2020年 · 第133卷第01期

Background: The Chinese appropriate use criteria (AUC) for coronary revascularization was released in 2016 to improve the use of coronary revascularization. This study aimed to evaluate the association between the appropriateness of coronary revascularization based on the Chinese AUC and 1-year outcomes in stable coronary artery disease (CAD) patients. Methods: We conducted a prospective, multi-center cohort study of stable CAD patients with coronary lesion stenosis ≥50%. After the classification of appropriateness based on Chinese AUC, patients were categorized into the coronary revascularization group or the medical therapy group based on treatment received. The primary outcome was a composite of death, myocardial infarction, stroke, repeated revascularization, and ischemic symptoms with hospital admission. Results: From August 2016 to August 2017, 6085 patients were consecutively enrolled. Coronary revascularization was associated with a lower adjusted hazard of 1-year major adverse cardiovascular and cerebrovascular events (MACCEs; hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.45–0.86; P = 0.004) than medical therapy in patients with appropriate indications (n = 1617). No significant benefit in 1-year MACCEs was found after revascularization compared to after medical therapy in patients with uncertain indications (n = 2658, HR: 0.81; 95% CI: 0.52–1.25; P = 0.338) and inappropriate indications (n = 1810, HR: 0.80; 95% CI: 0.51–1.23; P = 0.308). Conclusions: In patients with appropriate indications according to Chinese AUC, coronary revascularization was associated with significantly lower risk of MACCEs at 1 year. No benefit was found in coronary revascularization in patients with inappropriate indications. Our findings provide evidence for using Chinese AUC to guide clinical decision-making. Clinical trial registration: NCT02880605. https://www.clinicaltrials.gov.

Background: Blood glucose control is closely related to type 2 diabetes mellitus (T2DM) prognosis. This multicenter study aimed to investigate blood glucose control among patients with insulin-treated T2DM in North China and explore the application value of combining an elastic network (EN) with a machine-learning algorithm to predict glycemic control. Methods: Basic information, biochemical indices, and diabetes-related data were collected via questionnaire from 2787 consecutive participants recruited from 27 centers in six cities between January 2016 and December 2017. An EN regression was used to address variable collinearity. Then, three common machine learning algorithms (random forest [RF], support vector machine [SVM], and back propagation artificial neural network [BP-ANN]) were used to simulate and predict blood glucose status. Additionally, a stepwise logistic regression was performed to compare the machine learning models. Results: The well-controlled blood glucose rate was 45.82% in North China. The multivariable analysis found that hypertension history, atherosclerotic cardiovascular disease history, exercise, and total cholesterol were protective factors in glycosylated hemoglobin (HbA1c) control, while central adiposity, family history, T2DM duration, complications, insulin dose, blood pressure, and hypertension were risk factors for elevated HbA1c. Before the dimensional reduction in the EN, the areas under the curve of RF, SVM, and BP were 0.73, 0.61, and 0.70, respectively, while these figures increased to 0.75, 0.72, and 0.72, respectively, after dimensional reduction. Moreover, the EN and machine learning models had higher sensitivity and accuracy than the logistic regression models (the sensitivity and accuracy of logistic were 0.52 and 0.56; RF: 0.79, 0.70; SVM: 0.84, 0.73; BP-ANN: 0.78, 0.73, respectively). Conclusions: More than half of T2DM patients in North China had poor glycemic control and were at a higher risk of developing diabetic complications. The EN and machine learning algorithms are alternative choices, in addition to the traditional logistic model, for building predictive models of blood glucose control in patients with T2DM.

Background: Preterm premature rupture of membranes (PPROM) is associated with high neonatal morbidity and mortality. However, the influences of cesarean section (CS) on neonatal outcomes in preterm pregnancies complicated with PPROM are not well elucidated. The aim of this study was to investigate the influence of delivery modes on neonatal outcomes among pregnant women with PPROM. Methods: A retrospective cross-sectional study was conducted in 39 public hospitals in 14 cities in the mainland of China from January 1st, 2011 to December 31st, 2011. A total of 2756 singleton pregnancies complicated with PPROM were included. Adverse neonatal outcomes including early neonatal death, birth asphyxia, respiratory distress syndrome (RDS), pneumonia, infection, birth trauma, and 5-min/10-min Apgar scores were obtained from the hospital records. Binary variables and ordinal variables were respectively calculated by binary logistic regressions and ordinal regression. Numerical variables were compared by multiple linear regressions. Results: In total, 2756 newborns were involved in the analysis. Among them, 1166 newborns (42.31%) were delivered by CS and 1590 newborns belonged to vaginal delivery (VD) group. The CS proportion of PPROM obviously increased with the increase of gestational age (χ2 = 5.014, P = 0.025). Compared with CS group, VD was associated with a higher risk of total newborns mortality(odds ratio [OR], 2.38; 95% confidence interval [CI], 1.102–5.118; P = 0.027), and a lower level of pneumonia (OR, 0.32; 95% CI, 0.126–0.811; P = 0.016). However, after multivariable adjustment and stratification for gestational age, only pneumonia was significantly related with CS in 28 to 34 weeks group (OR, 0.34; 95% CI, 0.120–0.940; P = 0.038). There were no differences regarding to other adverse outcomes in the two groups, including neonatal mortality, birth asphyxia, Apgar scores, RDS, pneumonia, and sepsis. Conclusions: The proportion of CS of pregnant women with PPROM was very high in China. The mode of delivery does not affect neonatal outcomes of pregnancies complicated with PPROM.

Background: BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) is an important cause of dysfunction and failure of renal transplants. This study aimed to assess the diagnostic performance of morning urine specific gravity (MUSG) in diagnosing BKPyVAN in kidney transplant recipients. Methods: A total of 87 patients, including 27 with BKPyVAN, 22 with isolated BKPyV viruria, 18 with T cell-mediated rejection(TCMR), and 20 with stable graft function, were enrolled in the First Affiliated Hospital of Sun Yat-Sen University from March 2015 to February 2017. MUSG at biopsy and during a follow-up period of 24 months after biopsy was collected and analyzed. Receiver operating characteristic (ROC) curve analysis was used to determine the ability of MUSG to discriminate BKPyVAN. Results: At biopsy, the MUSG of BKPyVAN group (1.008 ± 0.003) was significantly lower than that of isolated BK viruria group(1.013 ± 0.004, P < 0.001), TCMR group (1.011 ± 0.003, P = 0.027), and control group (1.014 ± 0.006, P < 0.001). There was no significant difference in MUSG among the isolated BK viruria group, TCMR group, and control group (P = 0.253). In BKPyVAN group, the timing and trend of MUSG elevate were consistent with the timing and trend of the decline of viral load in urine and plasma, reaching a statistical difference at 3 months after treatment (1.012 ± 0.003, P < 0.001) compared with values at diagnosis. ROC analysis indicated that the optimal cut-off value of MUSG for diagnosis of BKPyVAN was 1.009, with an area under the ROC curve (AUC) of 0.803 (95% confidence interval [CI]: 0.721–0.937). For differentiating BKPyVAN and TCMR, the optimal MUSG cut-off value was 1.010, with an AUC of 0.811 (95% CI: 0.687–0.934). Conclusion: Combined detection of MUSG and BKPyV viruria is valuable for predicting BKPyVAN and distinguishing BKPyVAN from TCMR in renal transplant recipients.

Background: The purpose of this study was to analyze cases of AO31-A2 intertrochanteric fractures (ITFs) and to identify the relationship between the loss of the posteromedial support and implant failure. Methods: Three hundred ninety-four patients who underwent operative treatment for ITF from January 2003 to December 2017 were enrolled. Focusing on posteromedial support, the A2 ITFs were divided into two groups, namely, those with (Group A, n = 153) or without (Group B, n = 241) posteromedial support post-operatively, and the failure rates were compared. Based on the final outcomes (failed or not), we allocated all of the patients into two groups: failed (Group C, n = 66) and normal (Group D, n = 328). We separately analyzed each dataset to identify the factors that exhibited statistically significant differences between the groups. In addition, a logistic regression was conducted to identify whether the loss of posteromedial support of A2 ITFs was an independent risk factor for fixation failure. The basic factors were age, sex, American Society of Anesthesiologists (ASA) score, side of affected limb, fixation method (intramedullary or extramedullary), time from injury to operation, blood loss, operative time and length of stay. Results: The failure rate of group B (58, 24.07%) was significantly higher than that of group A (8, 5.23%) (χ2 = 23.814, P < 0.001). Regarding Groups C and D, the comparisons of the fixation method (P = 0.005), operative time (P = 0.001), blood loss (P = 0.002) and length of stay (P= 0.033) showed that the differences were significant. The logistic regression revealed that the loss of posteromedial support was an independent risk factor for implant failure (OR = 5.986, 95% CI: 2.667–13.432) (P < 0.001). Conclusions: For AO31-A2 ITFs, the loss of posteromedial support was an independent risk factor for fixation failure. Therefore, posteromedial wall reconstruction might be necessary for the effective treatment of A2 fractures that lose posteromedial support.

Background: Pulmonary arterial hypertension (PH) is a progressive disease with limited therapeutic options, ultimately leading to right heart failure and death. Recent findings indicate the role of the Warburg effect (aerobic glycolysis) in the development of PH. However, the effect of the glycolysis inhibitor 3-bromopyruvate (3-BrPA) on the pathogenesis of PH has not been well investigated. This study aimed to determine whether 3-BrPA inhibits PH and its possible mechanism. Methods: PH was induced in adult Sprague-Dawley rats by a single intraperitoneal injection of monocrotaline (MCT). 3-BrPA, or phosphate-buffered saline (PBS) was administered via intraperitoneal injection every other day from the first day of MCT-injection to 4 weeks of follow-up, and indices such as right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), pulmonary arteriolar remodeling indicated by percent media thickness (% MT), lactate levels and glucose consumption, were evaluated. Pulmonary arteriolar remodeling and right ventricular hypertrophy were observed in hematoxylin-eosin-stained lung sections. Western blotting, immunohistochemistry, and/or immunofluorescence analyses were used to measure the expression of relevant proteins. A cytochrome C release apoptosis assay and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining were used to measure cell apoptosis. Results: MCT-induced PH showed a significant increase in glucose consumption (0 vs. 4 weeks: 0.87 ± 0.23 vs. 2.94 ± 0.47, P = 0.0042) and lactate production (0 vs. 4 weeks: 4.19 ± 0.34 vs. 8.06 ± 0.67, P = 0.0004). Treatment with 3-BrPA resulted in a concomitant reduction in glucose consumption (1.10 ± 0.35 vs. 3.25 ± 0.47, P = 0.0063), lactate production (5.09 ± 0.55 vs. 8.06 ± 0.67, P= 0.0065), MCT-induced increase in RVSP (39.70 ± 2.94 vs. 58.85 ± 2.32, P= 0.0004), pulmonary vascular remodeling (% MT, 43.45% ± 1.41% vs. 63.66% ± 1.78%, P < 0.0001), and right ventricular hypertrophy (RVHI, 38.57% ± 2.69% vs. 62.61% ± 1.57%, P < 0.0001) when compared with those of the PBS-treated group. 3-BrPA, a hexokinase 2 inhibitor, exerted its beneficial effect on PH by decreasing aerobic glycolysis and was also associated with inhibiting the expression of glucose transporter protein-1, inducing apoptosis, and suppressing inflammation. Conclusions: 3-BrPA might have a potential beneficial effect on the PH treatment.

Background: The effects of keto acid (KA) supplements on Chinese patients receiving maintenance hemodialysis (MHD) are unclear. This study aimed to evaluate the effects of KA supplementation on nutritional status, inflammatory markers, and bioelectric impedance analysis (BIA) parameters in a cohort of Chinese patients with MHD without malnutrition. Methods: This was a prospective, randomized, controlled, single-center clinical study conducted in 2011 till 2014. Twenty-nine patients with MHD were randomly assigned to a control (n = 14) or a KA (n = 15) group. The control group maintained a dietary protein intake of 0.9 g/kg/day. The KA group received additional KA supplement (0.1 g/kg/day). BIA was used to determine the lean tissue mass, adipose tissue mass, and body cell mass. The patients’ nutritional status, dialysis adequacy, and biochemical parameters were assessed at the ends of the third and sixth months with t test or Wilcoxon rank-sum test. Results: The daily total energy intake for both groups was about 28 kcal/kg/day. After 6 months, the Kt/V (where K is the dialyzer clearance of urea, t is the dialysis time, and V is the volume of the distribution of urea) was 1.33 ± 0.25 in KA group, and 1.34 ± 0.25 in the control group. The median triceps skin-fold thickness in KA group was 12.00 and 9.00 mm in the control group. In addition, the median hand-grip strength in KA group was 21.10 and 25.65 kg in the control group. There were no significant differences between the groups with respect to the anthropometry parameters, dialysis adequacy, serum calcium and phosphorus levels, inflammatory markers, and amino-acid profiles, or in relation to the parameters determined by BIA. Both groups achieved dialysis adequacy and maintained nutritional status during the study. Conclusions: In this cohort of Chinese patients with MHD, the patients in the control group whose dietary protein intake was 0.9 g/kg/day and total energy intake was 28 kcal/kg/day, maintained well nutritional status during study period. The KA supplement(0.1 g/kg/day) did not improve the essential amino acid/non-essential amino acid ratio, nor did it change the patients’ mineral metabolism, inflammatory parameters, or body compositions.

Background: Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD). The study is to evaluate the efficacy and safety of tACS treating MDD. Methods: This is an 8-week, double-blind, randomized, placebo-controlled study. Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4), following a 4-week observation period (week 8). The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale (HDRS-17) score ≤7 at week 8. Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17, the proportion of participants having improvement in the clinical global impression-improvement, the change in HDRS-17 score (range, 0–52, with higher scores indicating more depression) over the study, and variations of brain imaging and neurocognition from baseline to week 4. Safety will be assessed by vital signs at weeks 4 and 8, and adverse events will be collected during the entire study. Discussion: The tACS applied in this trial may have treatment effects on MDD with minimal side effects. Trial registration: Chinese Clinical Trial Registry, ChiCTR1800016479; http://www.chictr.org.cn/showproj.aspx?proj=22048.

Type 1 diabetes (T1D) results from dysfunction of pancreatic islets β cells. Recent studies supported that endoplasmic reticulum (ER) stress takes an important role in pancreatic β cell excessive loss, resulting in T1D. Here, we aimed to review the relationship between ER stress and T1D. Additionally, we also reviewed the potential mechanisms underlying ER stress mediated T1D. Studies have shown that severe ER stress is directly involved in the pancreatic β cells destruction and pathogenesis of T1D. ER stress plays a key part in pancreatic β cells and T1D, which will help in developing new effective therapeutics for T1D.

Background: Conventional treatment has limited efficacy in relapsed/refractory B-cell lymphoma. Since chimeric antigen receptor T-cell (CAR-T) technology has shown high safety and results in high remission rates, we investigated its efficacy and safety in B-cell lymphoma treatment and analyzed potential affecting factors to provide evidence for therapeutic strategies and applications. Methods: We searched databases including PubMed, Embase, and Cochrane up to July 2019. Meta-analysis 1 was conducted to study the efficacy of CAR-T cell for treating B-cell lymphoma, measuring the response rate and complete remission rate as outcomes. Sub-group analysis was performed for age, pathological type, target antigen, co-stimulatory molecule, and conditioning chemotherapy. Meta-analysis 2 was undertaken on the safety of the treatment with the incidence rate of toxicity (cytokine-releasing syndrome [CRS], neurotoxicity) as an outcome. Results: Seventeen studies were included in the systematic review and meta-analysis. It was found that CAR-T cells had good therapeutic effects in the following cases: B-cell lymphoma (patients ≥65 years old); diffuse large B-cell lymphoma pathological type; patients with treatment target antigen other than CD19; patients treated with co-stimulatory molecules other than CD28, including 4-1BB+CD28 or 4-1BB; and patients treated with cyclophosphamide/fludarabine pre-treatment protocol conditioning chemotherapy. Although the CRS and neurotoxicity incidences were high, most were reversible with minimal risk of death. Conclusion: CAR-T cell treatment is safe for clinical application; however, toxicity effects should be monitored.