart Association's ideal cardiovascular health (ICH) with mortality in Asians is sparse, and the interaction between behavioral and medical metrics remained unclear. We aimed to fill the gaps. METHODS: A total of 198,164 participants without cancer and cardiovascular disease (CVD) were included from the China Kadoorie Biobank study (2004-2018), Dongfeng-Tongji cohort (2008-2018), and Kailuan study (2006-2019). Four behaviors (i.e., smoking, physical activity, diet, body mass index) and three medical factors (i.e., blood pressure, blood glucose, and blood lipid) were classified into poor, intermediate, and ideal levels (0, 1, and 2 points), which constituted 8-point behavioral, 6-point medical, and 14-point ICH scores. Results of Cox regression from three cohorts were pooled using random-effects models of meta-analysis. RESULTS: During about 2 million person-years, 20,176 deaths were recorded. After controlling for demographic characteristics and alcohol drinking, hazard ratios (95% confidence intervals) comparing ICH scores of 10-14 vs. 0-6 were 0.52 (0.41-0.67), 0.44 (0.37-0.53), 0.54 (0.45-0.66), and 0.86 (0.64-1.14) for all-cause, CVD, respiratory, and cancer mortality. A higher behavioral or medical score was independently associated with lower all-cause and CVD mortality among the total population and populations with different levels of behavioral or medical health equally, and no interaction was observed. CONCLUSIONS ICH was associated with lower all-cause, CVD, and respiratory mortality among Chinese adults. Both behavioral and medical health should be improved to prevent premature deaths.
Adult ; Humans ; Cardiovascular Diseases/prevention & control* ; East Asian People ; Prospective Studies ; Risk Factors ; Smoking

【Objective】 To establish a digital model of lumbar 4 and lumbar 5 vertebral bodies through three-dimensional imaging technology so as to explore the precise placement of pedicle screws during the lumbar posterior internal fixation operation. 【Methods】 CT scan image data set of lumbar spine included six specimens. Then lumbar modeling was produced using Mimics software， implanting pedicle screws was simulated with the computer to determine the reliability of pedicle screw for herringbone crest method， Weinstein method， and Magerl method. 【Results】 This study included six specimens （4 males and 2 females）， with an average age of 42.83 years. The distance from the right Magerl entry point to the actual entry point of the lumbar 4 vertebrae was significantly greater than that of the left side. The distance from the left herringbone crest entry point of lumbar 4 vertebrae to the actual entry point was significantly greater than Weinstein method and Magerl method （P<0.001 and P<0.001）， and the distance from the right herringbone crest entry point of lumbar 4 vertebrae to the actual entry point was significantly greater than Weinstein method （P=0.003）. Both left and right abduction angles of lumbar 4 vertebrae were true abduction angle >Magerl abduction angle > Weinstein abduction angle > herringbone abduction angle. The distances of true-Weinstein and true-herringbone ridges on the left side of lumbar 5 vertebrae were significantly greater than those on the right side （P=0.002 and P=0.004）， and the Weinstein abduction angle on the right side of lumbar 5 vertebrae was greater than that on the left side （P=0.003）. For the left and right sides of lumbar 5 vertebrae， the distance from herringbone crest entry point to the actual entry point was significantly greater than that of Weinstein method and Magerl method （P<0.001 and P<0.001）， and the distance from the Magerl entry point to the real entry point was significantly greater than that of the Weinstein method. The abduction angle of left and right sides of lumbar 5 vertebrae was as follows： true abduction angle > Magerl abduction angle > Weinstein abduction angle > herringbone abduction angle. 【Conclusion】 Both Weinstein entry point and Magerl entry point for lumbar 4 and lumbar 5 vertebra are close to the real entry point. The Weinstein abduction angle and Magerl abduction angle of lumbar 4 and lumbar 5 vertebrae have minor differences compared with real abduction angle. Therefore， it is recommended that Weinstein method is the preferred choice for lumbar 4 pedicle screw placement， while Weinstein method or Magerl method is the preferred choice for lumbar 5 pedicle screw placement.

【Objective】 Until now, most clinical and basic studies on Kashin-Beck disease (KBD) have focused on the visible deformed extremities, and there is a lack of reports concerning their spinal features, especially for the atlantoaxial joint. The purpose of this study was to determine the prevalence and radiographic features of atlantoaxial dislocation (AAD) in KBD in adult patients. 【Methods】 The prevalence and radiographic features of AAD were determined by the basic information collected, clinical symptoms, and lateral and dynamic plain radiography in 111 KBD patient and 120 non-KBD participants. In the KBD group, AAD and non-AAD patients were compared in age, gender, height, weight, BMI, smoking history, chronic history, disease duration and grade of disease so as to identify the related factors of the occurrence of AAD. 【Results】 Symptoms at the neck or neurological manifestations were present in 17.5% (21/120) in the non-KBD population and 39.6% (44/111) patients with KBD. AAD case was not detected in the non-KBD population, while in 16.2% (18/111) of KBD patients in the endemic area. The prevalence was higher in the KBD patients than in the non-KBD population, and there was a significant difference in the detection rate of AAD between the two groups (χ²=21.10, P<0.001). Plain radiography demonstrated that there were 10 (55.6%) cases with separation of the odontoid process and the other 8 (44.4%) cases with hypoplasia of odontoid process. Anterior AAD was noted in 12 (66.7%) patients and posterior AAD in 6 (33.3%) cases based on the displacement direction, while 16 (88.9%) cases were reducible and 2 (11.1%) cases were irreducible on the basis of the reducibility. Comparing the 93 patients with non-AAD KBD patients and 18 patients with AAD patients, there was no significant difference in age, sex, BMI, history of medical disease or smoking (all P>0.05). There were significant differences in height, weight, disease duration and grade of disease between AAD and non-AAD patients (all P<0.05). 【Conclusion】 KBD can cause the occurrence of atlantoaxial dislocation by inducing separation or hypoplasia of the odontoid process. This research may provide clinical evidence for screening, earlier prevention and treatment of atlantoaxial dislocation in adult KBD patients.

Background:It remains unclear about the association of muscle mass, strength, and quality with death in the general Chinese population of diverse economical and geographical backgrounds. The present study aimed to comprehensively examine such associations across different regions in China.Methods:Based on the China Kadoorie Biobank study, the present study included 23,290 participants who were aged 38 to 88 years and had no prevalent cardiovascular diseases or cancer. Muscle mass and grip strength were measured using calibrated instruments. Arm muscle quality was defined as the ratio of grip strength to arm muscle mass. Low muscle mass, grip strength, and arm muscle quality were defined as the sex-specific lowest quintiles of muscle mass index, grip strength, and arm muscle quality, respectively. Cox proportional hazards models yielded hazard ratios (HRs) and 95% confidence intervals (CIs) for risks of all-cause mortality in relation to muscle mass, strength, and quality.Results:During a median follow-up of 3.98 years, 739 participants died. The HR (95% CI) of all-cause mortality risk was 1.28 (1.08-1.51) for low appendicular muscle mass index, 1.38 (1.16-1.62) for low total muscle mass index, 1.68 (1.41-2.00) for low grip strength, and 1.41 (1.20-1.66) for low arm muscle quality in models adjusted for sociodemographic characteristics, lifestyle factors, and medical histories.Conclusion:Low muscle mass, grip strength, and arm muscle quality are all associated with short-term increased risks of mortality, indicating the importance of maintaining normal muscle mass, strength, and quality for general Chinese adults.

Objective:To investigate the effect and prognostic factors of rituximab-containing chemotherapy regimen in treatment of patients with mantle cell lymphoma (MCL).Methods:The clinical data of 56 patients aged ≤65 years in the First Affiliated Hospital of Soochow University from June 2007 to November 2018 were retrospectively analyzed. Rituximab-containing chemotherapy regimen was used, and the effects of clinical features, treatment regimen and biological indexes on overall survival (OS) and progression-free survival (PFS) were observed.Results:The median age of 56 patients was 57 years old, including 43 males and 13 females. Among these cases, 24 patients received R-CHOP chemotherapy regimen; 29 patients received cytarabine-containing chemotherapy regimen, including R-hyper CVAD/R-MA regimen used in 15 patients and R-CHOP alternating with R-DAHP regimen used in 14 patients; and 3 patients received other treatment regimens. Among 56 patients, 19 patients received autologous hematopoietic stem cell transplantation (ASCT) consolidation therapy. The median OS time was 74 months, 2-year OS rate was 83.8%, 3-year OS rate was 70.9%, 2-year PFS rate was 72.0% and 3-year PFS rate was 49.7%. International prognostic index (IPI) high-risk and receiving ASCT or not during the treatment were independent influencing factors of OS and PFS in MCL patients. The overall response rate (ORR) in cytarabine-containing regimen group was higher compared with that in R-CHOP regimen group (93.1% vs. 83.3%), and there was no statistically significant difference ( χ2=0.465, P=0.495). In addition, there were no significant differences between two groups in both OS ( χ2=0.291, P=0.590) and PFS ( χ2=0.912, P=0.339). ASCT consolidation prolonged the median OS time (72 months vs.124 months, χ2=3.973, P=0.040) and the median PFS time (34 months vs. 90 months, χ2=3.984, P=0.046) in MCL patients achieving remission after induction therapy. Among patients in simplified MCL IPI (sMIPI) score middle-high risk group, compared with those not receiving ASCT, patients receiving ASCT therapy could obtain better OS and PFS (OS: χ2=5.037, P=0.025; PFS: χ2=6.787, P=0.009); among patients of sMIPI score low risk, there were no statistically significant differences in OS and PFS between the group receiving ASCT and not (all P > 0.05). Conclusions:Cytarabine-containing chemotherapy regimen has no predicatively satisfactory value in improving the prognosis and survival for MCL patients. For MCL patients who have achieved remission after reduction therapy and those in sMIPI score middle-high risk group, ASCT consolidation therapy can improve the prognosis and can be taken as the first-line consolidation treatment in young patients.

Objective:To examine the efficacy of haploidentical stem-cell transplantation (haplo-SCT) for patients with refractory relapsed (R/R) non-Hodgkin lymphoma (NHL) by comparing with those contemporaneously undergoing HLA-matched SCT in myeloablative conditioning settings.Methods:Between January 2006 and December 2018, a total of 151 patients undergoing haplo-SCT ( n=81) or HLA-matched SCT ( n=70, sibling or unrelated) were enrolled. Median age of alloSCT was 30(5-59) years. And 150 patients received myeloablative conditioning (MAC) consisting of total body irradiation (12 Gy) plus cyclophosphamide or busulfan plus cyclophosphamide. Only one case had reduced intensity conditioning (RIC) with R-FBA (fludarabine, busulfan & cytarabina). It was followed by an infusion of granulocyte-colony stimulating factor-primed bone marrow (G-BM) and/or peripheral blood stem cells without in vitro T cell depletion. In haplo-SCT and HLA-matched unrelated donor for SCT, GVHD prophylaxis consisted of antithymocyte globulin, cyclosporine A, mycophenolate mofetil and a short course of methotrexate. Clinical efficacy, hematopoietic reconstitution and transplant-related complications were retrospectively analyzed. Results:Among them, 146(96%) patients engrafted with a median time to neutrophil and platelet recovery of 12 and 15 days respectively. During a median follow-up period of 19 months, 66 of them survived (43.7%) and 67 (44.4%) died (39 disease recurrence, 27 transplantation-related mortality). Between haplo-SCT and HLA-matched SCT groups, progression-free survival (PFS) rate was 49.4% and 50.5% ( P=0.577); overall survival (OS) rate 56.7% and 57.4% respectively ( P=0.963). The cumulative incidences of relapse (CIR) were 36.6% and 37.7% ( P=0.836) and those of cumulative incidences of non-relapse mortality (NRM) 22.0% and 24.7% ( P=0.530). And the cumulative incidences of chronic GVHD were 42.3% and 39.6% ( P=0.46) respectively. Conclusions:No inter-group difference exists in each major HSCT endpoint. Multivariate analysis reveals that occurrence of grade Ⅲ-Ⅳ aGVHD has a significantly worse prognosis. And primary chemorefractoriness is a strongest relapsing factor.