Objective:To analyze the blood differential metabolites of patients with intrahepatic cholestasis (IHC) by liquid chromatography-mass spectrometry metabolomics technology so as to find potential metabolic target.Method:Serum samples were collected from thirty patients with intrahepatic cholestasis and thirty healthy individuals after metabolomics analysis. The differential metabolites were initially screened based on the multiple differences and significance. KEGG enrichment analysis was performed on the differential metabolites to determine the candidate targets. The potential clinical application value of these characteristic metabolites was analyzed using the receiver operating characteristic curve.Result:A total of thirty patients with intrahepatic cholestasis and thirty healthy adults were included. The age difference between the two groups was not statistically significant ( P>0.05). The clinical condition was consistent with the statistically significant differences in liver biochemical indicators, blood routine, coagulation, and inflammatory indicators between the two groups ( P<0.05). Furthermore, a blood metabolomics screening analysis revealed 99 differentially expressed metabolites associated with intrahepatic cholestasis. Of these, 15 showed statistically significant differences. Glucose, lipid, and energy metabolisms were the various primary types of differential metabolites involved. The receiver operating characteristic curve>0.9 included the following twelve kinds of metabolites: 1H-indole-3-carboxaldehyde, 6-hydroxy-1H-indole-3-acetamide, phenylalanyl tryptophan, 1-methylguanosine, 2-ethoxy-5-methylpyrazine, p-hydroxybenzaldehyde, 5-(2-chlorophenyl)-3,4-dihydro-2H-pyrrole, methylthioadenosine, alanylisoleucine, anabsinthin, N-acetyl-DL-histidine monohydrate, N-methylnicotinamide, and others. The fifteen metabolites that were previously identified and calculated according to the differential quantitative value of the metabolite corresponding ratio exhibited fold-changes in the upregulated and downregulated potential biomarkers (phenylalanine tryptophan, phenylalanine, 5'-methylthioadenosine, anabsinthin, and N-methylnicotinamide) in combination with the area under the receiver operating characteristic curve>0.9. Conclusion:Phenylalanyl tryptophan, phenylalanylalanine, 5'-methylthioadenosine, anabsinthin, and N-methylnicotinamide may serve as potential metabolic markers to distinguish patients with cholestasis from healthy controls. N-methylnicotinamide, among them, is of great importance as a potential marker.

Objective To investigate the regulatory effect of miRNA-933 on the apoptosis and proliferation of human hepatic stellate cell line LX-2 and its mechanism.Methods Firstly,with human liver tissue for research,gene microarray technology was used to detect the differentially expressed genes in liver tissue between liver cirrhosis/chronic hepatitis B tissue and normal liver tissue,among which the significantly differentially expressed miRNAs were identified,and thus miRNA-933 was determined as the research object.Then,with the human hepatic stellate cell line LX-2 for research,miRNA-933 mimic and inhibitor(miRNA-933 siRNA)were used to construct the LX-2 models of overexpression and knockdown,and the cells transfected with mimic-NC(overexpression)or siRNA-NC(knockdown)were established as the negative control group.Quantitative real-time PCR and Western blot were used to measure the expression levels of miRNA-933 and activation biomarkers;techniques such as cell proliferation assay and flow cytometry were used to investigate the effect and mechanism of miRNA-933 on cell apoptosis,proliferation,and activation.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 Bonferroni correction was also performed.Results A total of 18 significantly differentially expressed miRNAs were obtained based on the results of gene microarray,among which miRNA-933 was significantly downregulated(P<0.05).After LX-2 cells were transfected with miRNA-933 mimic or siRNA,compared with the negative control group,miRNA-933 siRNA significantly downregulated the expression of miRNA-933(P=0.000 7),while miRNA-933 mimic significantly upregulated the expression of miRNA-933(P=0.000 3).Western blot and quantitative real-time PCR showed that miRNA-933 siRNA significantly upregulated the expression of collagen Ⅰ and α-SMA(P<0.001),while miRNA-933 mimic significantly inhibited the expression of collagen Ⅰ and α-SMA(P<0.05).Flow cytometry showed that compared with the negative control group,miRNA-933 siRNA significantly downregulated the apoptosis rate of LX-2 cells(P=0.031 9),and miRNA-933 mimic significantly upregulated the apoptosis rate of LX-2 cells(P=0.005 5).Western blot showed that compared with the negative control group,miRNA-933 siRNA could inhibit the expression of Caspase-3(P=0.006 7)and poly(ADP-ribose)polymerase-1(PARP-1)(P=0.003 0)and upregulate the expression of B-cell lymphoma-2(Bcl-2)in LX-2 cells(P=0.002 0),while miRNA-933 mimic could significantly upregulate the expression of Caspase-3(P=0.011 8)and PARP-1(P=0.049 5)and downregulated the expression of Bcl-2(P=0.002 1).Cell proliferation assay showed that compared with the negative control group,miRNA-933 siRNA could promote the proliferation of LX-2 cells(P=0.011 5),while on the contrary,miRNA-933 mimic could inhibit the proliferation of LX-2 cells(P=0.001 2).Western blot and quantitative real-time PCR showed that miRNA-933 siRNA significantly inhibited the expression of Kruppel-like factor 6(KLF6)and downregulated the expression of activating transcription factor 4(ATF4),activating transcription factor 3(ATF3),and C/EBP homologous protein(CHOP),while miRNA-933 mimic promoted the expression of the above proteins(all P<0.05).Conclusion This study shows that miRNA-933 may promote cell apoptosis and inhibit cell activation and proliferation by promoting the activation of the KLF6/ATF4/ATF3/CHOP/Bcl-2 signal axis in LX-2 cells.

Objective:To discuss the protective effect of sodium butyrate(NaB)on acute liver injury in the mice induced by lipopolysaccharide(LPS)combined with D-galactosamine(D-Gal),and to clarify its mechanism.Methods:Thirty male Kunming mice were randomly divided into control group,model group,and NaB group,and there were 10 mice in each group.The mice in NaB group were given 200 mg·kg-1·d-1 NaB,while the mice in control group and model group were given an equal volume of sterile water.The mice in model group and NaB group were intraperitoneally injected with 20 μg·kg-1 LPS and 600 mg·kg-1 D-Gal to induce the acute liver injury models.The body weights and liver weights of the mice in various groups were detcted,and the liver index was calculated.HE staining was used to observe the pathomorphology of liver tissue of the mice in various groups;kits were used to detect the activities of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum,and the activities of total superoxide dismutase(T-SOD)and catalase(CAT),and the levels of malondialdehyde(MDA)in liver tissue of the mice in various groups;Western blotting method was used to detect the expression levels of nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins in liver tissue of the mice in various groups.Results:There were no significant differences in body weights of the mice among various groups(P>0.05).Compared with control group,the liver index of the mice in model group was significantly increased(P<0.01).Compared with model group,the liver index of the mice in NaB group was significantly decreased(P<0.01).The HE staining results showed that the liver tissue of the mice in control group exhibited normal structure,with clear boundaries of hepatocytes,consistent size,radially arranged around the central vein,and the nucleus located in the center of the cells;in model group,the arrangement of hepatocytes was disordered,the cells were swollen,there were multiple foci of hepatocellular necrosis,inflammatory cell infiltration,and hemorrhage;compared with model group,the cells in NaB group showed improved hepatocellular structure and reduced inflammatory infiltration.Compared with control group,the activities of ALT and AST in serum of the mice in model group were significantly increased(P<0.01);compared with model group,the activities of ALT and AST in serum of the mice in NaB group were significantly decreased(P<0.05 or P<0.01).Compared with control group,the activities of T-SOD and CAT in liver tissue of the mice in model group were significantly decreased(P<0.01),and the level of MDA was significantly increased(P<0.01);compared with model group,the activities of T-SOD and CAT in liver tissue of the mice in NaB group were significantly increased(P<0.05 or P<0.01),and the level of MDA was significantly decreased(P<0.01).The Western blotting results showed that compared with control group,the expression levels of Nrf2 and HO-1 proteins in liver tissue of the mice in model group were significantly decreased(P<0.05);compared with model group,the expression levels of Nrf2 and HO-1 proteins in liver tissue of the mice in NaB group were significantly increased(P<0.01).Conclusion:NaB has a protective effect on LPS/D-Gal induced acute liver injury in the mice,and its mechanism may be related to the upregulation of the expressions of Nrf2 and HO-1 proteins and the increas of the activity of oxidant enzyme in liver tissue by NaB,thereby reduces the liver oxidative stress level of liver.

Objective:To compare the clinical efficacy and safety of conventional transcatheter arterial chemoembolization (TACE) with drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) in treatment of patients with unresectable hepatocellular carcinoma.Methods:The data of patients with unresectable hepatocellular carcinoma who underwent hepatic artery chemoembolization at General Hospital of Ningxia Medical University from July 2019 to April 2020 were retrospectively analyzed. Of 282 patients who were enrolled, there were 233 males and 49 females, aged (55.9±10.0) years. The groups were divided into the conventional TACE group ( n=179) and the DEB-TACE group ( n=103) based on the treatments. The efficacy of the two groups was compared according to the modified response evaluation criteria in solid tumors. Postoperative adverse effects and liver function between the two groups were compared. Results:The differences in comparing the preoperative and postoperative liver function indexes between the two groups were not statistically significant. Patients who died and were lost to follow-up at 6 months after surgery were excluded and 240 patients were excluded in the efficacy analysis, with 148 patients in the conventional TACE group and 92 patients in the DEB-TACE group. At 6 months after treatment in the conventional TACE group, there were 64 patients (43.2%) with complete remission, 18 patients (12.2%) with partial remission, 27 patients (18.2%) with stable disease, and 39 patients (26.4%) with disease progression. In the DEB-TACE group, the corresponding figures were 38 patients (41.3%), 17 patients (18.5%), 26 patients (28.3%), and 11 patients (12.0%), respectively. The efficacy of DEB-TACE was better than conventional TACE with statistically significant differences between the 2 groups (χ 2=8.96, P=0.030). The incidence of postoperative embolic syndrome was 53.1% (95/179) in the conventional TACE group, which was significantly higher than the 34.0% (35/103) in the DEB-TACE group (χ 2=7.34, P=0.007). Conclusion:The efficacy and safety of DEB-TACE for unresectable hepatocellular carcinoma were superior to those of the conventional TACE group.

OBJECTIVE To study the protective effects of twin drugs of tetramethylpyrazine-scutellarein （TMSC4） on cerebral ischemia-reperfusion injury （CIRI） model rats and its mechanism. METHODS One hundred and five SD rats were randomly divided into sham operation group， model group， scutellarein group （0.7 mmol/kg）， tetramethylpyrazine group （0.7 mmol/kg）， and TMSC4 low-dose， medium-dose and high-dose groups （0.35， 0.7， 1.4 mmol/kg）， with 15 rats in each group. Sham operation group and model group were given constant volume of normal saline intragastrically， and other groups were given relevant drug intragastrically， once a day， for consecutive 14 d. Except for sham operation group， all other groups were treated to establish the CIRI model using the thread occlusion method. After 2 hours of ischemia and 22 hours of reperfusion， the brain index and brain water content of the rats were measured. Serum levels of interleukin 1β （IL-1β）， IL-6 and tumor necrosis factor α （TNF-α）， the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px） and catalase （CAT） in brain tissues， the situation of neuronal cell apoptosis， and the protein expressions of B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax） and cleaved-caspase-3 were evaluated. RESULTS Compared with sham operation group， the brain index， brain water content， the serum levels of IL-1β， IL-6 and TNF-α， the levels of MDA in brain tissues， the brain cell apoptosis and the protein expressions of Bax and cleaved-caspase-3 in model group were significantly increased （P＜0.05）； the levels of SOD， GSH- Px and CAT and the protein expression of Bcl-2 in brain tissues were significantly decreased （P＜0.05）. Compared with model group， the above indexes of rats were reversed significantly in administration groups （P＜0.05）， while the reverse effects of TMSC4 medium-dose and high-dose groups were significantly better than those of scutellarein group and tetramethylpyrazine group （P＜0.05）. CONCLUSIONS TMSC4 has a certain protective effect in CIRI model rats， the mechanism of which may be related to relieving inflammatory reaction and oxidative stress， inhibiting cell apoptosis.

Objective:To analyze the clinical phenotype of adult patients with epidemic encephalitis B (encephalitis B) in Ningxia Hui Autonomous Region, and to explore the influence of related factors of the development of encephalitis B.Methods:The medical records of confirmed patients with encephalitis B admitted to the General Hospital of Ningxia Medical University from August to November 2018 were collected, and the general data of patients and the results of laboratory indexes such as blood routine examination and cerebrospinal fluid routine examination were analyzed. Logistic regression analysis and survival curve were used to evaluate the risk factors of the development of encephalitis B.Results:Totally 97 patients with encephalitis B were included, 32 of them died, with a case fatality rate of 32.99%. There were 63 males and 34 females, and the age of onset was (59.13 ± 14.70) years old. There were statistically significant differences in case distribution rate between different sexes and ages (χ 2 = 97.00, 291.00, P < 0.001). The most common clinical type was extremely severe (43 cases), followed by mild (27 cases), severe (15 cases) and ordinary (12 cases). The results of laboratory tests showed that the number of neutrophils, lymphocytes and monocytes in the blood of patients increased; and the white blood cells number in cerebrospinal fluid increased significantly, while neutrophils ratio increased slightly. There were significant differences in cerebrospinal fluid glucose level and neutrophil ratio among patients with different clinical types of encephalitis B ( H = 4.21, 2.74, P < 0.05). There were statistically significant differences in death, hypertension, cerebrovascular diseases, and pulmonary infection among patients with different clinical types of encephalitis B (χ 2 = 34.22, 16.97, 9.91, 15.59, P < 0.05). Logistic regression analysis showed that hypertension [ OR (95% CI) = 5.544 (1.450-21.191)] and pulmonary infection [ OR (95% CI) = 6.490 (1.887-22.325)] were risk factors for the development of encephalitis B patients ( P = 0.012, 0.003). Pulmonary infection was the influencing factor for the death of encephalitis B patients (χ 2 = 18.88, P < 0.001). The survival curve showed that the survival status of encephalitis B patients with cerebrovascular disease and pulmonary infection was significantly worse than that of patients without comorbidity or complications (χ 2 = 6.45, 20.33 , P < 0.05). Conclusions:The majority of encephalitis B patients in this outbreak are the elderly people, and the patient's nervous system has inflammatory reaction. Complicated pulmonary infection is an important factor for the aggravation and death of encephalitis B patients.

Objective: To evaluate the long-term effect and safety of chrono-chemotherapy combined with intensity modulated radiotherapy (IMRT) in locally advanced nasopharyngeal carcinoma (NPC). Methods: 160 patients with locally advanced NPC were randomly divided into a chrono group and conventional group according to random number table. In the first stage, all patients underwent two cycles of induced chemotherapy, consisting of docetaxel, cisplatin and 5-Fu every 21 days. Notably, patients received chrono-moduated chemotherapy according to circadian rhythm in the chrono group, and conventional chemotherapy in the conventional group. Then, 21 days after the completion of first stage, three cycles of concurrent cisplatin chemotherapy every 21 days were given to all patients during IMRT. The median follow-up after the completion of radiotherapy was 31 months. Long-term side effects and the survival of patients were observed. Results: Patients in the chrono group had significantly lower rates of hearing loss (22.72%), dysphagia (0) and neck fibrosis (4.54%) compared with those in the conventional group (39.13%、8.69%, 15.94%, respectively, all P<0.05). Meanwhile, the 1- year overall survival rates (97.0% vs 92.8%), 3-year overall survival rates (80.3% vs 81.2%), 1-year progression free survival rates (95.5% vs 87.0%), 3-year progression free survival rates (71.2% vs 73.9%), 1-year locoregional relapse-free survival rates (97.0% vs 95.7%), 1-year locoregional relapse-free survival rates (92.4% vs 92.8%), 1-year distant metastasis-free survival rates (97.0% vs 98.6%) and 3-year distant metastasis-free survival rates (90.9% vs 91.3%) between the chrono group and the conventional group were not statistically significant (all P>0.05). Conclusions Compared with conventional chemotherapy, chrono-chemotherapy combined with IMRT didn′t affect long-term survival, but reducing the incidence of adverse events in patients with locally advanced NPC.

Objective: To explore and analyze the correlation between nurses' willingness to stay in the operating room and job stressor, job burnout and work-family conflict. Methods: A total of 128 nurses from Mianyang Central Hospital, Third People′s Hospital of Mianyang, Mianyang People′s Hospital were selected as the research objects. The questionnaire of nurses' retention intention, the scale of nurses' job stressor, the scale of nurses' occupational fatigue and the scale of work stress conflict were used to investigate and analyze the correlation between nurses' retention intention and work stressor, occupational fatigue and family conflict. Results: The average retention intention of the nurses surveyed in this study was (3.16±0.71), and the retention intention of the nurses was in the middle level. Operating room nurses' total score of work stress was (95.27±15.28). Among them, the scores of time allocation and workload, nursing specialty and work were the highest (2.86 ± 0.73) and (2.75 ± 0.64), respectively. The highest score of personal achievement was (33.26 ± 8.39). The total score of work family conflict of nurses in operating room was (58.32 ± 11.29), and the total score was (3.09 ± 0.58). The average score of work family conflict based on time was the highest, which was (3.91 ± 0.64), which was the main source of work family conflict of nurses. Pearson correlation analysis showed that nurses' intention to stay was negatively correlated with work pressure, job burnout and work family conflict (r value was-0.374,-0.400,-0.327, P < 0.05). Conclusions Nurses' willingness to stay in the operating room is at a medium level. Nursing managers can reduce the pressure of occupational fatigue by reducing work stress and improve the willingness of nursing staff to stay.

Objective: To investigate the diagnostic value of serum α-enolase (ENO1) in the primary hepatocellular carcinoma. Methods: From May 2012 to March 2017, 163 cases with liver diseases who met the inclusion and exclusion criteria were admitted to the Infectious Diseases Department of the General Hospital of Ningxia Medical University. Among them, 28 cases were of chronic hepatitis B (CHB), 31 cases with liver cirrhosis (LC), 104 cases with hepatocellular carcinoma (HCC), and 18 healthy volunteers (NC). Patient data and serum samples were collected and liver disease related indicators were measured to detect ENO1 levels with enzyme-linked immunosorbent assay (ELISA). The measured indicators were expressed in median. Mann-Whitney U nonparametric test was used to analyze the differences between the data. A Spearman’s correlation analysis was used for bivariate correlation analysis. The sensitivity and specificity of ENO1 and alpha-fetoprotein in the diagnosis of liver cancer were analyzed by ROC curve. Results: Serum level of ENO1 in CHB group, LC group and HCC group was significantly higher than normal group. Serum level of ENO1 in HCC group was higher than CHB group (P = 0.001) and LC group (P < 0.01). Area under the curve (AUC) for serum ENO1 and alpha-fetoprotein were 0.782 (cut-off value 75.96, P = 0.000 1) and 0.800 (cut-off value 27.02, P = 0.000 1), respectively. There was a positive correlation between ENO1 and AFP (P = 0.001). The combined detection had significantly improved the detection efficiency (AUC = 0.835). Serum ENO1 was statistically significant (P < 0.05) in HCC tumor size (AUC = 0.663), tumor metastasis (AUC = 0.681), TNM stage (AUC = 0.710, stage I vs. II), and Edmondson grade (AUC = 0.685) (P < 0.05) and the elevated levels of ENO1 had significantly reduced (P < 0.05) the survival time. Conclusion ENO1 can be a new candidate marker for the diagnosis of early stage HCC and its progression.

Objective: To study the effects of endoscopic submucosal dissection(ESD) on long-term quality of life (QOL) and gastric function of patients with distal early gastric cancer (EGC), compared with those of surgery. Methods: Patients with EGC who received ESD or surgical resection in Peking Union Medical College Hospital over 1 year ago were selected to be followed up. QLQ-C30, SF-36, EQ-5D and dyspeptic symptom rating scale were used to evaluate QOL. Five-hour gastric emptying rate was used to evaluate distal gastric function. Electronic gastroscopy was used to observe whether the anastomotic stoma was stenotic. According to the age at resection, 1 to 1 matching was performed between the distal 1/3 gastric ESD (E_P) group and the distal subtotal gastrectomy (S_P) group, and then the QOL and gastric function between the two groups were compared. Results: Twenty-five patients were included in group E_P and group S_P respectively. According to QLQ-C30, the scores of cognitive function were 83.3 (83.3, 83.3) in group E_P and 83.3 (83.3, 100.0) in group S_P (P=0.056). The proportion of patients with symptoms (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) between the two groups were not statistically different. There was no statistical difference in the scores of EQ-5D and SF-36 between the two groups. According to dyspeptic symptom rating scale, 56.0% patients in group E_Phad burning sensation, but only 28.0% in group S_P had this symptom (P=0.054). 20.0% of patients in group S_Preported nausea, while only 4.0% in group E_P had this symptom (P=0.084). Gastric emptying results showed that the proportion of patients with abnormal 5-hour gastric emptying rate was 31.8% in group E_P, while there was no abnormal emptying in group S_P (P=0.003). Gastroscopy results showed that one patient in group E_P had pyloric stenosis, but 5-hour gastric emptying rate was normal. All anastomotic stomas in group S_p were unobstructed. Conclusion ESD and surgical resection for distal EGC show similar long-term effects on QOL of patients. But the long-term gastric emptying function may decrease after distal gastric ESD.