Hai-Tao Xu’s research while affiliated with Second Military Medical University and other places

Objectives Since December 2019, patients infected with a novel coronavirus disease (COVID-19) emerged in Wuhan city and rapidly spread globally. The risk for poor outcome dramatically increases once a patient progressed to the severe or critical stage. The present study aims to investigate the risk factors for disease progression in mild to moderate cases of COVID-19. Methods We conducted a cohort study which included 1007 mild to moderate cases with COVID-19 from 3 hospitals in Wuhan. Clinical characteristics and baseline laboratory findings were collected. Patients had been followed up for 28 days for observation of disease progression. The endpoint was the progression to a more severe disease stage. Results During a follow up of 28 days, 720 patients (71.50%) had recovered or been symptomatically stable, 222 patients (22.05%) had progressed to the severe stage, 22 patients (2.18%) had progressed to the critically ill stage, 43 patients (4.27%) had deceased. Multivariate Cox proportional hazards models identified that increased age (HR 2.56, 95% CI 1.97 to 3.33), male sex (HR 1.79, 95% CI 1.41 to 2.28), presence of hypertension (HR 1.44, 95% CI 1.11 to 1.88), diabetes (HR 1.82, 95% CI 1.35 to 2.44), chronic obstructive pulmonary disease (HR 2.01, 95% CI 1.38 to 2.93) and coronary artery disease (HR 1.83, 95% CI 1.26 to 2.66) were risk factors for disease progression. History of smoking was protective against disease progression (HR 0.56, 95% CI 0.34 to 0.91). Elevated procalcitonin (HR 1.72, 95% CI 1.02 to 2.90), urea nitrogen (HR 1.72, 95% CI 1.21 to 2.43), α-hydroxybutyrate dehydrogenase (HR 3.02, 95% CI 1.26 to 7.21) and D-dimer (HR 2.01, 95% CI 1.12 to 3.58) at baseline were also associated with risk for disease progression. Conclusions This study identified a panel of risk factors for disease progression in mild to moderate cases with COVID-19.

Prostaglandin E receptor subtype 4 (EP4) is widely distributed in the heart, but its role in hepatic ischemia/reperfusion (I/R), particularly in mitochondrial permeability transition pore (MPTP) modulation, is yet to be elucidated. In the present study, an EP4 agonist (CAY10598) was used in a rat model to evaluate the effects of EP4 activation on liver I/R and the mechanisms underlying this. I/R insult upregulated hepatic EP4 expression during early reperfusion. In addition, subcutaneous CAY10598 injection prior to the onset of reperfusion significantly increased hepatocyte cAMP concentrations and decreased serum ALT and AST levels and necrotic and apoptotic cell percentages, after 6 h of reperfusion. Moreover, CAY10598 protected mitochondrial morphology, markedly inhibited mitochondrial permeability transition pore (MPTP) opening and decreased liver reactive oxygen species levels. This occurred via activation of the ERK1/2‑GSK3β pathway rather than the janus kinase (JAK)2‑signal transducers and activators of transcription (STAT)3 pathway, and resulted in prevention of mitochondria‑associated cell injury. The MPTP opener carboxyatractyloside (CATR) and the ERK1/2 inhibitor PD98059 also partially reversed the protective effects of CAY10598 on the liver and mitochondria. The current findings indicate that EP4 activation induces ERK1/2‑GSK3β signaling and subsequent MPTP inhibition to provide hepatoprotection, and these observations are informative for developing new molecular targets and preventative therapies for I/R in a clinical setting.

Propofol (2,6‑diisopropylphenol) exerts protective effects on alveolar epithelial type II (ATII) cells, partly through attenuating hypoxia‑induced apoptosis. Autophagy is involved in the activation of apoptosis. Therefore, the present study investigated the modulating effect of propofol against autophagy in ATII cells under hypoxia. Western blot analysis was performed to detect the protein expression of the autophagy molecular marker, microtubule‑associated protein 1 light chain 3 (LC3)‑II, under various conditions. The effects of propofol on the accumulation of other autophagy‑associated proteins and apoptosis‑associated proteins were also determined using western blot analysis. The interactions between proteins were determined by co‑immunoprecipitation. Apoptosis of the ATII cells was monitored using FITC‑conjugated AV/PI staining. Furthermore, hypoxia‑inducible factor 1α (HIF 1α) small interfering (si) RNA was designed to construct si‑HIF 1α ATII cells. The efficiency of interference was measured using reverse transcription‑quantitative polymerase chain reaction and western blot analyses. Following pre‑treatment with propofol, the hypoxia‑induced accumulation of LC3‑II, HIF 1α and B‑cell lymphoma‑2 interacting protein 3 (Bnip3) were markedly decreased, accompanied with the activation of mammalian target of rapamycin. In addition, cleaved‑poly ADP‑ribose polymerase was suppressed, and hypoxia‑induced autophagic cell death was inhibited by propofol pre‑treatment. HIF 1α was inhibited by si‑HIF 1α, which simultaneously suppressed Bnip3 and LC3‑II under hypoxia. Taken together, propofol reduced hypoxia‑induced autophagic cell death through reducing the expression of HIF 1α in ATII cells, indicating a novel strategy for modulating autophagy via propofol in hypoxic ATII cells.

Sevoflurane and propofol are both widely used in clinical anesthesia. The aim of this study is to compare the effects of sevoflurane and propofol on right ventricular function and pulmonary circulation in patients receiving esophagectomy. Forty adult patients undergoing an elective open-chest thoracotomy for esophagectomy were randomized to receive either propofol (n=20) or sevoflurane (n=20) as the main anesthetic agent. The study was performed in Changzheng Hospital. Hemodynamic data were recorded at specific intervals: before the surgery (T0), BIS values reaching 40 after anesthesia induction (T1), two-lung ventilation (T2), ten minutes after one-lung ventilation (T3), the end of the operation (T4) using PiCCO2 and Swan-Ganz catheter. CI, RVEF, RVSWI and RVEDVI were significantly smaller in propofol group than those in sevoflurane group throughout the surgery (P<0.05). However, SVRI was significantly greater in propofol group than that in sevoflurane group (P<0.05). Compared with the patients in propofol group, the patients who received sevoflurane had a greater reduction in OI and increase in Os/Ot (P<0.05). And, PVRI was significantly smaller in sevoflurane group than in propofol group (P<0.05). Anesthesia with sevoflurane preserved better right ventricular function than propofol in patients receiving esophagectomy. However, propofol improved oxygenation and shunt fraction during one-lung ventilation compared with sevoflurane anesthesia. To have the best effect, anesthesiologists can choose the two anesthetics flexibly according to the monitoring results.

Left ventricular diastolic dysfunction is receiving more attention in patients with end-stage liver diseases. The importance of diastolic dysfunction observed before orthotopic liver transplantation (OLT) and its adverse effects on hemodynamics and outcomes of OLT patients, have not been fully explored. We carried a retrospective study to investigate the influence of diastolic dysfunction on OLT patients. Included in this retrospective study were 330 consecutive patients scheduled for cadaveric OLT over a 5-year period. According to preoperative Doppler echocardiogram (ECHO) findings, patients were divided into two groups: DD group (patients with diastolic dysfunction) and control group (patients with normal ECHO). Patient characteristics, operation variables, hemodynamic course, blood products and drug requirements, postoperative courses and outcomes were evaluated. 306 patients met the study entry criteria and 100 had preoperative diastolic dysfunction. Mean artery blood pressure was significantly lower in DD group after graft reperfusion than that in control group (P<0.01). More patients in DD group required epinephrine, and the mean dose of epinephrine was higher in DD group than that in control group (P<0.01). There was no significant difference in postoperative ventilation time, duration of ICU and hospital stay, renal failure and postoperative mortality between the two groups. Diastolic dysfunction is common in liver transplant recipients. Patients with diastolic dysfunction may be associated with substantial hemodynamic alterations after graft reperfusion and need more inotropic support during OLT. Diastolic dysfunction was not associated with significant adverse postoperative outcomes.

Studies have demonstrated the role of circulating endothelial progenitor cells (EPCs) in maintaining normal endothelial function and in endothelial repairing. This study was aimed to observe the protective effects of autologous transplantation of circulating EPCs against endotoxin-induced acute lung injury in rabbits and to investigate the underlying mechanisms. One-hundred-and-fifty rabbits were enrolled. After acute lung injury was induced by endotoxin, autologous circulating EPCs, endothelial cell, or normal saline were transfused intravenously, respectively. Pao(2)/FiO(2) ratios, concentrations of plasma nitric oxide, malonyldialdehyde, and activity of superoxide dismutase were examined. The lung wet-to-dry weight ratios were counted; polymorphonuclear cell ratios and areas of hyaline membrane formation and hemorrhage were measured. The levels of interleukin-1β, E-selectin, intercellular adhesion molecule-1, interleukin-10, vascular endothelial growth factor protein, and inducible nitric oxide synthase protein were analyzed. Pao(2)/FiO(2) ratios were significantly increased with EPC transfusion. Infiltration of polymorphonuclear cells, lung wet-to-dry weight ratios, and area of hyaline membrane and hemorrhage in lung tissue were significantly decreased after EPC transplantation. Plasma level of nitric oxide and malondialdehyde were significantly inhibited, and the activity of superoxide dismutase was enhanced in the EPC-treated animals. EPC transplantation significantly increased level of interleukin-10 and vascular endothelial growth factor protein and reduced levels of interleukin-1β, E-selectin, intercellular adhesion molecule-1, and inducible nitric oxide synthase in injury lung tissues. Autologous transplantation of circulating EPCs can partly restore the pulmonary endothelial function and effectively attenuate endotoxin-induced acute lung injury by direct endothelial repair and indirect immunomodulation of antioxidation and antiinflammation.

Marked hemodynamic alteration, commonly referred to as postreperfusion syndrome (PRS), often occurs after revascularization of the donor organ during orthotopic liver transplantation (OLT) and is associated with poor outcomes. This study aimed to investigate the incidence, predictive factors and clinical outcomes of PRS in Chinese patients following OLT at a liver transplantation center in China. Over a 5-year period, 330 consecutive patients who had undergone OLT for hepatocellular carcinoma or cirrhosis were included in this retrospective study. PRS was defined as a >30% decrease in the mean arterial pressure compared with that before revascularization for more than 1 minute during the first 5 minutes of graft reperfusion. The patients were divided into 2 groups according to the development of PRS: group 1 (patients with PRS, n=56) and group 2 (patients without PRS, n=274). The demographic characteristics, operative and postoperative courses, and outcomes of the patients were analyzed using SPSS version 18.0. Multivariate regression analysis showed that left ventricular diastolic dysfunction determined by echocardiography and prolonged cold ischemia time were the independent risk factors for PRS. More patients in group 1 showed postoperative renal dysfunction than those in group 2 (19.23% vs 8.4%). Moreover, patients in group 1 also had higher intraoperative (7.14% vs 0%) and postoperative mortalities (26.92% vs 12.04%). Left ventricular diastolic dysfunction and prolonged cold ischemia time contribute to a high incidence of PRS, which is associated with adverse outcomes in Chinese patients following OLT.

The objective of this study was to appraise the safety profiles of HES preparations and to find out which HES preparation was the most acceptable in cardiovascular surgery through a comparison with control solutions. Pertinent randomized controlled trials were selected through a search of Pubmed, Embase, and Cochrane Controlled Trials Register. Quantitative and qualitative analysis was carried out to evaluate blood loss, blood transfusion, renal function, complications, reoperation, and mortality. A total of 3,234 patients from 52 randomized controlled trials were included. HES preparations versus control solutions in blood loss: HES 130 kD vs. albumin (SMD -0.61, 95% CI -0.82, -0.40), HES 200 kD vs. albumin (SMD -0.01, 95% CI -0.29, 0.28), HES 450 kD vs. albumin (SMD 0.47, 95% CI 0.26, 0.68). When comparing control solutions with HES preparations, 50% (HES 450 kD), 40.9% (HES 200 kD), and 18.2% (HES 130 kD) of the comparisons showed more blood/blood products infusion with HES than with control solutions. A numerically lower mortality rate seemed to be related to HES preparations (2.68 vs 4.23%). No difference was found in terms of complications, renal failure, or reoperation. Perioperative administration of HES preparations is comparatively safe. The data appraising safety profiles of HES preparations are insufficient to make direct comparisons among themselves. As the third generation of HES preparations, HES 130 kD showed a trend toward lower blood loss and transfusion rates and is a suitable choice for cardiovascular surgery.