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 To investigate the efficacy of CT-guided percutaneous microwave ablation for the treatment of primary hepatocellular carcinoma.Methods A total of 132 patients with primary hepatocellular carcinoma were divided into control group and study group(66 cases in each group)according to different treatment plans.The control group received transcatheter arterial chemoembolization(TACE)treatment,while the study group received TACE combined with percutaneous microwave ablation under CT guidance.The changes in serum tumor markers and liver function indicators were observed before and after treatment in the two groups,and the efficacy(short-and long-term)and safety of the two groups were compared.Results The levels of serum carcinoembryonic antigen(CEA),alpha-fetoprotein(AFP),carbohydrate antigen 125(CA125),and carbohydrate antigen 19-9(CA19-9)in both groups decreased significantly after treatment compared to those before treatment,and intergroup comparison showed that the levels of CEA,AFP,CA125,and CA1 9-9 in the study group were significantly lower those after treatment(P＜0.05).Compared with those before treatment,the levels of alanine transaminase(ALT)and aspartate transaminase(AST)were decreased,and the level of albumin(ALB)was increased of both groups after treatment.The intergroup comparison showed that the study groups ALT and AST levels were lower and ALB level was higher(P＜0.05).The total effective rate of the study group was clearly higher than that of the control group(75.76％vs 46.97％,P＜0.05).The 1-year survival rates of the two groups were similar(90.91％vs 81.82％,P＞0.05),however,the 2-year survival rate of the study group was clearly higher than that of the control group(84.85％vs 63.64％,P＜0.05).Conclusion CT-guided percutaneous microwave ablation for the adjuvant TACE treatment of primary hepatocellular carcinoma can effectively reduce tumor burden and lower tumor marker levels,its short-and long-term efficacy is significant,with a low incidence of adverse reactions and good safety.

Objective:To understand the current antiviral treatment status and various clinical types of treatment plans in Xiamen City so as to explore ways to improve and optimize the diagnosis and treatment standards for chronic hepatitis B.Methods:A cross-sectional survey method was used to study the antiviral treatment status and treatment plans for chronic hepatitis B patients who visited and were diagnosed in the Department of Infectious Diseases and Hepatology of all tertiary hospitals in Xiamen City at 0:00~23:59 on May 25, 2022.Results:A total of 665 cases were surveyed in this study, with an antiviral treatment rate of 81.2%(540/665). The antiviral treatment rate of patients who accorded with the current guidelines for antiviral treatment indications was 85.8%(507/591). The antiviral treatment rate for 362 outpatients was 72.9%(264/362). Among them, the antiviral treatment rates were 80.1%, 89.3%, and 25.0%(226/282, 25/28, 13/52), respectively, for patients diagnosed with chronic hepatitis B, hepatitis B cirrhosis, and hepatitis B surface antigen-carrying status. The treatment plan for all outpatient patients was mainly oral nucleos(t)ide analogues, accounting for 59.1%(214/362). The antiviral treatment rate for 303 inpatients was 91.1%(276/303). The various clinical types of antiviral therapy rates among all patients were 70%~95%. The antiviral treatment plan for inpatients was mainly based on pegylated interferon alpha treatment, accounting for 72.6%(220/303).Conclusion:Antiviral treatment for chronic hepatitis B in Xiamen City can still be strengthened to meet the current demand for expanding antiviral treatment indications. Antiviral treatment rates and various types of treatment plans differ between outpatients and inpatients; thus, further awareness and acceptance of the goal of improving antiviral therapy, especially in outpatients, and the possibility for a clinical cure based on pegylated interferon alpha treatment are needed to maximize the benefit to more patients.

Objective:Based on the framework of 5W1H analysis, to establish the continuous nursing project by delphi expert consultation method for children with congenital imperforate anus after discharge.Methods:This study is observational. Through the literature review, qualitative interview and group discussion to establish the expert correspondence questionnaire from April 2021 to March 2022. Delphi consultation was applied to experts for two rounds of expert consultation, to evaluate the initiative, authority and coordination of expert opinions.Results:Two rounds of expert consultation were carried out with 20 experts.The response rates of two rounds of expert questionnaires were 19/20 and 20/20 respectively, the expert authority coefficients were 0.873 and 0.893 respectively, and the Kendall′s coefficients were 0.311 and 0.405 respectively. The coordination of expert opinions was statistically significant ( P<0.05); After two rounds of expert consultation, it was finally determined that the continuing care plan for children with anal atresia included three first-level indicators (composition and responsibilities of continuing care personnel, implementation methods of continuing care, and implementation content of continuing care), 23 second-level indicators, and 46 third-level indicators. Conclusions:This study have high enthusiasm and authority of experts, and concentrated expert opinions on various indicators. The results are reliable, scientific and comprehensive, which will provide a basis for clinical medical staff to carry out the continuous nursing of children with congenital imperforate anus.

ObjectiveTo explore the inhibitory effect of Bushen Jiedu prescription （BSJDP） on the metastasis of colorectal cancer （CRC） via activation of M2 tumor-associated macrophages （M2-TAMs） in vivo. MethodThe model of xenograft tumor was established with C57BL/6 mice， and then the model mice were randomly assigned into blank control group， Bushen Jiedu recipe-low dose （11.2 g·kg^-1） group （BSJDP-L）， and Bushen Jiedu Recipe-high dose （22.4 g·kg^-1） group （BSJDP-H）. Tumors were abolished when the volume reached 1.5-2.0 cm³. The mice were sacrificed 28 days post tumor abolishing and then the lung metastasis was observed. Histopathological changes in lung metastasis were examined by hematoxylin-eosin （HE） staining of metastasis tissues， and immunofluorescence （IF） staining was employed to observe the effect of BSJDP on tumor apoptosis and hypoxia. Flow cytometry was performed to analyze the macrophages M1/M2 ratio of tumor tissue. The expression levels of the genes （Arg1， CD206， and CD163） associated with the polarization of M2-TAMs were determined by Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）. ResultThe metastasis rate was 70%， 40%， and 10% in the blank control group， BSJDP-L group， and BSJDP-H group， respectively. The lower metastasis rates of BSJDP-L and BSJDP-H groups proved that BSJDP significantly inhibited lung metastasis of CRC. Compared with the blank control group， BSJDP-L and BSJDP-H reduced the tumor cell infiltration in tumor tissue （P<0.01）， increased the apoptosis of tumor cells， alleviated the hypoxic environment， and down-regulated the expression of Arg1， CD206， and CD163 in the tumor tissue （P<0.01）. In addition， the ratio of M2 macrophages ranked in a descending order of blank control group （34.867%） > BSJDP-L group （22.033%） > BSJDP-H group （11.633%） （P<0.01）. ConclusionBSJDP inhibits the lung metastasis of CRC by inhibiting the activation of M2-TAMs in the tumor microenvironment.

Objective:To investigate the expression of promyelocytic leukemia zinc finger (PLZF) in human peripheral blood with asthma and its clinical significance.Methods:Forty patients with stable asthma from May 2021 to October 2021 in the Department of Respiratory Medicine of the Shanghai Fifth People's Hospital were enrolled, and forty healthy controls were recruited in the study. The levels of cytokines in serum were measured by enzyme-linked immunosorbent assay (ELISA). Quantitative real-time PCR (qPCR) was used to detect the expression of PLZF mRNA in plasma. The level and distribution of PLZF+ cells in PBMCs were detected by flow cytometry after isolating peripheral blood mononuclear cells (PBMCs). Independent sample t test, Mann-Whitney U test, χ 2 test, ROC curve and Logistic regression were used to analyze the results with SPSS 26.0 and Graphpad Prism 7.0. A P<0.05 was considered statistically significant. Results:The levels of cytokines IFN-γ, IL-2, IL-4, TNF-α and IL-17 in human peripheral blood from the asthma group were obviously higher than those in the control group ( P<0.05), whereas there was no significant difference in the level of cytokine IL-10 between the two groups. The level of PLZF mRNA in PBMCs from the asthma group was significantly up-regulated compared to that in the control group [(3.40%±2.52%) vs. (1.23%±0.78%), P<0.05]. CD8+PLZF+ and Vβ11+PLZF+T cells in the asthma group were significantly outnumbered than those in the control group ( P<0.05). Logistic regression and ROC curve analysis showed that PLZF expression in PBMC was a risk factor for the development of asthma ( OR =3.67, AUC=0.87, P<0.05). Conclusions:The high expression of PLZF in peripheral blood may play an important role in the development of asthma, which needs to be further confirmed by large sample studies.

Objective:To analyze the clinical characteristics of children with 2019 novel coronavirus (2019-nCoV) infection in Putian City, and to provide a reference for the diagnosis and treatment of children with 2019-nCoV infection.Methods:Clinical characteristics, laboratory examination, pulmonary compated tomography findings, treatment, and clinical outcomes of 78 children with 2019-nCoV infection who were admitted to Putian University Affiliated Hospital Medical Group Putian City Children′s Hospital from September 10 to October 20, 2021 were retrospectively collected and analyzed.Results:Of the 78 children included in the analysis, two cases (2.6%) were asymptomatic infection, 36 cases (46.2%) were mild and 40 cases (51.3%) were ordinary. Five children were vaccinated against 2019-nCoV. The main symptoms were fever (24 cases), cough (13 cases), and fatigue (nine cases). A total of 34 cases (43.6%) had neutropenia, 29 cases (37.2%) had lymphopenia, 36 cases (46.2%) had D-dimer increase, 38 cases (48.7%) had hypokalemia, 27 cases (34.6%) had hypoglycemia and 11 cases (14.1%) had elevated creatine kinase isoenzyme. The neutropenia mostly occurred two to four days after admission. Fifty-six cases (71.8%) showed pulmonary computed tomography abnormalities. The cycle threshold of virus open reading frame ( ORF)1 ab was 20.90±7.15 and the cycle threshold of N gene was 20.29±7.78 in the first nucleic acid detection of 78 children after admission. The time of nucleic acid negative conversion of the 78 children was (20.73±6.94) days. IgM antibody titer in five vaccinated children was 0.36 (0.34, 4.89) and IgG antibody was 10.42 (0.50, 19.42). IgM antibody titer was 1.82 (1.66, 8.12) and IgG antibody was 76.63 (16.92, 79.84) in cases with disease duration ≥10 days. Nine children (11.5%) had resurgence of virus and were sent to the isolation site. All the other children were cured and discharged from hospital. Conclusions:Children with 2019-nCoV infection have mild clinical symptoms, and some children have lymphopenia, neutropenia, and D-dimer elevation during the course of the disease. The overall prognosis is good. The children vaccinated against 2019-nCoV have higher antibody levels.

Objective:To retrieve, evaluate, and summarize the best evidence for the assessment of gastrointestinal function in critically ill patients by bedside ultrasound.Methods:Guidelines, evidence summaries, group standards, expert consensus, systematic reviews, and randomized controlled trials on the assessment of gastrointestinal function in critically ill patients by bedside ultrasound were retrieved by computer on domestic and foreign guideline websites, society websites and databases based on evidence-based nursing. The search period was from January 1, 2010 to April 30, 2021. The quality of the article was independently assessed by two researchers using the Appraisal of Guidelines for Research and Evaluation Ⅱ and the critical appraisal tool of the Joanna Briggs Institute (JBI) in Australia (2016) . Combined with the judgment of the research team, the data from the article that met the criteria were extracted and the evidence was graded and recommended according to the JBI quality level of evidence system (2014 Edition) .Results:A total of 22 articles were included, involving 5 guidelines, 1 evidence summary, 1 group standard, 6 expert consensuses, 4 systematic reviews, and 5 randomized controlled trials. A total of 33 pieces of evidence were summarized from 6 aspects, namely, the feasibility of nurses applying bedside ultrasound, fundamentals of ultrasound assessment of gastrointestinal tract, ultrasound assessment of gastric contents, ultrasound assessment of gastric motility, ultrasound assessment of bowel, ultrasound guided enteral nutrition program.Conclusions:Nurses who have been systematically trained can use ultrasound to assess gastrointestinal function in critically ill patients in real time. Ultrasound-guided enteral nutrition for critically ill patients needs to be standardized and improved, and many studies need to be carried out.

COVID-19 ; Coronavirus Nucleocapsid Proteins ; Humans ; Nucleocapsid Proteins ; Phosphoproteins ; SARS-CoV-2

Genomic studies of cancer cell alterations,such as mutations,copy number variations(CNVs),and translocations,greatly promote our understanding of the genesis and development of cancers.However,the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical difficulties.To explore the 3D genome structure in clin-ical lung cancer,we performed Hi-C experiments using paired normal and tumor cells harvested from patients with lung cancer,combining with RNA sequenceing analysis.We demonstrated the feasibility of studying 3D genome of clinical lung cancer samples with a small number of cells(1×104),compared the genome architecture between clinical samples and cell lines of lung cancer,and identified conserved and changed spatial chromatin structures between normal and cancer sam-ples.We also showed that Hi-C data can be used to infer CNVs and point mutations in cancer.By integrating those different types of cancer alterations,we showed significant associations between CNVs,3D genome,and gene expression.We propose that 3D genome mediates the effects of cancer genomic alterations on gene expression through altering regulatory chromatin structures.Our study highlights the importance of analyzing 3D genomes of clinical cancer samples in addition to cancer cell lines and provides an integrative genomic analysis pipeline for future larger-scale studies in lung cancer and other cancers.