Objective To investigate the effects and related mechanisms of mitochondrial-derived peptide MOTS-c on glycochenodeoxycholic acid (GCDCA)-induced injury in human hepatocytes (THLE-3 cells). Methods THLE-3 cells were cultured in vitro and treated with different concentrations of GCDCA and MOTS-c. The optimal concentrations of GCDCA and MOTS-c were determined by cell counting kit (CCK)-8 method. Subsequently, THLE-3 cells were treated or pre-treated with GCDCA (200 µmol/L), MOTS-c (15, 30, 60 µmol/L), the multidrug resistance protein 2 (MRP2) inhibitor Probenecid (500 µmol/L), and the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385 (10 µmol/L). Cell proliferation was assessed by CCK-8 method. Lactate dehydrogenase (LDH) levels in the culture medium were measured by biochemical method. Cell apoptosis rates were determined by flow cytometry. MRP2 messenger RNA (mRNA) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). MRP2 and Nrf2 protein expression levels were analyzed by Western blotting. Results As the concentration of GCDCA increased, the proliferation activity of THLE-3 cells gradually decreased, while LDH activity in the culture medium and apoptosis levels increased, and the expression levels of MRP2 in the cells decreased (all P<0.05). Treatment with 30 and 60 µmol/L MOTS-c significantly enhanced the proliferation activity of THLE-3 cells exposed to GCDCA, upregulated the expression of MRP2 and Nrf2, and reduced LDH activity and apoptosis levels (all P<0.05). Co-treatment with Probenecid partially reversed the protective effects of MOTS-c on GCDCA-induced THLE-3 cells injury, while co-treatment with ML385 partially inhibited the induction of MRP2 expression by MOTS-c in THLE-3 cells exposed to GCDCA. Conclusions MOTS-c may alleviate GCDCA-induced injury in human hepatocytes (THLE-3 cells), and its mechanism may be related to the upregulation of MRP2 expression mediated by Nrf2.

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

ObjectiveTo explore the role and molecular mechanism of Weifuchun （WFC） in inhibiting inflammation and alleviating gastric precancerous lesions （GPL）. MethodHuman gastric mucosal epithelial cells （GES-1） were stimulated with N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） for the modeling of GPL （MC cells）， with Caspase-3 inhibition by Z-DEVD-FMK. MC cells were divided into control （20% blank serum）， WFC （15% and 20% WFC-containing serum）， and caspase-3 inhibitor groups. The cell counting kit-8 （CCK-8） was used to examine the viability of GES-1 cells or MC cells. The Transwell assay and 5-acetylidene-2′-deoxyuridine （EdU） staining were employed to examine cell invasion and proliferation， respectively. Flow cytometry was employed to determine the level of reactive oxygen species. Real-time PCR was conducted to determine the mRNA levels of interleukin （IL）-1， IL-6， and tumor necrosis factor （TNF）-α. Gene Expression Omnibus （GEO） was used to analyze the role of pyroptosis in gastric cancer progression. Western blotting was employed to determine the protein levels of nuclear factor-κB （NF-κB） p65， gasdermin E （GSDME）， and Caspase-3. Immunofluorescence staining was employed to detect the NF-κB p65 protein level and nuclear translocation. Hematoxylin-eosin staining was carried out to observe the pathological changes in the gastric mucosa before and after WFC treatment in the patients. ResultCompared with the control group， MC cells presented enhanced proliferation and invasion energy （P<0.01）. Compared with the blank serum group， WFC-containing serum inhibited the proliferation and invasion of MC cells （P<0.01）， down-regulated the mRNA levels of IL-1， IL-6， and TNF-α， and lowered the level of reactive oxygen species （P<0.05， P<0.01）. The transcriptome data at different stages of gastric cancer showed that pyroptosis was involved in gastric cancer progression， and the GSDME level was significantly higher in GPL patients than in the normal group. Compared with the blank serum， WFC-containing serum lowered the level of NF-κB and inhibited the nuclear translocation of NF-κB （P<0.05）， and it inhibited pyroptosis by suppressing the cleavage of Caspase-3 on GSDME （P<0.05， P<0.01）. The analysis of patient specimens further demonstrated that WFC treatment down-regulated the NF-κB level and GSDME cleavage （P<0.01）， inhibited pyroptosis， and alleviated gastric mucosal inflammation and intestinal epithelial metaplasia. ConclusionPyroptosis is involved in the progression of gastric cancer， and WFC inhibits pyroptosis via the NF-κB/GSDME pathway， thereby alleviating gastric mucosal inflammation in GPL.

Urine nontargeted metabolomics technology was developed for investigating the effect and mechanism of improving learning and memory ability in APP/PS1 mice of Psoralea corylifolia. All animal experiments were approved by the Animal Ethics Committee of Heilongjiang University of Chinese Medicine (Approval No.: 2020092502). Sixteen APP/PS1 mice were randomly divided into the model group and Psoralea corylifolia group (0.5 g·kg^-1), and eight male C57BL/6J mice of the same background were selected as control group, step-through test and novel object recognition were used as evaluation indexes. Changes in urine endogenous metabolites of mice from eachgroup were determined by ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS), and differential metabolites were screened, and metabolic pathway enrichment analysis was performed. The results of pharmacodynamic investigation showed that Psoralea corylifolia can reduce the dark incubation period and number of errors in APP/PS1 mice (P < 0.01) and improve the new object recognition index of APP/PS1 mice (P < 0.01). Metabolomics analysis identified 15 differential metabolites, and 9 differential metabolites were significantly call back by Psoralea corylifolia. Metabolic pathway analysis showed that histidine metabolism, citric acid cycle, taurine and hypotaurine metabolism and glucose metabolism were the main metabolic pathways of Psoralea corylifolia in improving learning and memory ability. These studies suggest that Psoralea corylifolia improves the learning and memory ability of APP/PS1 mice, and its mechanism may be related to improving mitochondrial dysfunction, reducing peripheral histamine level, regulating energy metabolism disorders and antioxidant levels.

Objective:To summarize the best evidence for non-pharmacological management of postoperative delirium in adult liver transplant recipients, providing reference for postoperative delirium management in liver transplant recipients.Methods:Evidence on non-pharmacological management of postoperative delirium in adult liver transplant recipients was retrieved through computer in databases such as UpToDate, British Medical Journal (BMJ) Best Practice, Embase, PubMed, Cochrane Library, Joanna Briggs Institute Evidence-Based Health Care Center Database, Guidelines International Network, China Biology Medicine disc, China National Knowledge Infrastructure, WanFang Data, and VIP. The search period was from database establishment to January 31, 2023. The types of literature included guidelines, clinical decision-making, best practices, systematic review, summary of evidence, and expert consensus. Two researchers conducted quality evaluation and evidence extraction on the included literature.Results:A total of 10 articles were included, involving 1 clinical decision-making, 4 guidelines, 3 systematic reviews, and 2 expert consensuses. A total of 25 best pieces of evidence for non-pharmacological management of postoperative delirium in adult liver transplant recipients were summarized from four aspects, including screening, evaluation, non-pharmacological prevention, and non-pharmacological treatment.Conclusions:The best evidence on non-pharmacological management of postoperative delirium in adult liver transplant recipients summarized provides a reference for postoperative delirium management in liver transplant recipients.

Objective:To explore the relationship between individual resilience, work stress, and work engagement among nurses in Emergency Department.Methods:A questionnaire survey was conducted on 350 nurses from six Class Ⅲ Grade A hospitals in Shandong Province from April to September 2022, using the General Information Questionnaire, the Chinese version of the Stressor Scale for Emergency Nurse, the Chinese version of the Utrecht Work Engagement Scale, and the Medical Staff Composition Resilience Scale. Pearson correlation was used to analyze the correlation between nurse work stress, work engagement, and individual resilience. The structural equation model was constructed using a mediating effect testing program to analyze the relationships between variables.Results:A total of 350 questionnaires were distributed, and 330 valid questionnaires were collected, with an effective response rate of 94.28%. The scores of nurse work engagement, work stress, and individual resilience were (54.26±10.08), (77.36±25.48), and (67.76±12.33), respectively. Work stress was negatively correlated with work engagement and individual resilience (all P<0.01), while individual resilience was positively correlated with work engagement ( P<0.01). Individual resilience was a mediating variable between work stress and work engagement among nurses in Emergency Department, with a mediating effect accounting for 31.38% of the total effect. Conclusions:Most nurses of Emergency Department have moderate levels of work stress, work engagement, and individual resilience. Individual resilience partially mediates the relationship between work stress and work engagement among nurses in Emergency Department. Nursing managers should attach importance to the organizational culture atmosphere and develop corresponding measures to enhance the individual resilience of nurses and encourage them to be energetic and enthusiastic in their work.

Objective:To study therapeutic effect of Qiliqiangxin capsule combined Xinhuosu on refractory heart fail-ure(RHF)and its influence on miR-132 and miR-155.Methods:A total of 100 RHF patients treated in our hos-pital were divided into Xinhuosu group(received Xinhuosu based on routine treatment)and combined treatment group(received Qiliqiangxin capsule based on Xinhuosu group).Both groups were treated for one month.Serum levels of N-terminal pro-brain natriuretic peptide(NT-proBNP),transforming growth factor(TGF)-β1,ma-trix metalloproteinase(MMP)-9,interleukin(IL)-6,tumor necrosis factor(TNF)-αand soluble intercellu-lar adhesion molecule-1(sICAM)-1,expression levels of miR-132 and miR-155 before and after treatment and total effective rate were compared between two groups.Results:Compared with Xinhuosu group,after treat-ment,there were significant reductions in serum levels of NT-proBNP[(2838.76±380.26)pg/ml vs.(2450.53±289.83)pg/ml],TGF-β1[(39.74±5.40)μg/ml vs.(35.34±4.72)μg/ml],MMP-9[(276.62±30.61)ng/L vs.(230.37±27.86)ng/L],IL-6[(7.09±1.54)ng/L vs.(5.10±1.25)ng/L],TNF-α[(90.11±16.38)ng/L vs.(63.82±12.25)ng/L]and sICAM-1[(239.30±45.30)ng/ml vs.(192.33±34.41)ng/ml],and ex-pression level of miR-155[(1.37±0.22)vs.(1.24±0.22)],and significant rise in expression level of miR-132[(1.47±0.24)vs.(1.62±0.33)]in combined treatment group(P＜0.05 or＜0.01).Total effective rate of combined treatment group was significantly higher than that of Xinhuosu group(94.00%vs.76.00%,P=0.012).Conclusion:Qiliqiangxin capsule combined Xinhuosu can significantly improve clinical therapeutic effect,relieve my-ocardial injury,improve myocardial fibrosis and ventricular remodeling,alleviate inflammatory response and regu-late expression of miR-132 and miR-155 in patients with refractory heart failure.

Objective:To evaluate the clinical efficacy and safety of retrograde intrarenal surgery(RIRS) and miniaturized percutaneous nephrolithotomy(mini-PCNL) in the treatment of lower pole kidney stones with a diameter <1.5 cm.Methods:The data of 95 patients with lower pole kidney stones with a diameter <1.5 cm treated in Renmin Hospital of Wuhan University from June 2017 to October 2020 were retrospectively analyzed. According to different surgical methods, the patients were divided into RIRS group and mini-PCNL group. There were 51 cases in RIRS group and 44 cases in mini-PCNL group. There was no significant difference in age [(48.2±11.4) years vs. (46.4±14.1) years], body mass index [(21.9±2.4) kg/m 2 vs. (20.7±3.2) kg/m 2], gender [male/female: 37/14 vs. 24/20], stone CT [(746.42±164.24)HU vs. (858.62±148.72)HU], creatinine [(71.3±21.6)μmol/L vs. (63.5±20.3)μmol/L], stone location (left/right: 26/25 vs. 23/21), stone diameter [(10.5±2.1) mm vs. (12.5±2.4) mm], infundibulopelvic angle [(43.32±9.42) degrees vs. (43.82±10.34) degrees], infundibular length [(24.92±4.85)mm vs. (24.37±5.26)mm] and infundibular [(9.26±3.04)mm vs.(9.46±2.94)mm] between the two groups ( P>0.05). The operation time, stone-free rate, hospital stay and postoperative complications between the two groups were compared. Results:Compared with the mini-PCNL group, the RIRS group had significantly smaller decrease in postoperative hemoglobin [(1.53±0.92) g/L vs. (4.54±2.46) g/L, P<0.05], the postoperative hospital stay was shorter [(2.52±0.94) d vs. (4.51±1.25)d, P<0.05], and postoperative visual analogue score was lower [(2.43±0.92) vs. (3.24±0.76), P<0.05]. The operation time of the mini-PCNL group was shorter than that of the RIRS group [(42.32±13.28) min vs. (54.24±14.43)min, P<0.05]. There was no significant difference in postoperative complications [5.9% (3/51) vs. 11.4% (5/44), P>0.05], postoperative cveatinine [(71.3±21.6) μmol/L vs. (63.5±20.3) μmol/L, P>0.05], postoperative intestinal function recovery time [(25.46±10.28)h vs. (32.43±9.25)h, P>0.05] and stone-free rate [92.2% (47/51) vs. 97.7% (43/ 44), P>0.05] between the two groups. Conclusions:Both RIRS and mini-PCNL are effective and safe minimally invasive treatments for lower pole kidney stones with a diameter < 1.5 cm. RIRS has shorter operation time, less blood loss, lower pain score and faster postoperative recovery.

Objective:To explore the feasibility and clinical outcomes of punch excision combined with superficial X-ray and intralesional drug injection in the treatment of chest multiple keloids.Methods:Patients with chest multiple keloids in Dermatology Hospital of Southern Medical University from March 2020 to June 2021 were selected and randomly divided into observation group and control group according to random number table. In the observation group, punch excision was performed first, superficial X-ray was irradiated once within 24 h after surgery, and then once a week, for a total of 4 sessions. One week after radiotherapy, intralesional injection was performed with 5 ml mixture of 1 ml triamcinolone acetate injection, 0.6 ml fluorouracil injection and 3.4 ml 2% lidocaine hydrochloride injection, once a month, for a total of 4 times. Single injection endpoint reaction was keloid whiteness. The control group did not receive punch excision, and other treatments were the same as those in the observation group. Vancouver scar scale (VSS) score and efficacy evaluation (cure, excellent, improvement, ineffective) were performed before treatment and 3, 6, 12 months after treatment. Total keloids volume, intralesional injection volume and adverse reactions before and after treatment were recorded. SPSS 26.0 software was used for data analysis, and the measurement data were expressed as Mean±SD. Independent sample t-test was used for comparison between two groups, and repeated measurement data analysis of variance was used for comparison before and after treatment in the same group. Statistical data were expressed as % and χ2 test was used for comparison between groups. P<0.05 was considered statistically significant. Results:A total of 58 patients were included, 29 in each group. There were 36 males and 22 females. The age ranged from 18 to 59 years old, with an average age of 29. The number of chest keloids in each patient was 5-12. Before treatment, the VSS scores of observation group and control group was 13.21±1.24 and 12.90±1.21 respectively. There was no significant difference in VSS scores between the two groups before treatment ( t=0.97, P=0.337). After 3, 6 and 12 months of follow-up, the VSS scores of the observation group were 4.21±1.26, 4.34±1.40 and 4.55±1.33 respectively, while those of the control group were 5.66±1.32, 6.07±1.44 and 6.62±1.40 respectively. The differences between the two groups were statistically significant ( t=-4.27, -4.63, -5.78, all P<0.001). Intra-group comparison showed that there were no statistically significant differences in VSS scores at 3, 6 and 12 months after treatment in the observation group ( F=2.50, P=0.111), while VSS scores at 3, 6 and 12 months after treatment in the control group showed a gradually increasing trend, with statistically significant difference ( F=30.75, P<0.001). In the observation group, 22 cases showed excellent effect, 7 cases improved, and the excellent rate was 75.86%(22/29). In the control group, there were 6 cases of excellent effect and 23 cases of improvement, the excellent rate was 20.69%(6/29), and the difference between the two groups was statistically significant ( χ2=17.68, P<0.001). Before treatment, the total keloids volume of the observation group was (7.76±1.71) cm 3, which was (8.27±1.26) cm 3 of the control group, and there was no significant difference between the two groups before treatment ( t=-1.28, P=0.207). In the follow-up of 12 months after treatment, the total keloids volume of the observation group[(2.57±0.59) cm 3] was significantly smaller than that of the control group[(5.51±1.39) cm 3], and the difference was statistically significant ( t=-10.47, P<0.001). The total amount of intralesional injection in the observation group[(6.45±1.25) ml] was less than that in the control group[(11.00±1.73) ml], and the difference was statistically significant ( t=-11.48, P<0.001). Transient hyperpigmentation appeared in the irradiation area 3-5 days after superficial X-ray, which subsided naturally within 6 months in both groups. In addition, there were 5 adverse reactions in the observation group, including delayed healing (2 cases), telangiectasia (2 cases) and abnormal menstrual cycle (1 case). There were 13 cases of adverse reactions in the control group, including telangiectasia (7 cases), abnormal menstrual cycle (2 cases), and atrophic and sunken skin (4 cases). The incidence of adverse reactions in the observation group was significantly lower than that in the control group, and the difference was statistically significant [17.24%(5/29) vs. 44.83%(13/29), χ2=5.16, P<0.001]. Conclusion:Punch excision combined with superficial X-ray and intralesional drug injection for the treatment of chest multiple keloids has the advantages of simple operation, good therapeutic effect and less adverse reactions.

Objective:To explore the feasibility and clinical outcomes of punch excision combined with superficial X-ray and intralesional drug injection in the treatment of chest multiple keloids.Methods:Patients with chest multiple keloids in Dermatology Hospital of Southern Medical University from March 2020 to June 2021 were selected and randomly divided into observation group and control group according to random number table. In the observation group, punch excision was performed first, superficial X-ray was irradiated once within 24 h after surgery, and then once a week, for a total of 4 sessions. One week after radiotherapy, intralesional injection was performed with 5 ml mixture of 1 ml triamcinolone acetate injection, 0.6 ml fluorouracil injection and 3.4 ml 2% lidocaine hydrochloride injection, once a month, for a total of 4 times. Single injection endpoint reaction was keloid whiteness. The control group did not receive punch excision, and other treatments were the same as those in the observation group. Vancouver scar scale (VSS) score and efficacy evaluation (cure, excellent, improvement, ineffective) were performed before treatment and 3, 6, 12 months after treatment. Total keloids volume, intralesional injection volume and adverse reactions before and after treatment were recorded. SPSS 26.0 software was used for data analysis, and the measurement data were expressed as Mean±SD. Independent sample t-test was used for comparison between two groups, and repeated measurement data analysis of variance was used for comparison before and after treatment in the same group. Statistical data were expressed as % and χ2 test was used for comparison between groups. P<0.05 was considered statistically significant. Results:A total of 58 patients were included, 29 in each group. There were 36 males and 22 females. The age ranged from 18 to 59 years old, with an average age of 29. The number of chest keloids in each patient was 5-12. Before treatment, the VSS scores of observation group and control group was 13.21±1.24 and 12.90±1.21 respectively. There was no significant difference in VSS scores between the two groups before treatment ( t=0.97, P=0.337). After 3, 6 and 12 months of follow-up, the VSS scores of the observation group were 4.21±1.26, 4.34±1.40 and 4.55±1.33 respectively, while those of the control group were 5.66±1.32, 6.07±1.44 and 6.62±1.40 respectively. The differences between the two groups were statistically significant ( t=-4.27, -4.63, -5.78, all P<0.001). Intra-group comparison showed that there were no statistically significant differences in VSS scores at 3, 6 and 12 months after treatment in the observation group ( F=2.50, P=0.111), while VSS scores at 3, 6 and 12 months after treatment in the control group showed a gradually increasing trend, with statistically significant difference ( F=30.75, P<0.001). In the observation group, 22 cases showed excellent effect, 7 cases improved, and the excellent rate was 75.86%(22/29). In the control group, there were 6 cases of excellent effect and 23 cases of improvement, the excellent rate was 20.69%(6/29), and the difference between the two groups was statistically significant ( χ2=17.68, P<0.001). Before treatment, the total keloids volume of the observation group was (7.76±1.71) cm 3, which was (8.27±1.26) cm 3 of the control group, and there was no significant difference between the two groups before treatment ( t=-1.28, P=0.207). In the follow-up of 12 months after treatment, the total keloids volume of the observation group[(2.57±0.59) cm 3] was significantly smaller than that of the control group[(5.51±1.39) cm 3], and the difference was statistically significant ( t=-10.47, P<0.001). The total amount of intralesional injection in the observation group[(6.45±1.25) ml] was less than that in the control group[(11.00±1.73) ml], and the difference was statistically significant ( t=-11.48, P<0.001). Transient hyperpigmentation appeared in the irradiation area 3-5 days after superficial X-ray, which subsided naturally within 6 months in both groups. In addition, there were 5 adverse reactions in the observation group, including delayed healing (2 cases), telangiectasia (2 cases) and abnormal menstrual cycle (1 case). There were 13 cases of adverse reactions in the control group, including telangiectasia (7 cases), abnormal menstrual cycle (2 cases), and atrophic and sunken skin (4 cases). The incidence of adverse reactions in the observation group was significantly lower than that in the control group, and the difference was statistically significant [17.24%(5/29) vs. 44.83%(13/29), χ2=5.16, P<0.001]. Conclusion:Punch excision combined with superficial X-ray and intralesional drug injection for the treatment of chest multiple keloids has the advantages of simple operation, good therapeutic effect and less adverse reactions.