ObjectiveTo investigate the difference in the risk of cardiovascular diseases between patients with different subtypes of non-alcoholic fatty liver disease （NAFLD） from the perspective of metabolism， since cardiovascular events induced by metabolic disorders are the leading cause of death in NAFLD. MethodsThe cluster sampling method was used to conduct a multicenter cross-sectional study among three representative hospitals in Pudong New Area of Shanghai， China. A total of 37 122 sets of physical examination data from July 2022 to June 2023 were collected and stratified according to body mass index （BMI）. The chi-square test was used for comparison of continuous data between groups， and a multivariable Logistic regression analysis was used to investigate the association between NAFLD subtypes and cardiometabolic risk factors. ResultsA total of 9 372 cases of NAFLD were detected， with a detection rate of 25.25%， and more than 97% of these patients were diagnosed with metabolic associated fatty liver disease （MAFLD）. The subgroup analysis showed that the detection rates of lean， overweight， and obese NAFLD were 7.72%， 33.99%， and 63.56%， respectively. Compared with the patients with lean or overweight NAFLD， the patients with obese NAFLD showed a significantly higher proportion of patients with abnormalities in blood pressure， blood glucose， triglyceride （TG）， high-density lipoprotein （HDL） or uric acid （all P<0.001）. Among related risk factors， lean NAFLD was associated with the increase in total cholesterol （TC）（P<0.05）， while overweight NAFLD and obese NAFLD were not associated with TC abnormalities （P>0.05）； obese NAFLD was not associated with TG abnormalities， while lean NAFLD and overweight NAFLD were associated with TG abnormalities （both P<0.05）； all types of NAFLD were associated with the abnormalities of waist-hip ratio， blood pressure， blood glucose， low-density lipoprotein， HDL， and uric acid （all P<0.05）. ConclusionThe detection rates of different subtypes of NAFLD in Shanghai Pudong are close to those reported in China and globally， and the epidemiologic data of NAFLD can be used analogously for MAFLD. There are certain differences in the distribution and association of cardiometabolic risk factors between different subtypes of NAFLD， and targeted interventions should be formulated based on the metabolic characteristics of each type of NAFLD.

BACKGROUND:Umbilical cord mesenchymal stem cells(UMSCs)have been proven to have therapeutic effects on cartilage injury,and exosomes are the main carriers for UMSCs to exert therapeutic effects in vivo.Our research group previously found that lncRNA H19 is an important active molecule that mediates the activity of UMSCs-derived exosomes regulating chondrocytes.LncRNA H19 could adsorb miR-29b-3p to promote the proliferation and regeneration of chondrocytes,but its downstream mechanism is still unclear. OBJECTIVE:To reveal the specific mechanism of UMSCs in the treatment of cartilage injury from the perspective of exosomes and lncRNAs,so as to provide a new target for the treatment of cartilage injury. METHODS:UMSCs stably overexpressing lncRNA H19 were constructed.H19-Exos were extracted by ultra-centrifugation.The exosomes were identified by transmission electron microscopy,Nanosight,western blot assay and exosome uptake assay.The effect of miR-29b-3p overexpression and silencing on the TGF-β1/Smad3 pathway was detected by western blot assay,qPCR and dual luciferase reporter gene system.The biological effect of H19-Exos on cartilage regeneration was verified by the specific TGF-β1/Smad3 inhibitor in vitro and in vivo. RESULTS AND CONCLUSION:(1)H19-Exos showed a typical cup shape under an electron microscope,and the particle size was approximately 130 nm.H19-Exos expressed CD63,CD81 and TSG1010.(2)Overexpression of miR-29b-3p could down-regulate the mRNA and protein levels of TGF-β1 and Smad3,while silencing miR-29b-3p could up-regulate the mRNA and protein levels of TGF-β1/Smad3.(3)Dual-luciferase reporter gene system showed that miR-29b-3p had significant differences in the activities of downstream target genes TGF-β1 and Smad3.(4)The osteoarthritis models of rats were successfully established by injection of type II collagenase into the knee joint.H19-Exos significantly promoted cartilage regeneration.The specific TGF-β1/Smad3 inhibitor SB-431542 could block the biological effect of H19-Exos on cartilage regeneration in vitro and in vivo.(5)This study systematically demonstrated the promotion effect of UMSCs-derived exosomes highly expressing lncRNA H19 on cartilage regeneration,and the specific mechanism is that lncRNA H19 promotes cartilage regeneration by targeting miR-29b-3p/TGF-β1/Smad3 pathway.

BACKGROUND:The displacement change parameters of the bone structure of the first metatarsal bone at the two-dimensional level of hallux valgus deformity are of great significance for clinical diagnosis and treatment,while the quantitative analysis of the three-dimensional deformity index may have some influences on the postoperative efficacy. OBJECTIVE:To explore the quantitative change of the three-dimensional deformity index of the first metatarsal bone after routine osteotomy and orthosis for hallux valgus deformity and to provide reference for clinical work. METHODS:100 patients with hallux valgus deformity(foot)in Hengshui People's Hospital from October 2020 to April 2023 were selected and all of them underwent conventional osteotomy and orthosis.Foot function was assessed by the American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale 6 months after surgery.Anterolateral X-rays of the foot in weight-bearing position and CT images in simulated weight-bearing position were taken before surgery and 6 months after surgery.The three-dimensional deformity indexes of the first metatarsal bone before and after surgery were quantitatively analyzed in patients with different ages,genders and therapeutic effects,including first-second intermetatarsal angle,hallux valgus angle,distal metatarsal articular angle,tibial sesamaid position,and first metatarsal rotation α angle.The value of the difference of three-dimensional deformity indexes of the first metatarsal bone before and after operation in evaluating the curative effect was analyzed. RESULTS AND CONCLUSION:(1)Six months after operation,the American Orthopedic Foot and Ankle Society score was 75-98(88.25±4.14)points,among which 56 cases were excellent,28 cases were good,14 cases were average,and 2 cases were poor.The excellent and good rate was 84%(84/100).(2)Compared with the preoperative results,first-second intermetatarsal angle,hallux valgus angle,distal metatarsal articular angle,tibial sesamaid position,and first metatarsal rotation α angle were significantly improved in patients of different ages and genders 6 months after surgery(P<0.05).First-second intermetatarsal angle,hallux valgus angle,distal metatarsal articular angle,tibial sesamaid position,and first metatarsal rotation α angle were all lower in patients with good curative effect 6 months after surgery than those with poor curative effect,and the difference before and after surgery was greater than those with poor curative effect(P<0.05).(3)The area under the curve of the difference evaluation of the first metatarsal three-dimensional deformity index before and after surgery was above 0.7,and the area under the curve of the combined evaluation of all indexes was the largest(0.902),which was significantly greater than the first metatarsal rotation α angle and distal metatarsal articular angle(P<0.05).(4)The quantitative analysis of the three-dimensional deformity index of the first metatarsal in patients with hallux valgus deformity is related to the postoperative effect,which has important guiding significance for improving the accuracy and comprehensiveness of preoperative evaluation and improving the treatment plan.

Objective:To investigate the relationship between intramuscular adipose tissue index (IATI) calculated from computed tomography images at transverse process of the first lumbar and all-cause mortality in maintenance dialysis patients, and to provide a reference for improving the prognosis in these patients.Methods:It was a multicenter retrospective cohort study. The clinical data of patients who received maintenance hemodialysis or peritoneal dialysis treatment from January 1, 2017 to December 31, 2019 in 4 grade Ⅲ hospitals including Zhongda Hospital Affiliated to Southeast University, Taizhou People's Hospital Affiliated to Nanjing Medical University, Affiliated Hospital of Yangzhou University, and the Third Affiliated Hospital of Soochow University were retrospectively collected. IATI was calculated by low attenuation muscle (LAM) density/skeletal muscle density. The receiver-operating characteristic curve was used to determine the optimal cut-off value of IATI, and the patients were divided into high IATI group and low IATI group according to the optimal cut-off value. The differences of baseline clinical data and measurement parameters of the first lumbar level between the two groups were compared. The follow-up ended on December 23, 2022. The endpoint event was defined as all-cause mortality within 3 years. Kaplan-Meier survival curve and log-rank test were used to analyze the survival rates and the differences between the two groups. Multivariate Cox regression analysis models were used to analyze the association between IATI and the risk of all-cause mortality in maintenance dialysis patients. Multivariate logistic regression analysis model was used to analyze the influencing factors of high IATI.Results:A total of 478 patients were eligibly recruited in this study, with age of (53.55±13.19) years old and 319 (66.7%) males, including 365 (76.4%) hemodialysis patients and 113 (23.6%) peritoneal dialysis patients. There were 376 (78.7%) patients in low IATI (<0.42) group and 102 (21.3%) patients in high IATI (≥0.42) group. The proportion of age ≥ 60 years old ( χ2=24.746, P<0.001), proportion of diabetes mellitus ( χ2=5.570, P=0.018), fasting blood glucose ( t=-2.145, P=0.032), LAM density ( t=-3.735, P<0.001), LAM index ( t=-7.072, P<0.001), and LAM area/skeletal muscle area ratio ( Z=-9.630, P<0.001) in high IATI group were all higher than those in low IATI group, while proportion of males ( χ2=11.116, P<0.001), serum albumin ( Z=2.708, P=0.007) and skeletal muscle density ( t=12.380, P<0.001) were lower than those in low IATI group. Kaplan-Meier survival analysis showed that the 3-years overall survival rate of low IATI group was significantly higher than that in high IATI group (Log-rank χ2=19.188, P<0.001). Multivariate Cox regression analysis showed that IATI<0.42 [<0.42/≥0.42, HR(95% CI): 0.50 (0.31-0.83), P=0.007] was an independent protective factor of all-cause mortality, and age ≥60 years old [ HR (95% CI): 2.61 (1.60-4.23), P<0.001], diabetes mellitus [ HR (95% CI): 1.71 (1.06-2.78), P=0.029] and high blood neutrophil/lymphocyte ratio [ HR (95% CI): 1.04 (1.00-1.07), P=0.049] were the independent risk factors of all-cause mortality in maintenance dialysis patients. Stepwise Cox regression analysis showed that IATI<0.42 was still an independent protective factor of all-cause mortality in maintenance dialysis patients [<0.42/≥0.42, HR (95% CI): 0.45 (0.27-0.76), P=0.003]. Multivariate logistic regression analysis showed that low skeletal muscle density [ OR (95% CI): 0.84 (0.81-0.88), P<0.001] and high serum triglyceride [ OR (95% CI): 1.39 (1.07-1.82), P=0.015] were the independent influencing factors of IATI≥0.42. Conclusion:IATI<0.42 of the first lumbar level is an independent protective factor of all-cause mortality in maintenance dialysis patients. Localized myosteatosis within high-quality skeletal muscle may reduce the risk of all-cause mortality in these patients.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

AIM:To investigate the effect of spermidine(SPD)on pressure overload-induced cardiac hyper-trophy and heart failure model in mice and its underlying mechanisms.METHODS:(1)Eight-week-old male C57BL/6J mice were randomly divided into 4 groups:sham group,sham+SPD group,transverse aortic constriction(TAC)group,and TAC+SPD group.After TAC,the mice in sham+SPD group and TAC+SPD group were fed with 3 mmol/L SPD via drinking water,and the mice in other groups were fed with normal water.Western blot was used to detect the protein ex-pression levels of silent information regulator 6(SIRT6),peroxisome proliferator-activated receptor γ coactivator-1(PGC-1)and mitofusin 2(MFN2).Adult mouse cardiomyocytes were isolated to detect cell length and width.Wheat germ agglu-tinin staining was used to detect the cardiac cell size.Masson staining was used to detect the extent of fibrosis.Echocar-diography was used to detect cardiac function and myocardial hypertrophy.Transmission electron microscopy was used to analyze mitochondrial morphology.Oxygraph-2k high-resolution respirometer was used to detect cardiac mitochondrial oxy-gen consumption.(2)In vitro,primary rat ventricular cardiomyocytes were cultured and treated with angiotensin II(Ang II;1 μmol/L)to construct a hypertrophy model of cardiomyocytes.These cardiomyocytes were divided into control(Con)group,Con+SPD(1 mmol/L)group,Ang II group,Ang II+SPD group and Ang II+SPD+SIRT6 siRNA(siSIRT6)group.Confocal microscopy was used to detect cardiomyocytes area and mitochondrial.RESULTS:(1)Compared with sham group,cardiac function of the mice in TAC group was significantly decreased(P＜0.05),the degree of myocardial hyper-trophy was significantly increased(P＜0.05),and the expression levels of SIRT6,PGC-1 and MFN2 in the myocardial tis-sue were significantly decreased(P＜0.05).Compared with TAC group,the expression levels of SIRT6,PGC-1 and MFN2 in mouse myocardial tissues of TAC+SPD group were significantly increased(P＜0.05),pathological myocardial hy-pertrophy was reduced(P＜0.05),the numbers of mitochondria and mitochondrial cristae were increased(P＜0.05),mito-chondrial function was restored(P＜0.05),myocardial fibrosis was alleviated(P＜0.05),and cardiac function was im-proved(P＜0.05).(2)In vitro,compared with Con group,the expression levels of SIRT6,PGC-1 and MFN2 in cardio-myocytes of Ang II group were decreased(P＜0.05),and the degree of cardiomyocyte hypertrophy was significantly in-creased(P＜0.05).Treatment with SPD increased the expression levels of SIRT6,PGC-1 and MFN2 in cardiomyocytes of Ang II group(P＜0.05),reversed myocardial hypertrophy and improved mitochondrial dynamics(P＜0.05).Compared with Ang II group,the expression levels of SIRT6,PGC-1 and MFN2 in Ang II+SPD+siSIRT6 group showed no significant changes,and the degree of cardiomyocyte hypertrophy and mitochondrial dynamics also had no statistically significant changes.CONCLUSION:Spermidine promotes the expression of SIRT6,PGC-1 and MFN2,thus improving mitochon-drial function,reducing myocardial hypertrophy and alleviating heart failure in mice with pressure overload.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

The paper reports a rarely case of hemophagocytic syndrome complicated with thrombotic microangiopathy, first presented with fever of unknown origin. A 37-year-old female patient mainly presented with fever, hemolytic anemia, thrombocytopenia, and progressive decline in renal function. After infusion of fresh frozen plasma and high dose of glucocorticoid after double plasma exchange, the patient showed good prognosis, no further fever or hemolysis occurred, recovered platelet and renal function. After acute episode phase, kidney biopsy was performed and acute tubular necrosis was diagnosed. During the follow-up period, the disease did not recur, and the renal function was normal.

The paper reports a 68-year-old female patient admitted with "recurrent fever for 2 years" with a previous history of chronic kidney disease (stage 5) and receiving maintenance hemodialysis for 2 years. After 15 days of anti-infection treatment with vancomycin, the patient showed a steep drop in peripheral platelet count to <1×10 9/L. Combined with the clinical manifestations and platelet antibody screening, considering vancomycin-induced thrombocytopenia (VIT), vancomycin was immediately stopped, and active plasma exchange was adopted. Finally, the peripheral blood platelet count of the patient returned to normal, supporting the diagnosis of VIT. Vancomycin is widely used in dialysis patients, and the clinicians should be aware of the rare but severe adverse effect of VIT. Once present, vancomycin should be stopped early and individualized treatment should be taken to avoid the risk of massive bleeding or death.

Objective:To investigate the changing trends in cardiac function following xenogeneic heterotopic heart transplantation of multi-gene edited pig hearts and assess the impact of recipient immune responses on donor heart, laying experimental groundwork for the clinical application of gene editing technology.Methods:On December 16, 2023, xenogeneic heterotopic heart transplantation was performed between pigs and rhesus monkeys. Functional status of the graft under post-transplantation load conditions and recipient immune indicators were observed.Results:The recipient monkeys survived for 40 days with satisfactory functionality of both donor and recipient hearts, and no hyperacute or acute immune rejection reactions were observed.Conclusion:Multi-gene editing technology provides potential for xenotransplantation, yet further exploration is needed for its clinical application.