Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

OBJECTIVE: Microcirculatory disturbance is pathologically critical to acute pancreatitis (AP), which can be effectively alleviated by traditional Chinese medicine (TCM) formulas that activate blood flow. However, there has been no evidence-based research to date. Therefore, a well-designed systematic review and meta-analysis is necessary to elucidate the therapeutic transformative benefit of improving microcirculation during AP. This study aims to confirm the therapeutic efficacy of TCM formulas and explore the potential mechanisms underlying their effects on AP treatment. METHODS: Studies from eight databases including Pubmed, Embase, Web of Science, Cochrane Library, CNKI, CBM, Wanfang, and Chinese VIP, were screened for the eligible randomized controlled trials (RCTs). The APACHE II score and effectiveness rate were set as primary outcomes, while mortality rate, complications, total hospital stays, serum amylase recovery time, the time until the disappearance of abdominal pain, microcirculation indicators, and inflammation indicators were chosen as secondary outcomes. A systematic review and meta-analysis were subsequently conducted. Network pharmacology analysis was performed to analyze potential bioactive components with relevant targets of the core herbs included in the TCM formulas for activating blood flow. RESULTS: A total of 51 RCTs (n = 3 721) were included. Compared with conventional western medical treatments alone, TCM groups were associated with lower APACHE II score (SMD =  - 1.36, 95% CI: -2.01 to - 0.71, P = 0.000) and higher effectiveness rate (RR: 1.22, 95% CI: 1.18 to 1.26, P = 0.000). Furthermore, the formulas for activating blood flow demonstrated significant efficacy in improving both microcirculation and inflammation indicators. Additionally, six core Chinese herbal medicines including Rhei Radix et Rhizoma with the highest frequency, Aurantii Fructus Immaturus, Paeoniae Radix Rubra, Bupleuri Radix, Salviae Miltiorrhizae Radix et Rhizoma, and Corydalis Rhizoma were filtered out from the adopted TCM formulas. Finally, 166 shared targets between the six herbs and AP were identified. KEGG analysis indicated that lipid and atherosclerosis pathway is highly related to microcirculation. CONCLUSION TCM formulas for activating blood flow significantly improve microcirculation and alleviate AP. Further high-quality, well-designed RCTs and deep mechanism exploration are required.

ObjectiveTo investigate the role and mechanism of DNA repair regulation in the process of hepatocellular carcinoma （HCC） recurrence. MethodsHCC tissue samples were collected from the patients with recurrence within two years or the patients with a good prognosis after 5 years， and the Tandem Mass Tag-labeled quantification proteomic study was used to analyze the differentially expressed proteins enriched in the four pathways of DNA replication， mismatch repair， base excision repair， and nucleotide excision repair， and the regulatory pathways and targets that play a key role in the process of HCC recurrence were analyzed to predict the possible regulatory mechanisms. The independent samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsFor the eukaryotic replication complex pathway， there were significant reductions in the protein expression levels of MCM2 （P=0.018）， MCM3 （P=0.047）， MCM4 （P=0.014）， MCM5 （P=0.008）， MCM6 （P=0.006）， MCM7 （P=0.007）， PCNA （P=0.019）， RFC4 （P=0.002）， RFC5 （P<0.001）， and LIG1 （P=0.042）； for the nucleotide excision repair pathway， there were significant reductions in the protein expression levels of PCNA （P=0.019）， RFC4 （P=0.002）， RFC5 （P<0.001）， and LIG1 （P=0.042）； for the base excision repair pathway， there were significant reductions in the protein expression levels of PCNA （P=0.019） and LIG1 （P=0.042） in the HCC recurrence group； for the mismatch repair pathway， there were significant reductions in the protein expression levels of MSH2 （P=0.026）， MSH6 （P=0.006）， RFC4 （P=0.002）， RFC5 （P<0.001）， PCNA （P=0.019）， and LIG1 （P=0.042） in recurrent HCC tissue. The differentially expressed proteins were involved in the important components of MCM complex， DNA polymerase complex， ligase LIG1， long patch base shear repair complex （long patch BER）， and DNA mismatch repair protein complex. The clinical sample validation analysis of important differentially expressed proteins regulated by DNA repair showed that except for MCM6 with a trend of reduction， the recurrence group also had significant reductions in the relative protein expression levels of MCM5 （P=0.008）， MCM7 （P=0.007）， RCF4 （P=0.002）， RCF5 （P<0.001）， and MSH6 （P=0.006）. ConclusionThere are significant reductions or deletions of multiple complex protein components in the process of DNA repair during HCC recurrence.

Objective:To explore the risk factors of microvascular invasion (MVI) in hepatocellular carcinoma (HCC), and to predict MVI preoperatively, non-invasively and accurately.Methods:A total of 150 HCC patients (183 HCC lesions) were retrospectively collected in the First Affiliated Hospital of Xi′an Jiaotong University from January 2016 to June 2022.The clinical data and hematological data, gray-scale ultrasonography (US), contrast-enhanced ultrasonography (CEUS), enhanced magnetic resonance imaging with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (EOB-MRI) and pathological data of these patients were recorded. According to the pathological diagnosis of MVI, the lesions were divided into MVI (+ ) group and MVI (-) group. The indicators between the two groups were compared. All 183 lesions were put into the training set, and the prediction model with nomogram was constructed according to the risk factors of MVI selected by multivariate Logistic regression. The internal verification was carried out by ten-fold cross-validation method.Results:There were significant statistical differences in the following parameters between MVI (+ ) group ( n=109) and MVI (-) group ( n=74) (all P<0.05). These were cirrhosis, serological parameters (alpha-fetoprotein, albumin, total bilirubin), qualitative indexes of US (size, boundary, internal echo), qualitative indexes of CEUS (hyper/iso/hypovascularity of lesions in arterial phase, portal phase, and delayed phase compared with hepatic parenchyma), and quantitative indexes of EOB-MRI [post enhancement rate (post ratio) and gadolinium disodium rate (EOB ratio)] calculated mainly in terms of lesions and surrounding liver parenchyma in hepatobiliary phase and unenhanced T1 images). Finally, cirrhosis of patients, the size, boundary, internal echo of lesions in US; arterial phase (AP), portal phase (PP), post-vascular phase (PVP) features in CEUS; the EOB rate and post rate of EOB-MRI entered the prediction model of MVI. The training set exhibited good calibration and net gain rate. The areas under the ROC curve for the training set and the validation set were 0.981 and 0.961, respectively, while the diagnostic accuracy were 92.9% and 85.8%, respectively. Conclusions:The model constructed mainly by multimodality imaging methods can achieve favorable predictive performance for MVI, which provides valuable ideas for noninvasively predicting the incidence of MVI and optimizing the MVI-related treatment of MVI in HCC patients.

Objective:To assess the diagnostic efficacy of upper gastrointestinal endoscopic image assisted diagnosis system (ENDOANGEL-LD) based on artificial intelligence (AI) for detecting gastric lesions and neoplastic lesions under white light endoscopy.Methods:The diagnostic efficacy of ENDOANGEL-LD was tested using image testing dataset and video testing dataset, respectively. The image testing dataset included 300 images of gastric neoplastic lesions, 505 images of non-neoplastic lesions and 990 images of normal stomach of 191 patients in Renmin Hospital of Wuhan University from June 2019 to September 2019. Video testing dataset was from 83 videos (38 gastric neoplastic lesions and 45 non-neoplastic lesions) of 78 patients in Renmin Hospital of Wuhan University from November 2020 to April 2021. The accuracy, the sensitivity and the specificity of ENDOANGEL-LD for image testing dataset were calculated. The accuracy, the sensitivity and the specificity of ENDOANGEL-LD in video testing dataset for gastric neoplastic lesions were compared with those of four senior endoscopists.Results:In the image testing dataset, the accuracy, the sensitivity, the specificity of ENDOANGEL-LD for gastric lesions were 93.9% (1 685/1 795), 98.0% (789/805) and 90.5% (896/990) respectively; while the accuracy, the sensitivity and the specificity of ENDOANGEL-LD for gastric neoplastic lesions were 88.7% (714/805), 91.0% (273/300) and 87.3% (441/505) respectively. In the video testing dataset, the sensitivity [100.0% (38/38) VS 85.5% (130/152), χ2=6.220, P=0.013] of ENDOANGEL-LD was higher than that of four senior endoscopists. The accuracy [81.9% (68/83) VS 72.0% (239/332), χ2=3.408, P=0.065] and the specificity [ 66.7% (30/45) VS 60.6% (109/180), χ2=0.569, P=0.451] of ENDOANGEL-LD were comparable with those of four senior endoscopists. Conclusion:The ENDOANGEL-LD can accurately detect gastric lesions and further diagnose neoplastic lesions to help endoscopists in clinical work.

Objective:To construct a real-time artificial intelligence (AI)-assisted endoscepic diagnosis system based on YOLO v3 algorithm, and to evaluate its ability of detecting focal gastric lesions in gastroscopy.Methods:A total of 5 488 white light gastroscopic images (2 733 images with gastric focal lesions and 2 755 images without gastric focal lesions) from June to November 2019 and videos of 92 cases (288 168 clear stomach frames) from May to June 2020 at the Digestive Endoscopy Center of Renmin Hospital of Wuhan University were retrospectively collected for AI System test. A total of 3 997 prospective consecutive patients undergoing gastroscopy at the Digestive Endoscopy Center of Renmin Hospital of Wuhan University from July 6, 2020 to November 27, 2020 and May 6, 2021 to August 2, 2021 were enrolled to assess the clinical applicability of AI System. When AI System recognized an abnormal lesion, it marked the lesion with a blue box as a warning. The ability to identify focal gastric lesions and the frequency and causes of false positives and false negatives of AI System were statistically analyzed.Results:In the image test set, the accuracy, the sensitivity, the specificity, the positive predictive value and the negative predictive value of AI System were 92.3% (5 064/5 488), 95.0% (2 597/2 733), 89.5% (2 467/ 2 755), 90.0% (2 597/2 885) and 94.8% (2 467/2 603), respectively. In the video test set, the accuracy, the sensitivity, the specificity, the positive predictive value and the negative predictive value of AI System were 95.4% (274 792/288 168), 95.2% (109 727/115 287), 95.5% (165 065/172 881), 93.4% (109 727/117 543) and 96.7% (165 065/170 625), respectively. In clinical application, the detection rate of local gastric lesions by AI System was 93.0% (6 830/7 344). A total of 514 focal gastric lesions were missed by AI System. The main reasons were punctate erosions (48.8%, 251/514), diminutive xanthomas (22.8%, 117/514) and diminutive polyps (21.4%, 110/514). The mean number of false positives per gastroscopy was 2 (1, 4), most of which were due to normal mucosa folds (50.2%, 5 635/11 225), bubbles and mucus (35.0%, 3 928/11 225), and liquid deposited in the fundus (9.1%, 1 021/11 225).Conclusion:The application of AI System can increase the detection rate of focal gastric lesions.

Objective To investigate the nursing clinical practice of ICU ventilator-associated pneumonia(VAP)prevention and control of tertiary hospitals in China,and analyze relevant countermeasures.Methods A self-designed questionnaire consisted of 3 parts and 26 items.A questionnaire survey was conducted among nurses in 380 ICUs in 194 tertiary hospitals in 26 provinces from September 1 to 15,2021,using the convenient sampling method.Results A total of 380 valid questionnaires were collected,with an effective rate of 100%.In the system process,369(97.11%)ICUs had files to prevent VAP;291(76.58%)ICUs had a checklist of measures to prevent VAP clustering;274(72.11%)ICUs had continuous improvement projects about VAP in the last 3 years.In the aspect of body position management,semi-decubitus position was the first choice for the patients with invasive mechanical ventilation of 338(88.95%)ICUs.For nursing operation,224(58.95%)ICUs used Subglottic suction,and 128(33.68%)among them used air shock to remove the retention on the balloon;normal saline is still routinely injected before sputum aspiration in 72(18.95%)ICUs.In terms of balloon pressure monitoring,253(66.58%)ICUs did the oral care 3-4 times a day.In the balloon pressure monitoring,313(82.37%)ICUs use airbag pressure gauges to intermittently monitor airbag pressure;293(77.11%)ICUs replaced the ventilator pipeline once a week.There are significant differences in the current practice status of different types of ICUs in terms of compliance strategies for bed head lifting,subglottic secretion drainage,airbag pressure monitoring,and oral care(P<0.05).Conclusion At present,the relevant systems and procedures to prevent VAP have been improved,but the specific prevention and control measures need to be further unified.Therefore,it is suggested to analyze the weak links of VAP nursing prevention and control practice in various medical structures,carry out relevant training and quality control for the weak links,and further improve the working mechanism of continuous quality improvement,thus effectively reduce the incidence of VAP.

ObjectiveTo observe the primary tumor of tree shrews and to provide a basis for studying the pathogenesis and prevention of trichoepithelioma. MethodsA tumor was discovered in the chest and abdomen of a tree shrew during natural cultivation. The tree shrew was anesthetized, and the tumor was surgically removed. Hematoxylin and eosin (HE) staining and immunohistochemical staining were performed on the tumor tissue after paraffin section, and the tumor cells were isolated and cultured by passage. The isolated tumor cells were subcutaneously injected into healthy tree shrews and nude mice. The tumorigenesis of tumor cells in vivo was observed once a day, with nude mice continuously observed for 2 months and tree shrews observed for more than 6 months. ResultsHE staining showed that the basal cells in the dermis were arranged as a whole, like a string of petals, forming nests and stripe-like structures with clear boundaries. The observation results after magnification revealed that the tumor cells were arranged in a pallisade-like and basal pattern, with deep nuclear staining and minimal cytoplasmic. Immunohistochemical staining showed the high expression of CK protein and low proportion expression of ki-67 protein in tumor cells, as well as the high expression of vimentin and low expressions of Bcl2 and CD10 in tumor cell mesenchyme. The isolated tumor cells grew well in DMEM medium containing 10% fetal bovine serum and could be cultured by passage, but no tumor formation was observed in healthy tree shrews and nude mice inoculated with tumor cells. ConclusionCombined with the location of the tumor, overall morphology, HE staining, and immunohistochemical results, the thoracoabdominal mass of the tree shrew was diagnosed as a trichoepithelioma.

Objective:To explore the mediating effect of self-efficacy and fatigue between depression and cognitive function in patients with spinal cord injury.Methods:General information questionnaire, Hamilton Depression Scale, Montreal Cognitive Scale, Rehabilitation Exercise Self-Efficacy Scale, Fatigue Revised Scale were used to investigate 256 cases of spinal cord injury patients from December 2018 to August 2020. The deviation-corrected percentile Bootstrap method was used to test the chain mediating effect of rehabilitation exercise self-efficacy and fatigue on depression and cognitive function.Results:Correlation analysis showed that depression was negatively correlated with cognitive function ( r=-0.146, P<0.01), self-efficacy of rehabilitation exercise ( r=-0.115, P<0.01), and positively correlated with fatigue ( r=0.317, P<0.01), self-efficacy of rehabilitation exercise was positively correlated with cognitive function ( r=0.903, P<0.01), and negatively correlated with fatigue ( r=-0.889, P<0.01), and fatigue was negatively correlated with cognitive function ( r=-0.217, P<0.01). The mediation model test showed that depression had a significant direct effect on cognitive function, with an effect value of -0.141 and an effect size of 50.20%. Self-efficacy of rehabilitation exercise and fatigue had a significant mediating effect between depression and cognitive function. The effect value was -0.096, -0.026, the effect size was 34.1%, 9.3%, and the chain mediation effect of rehabilitation exercise self-efficacy-fatigue was also significant, the effect value was -0.018, and the effect size was 6.4%. Conclusions:Depression in patients with spinal cord injury not only directly affects cognitive function, but also indirectly affects cognitive function through the mediating effects of self-efficacy of rehabilitation exercise and fatigue, and the chain-type mediating effect of rehabilitation exercise self-efficacy and fatigue.

Objective:To explore the effects of different blood glucose management modes on self-management ability and glucose and lipid metabolism in patients with type 2 diabetes mellitus (T2DM) based on the WeChat platform.Methods:240 patients with T2DM were selected in Taiyuan Central Hospital from January to June 2020 for the study. They were randomly divided into general management groups, medical care management groups, peer management groups, and medical care and peer co-management groups using random number table, with 60 cases in each group. The general management group received routine outpatient follow-up. The medical care management group, peer management group, and medical care and peer management group established WeChat groups for management, respectively. Each group′s self-management ability and glucose and lipid metabolism indexes were compared before and after six months of intervention. t-test or nonparametric tests were used to compare. Results:After the intervention, self-management abilities such as diet, exercise, blood glucose monitoring, medication compliance, foot care, smoking and fasting blood glucose (FBG), and glycosylated hemoglobin (HbA 1c) were improved in the four groups (all P<0.05). The medical care management, peer management, and medical care and peer co-management groups were further improved than the general group (all P<0.05). Except for smoking, the above medical care and peer co-management group indicators were statistically different from those of the separate medical care management and peer management group (all P<0.05). Triacylglycerol (TG) of the four groups were improved compared with the previous [1.9(1.2, 2.7) compared with 2.3(1.6, 3.5)mmol/L, 1.4(1.2, 2.1) compared with 2.2(1.6, 3.2)mmol/L, 1.6(1.1, 2.0) compared with 2.2(1.4, 3.2)mmol/L, 1.5(1.0, 2.1) compared with 2.4(1.3, 3.1)mmol/L] (all P<0.05), and after the intervention, the total cholesterol (TC) of the four groups was also improved compared with that before the intervention [(4.7±0.9) compared with (5.1±1.2)mmol/L, (4.2±1.1) compared with (5.2±1.2)mmol/L, (4.3±1.1) compared with (5.4±1.3)mmol/L, (4.2±1.1) compared with (5.0±1.4)mmol/L] (all P<0.05), and TG and TC of the medical care management, peer management, and medical care and peer co-management groups were lower than those of the general group (all P<0.05). Conclusion:Based on the WeChat platform, the management mode of medical care and peer co-management is conducive to T2DM patients′ better self-management and blood glucose control.