AIM: To predict the core targets and related signaling pathways of Yi-xin-yin oral liquid for the treatment of arrhythmia, heart failure and myocarditis based on UHPLC-Q-TOF/MS, network pharmacology, molecular docking methods, cell experiments, according to the“homotherapy for heteropathy”theory in traditional Chinese medicine. METHODS: UHPLC-Q-TOF / MS was used to analyze and identify the chemical composition of Yi-xin-yin oral liquid Extract and the blood-absorbing components of rats oral administrated with Yi-xin-yin oral liquid extract, which compounds were applied in the databases searching for the potential targets (TCMSP, SwissTargetPrediction) and disease targets (OMIM, Genecard). Venn diagram was used for target intersection, and the subsequent protein-protein interaction network obtained core targets by STRING11.5 database, and then construct a "disease-component-target" network by cytoscape3.9.0. Finally, DAVID database was used to analysis GO function and KEGG enrichment analysis of core targets, and molecular docking validation was performed using Autodock vina software. And, validated with H9c2 cells for potential active ingredients and targets. RESULTS: A total of 156 compounds were identified from Yi - xin-yin Oral Liquid extract; 34 compounds were identified from rat serum, including 6-gin-gerol, isoliquiritigenin, glycyrrhizic acid and other compounds, and 139 intersecting targets were obtained. The KEGG pathway enrichment analysis mainly involved the TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway and so on. The TNF and IL-6 targets were selected for molecular docking with the main compounds, and the docking results were good (less than -5 kcal/mol). In vitro cellular experiments have shown that Yi-xin-yin oral liquid can exert therapeutic effects by regulating TNF and IL-6. CONCLUSION: The main potential active ingredients of Yi-xin-yin oral liquid may be isoliquiritigenin, glycyrrhetinic acid, calycosin-7-glucoside, salvianolic acid B, and 6-gingerol, which mainly act on TNF, IL-6 and other targets to regulate specific signaling pathways and exert therapeutic effects.

Objective:To investigate the effects of unilateral ureteral obstruction on renal pelvic peristalsis and pacemaker cells in neonatal rats.Methods:An animal experimental study.Thirty-six 2-day-old newborn SD rats were randomly divided into the partial unilateral ureteral obstruction (PUUO) group, complete unilateral ureteral obstruction (CUUO) group, and sham operation group, with 12 rats in each group.One week after surgery, all rats were subjected to renal pelvic pressure (RPP) measurement by puncture.After measurement, the rats were euthanized, and their left renal pelvis and ureter were removed and fixed for histological examination.Parameters such as RPP, peristaltic wave frequency and amplitude at different perfusion speeds were recorded and compared, and the changes in pacemaker cells (atypical smooth muscle cells and Cajal-like interstitial cells) were also compared.The independent samples t-test was used for comparison between 2 groups, and the one-way ANOVA of variance was used for comparison among 3 groups. Results:In the sham operation group, the RPP increased gradually with the increase of perfusion speed; the frequency of peristaltic waves rose rapidly and then dropped after reaching the highest level with the increase of perfusion speed; similarly, the amplitude of peristaltic waves first increased and then decreased as the perfusion speed increased.In the PUUO group, the RPP increased rapidly with the increase of perfusion speed, higher than that in the sham operation group; the frequency of peristaltic waves was higher than that in the sham operation group, and it was relatively constant under the perfusion speed of 40 mL/h, but when the perfusion speed increased again, the frequency began to decline; the amplitude of peristaltic waves increased quickly and then declined at a faster rate than the sham operation group with the increase of perfusion speed.In the CUUO group, the basic RPP was 12 cmH 2O(1 cmH 2O=0.098 kPa); at the perfusion speed of 5 mL/h, the RPP rose gradually, and no plateau appeared; when the RPP reached 73 cmH 2O, the perfusate retrograded from the side of the puncture needle, then the RPP slightly decreased and then balanced, and no regular peristaltic waves were observed in the renal pelvis throughout the whole perfusion process.Immunofluorescence staining analysis showed the pacemaker cells were all located in the smooth muscle of the renal pelvic wall.The sham operation group had the highest positive rate, followed by the PUUO group and then the CUUO group. Conclusions:Ureteral obstruction has a significant impact on the peristalsis of the renal pelvis, and its impact on the peristaltic wave frequency and amplitude and RPP can be predicted.The reduction of pacemaker cells in the renal pelvis may be involved in the changes of renal pelvic peristalsis caused by ureteral obstruction, but further research is needed on how pacemaker cells regulate the peristalsis of the renal pelvis and ureter.

Objective:To develop a recombinant protein vaccine based on KPC-2, a drug resistance target in Klebsiella pneumoniae, and evaluate its immunogenicity, protective efficacy and mechanism in a mouse model of pneumonia. Methods:KPC-2 was expressed in Escherichia coli and purified using GST affinity chromatography. A recombinant protein vaccine was prepared with KPC-2 and used to immunize New Zealand rabbits through subcutaneous injection. Serum samples were isolated from cardiac blood and Protein G chromatography was used to purify polyclonal antibodies against KPC-2. Opsonophagocytic killing assay was used to assess the bactericidal activity of the polyclonal antibodies in vitro. Female BALB/c mice were immunized three times with the recombinant protein vaccine, and the titers of specific IgG antibodies in serum were measured by indirect ELISA. One week after the last vaccination, the mice were infected with Klebsiella pneumoniae strain SRT through tracheal intubation, and received a single intravenous dose of meropenem (0.1 mg) 1 h later. The protective efficacy of the KPC-2 recombinant protein vaccine was evaluated by comparing the survival rates, bacterial colonization and histopathological changes between vaccine group and adjuvant group as well as the survival rates between meropenem group and normal saline group. Moreover, the protective efficacy of polyclonal antibodies against KPC-2 was evaluated through passive immunization. Results:The level of specific IgG antibodies in serum was significantly higher in the vaccine group than in the adjuvant group ( t=4.325, P<0.05). The survival rate in the vaccine group was also higher than that of the adjuvant group [70% (7/10) vs 10% (1/10), P<0.05]. Furthermore, lung inflammation was less severe and bacterial burden was reduced in the vaccine group as compared with those of the control group ( t=3.127, P<0.05). Both active and passive vaccination strategies demonstrated strong protective efficacy against Klebsiella pneumoniae infection, and had a synergistic effect when used in combination with antibiotic therapy. The polyclonal antibodies against KPC-2 had bactericidal activity in vitro ( t=5.427, P<0.05). Conclusions:The prepared KPC-2 vaccine has better immunogenicity and protective efficacy. It can induce strong humoral immune responses. This study suggest that drug resistance target may be used as a candidate antigen for future vaccine development.

Objective To investigate the protective effect of total saponins of Panax japonicus(TSPJ)against CCl4-induced acute liver injury(ALI)in rats and explore the underlying pharmacological mechanisms.Methods Male SD rat models of CCl4-induced ALI were given intraperitoneal injections of distilled water,100 mg/kg biphenyl bisabololol,or 50,100,and 200 mg/kg TSPJ during modeling(n=8).Liver functions(AST,ALT,TBil and ALP)of the rats were assessed and liver pathologies were observed with HE staining.Immunohistochemistry was used to detect the expressions of PI3K/Akt/NF-κB signaling pathway molecules in liver tissue;ELISA was used to determine the levels of T-SOD,GSH-Px,and MDA.Western blotting was performed to detect the expression levels of PI3K-Akt and SIRT6-NF-κB pathways in the liver tissue.Results Network pharmacological analysis indicated that the key pathways including PI3K/Akt mediated the therapeutic effect of TSPJ on ALI.In the rat models of ALI,treatments with biphenyl bisabololol and TSPJ significantly ameliorated CCl4-induced increase of serum levels AST,ALT,ALP,TBil and MDA and decrease of T-SOD and GSH-Px levels(all P<0.01).The rat models of ALI showed significantly increased expression of p-NF-κB(P<0.01),decreased expressions of PI3K,p-Akt and SIRT6 proteins,and elevated expression levels of p-NF-κB,TNF-α and IL-6 proteins in the liver,which were all significantly improved in the treatment groups(P<0.05 or 0.01).Conclusion TSPJ can effectively alleviate CCl4-induced ALI in rats by suppressing inflammatory responses and oxidative stress in the liver viaregulating the PI3K/Akt and SIRT6/NF-κB pathways.

Mesenchymal stem cell (MSC) has been shown to attenuate injuries in a variety of radiation animal models and has been explored for the treatment of radiation-induced patients, due to its potent immunomodulatory and tissue repair capabilities. Based on its high safety and multiple biological functions, MSC is expected to be used for the treatment of radiation sickness. In this review, the research progress of MSC and its secretions in the treatment of radiation-induced injuries was summarized, such as skin injury, intestinal injury, brain injury, acute radiation syndrome of the hematopoietic system, lung injury, liver injury, and cardiac injury.

Objective To investigate the protective effect of total saponins of Panax japonicus(TSPJ)against CCl4-induced acute liver injury(ALI)in rats and explore the underlying pharmacological mechanisms.Methods Male SD rat models of CCl4-induced ALI were given intraperitoneal injections of distilled water,100 mg/kg biphenyl bisabololol,or 50,100,and 200 mg/kg TSPJ during modeling(n=8).Liver functions(AST,ALT,TBil and ALP)of the rats were assessed and liver pathologies were observed with HE staining.Immunohistochemistry was used to detect the expressions of PI3K/Akt/NF-κB signaling pathway molecules in liver tissue;ELISA was used to determine the levels of T-SOD,GSH-Px,and MDA.Western blotting was performed to detect the expression levels of PI3K-Akt and SIRT6-NF-κB pathways in the liver tissue.Results Network pharmacological analysis indicated that the key pathways including PI3K/Akt mediated the therapeutic effect of TSPJ on ALI.In the rat models of ALI,treatments with biphenyl bisabololol and TSPJ significantly ameliorated CCl4-induced increase of serum levels AST,ALT,ALP,TBil and MDA and decrease of T-SOD and GSH-Px levels(all P<0.01).The rat models of ALI showed significantly increased expression of p-NF-κB(P<0.01),decreased expressions of PI3K,p-Akt and SIRT6 proteins,and elevated expression levels of p-NF-κB,TNF-α and IL-6 proteins in the liver,which were all significantly improved in the treatment groups(P<0.05 or 0.01).Conclusion TSPJ can effectively alleviate CCl4-induced ALI in rats by suppressing inflammatory responses and oxidative stress in the liver viaregulating the PI3K/Akt and SIRT6/NF-κB pathways.

Objective To explore the comparison of the clinical efficacy of laparoscopic cholecystectomy based on propensity score matching through the umbilical single hole method and three holes method in the treatment of acute cholecystitis.Methods 106 patients with acute cholecystitis who underwent laparoscopic cholecystectomy in our hospital from January 2020 to December 2022 were selected as research subjects.According to different treatment methods,they were divided into the study group(n=64)and the control group(n=42).The patients in the study group were treated with single port via umbilical laparoscopic cholecystectomy,while the control group was treated with three port laparoscopic cholecystectomy.Compare the surgical related indicators,postoperative recovery,and postoperative complications between the two groups of patients.Results Comparing the general information of the two groups of patients,there was no significant difference in body mass index(BMI),BMI,and gallbladder ultrasound results(P＞0.05),but the average age of the study group patients was greater than that of the control group patients(P＜0.05).By comparing the general data of the two groups of patients after propensity score matching,it was found that there was no significant difference in gender,age,BMI,and gallbladder ultrasonography results between the two groups(P＞0.05).The surgical time for the study group patients was(61.48±10.24)minutes,while for the control group,it was(40.42±8.35)minutes;And the visual analog scale(VAS)scores at 6 and 24 hours after surgery were(5.63±1.04)and(3.42±0.65)for the study group,respectively,while(7.22±1.61)and(5.48±1.02)for the control group.The pain sensation was more pronounced(P＜0.05);However,there was no statistically significant difference in blood loss during surgery between the two groups of patients(P＞0.05).The hospitalization time and gastrointestinal function recovery time of the study group patients were(2.05±0.42)days and(33.46±4.30)hours,respectively,while the control group was(3.95±1.02)days and(47.58±7.62)hours,respectively;And the satisfaction score of the study group patients with incision scars was(4.58±0.42)points,while the control group was(3.02±0.38)points(P＜0.05).The total incidence of complications in the study group was 2.78％,while in the control group it was 16.67％,significantly lower in the study group(P＜0.05).Conclusion Patients with acute cholecystitis treated with the umbilical single hole method have significantly lower postoperative pain,shorter hospital stay,and recovery time of gastrointestinal function compared to the three hole method.Patients also have higher scores of satisfaction with incision scars,and the overall incidence of postoperative complications is also lower.

Objective:To understand the current situation of nurses in 52 hospitals in China on mastery of knowledge about skin injury in the elderly based on the background of mixed-mode homogenization training.Methods:Using the convenient sampling method, a total of 1 067 nurses from 52 hospitals in China were selected as the research objects in January 2021. A self-designed questionnaire on knowledge of skin injury in the elderly was used to investigate the nurses through the questionnaire star and univariate analysis was used to analyze the influencing factors. A total of 1 067 questionnaires were distributed and 1 067 valid questionnaires were recovered, and the effective recovery rate was 100%.Results:The knowledge scores of pressure injury, incontinence-associated dermatitis, skin tear and xerosis cutis among 1067 nurses were (95.66±7.37) , (95.65±9.15) , (91.37±15.45) and (87.67±15.91) , respectively. The results of univariate analysis showed that hospital grade was the influencing factor of nurses' knowledge score of pressure injury, skin tear and incontinence-associated dermatitis ( P<0.05) , educational background was the influencing factor of nurses' knowledge score of skin tear ( P<0.05) , professional title was the influencing factor of nurses' knowledge scores of pressure injury, incontinence-associated dermatitis and xerosis cutis ( P<0.05) . Conclusions:Hospitals at all levels need to strengthen the theoretical and practical knowledge training for nurses on skin xerosis and skin tear in the elderly, especially for nurses with primary titles and lower education in grassroots hospitals.

AIM: The main chemical components of Yufang Fangji II (Hubei Fang) of COVID-19 were studied systematically and combined with network pharmacology to provide a reference for the study of its effective substances. METHODS: Ultra high-performance liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-Q-TOF/MS) was applied to identify the absorbed components of the prescription in rat plasma. TCMSP database and Swiss Target Prediction data platform were used to predict the target of the identified blood components, and network visualization software Cytoscape 3.7.2 was used draw the association network diagram, and GO enrichment analysis and KEGG pathway enrichment analysis were conducted for the key targets. With the help of CB-Dock online molecular docking platform, the molecular docking of key targets and blood entering compounds was carried out, and the docking combination with good affinity value was displayed by ligplot software to verify the preventive effect of Yufang Fangji II on COVID-19. RESULTS: A total of 52 chemical components identified in the prescription, in which 13 components were absorbed in the rat plasma as the prototype, and they were from Astragalus membranaceus, Atractylodes macrocephala, Saposhnikoviae Radix, Lonicerae Japonicae Flos, and Citri Reticulatae Pericarpium, respectively. These compounds were recognized to act on 17 core targets, including mapk3, TNF and other targets related to inflammation, MPO and other targets related to oxidative stress, VEGFR, KDR and other targets related to vascular endothelium. The results of molecular docking showed that the absorbed components had good binding activity with the key targets. CONCLUSION: Compounds in Yufang Fangji II are involved in regulating inflammation, oxidative stress, vascular and cellular physiological activities, which have preventive effects on COVID-19 through regulating IL-17, PI3K Akt, MAPK and other pathways.

Intrahepatic cholangiocarcinoma is a malignant tumor that originates from the bile duct above the confluence of left and right hepatic ducts, and is one of the commonest types of primary liver cancer. The early symptoms of intrahepatic cholangiocarcinoma are not obvious, most patients with non-specific abdominal symptoms in the advanced stage. CT, MRI, etc. are helpful for diagnosis, but most patients are in advanced stage when they are diagnosed. Hepatectomy is the main treatment, radiotherapy, chemotherapy are significant adjuvant treatment, and the overall prognosis is poor. This article reviews the current status and progress in diagnosis and treatment of intrahepatic cholangiocarcinoma.