Bacillus is a class of spore-producing Gram-positive bacteria that produce a variety of antimicrobial substances with different structures and functions. The application of the antimicrobial substances produced by Bacillus can effectively inhibit the activity of harmful bacteria and fungi and promote the sustainable development of green agriculture. The antimicrobial substances produced by Bacillus mainly include proteins, lipopeptides, polyketones, and polypeptides. This paper reviews the synthesis gene clusters, synthesis pathways, structures, and mechanisms of various antimicrobial substances produced by Bacillus and discusses the challenges in the industrial application of these antimicrobial substances. Furthermore, this paper clarifies the future research and development focuses and prospects the application prospects, and provides comprehensive theoretical support for the in-depth research and wide application of the antimicrobial substances produced by Bacillus.
Bacillus/genetics* ; Anti-Infective Agents/metabolism* ; Bacterial Proteins/genetics* ; Antimicrobial Peptides/biosynthesis* ; Lipopeptides/biosynthesis*

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.

Cancer immunotherapy has great potential and is expected to become the mainstream method of cancer treatment.In the current application of cancer immunotherapy,immune checkpoint inhibitors(ICIs)have achieved remarkable results.The cur-rently widely used ICIs in clinical practice include inhibitors targeting cytotoxic T lymphocyte-associated antigen-4(CTLA-4),pro-grammed death-1(PD-1)and programmed death-ligand 1(PD-L1).In addition,new immunotherapies such as oncolytic viruses and chimeric antigen receptor T cells are gradually entering the clinical practice,and combination therapy related to ICIs has shown unique advantages.This article will focus on the current application status of ICIs,oncolytic viruses,and chimeric antigen receptor T cell ther-apies in solid tumors either their individual or combined forms.

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.

Objective:To investigate COVID-19 vaccination status and relevant adverse reactions in patients with psoriasis treated with biological agents, and to explore the effect of COVID-19 vaccination on psoriatic lesions.Methods:Clinical data were collected from 572 psoriasis patients aged 18 - 60 years, who were registered in the management system of psoriasis patients treated with biological agents in the University of Hong Kong-Shenzhen Hospital from May 2019 to June 2021. The COVID-19 vaccination status was investigated by telephone interviews, and the vaccination-related information was obtained by fixed healthcare workers during a fixed time period according to a predesigned questionnaire. Measurement data were compared between two groups by using t test, and enumeration data were compared by using chi-square test or Fisher′s exact test. Results:The COVID-19 vaccination coverage rate was 43.13% (226 cases) among the 524 patients who completed the telephone interview, and was significantly lower in the biological agent treatment group (30.79%, 105/341) than in the traditional drug treatment group (66.12%, 121/183; χ2 = 60.60, P < 0.001) . The main reason for not being vaccinated was patients′ fear of vaccine safety (49.66%, 148/298) , followed by doctors′ not recommending (26.51%, 79/298) . In the biological agent treatment group after vaccination, the exacerbation of psoriatic lesions was more common in patients receiving prolonged-interval treatment (42.86%, 6/14) compared with those receiving regular treatment (4.40%, 4/91; Fisher′s exact test, P < 0.001) . Skin lesions were severely aggravated in two patients after COVID-19 vaccination, who ever experienced allergic reactions and whose skin lesions did not completely subside after the treatment with biological agents. Conclusions:The COVID-19 vaccination coverage rate was relatively low in the psoriasis patients treated with biological agents, and no serious adverse reaction was observed after vaccination. Prolonged-interval treatment due to COVID-19 vaccination ran the risk of exacerbation of skin lesions.

Objective:To investigate the predictive value of high-sensitive C-reactive protein (hs-CRP) for early hematoma enlargement in patients with primary intracerebral hemorrhage.Methods:Patients with intracerebral hemorrhage admitted to the Department of Neurosurgery, the First Affiliated Hospital of Zhengzhou University from January 2014 to January 2019 were enrolled retrospectively. The patients were sent to hospital within 6 h after onset, and the diagnosis of cerebral hemorrhage was confirmed by head CT. The head CT was reexamined within 24 h after the first head CT. Hematoma enlargement was defined as hematoma volume increase >6 ml or relative volume increase >33%. Multivariate logistic regression analysis was used to investigate the independent risk factors for influencing early hematoma enlargement. Receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of hs-CRP for hematoma enlargement. Results:A total of 154 patients with intracerebral hemorrhage were included, including 99 males (64.3%), aged 58.7±11.1 years. The median baseline Glasgow Coma Scale score was 13. The time from onset to first CT scan was 2.92±1.35 h. The time from the first CT to the second one was 16.05±4.40 h. The baseline volume of hematoma was 21.82±11.08 ml. Among them, 27 patients (17.5%) had hematoma that broke into the ventricle, 40 (26.0%) had hematoma enlargement. The average hs-CRP level at admission in the enlarged hematoma group was significantly higher than that in the non-enlarged hematoma group (11.56±3.72 mg/L vs. 9.51±4.31 ml; t=-2.669, P=0.008). Multivariate logistic regression analysis showed that hs-CRP at admission (odds ratio [ OR] 1.123, 95% confidence interval [ CI] 1.017-1.241; P=0.022), irregular hematoma shape ( OR 4.160, 95% CI 1.714-10.098; P=0.002) and the time from onset to the first CT scan ( OR 0.510, 95% CI 0.323-0.803; P=0.004) were significantly correlated with hematoma enlargement. Pearson correlation analysis showed that hs-CRP was positively correlated with baseline hematoma volume ( r=0.237, P=0.003). ROC curve analysis showed that the area under the curve of hs-CRP predicting hematoma enlargement was 0.678 (95% CI 0.584-0.772). The optimal cut-off value was 10.55 mg/L. The sensitivity and specificity for predicting hematoma enlargement were 86.9% and 60.0%, respectively. Conclusion:For patients with hs-CRP ≥10.55 mg/L at admission, irregular hematoma shape, and the time from admission to the first CT scan <3 h, should be focused the management and be alert to the occurrence of early hematoma enlargement.

The subaxial cervical facet dislocation is an important and common cause of cervical spinal cord injury, which often leads to the destruction of the three column structure of the cervical spine. At present, the treatment principle of the subaxial cervical facet dislocation is generally reduction as soon as possible, complete decompression, restoration of the intervertebral height and the normal sequence of the cervical spine and reconstruction of the stability of the cervical spine. Early reduction is particularly important for patients with spinal cord injury. Although there are many ways of reduction, the best way to achieve reduction and stability is still controversial. The authors review related literatures and summarize the reduction methods of the subaxial cervical facet dislocation, so as to provide reference for the clinical treatment of the subaxial cervical facet dislocation.

Objective:To explore the possible mechanism of Bcl-2/adenovirus E1B 19kDa-interacting protein 3-like (also known as NIX) mediating mitophagy in PC12 cells.Methods:The PC12 cells (rat adrenal pheochromocytoma cells) were cultured in a hypoxic incubator with a volume fraction of 1% O 2 to establish hypoxic injury models. The cells were divided into normoxia group and hypoxia groups at 6, 12, 24 and 48 hours after cells were exposed to hypoxic conditions. Afterwards, the expression levels of NIX, microtubule-associated protein 1 light chain 3 (LC3), translocase of outer mitochondrial membrane 20 (TOMM20), and cyclooxegenase 4 (COX4) were determined by Western blot analysis. Electron microscopy was used to observe the formation of autophagosomes after 24 hours of hypoxia. The mitochondria-NIX-LC3-autophagosome complexes were detected by confocal microscopy after the overexpression of NIX for 48 hours. The interaction between NIX and LC3 was verified by Co-immunoprecipitation (CoIP). After downregulation of NIX, the changes in mitochondria morphology were detected by confocal microscopy. The PC12 cells were divided into normoxia group, normoxia+ NIXshRNA group, hypoxia group and hypoxia+ NIXshRNA group, then the expression levels of NIX, LC3, TOMM20 and COX4 in each group were detected via Western blotting. Results:Compared to normoxia group, hypoxia group showed up-regulated expressions of NIX and LC3 [(0.44±0.03)∶(0.21±0.01), (1.04±0.03)∶(0.32±0.01)], and down-regulated expressions of TOMM20 and COX4 [(0.78±0.07)∶(1.46±0.08), (0.52±0.04)∶(0.98±0.06)] after 24 hours of hypoxia ( P<0.05). Autophagosomes containing mitochondria were detected by electron microscopy after 24 hours of hypoxia. The formation of the mitochondria-NIX-LC3-autophagosome complex were detected by confocal microscopy after the overexpression of NIX for 48 hours. CoIP demonstrated an interaction between NIX and LC3. Furthermore, inhibition of NIX preserved the integrity of the mitochondria compared with hypoxia group. Western blot analysis showed decreased expressions of NIX and LC3 in hypoxia+ NIXshRNA group [(0.90±0.04)∶ (1.30±0.19), (0.55±0.03)∶(0.75±0.03)] and increased expressions of TOMM20 and COX4 [(0.78±0.06)∶( 0.69±0.08), (0.81±0.07)∶( 0.81±0.07) in comparison to hypoxia group ( P<0.05). Conclusions:NIX can interact with LC3 to mediate mitophagy in PC12 cells. Therefore, the inhibition of NIX can preserve the integrity of the mitochondria and decrease the level of mitophagy, thus provide a protective effect.

Objective:To investigate the risk factors of tracheotomy after cervical spinal cord injury (CSCI) and the predictive role of key muscle strength in guiding bedside tracheotomy.Methods:A retrospective case-control study was used to analyze the clinical data of 294 patients with CSCI admitted to Xinqiao Hospital of Army Medical University from January 2009 to December 2013, including 243 males and 51 females, with the age range of 10-82 years [(48.9±14.7)years]. A total of 52 patients treated with tracheotomy (tracheotomy group), while 242 patients did receive tracheotomy (non-tracheotomy group). The indices were collected and compared between groups, including demographic data (gender, age, smoking history, cause of injury), injury severity data [level of injury, combined injury, cervical dislocation, American Spinal Cord Injury Association (ASIA) classification], and key muscle function strength [shrug (trapezius), shoulder abduction (deltoid) and elbow flexion (biceps)]. The risk factors affecting the tracheotomy were identified by the univariate logistic regression analysis and binary logistic regression analysis. The independent risk factor for tracheostomy and predictive role of key muscle strength was determined by the multiple logistic regression analysis.Results:Smoking history, falling injury, cervical dislocation, C 2-C 4 AISA scale A, shoulder-shrugging muscle strength, shoulder abduction muscle strength and elbow flexion strength were significantly different between groups ( P<0.05). Through the binary logistic regression analysis, it was preliminarily concluded that smoking history, traffic injury, falling injury, cervical dislocation, C 2-C 4 AISA scale A, and C 5-C 8 AISA scale A were statistically significant between groups ( P<0.05). The multiple logistic regression analysis showed smoking history( OR=2.27), cervical dislocation( OR=3.70) and C 2-C 4 AISA scale A ( OR=8.31) were significantly related to tracheostomy ( P<0.05). The multiple logistic regression analysis showed shoulder-shrugging muscle strength grade 3 and below and shoulder abduction muscle strength grade 2 and below had significant correlations with CSCI patients who required tracheotomy ( P<0.05). Conclusions:C 2-C 4 AISA scale A, cervical dislocation and smoking history are independent risk factors for determining whether the CSCI patients require tracheostomy. Shoulder-shrugging muscle strength grade 3 and below and shoulder abduction muscle strength grade 2 and below can be used to differentiate the bedside tracheotomy.