BACKGROUND:Sepsis is one of the main causes of mortality in intensive care units(ICUs).Early prediction is critical for reducing injury.As approximately 36%of sepsis occur within 24 h after emergency department(ED)admission in Medical Information Mart for Intensive Care(MIMIC-IV),a prediction system for the ED triage stage would be helpful.Previous methods such as the quick Sequential Organ Failure Assessment(qSOFA)are more suitable for screening than for prediction in the ED,and we aimed to find a light-weight,convenient prediction method through machine learning. METHODS:We accessed the MIMIC-IV for sepsis patient data in the EDs.Our dataset comprised demographic information,vital signs,and synthetic features.Extreme Gradient Boosting(XGBoost)was used to predict the risk of developing sepsis within 24 h after ED admission.Additionally,SHapley Additive exPlanations(SHAP)was employed to provide a comprehensive interpretation of the model's results.Ten percent of the patients were randomly selected as the testing set,while the remaining patients were used for training with 10-fold cross-validation. RESULTS:For 10-fold cross-validation on 14,957 samples,we reached an accuracy of 84.1%±0.3%and an area under the receiver operating characteristic(ROC)curve of 0.92±0.02.The model achieved similar performance on the testing set of 1,662 patients.SHAP values showed that the five most important features were acuity,arrival transportation,age,shock index,and respiratory rate. CONCLUSION:Machine learning models such as XGBoost may be used for sepsis prediction using only a small amount of data conveniently collected in the ED triage stage.This may help reduce workload in the ED and warn medical workers against the risk of sepsis in advance.

Background/Aims: The aim of this study was to analyze the chronological changes in postoperative complications in surgical ulcerative colitis patients over the past decade in China and to investigate the potential parameters that contributed to the changes. Methods: Ulcerative colitis patients who underwent surgery during 2008–2017 were retrospectively enrolled from 13 hospitals in China. Postoperative complications were compared among different operation years. Risk factors for complications were identified by logistic regression analysis. Results: A total of 446 surgical ulcerative colitis patients were analyzed. Fewer short-term complications (24.8% vs. 41.0%, P=0.001) and more laparoscopic surgeries (66.4% vs. 25.0%, P<0.001) were found among patients who received surgery during 2014–2017 than 2008–2013. Logistic regression suggested that independent protective factors against short-term complications were a higher preoperative body mass index (odds ratio [OR], 0.870; 95% confidence interval [CI], 0.785–0.964; P=0.008), laparoscopic surgery (OR, 0.391; 95% CI, 0.217–0.705; P=0.002) and elective surgery (OR, 0.213; 95% CI, 0.067–0.675; P=0.009). The chronological decrease in short-term complications was associated with an increase in laparoscopic surgery. Conclusions Our data revealed a downward trend of short-term postoperative complications among surgical ulcerative colitis patients in China during the past decade, which may be due to the promotion of minimally invasive techniques among Chinese surgeons.

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

Berberine (BBR) as one of the most effective natural products has been increasingly used to treat various chronic diseases due to its immunosuppressive/tolerogenic activities. However, it is unknown if BBR can be applied without abrogating the efforts of vaccination. Here we show that priming of CD8⁺ T cells in the presence of BBR lead to improved central memory formation (Tcm) with substantially reduced effector proliferation, primarily orchestrated through activation of AMPK and Stat5. Tcm derived from vaccinated mice fed with BBR were able to adoptively transfer protective immunity to naïve recipients. Vaccination of BBR-fed mice conferred better memory protection against infection without losing immediate effector efficacy, suggesting appreciable benefits from using BBR in vaccination. Thus, our study may help to lay the groundwork for mechanistic understanding of the immunomodulatory effects of natural products and their potential use as adjuvant that allows the design of novel vaccines with more desirable properties.

Objective     To share the clinical experience of video-assisted thoracoscopic surgery (VATS) anatomic basal segmentectomy by single-direction method. Methods     The clinical data of 352 patients who underwent VATS anatomic basal segmentectomy in West China Hospital between April 2015 and April 2021 were retrospectively reviewed, including 96 males and 256 females with a median age of 50 (range, 26-81) years. All basal segmentectomies were performed under thoracoscopy, through the interlobar fissure or inferior pulmonary ligament approach, and following the strategy of single-direction and the method of "stem-branch". Results    All patients underwent basal segmentectomy successfully (49 patients of uniportal procedure, 3 patients of biportal procedure and 300 patients of triportal procedure) without addition of incisions or conversion to thoracotomy and lobectomy. The median operation time was 118 (range, 45-340) min, median intraoperative blood loss was 20 (range, 5-500) mL, median drainage time was 2 (range, 1-22) d and median postoperative hospital stay was 4 (range, 2-24) d. The postoperative complications included pneumonia in 6 patients, prolonged drainage (air leakage duration>5 d or drainage duration>7 d) in 18 patients, cerebral infarction in 1 patient and other complications in 2 patients. All patients were treated well and discharged without main complaints. No perioperative death happened. Conclusion    VATS anatomic basal segmentectomy is feasible and safe. It can be performed in a simple manner following the strategy of single-direction.

Objective:To compare the efficacy and safety of intravitreal injection of anti-vascular endothelial growth factor drug conbercept and intravitreal dexamethasone implant Ozurdex in the treatment of diabetic macular edema (DME).Methods:A randomized controlled clinical study was performed.Thirty-six DME patients (36 eyes) were enrolled in Weifang Eye Hospital from March 2018 to June 2019.The patients were randomized into Ozurdex group and conbercept group via a random number table, with 18 eyes in each group.Patients received Ozurdex injection once, which was maintained for 6 months, or conbercept injection once a month for 3 times according to grouping.Before and after treatment, the best corrected visual acuity (BCVA) was examined with the International Standard Visual acuity chart and converted to logarithm of minimal angle resolution unit.The intraocular pressure (IOP) was measured using a non-contact tonometer.The central retinal thickness (CRT) was detected by optical coherence tomography (OCT).This study followed the Declaration of Helsinki and was approved by the Ethics Committee of Weifang Eye Hospital.Results:All patients were followed up for 6 months.In Ozurdex group, the BCVA pre-injection and at 1 month, 3, 4, 6 months after the first injection was 0.59±0.22, 0.53±0.20, 0.41±0.16, 0.38±0.19 and 0.56±0.19, respectively.The BCVA at 1 month, 3 and 4 months after the first injection were better than that before injection, and the differences were statistically significant (all at P<0.05).In conbercept group, the BCVA pre-injection and at 1 month, 3, 4, 6 months after the first injection were 0.60±0.23, 0.51±0.17, 0.29±0.13, 0.56±0.18 and 0.60±0.18, respectively.The BCVA at 1 month and 3 months after the first injection were better than that before injection, showing statistically significant differences (all at P<0.05).The CRT at 1 month, 3 and 4 months after the first injection were significantly lower than that before treatment in both the two groups (all at P<0.05).The CRT pre-injection was (498.61±77.14)μm in Ozurdex group, which was significantly higher than (462.17±48.74)μm at 6 months after the first injection ( P<0.05).No significant difference in CRT was found between pre-injection and 6 months after the first injection in conbercept group ( P>0.05).The incidence of high IOP in Ozurdex group was 33.3%(6/18), which was higher than 5.56%(1/18) in conbercept group, with a significant difference ( χ2=4.433, P=0.035).No adverse effects such as aggravation of cataract, lens injury, endophthalmitis, vitreous hemorrhage and retinal detachment was found during the follow-up. Conclusions:For DME, both conbercept and Ozurdex can improve BCVA and reduce CRT.Ozurdex shows durable efficacy and needs fewer injections than conbercept, but conbercept has less effect on IOP and is safer than Ozurdex.

Objective:To establish a quick on-site emergency detection method for severe fever with thrombocytopenia syndrome virus (SFTSV), dengue virus (DENV), and hantaan virus (HTNV).Methods:This research was based on the traditional TaqMan fluorescent probe technology, using the domestic rapid one-step quantitative RT-PCR kit, combined with the Magnetic induction cycler (Mic) qPCR instrument. The detection limit, specificity and repeatability of this method were evaluated by simulated samples, other virus infected samples and normal human blood samples.Results:Compared with the traditional RT-PCR assay, the required time of this method was greatly shortened, and the detection can be completed within 35 minutes. The limit of quantitation for SFTSV, DENV and HTNV are less than 100copies/PCR. No nonspecific amplification was found in the simulated negative samples and other virus infected samples. All the simulated positive sample for verification could be detected, and coefficient of variation Ct value of each group was less than 4%. Conclusions:The rapid fluorescence quantitative RT-PCR assays have certain application prospects for on-site emergency detection, and provide important technical supports and new directions for the prevention and control of common hemorrhagic fever viruses.

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.

Objective     To identify the risk factors for postoperative recurrence of peripheral solid small-nodule lung cancer (PSSNLC) (T≤2 cm), and to explore the effects of surgery types on prognosis. Methods     We extracted data from Western China Lung Cancer Database (WCLCD), a prospectively maintained database at the Department of Thoracic Surgery, West China Hospital, Sichuan University, and Surveillance, Epidemiology, and End Results (SEER)  database for peripheral solid small-nodule lung cancer patients (T≤2 cm N0M0, stageⅠ) who underwent surgery between 2005 and 2016. We used univariable and multivariable logistic regression to analyze risk factors for recurrence of PSSNLC. We applied propensity-score matching to compare the long-term results of segmentectomy and lobectomy, as well as the survival of patients from WCLCD and SEER. We finally included 4 800 patients with PSSNLC (T≤2 cm N0M0)(WCLCD: SEER=354∶4 446). We matched 103 segmentectomies and 350 lobectomies in T≤1 cm, and 280 segmentectomies and 1 067 lobectomies in 1 cm

Objective:To investigate the effects of allicin on the proliferation, migration and angiogenesis of rat vascular endothelial cells (RVES), and to explore the influencing mechanism of allicin on epidural fibrosis.Methods:According to the results of preliminary experiments, RVECs were divided into control group (0 mg/L), low concentration group (25 mg/L), medium concentration group (50 mg/L) and high concentration group (100 mg/L). The morphology, viability, migration rate, cell cycle, apoptosis rate and cell lumen formation ability were measured using fluorescence microscope, AnnexinV-FITC double staining, PI/RN-asestaining, scratch assay and Transwell experiments test. Western Blot was used to measure the protein expression level of JAK2, STAT3, p-STAT3, PCNA, Bax and Bcl-2 protein. Using random number method, 36 adult male SD rats were divided into sham operation group, saline group and allicin group, with 12 rats in each group. Hematoxylin-eosin (HE) staining, Masson staining and immunohistochemical staining were used to analysis the epidural fibrosis in each group.Results:With the increase of concentration of allicin, cell viability, cell migration and lumen formation ability significantly lower than that of control group ( P<0.05). With the increase of allicin concentration, the percentage of cells in the G1 and S phases gradually decreased ( P<0.05), the percentage of cells in the G2 phase and the apoptosis rate gradually increased ( P<0.05), and the cells were blocked in the G2/M phase. With the increase of allicin concentration, the protein expression levels of JAK2, STAT3, p-STAT3, PCNA and Bcl-2 were gradually down-regulated ( P<0.05), while the protein expression level of Bax was gradually up-regulated ( P<0.05), the ratio of p-STAT3/STAT3 was decreased ( P<0.05), and the ratio of Bax/Bcl-2 was increased ( P<0.05). There was no death, infection or abnormal gait in all the experimental animals. Dense scar tissue could be observed in the extradural area of the sham operation group and the epidural area of the control group, but there was obvious space between the epidural scar and the dura mater in the allicin group, and the density of collagen, the number of blood vessels, and the protein density of p-STAT3 were significantly lower than those in the control group ( P<0.05). Conclusion:Allicin inhibits angiogenesis and the severity of epidural scar after laminectomy, and the mechanism may be through inhibiting the JAK2/STAT3 signaling pathway of vascular endothelial cells.