BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

OBJECTIVE: To explore characteristics, management strategies and preventive measures of fusion device displacement after oblique lateral interbody fusion (OLIF) in treating lumbar lesions. METHODS: The clinical data of 12 patients with fusion device displacement after OLIF for lumbar lesions in 4 medical centers from October 2014 to December 2018 were retrospectively analyzed, including 4 males and 8 females, aged from 53 to 81 years old;2 patients with lumbar disc degeneration, 4 patients with lumbar spinal stenosis, 3 patients with lumbar degenerative spondylolisthesis and 3 patients with lumbar degenerative kyphosis;preoperative dual-energy X-ray bone mineral density (BMD) was detected in 1 patient with T-value > -1 SD, 5 patients with T-value >-1~-2.5 SD, and 6 patients with T-value <-2.5 SD;9 patients with single-segment fusion, 1 patient with 2-segment fusion, and 2 patients with 3-segment fusion;standalone OLIF was performed in 9 patients and OLIF combined with posterior pedicle screws in 3 patients. Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate low back pain and lumbar function recovery at the time of fusion graft displacement and at the latest follow-up, respectively. In addition, according to imaging results during follow-up, the fusion device subsidence or redisplacement, loosening or fracture of internal fixation, and interbody fusion were observed, and the changes in the height of interbody space on the segment with fusion device displacement were measured and compared. RESULTS: There were no necrosis or infection in skin incision of 10 patients after reoperation, and 12 patients were followed up for 12 to 48 months. VAS for low back pain decreased from 3 to 8 points at the time of fusion device displacement to 0 to 2 points at the latest follow-up. ODI recovered from 31% to 51% at the time of fusion transfer to 5% to 13% at the latest follow-up. There was no loosening or fracture of the pedicle screw system during follow-up. All 11 patients with bone grafting with fusion apparatus had fusion apparatus subsidence and no further displacement of fusion apparatus. The vertebral space height recovered from 9.0 to 12.7 mm at the time of fusion graft displacement to 8.0 to 11.8 mm at the latest follow-up. Interbody fusion was obtained in all patients except 1 with no imaging results at the latest follow-up. CONCLUSION OLIF could be used for fusion of lumbar lesions, and there is a risk of fusion organ displacement after operation, especially in cases of bone loss or osteoporosis before surgery, end-plate injury during surgery, and Stand-alone mode, and most of them occur within 3 months after operation. Surgery is required for the transposition of the fusion apparatus in the Stand-alone OLIF mode during the primary operation. Although good clinical results could be obtained by timely detection and accurate treatment, it is still necessary to emphasize the precise selection of cases before operation, the appropriate application of OLIF, and precise operation during operation to prevent displacement of fusion device.
Humans ; Spinal Fusion/instrumentation* ; Female ; Male ; Middle Aged ; Aged ; Aged, 80 and over ; Lumbar Vertebrae/surgery* ; Retrospective Studies ; Pedicle Screws

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m², NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m², albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

OBJECTIVE: To analyze the causes of vertebral fracture during oblique lateral interbody fusion in the treatment of lumbar spondylopathy, summarize the clinical results, and propose preventive measures. METHODS: Retrospective analysis was made on the data of 8 cases of lumbar spondylopathy and vertebral fracture treated by oblique lateral interbody fusion in three medical centers from October 2014 to December 2018. All were female, aged from 50 to 81 years with an average of 66.4 years. Disease types included 1 case of lumbar degenerative disease, 3 cases of lumbar spinal stenosis, 2 cases of lumbar degenerative spondylolisthesis and 2 cases of lumbar degenerative scoliosis. Preoperative dual energy X-ray bone mineral density test showed that 2 cases had T-value >-1 SD, 2 cases had T-value -1 to -2.5 SD, and 4 cases had T-value <-2.5 SD. Single segment fusion was in 5 cases, two segment fusion in 1 case and three segment fusion in 2 cases. Four cases were treated with OLIF Stand-alone and 4 cases were treated with OLIF combined with posterior pedicle screw fixation. Postoperative imaging examination showed vertebral fracture, and all of them were single vertebral fracture. There were 2 cases of right lower edge fracture of upper vertebral body at fusion segment, 6 cases of lower vertebral body fracture at fusion segment, and 6 cases with endplate injury and fusion cage partially embedded in vertebral body. Three cases of OLIF Stand-alone were treated with pedicle screw fixation via posterior intermuscular approach, while one case of OLIF Stand-alone and four cases of OLIF combined with posterior pedicle screw fixation were not treated specially. RESULTS: The 5 cases of initial operation and 3 cases of reoperation did not show wound skin necrosis or wound infection. The follow-up time was from 12 to 48 months with an average of 22.8 months. Visual analogue scale (VAS) of low back pain was preoperative decreased from 4 to 8 points (averagely 6.3 points) and postoperative 1 to 3 points (averagely 1.7 points) at the final follow-up. Oswestry disability index (ODI) was preoperative 39.7% to 52.4% (averagely 40.2%), and postoperative 7.9% to 11.2% (averagely 9.5%) at the final follow-up. During the follow-up, there was no loosening or fracture of the pedicle screw system, and no lateral displacement of the fusion cage;however, the fusion cage at the vertebral fracture segment had obvious subsidence. The intervertebral space height of vertebral fracture segment was preoperaive 6.7 to 9.2 mm (averagely 8.1 mm), and postoperative 10.5 to 12.8 mm (averagely 11.2 mm). The improvement rate after operation was 37.98% compared to preoperative. The intervertebral space height at final follow-up was 8.4 to 10.9 mm (averagely 9.3 mm), and the loss rate was 16.71% compared with that after operation. At the final follow-up, interbody fusion was achieved in all cases except for one that could not be identified. CONCLUSION The incidence of vertebral fracture during oblique lateral interbody fusion in the treatment of lumbar spondylopathy is lower, and there are many reasons for fracture, including preoperative bone loss or osteoporosis, endplate injury, irregular shape of endplate, excessive selection of fusion cage, and osteophyte hyperplasia at the affected segment. As long as vertebral fracture is found in time and handled properly, the prognosis is well. However, it still needs to strengthen prevention.
Humans ; Female ; Male ; Spinal Fractures/surgery* ; Retrospective Studies ; Treatment Outcome ; Lumbar Vertebrae/surgery* ; Spondylolisthesis/surgery* ; Scoliosis ; Spinal Fusion/methods*

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.
Humans ; U937 Cells ; RUNX1 Translocation Partner 1 Protein ; Leukemia/genetics* ; Core Binding Factor Alpha 2 Subunit/genetics* ; Oncogene Proteins, Fusion/genetics* ; Leukemia, Myeloid, Acute/genetics*

Adult ; Aged ; China/epidemiology* ; Cohort Studies ; Female ; Humans ; Male ; Metabolic Syndrome/etiology* ; Middle Aged ; Parks, Recreational/supply & distribution* ; Prevalence ; Residence Characteristics/statistics & numerical data* ; Rural Population/statistics & numerical data* ; Young Adult

Objective: To analyze the dynamic changes and influencing factors of HIV-1 DNA load in HIV-1 infected individuals under antiretroviral therapy (ART) in Dehong Dai and Jingpo autonomous prefecture, Yunnan province, and provide information support for the clinical use of HIV-1 DNA quantitative detection. Methods: The HIV infection cases in recent infection cohort from Dehong Center for Disease Control and Prevention during 2009-2018 were selected as study subjects. The dynamic curve of HIV-1 DNA load varrying with time was generated and logistic regression analysis was conducted to identify the risk factors for HIV-1 load in the recent follow up after ART and statistical analysis was performed by using SPSS 17.0. Results: Among the 113 HIV infection cases detected from the recent infection cohort, the recent HIV infection rate were 49.6%(56/113) males, sexual transmission cases and drug injection transmission cases accounted for 53.1% (60/113), 80.5% (91/113) and 19.5% (22/113), respectively. The dynamic changes curve showed that HIV-1 DNA load was relatively high (>800 copies /10⁶ PBMCs) before ART, and droped rapidly (<400 copies /10⁶ PBMCs) after ART for 1 year. However, HIV-1 DNA load decreased insignificantly from the second year of ART, and remained to be 269 copies/10⁶ PBMCs after ART for 6 years. Univariable logistic regression analysis indicated that OR (95%CI) of CD8, CD4/CD8 and HIV-1 DNA load were 1.00 (1.00-1.00), 0.30 (0.09-1.05) and 1.01 (1.00-1.01), respectively. Multivariable logistic regression analysis showed that OR value of HIV-1 DNA load base was 1.00 (1.00-1.01). Conclusions: HIV-1 DNA load decreased significantly in the first year of ART, then remained stable for years. HIV-1 DNA load base was the key factor associated with the decrease of HIV-1 DNA load, the lower the HIV-1 DNA load base, the lower HIV-1 DNA load. Therefore, earlier ART can contribute to the decrease of HIV-1 DNA load.
China/epidemiology* ; DNA/therapeutic use* ; HIV Infections/drug therapy* ; HIV Seropositivity ; HIV-1/genetics* ; Humans ; Male ; Viral Load

Objective:To explore the possible mechanism of Yanghe Huayantang in reversing the drug resistance of breast cancer by observing the effect of Yanghe Huayantang on the transplant tumor of tamoxifen （TAM）-resistant breast cancer and its influences on the interaction pathway of estrogen receptor （ER）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian rapamycin target protein （mTOR）. Method:Fifty mice were randomly divided into 5 groups： blank group， model group， Yanghe Huayantang group， everolimus group， and Yanghe Huayantang+everolimus group. The model of kidney deficiency was established by bilateral ovariectomy， and the blank group was treated with sham operation. Three days after the establishment of the model， all the five groups of mice were inoculated with breast cancer TAM drug-resistant cells （MCF-7/TAM^-） to establish breast cancer TAM -resistant transplanted tumor model. After successful modeling， Yanghe Huayantang group received intragastric administration of Yanghe Huayantang （traditional Chinese medicine preparation 20 mL·kg^-1）， everolimus group received intraperitoneal injection of everolimus （10 mg·kg^-1）. Yanghe Huayantang + everolimus group received Yanghe Huayantang by intragastric administration and everolimus by intraperitoneal injection. The blank group and model group received intragastric administration and intraperitoneal injection of phosphate buffer （PBS）. Drug administration was lasted for 28 days in all groups， once a day. After administration， the tumor tissue was separated and weighed， and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of tumor tissue. Immunofluorescence and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of PI3K， Akt， mTOR， ER protein and mRNA in tumor tissue. Result:Compared with the model group， the tumor volume and tumor weight of Yanghe Huayantang group decreased significantly on the 12th， 20th and 28th days （P<0.01）， and the tumor inhibition rate increased significantly （P<0.01）.Yanghe Huayantang group significantly reduced the density of tumor cells and caused tumor cell necrosis. Compared with the model group， Yanghe Huayantang group， everolimus group and Yanghe Huayantang+everolimus group inhibited the expression of PI3K， Akt， mTOR protein and mRNA （P<0.05， P<0.01）. Compared with the blank group， Yanghe Huayantang group， everolimus group and Yanghe Huayantang+everolimus group all inhibited the protein and mRNA expression of ER， and mRNA expression of ER in Yanghe Huayantang+everolimus group was significantly lower than that in the model group （P<0.01）. Conclusion:Yanghe Huayantang can inhibit the growth of TAM-resistant breast cancer. The mechanism may be that Yanghe Huayantang can reverse the TAM resistance of breast cancer by down-regulating the expression of key molecules of ER/PI3K/Akt/mTOR cross-signal pathway.

Animals ; Chemical and Drug Induced Liver Injury ; drug therapy ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Dyslipidemias ; drug therapy ; Glycemic Load ; drug effects ; Male ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Specific Pathogen-Free Organisms ; Stilbenes ; pharmacology