Objective:To clarify the indications and efficacy after simultaneous surgical treatment in gastric cancer patients with synchronous hepatic metastases (GCHM).Methods:A total of 21 GCHM patients who underwent D2 gastrectomy with R0 hepatic resection (11 cases) or non-R0 hepatic resection (10 cases) from March 2004 to April 2016 were analyzed retrospectively.The clinicopathological characteristics and survival were compared between the two groups.Results:Cumulative survival rate was improved in R0 hepatic resection group compared with non-R0 hepatic resection group:1-year (54.5％ vs 48.0％),2-year(27.3％ vs 0％),and 5-year(27.3％ vs 0％,P=0.044).The median survival time in R0 hepatic resection group and non-R0 hepatic resection group were 16.2 and 5.9 months (P=0.008).Univariate analysis revealed that Bormann's classification (P=0.010) and state of regional lymph node (P=0.004) were significant predictive factors regarding cumulative survival rate.However,there was no significant prognostic factor (P=0.031) in multivariate analysis might partly owing to interaction among them and/or a small number of patients.Conclusion:Multidisciplinary treatments based on R0 hepatic resection combined with D2 gastrectomy could improve survival in selected GCHM patients.

Objective To determine the influence of continuous mild sedation versus usual sedation on the sedative effect and inflammatory factor level in ICU patients with multiple trauma.Methods In this prospective, randomized double-blind investigation, 58 multiple trauma patients hospitalized from October 2013 to April 2015 were randomized into continuous mild sedation group (continuous group, n =30) and conventional sedation group (conventional group, n =28) using the sealed envelopes.Between-group differences were made on the duration of mechanical ventilation, length of stay in the ICU, ratio of inception of continuous renal replacement therapy (CRRT), tracheotomy rate, accidental extubation rate, sepsis rate, multiple organ failure (MOF) rate and mortality.Serum inflammatory factor levels of the patients were recorded.Results There were 3 deaths (10％) in continuous group versus 4 deaths (14％) in conventional group (P ＞ 0.05).Patients in continuous group showed significantly less time spent on mechanical ventilation [(4.8 ±2.7) vs.(8.9 ±3.1)d] and in the ICU [(10.7 ± 5.4) vs.(16.9 ± 7.3) d] compared with conventional group (P ＜ 0.01).Between-group differences were insignificant regarding the ratio of CRRT inception, tracheotomy rate, accidental extubation rate, sepsis rate and MOF rate (P ＞ 0.05).Serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, Creactive protein (CRP) were lower in continuous group than those in conventional group at 24 h, 48 h and 72 h post-ICU, but significant differences were only observed at 48 h (P ＜ 0.05).At these time periods, serum IL-10 levels in continuous group were significantly higher than those in conventional group (P ＜0.05).In receiver operative characteristic curve (ROC) analysis, the area under the curve for IL-6, IL-10, TNF-α and CRP in continuous group was 0.726, 0.608, 0.729 and 0.757 respectively at 48 h post-ICU, indicating a predictive value of these markers for sepsis.Conclusion Continuous mild sedation results in shortened length of stay in the ICU and decreased inflammatory response in the treatment of patients with multiple trauma.

Objective To investigate the clinical therapeutic value of CRRT on severe sepsis coincidence with capillary leak syndrome in surgical patients. Methods 38 patients suffering from severe sepsis coincidence with capillary leak syndrome were random divided into routine group ( n = 18 ) and CRRT group ( n =20). Both groups were given routine treatment, while the patients of CRRT group were given CRRT in addition. Red blood cell count (RBC), haematoglobin level, blood platelets count, leukocyte count, hematocrit (HCT), plasma-albumin level, central venous pressure ( CVP), arterial blood pressure ( ABP), urinary production change of every hour, oxygenation index condition ( PO2\FiO2 ) were measured at 0, 12, 24, 48,72 hour following routine treatment or CRRT. Additionally, serum levels of tumor necrosis factor- a (TNF-α), interleukin-6 (IL-6) and interleukin-8(IL-8) were determined at the same time. Results Blood platelets count, HCT, plasma-albumin level in CRRT group were significantly higher than those of routine group [72 h: (211. 75 ± 45. 23 ) × 109 vs ( 135.67 ± 41.45 ) × 109 ;0. 43 ± 0. 05 vs 0. 35 ±0. 04; (48. 60 ±4. 76) g/L vs (41.17 ±4. 64) g/L, P <0. 01 ]. WBC were significantly lower than those of routine group[72 h:(7.58 ±2.31) ×109 vs (13.77 ±2.67) × 109, P <0.01]. Change of ABP, PO2\FiO2, urinary production for every hour was notably increased than those of routine group [72 h: (94. 25 ±8.60) mmHg vs ( 84. 22 ± 7. 37 ) mmHg; 345. 25 ± 35. 21 vs 304. 22 ± 38. 74; ( 80. 15 ± 14. 54 ) ml vs (62. 72 ± 12. 33) ml, P <0. 01 ]. The serum levels of TNF-α, IL-6 and IL-8 of CRRT group were markedly decreased compared with those of routine group(72 h:249. 55 ±99. 60 vs 368. 83 ±97. 11 ;600. 75 ±98. 31 vs 718. 94 ± 92. 00 ;665. 35 ±138. 44 vs 843. 22 ±123. 95 , P <0. 01,P <0.05). Conclusions CRRT can significantly improve patient's condition, which may be an effective nechanism to treat the surgical patients with severe sepsis coincidence with capillary leak syndrome.

Objective:To investigate the regulatory effect of astaxanthin on oxidative stress injury induced by hydrogen peroxide (H 2O 2) in lens epithelial cells and its possible mechanism. Methods:The HLEB-3 cells were cultured with different concentrations (0, 50, 100, 200, 500, 750 μmol/L) of H 2O 2.The cell inhibition rate was detected by the methyl thiazolyl tetrazolium (MTT) method, and the 50%inhibiting concentration (IC50) was calculated.HLEB-3 cells were cultured with different concentrations (0, 5, 10, 20, 50 μmol/L) of astaxanthin.The cell survival rate was detected by the MTT method.HLEB-3 cells were divided into four groups for 24-hour culture, namely normal control group cultured with complete medium, oxidative stress group cultured with 250 μmol/L H 2O 2, 10 μmol/L astaxanthin group cultured with 10 μmol/L astaxanthin and 250 μmol/L H 2O 2, and 20 μmol/L astaxanthin group cultured with 20 μmol/L astaxanthin and 250 μmol/L H 2O 2.The cell apoptosis rate was determined by flow cytometry.The nitric oxide (NO) concentration, superoxide dismutase (SOD) activity, glutathione (GSH) activity and malondialdehyde (MDA) content were detected by ELISA.The protein expressions of nuclear factor erythroid-2 related factor 2 (Nrf2) in nuclei, cytoplasmic Nrf2, heme oxygenase-1 (HO-1) and NAD (P) H, quinine oxidoreductase 1 (NQO1) were detected by Western bolt.The cells were divided into four groups, namely normal control-small interfering RNA (NC-siRNA) group, Nrf2-siRNA group, NC-siRNA+ astaxanthin group and Nrf2-siRNA+ astaxanthin group.The cells were transfected with NC-siRNA or Nrf2-siRNA accordingly.The cells were co-cultured for 24 hours with 0/10 μmol/L astaxanthin and 250 μmol/L H 2O 2 24 hours after transfection, respectively.The cell apoptosis rate was determined by flow cytometry.The NO concentration, SOD activity, GSH activity and MDA content were detected by ELISA. Results:With the increase of H 2O 2 concentration, the inhibition rate of HLEB-3 cells increased.There were significant differences in the inhibition rate of HLEB-3 cells treated with different concentrations of H 2O 2 ( F=12.358, P<0.05). The IC50 value of H 2O 2 on HLEB-3 cells was 264.20 μmol/L.The survival rates of HLEB-3 cells treated with 0, 5, 10, 20 and 50 μmol/L astaxanthin were (100.00±0.00)%, (102.20±1.34)%, (109.50±3.60)%, (115.40±4.13)%, (93.60±2.59)%, respectively.Then 10 μmol/L and 20 μmol/L were chosen as the experimental dose.The cell apoptosis rate of oxidative stress group was (38.50±2.38)%, which was higher than (9.20±0.24)% of normal control group, with a statistically significant difference ( P<0.05). The cell apoptosis rate of 10 μmol/L astaxanthin group was (27.60±4.33)%, which was lower than (38.50±2.38)% of oxidative stress group, but higher than (14.90±1.23)% of 20 μmol/L astaxanthin group and (9.20±0.24)% of normal control group, showing statistically significant differences (all at P<0.05). The NO and MDA contents were higher and the SOD and GSH concentrations were lower in oxidative stress group than in normal control group, 10 μmol/L astaxanthin group and 20 μmol/L astaxanthin group, and the differences were statistically significant (all at P<0.05). The NO and MDA contents were higher and the SOD and GSH concentrations were lower in 10 μmol/L astaxanthin group than in normal control group and 20 μmol/L astaxanthin groups, and the differences were statistically significant (all at P<0.05). There were significant differences in the relative expression levels of nuclear Nrf2, cytoplasmic Nrf2, HO-1 and NQO1 proteins among normal control group, oxidative stress group, 10 μmol/L astaxanthin group and 20 μmol/L astaxanthin group ( F=43.512, 20.381, 31.014, 23.435; all at P<0.001). The relative expression of nuclear Nrf2 protein gradually decreased, and the relative expression of nuclear Nrf2, HO-1 and NQO1 proteins increased gradually in normal control group, oxidative stress group, 10 μmol/L astaxanthin group and 20 μmol/L astaxanthin group, and there were significant differences when compared in pairs (all at P<0.05). The apoptosis rates of Nrf2-siRNA group and Nrf2-siRNA+ astaxanthin group were higher than those of NC-siRNA group and NC-siRNA+ astaxanthin group, and the differences were statistically significant (all at P<0.05). The cell apoptosis rate was higher in NC-siRNA group than in NC-siRNA+ astaxanthin group, showing a statistically significant difference ( P<0.05). There was no significant difference in the apoptosis rate between Nrf2-siRNA+ astaxanthin group and Nrf2-siRNA group ( P>0.05). The NO and MDA concentrations were higher and the SOD and GSH activities were lower in Nrf2-siRNA group than in the NC-siRNA group, with statistically significant differences (all at P<0.05). The NO and MDA concentrations were lower and the SOD and GSH activities were higher in NC-siRNA+ astaxanthin group than in NC-siRNA group and Nrf2-siRNA+ astaxanthin group, and the differences were statistically significant (all at P<0.05). There was no significant difference in NO and MDA concentrations or the SOD and GSH activities between Nrf2-siRNA+ astaxanthin group and Nrf2-siRNA group (all at P>0.05). Conclusions:Astaxanthin enhances the resistance of lens epithelial cells to H 2O 2-induced oxidative stress damage, which may be achieved by activating the Nrf2-related signaling pathway.

Objective:To investigate the predictive value of controlled nutritional status (CONUT) score for overt hepatic encephalopathy (OHE) after transjugular intrahepatic portosys-temic stent-shunt (TIPSS) in Budd-Chiari syndrome patients.Method:The retrospective case-control study was conducted. The clinicopathological data of 48 Budd-Chiari syndrome patients who underwent TIPSS in the First Affiliated Hospital of Zhengzhou University from August 2014 to March 2021 were collected. There were 26 males and 22 females, aged (46±13)years. Observation indicators: (1) surgical situations and follow-up; (2) analysis of influencing factors of OHE after TIPSS; (3) predic-tion of OHE after TIPSS. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was performed using the t test. Measurement data with skewed distribution were represented by M( Q1, Q3), and comparison between groups was performed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was performed using the chi-square test or Fisher exact probability. Multivariate analysis was performed using the Logistic regression model with forward method. The receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to evaluate the efficacy. Comparison among AUC was performed using the Delong test. Results:(1) Surgical situations and follow-up. All 48 patients underwent TIPSS successfully, and the operation time of the 48 patients was (131±29)minutes. All patients were implanted with 8 mm covered stent. All 48 patients were followed up for 46(25,71)months, and there were 14 cases with OHE and 34 cases without OHE after TIPSS. Of the 14 cases with OHE, 12 cases were evaluated as West-Haven Ⅱ grade and 2 cases were evaluated as West-Haven Ⅲ grade. (2) Analysis of influencing factors of OHE after TIPSS. Results of multivariate analysis showed that history of hepatic encephalo-pathy and CONUT score were independent factors influencing the incidence of OHE of Budd-Chiari syndrome patients who underwent TIPSS ( odds ratio=8.36, 1.74, 95% confidence interval as 1.02?68.75, 1.12?2.69, P<0.05). (3) Prediction of OHE after TIPSS. Results of ROC curve showed that the AUC of the CONUT score, the Child-Pugh score of liver function and the integrated model of end-stage liver disease (iMELD) score in predicting the incidence of OHE after TIPSS was 0.77(95% confidence interval as 0.64?0.91, P<0.05), 0.71(95% confidence interval as 0.56?0.87, P<0.05) and 0.71(95% confidence interval as 0.53?0.88, P<0.05), respectively, and there was no significant difference between the AUC of the CONUT score and the Child-Pugh score of liver function or the iMELD score ( Z=0.84, 0.59, P>0.05). The optimal cutoff value of CONUT score in predicting the incidence of OHE after TIPSS was 7, with the sensitivity, specificity and Yodon index as 78.6%, 61.8% and 0.40, respectively. Conclusion:The CONUT score can be used to predict the incidence of OHE in Budd-Chiari syndrome patients who underwent TIPSS, and the discrimination of CONUT score is equivalent to the Child-Pugh score of liver function and the iMELD score.

Objective:To study the factors influencing short-term prognosis of patients with Budd-Chiari syndrome (B-CS) presenting with upper gastrointestinal bleeding and to assess the predictive value of platelet-albumin-bilirubin score (PALBI) on death within 30 d in these patients.Methods:A retrospective study was conducted on 74 patients with B-CS who presented with upper gastrointestinal bleeding and were treated at the First Affiliated Hospital of Zhengzhou University from January 2014 to February 2020. There were 51 males and 23 females, with age of (46.5±11.1) years old. These patients were divided into the survival group ( n=58) and the death group ( n=16) according to the disease outcomes up to 30 d of follow-up. Factors influencing short-term deaths of these patients were analyzed, and the predictive values of PALBI, ALBI, CTP and MELD scores on short-term prognosis of the patients were assessed. The receiver operating characteristic (ROC) curves were plotted, and the areas under the curve (AUC) were calculated and compared. Results:The differences between patients in the survival and death groups for white blood cell, platelet, PALBI score, PALBI classification, ALBI score, CTP score, MELD score, and presence or absence of hepatic encephalopathy were significantly different (all P<0.05). Multivariate logistic regression analysis showed that CTP score≥10 or CTP grade C ( OR=1.669, 95% CI: 1.048-2.661), and PALBI score >-2.09 or PALBI grade 3 ( OR=5.245, 95% CI: 2.128-12.924) were independent risk factors for predicting death within 30 days. The areas under the ROC curves for PALBI, ALBI, CTP and MELD score were 0.89, 0.72, 0.77 and 0.76, with the cut-off values of -1.92, -1.60, 8.50 and 13.60, respectively. The differences between the PALBI score and ALBI, CTP scores were significantly different ( P<0.05). Conclusion:The PALBI score showed a positive predictive value on short-term prognostic assessment of patients with B-CS presenting with upper gastrointestinal bleeding. It was comparable to the effect of the MELD score but was significantly better than the ALBI and CTP scores.

To study the clinical effects of beprost sodium tablets combined with Epley manual reduction in treatment of benign paroxysmal positional vertigo（BPPV）. Methods A total of 338 patients with posterior semicircular canal BPPV who were treated in the neurogy clinic of our hospital from January 2019 to December 2020 were enrolled in the study，who were randomly divided into the observation group，who were treated in Epley manual reduction combined with oral beprost sodium tablets，118 cases；control group 1，who were treated with only Epley manual reduction，114 cases and control group 2，who were treated with Epley manual reduction combined with oral betahistine mesilate tablets，106 cases. The clinical efficacy，vestibular symptom index（VSI），dizziness handicap inventory（DHI） and relapse rate were observed and compared between the three groups. Results The total effective rate in the observation group was 91.53%，which was significantly higher than that（73.68） in control group1 and（86.79%） in control group2，the difference was statistically significant（P<0.05）. One week and one month After manual reduction，the vestibular symptom index（VSI） scores and the dizziness handicap inventory（DHI） scores in three group were significantly lower than pretreatment，moreover，the decrease degree in the observation group was more significant than the other two control groups，the difference was statistically significant（P<0.05）. Within 3 months after treatment，the relapse rate in the observation group（18.64%）was lower than that in control group1（34.21%） and in control group2（27.36%），the difference was statistically significant（P<0.05）. Conclusion The clinical effects of beprost sodium tablets combined with Epley manual reduction in treatment of posterior semicircular canal BPPV are superior to those by simple Epley manual reduction and by Epley manual reduction combined with betahistine mesilate.

To examine the growth activity and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) in rats with Type 2 diabetes mellitus (T2DM) as well as the expression level of Dickkopf-1 (DKK-1) in bone marrow, and to explore the relationship between the osteogenic activity of BMSCs and the expression of DKK-1.
 Methods: The BMSCs were isolated from T2DM rats and were cultured in vitro. The BMSCs were divided into a T2DM group and a control group. The proliferation of BMSCs was detected by cell counting kit-8 (CCK8). Apoptosis rate was detected by annexin V- fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining. In the osteogenic induction phase, the expression level of alkaline phosphatase (ALP) in BMSCs was detected by ALP staining and ALP activity assay kit. The osteogenic differentiation of BMSCs was analyzed by alizarin red staining and mineralized nodule quantification. In addition, the expression of Runx2 and DKK-1 in BMSCs was detected by qRT-PCR.
 Results: Compared with the control group, the proliferation of BMSCs was decreased and the apoptosis was increased in the T2DM group (both P<0.01). In the osteogenic induction process of BMSCs, the expression of ALP significantly decreased, the formation of calcium nodules reduced, and the expression of osteoblast transcription factor Runx2 was down-regulated in the T2DM group compared with those in the control group (all P<0.01). The levels of DKK-1 protein and mRNA were up-regulated in the T2DM group, which were higher than those in the control group (both P<0.01). The levels of DKK-1 protein and mRNA were related to the increase of Runx2 (both P<0.01).
 Conclusion: The growth activity of BMSCs and the potential of osteogenic differentiation are attenuated in the T2DM rats, which may be related to the increase of DKK-1 expression in BMSCs.
Animals ; Bone Marrow Cells ; Cell Differentiation ; Cells, Cultured ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 2 ; physiopathology ; Gene Expression Regulation ; Intercellular Signaling Peptides and Proteins ; genetics ; Mesenchymal Stem Cells ; Osteogenesis ; genetics ; Rats

Objective To investigate the effect of metformin on liver fibrosis in a mouse model of Budd-Chiari syndrome and its mechanism. Methods A total of 30 male C57 mice were randomly divided into sham-operation group (SHAM group) with 6 mice, sham operation+ metformin group (SHAM+M group) with 5 mice, Budd-Chiari model group (BCS group) with 10 mice, and Budd-Chiari model+metformin group (BCS+M group) with 9 mice. The mice in the model group were treated with partial ligation of the inferior vena cava, those in the SHAM group were not treated with ligation, and those in the metformin group were given 0.1% metformin in drinking water besides modeling. The mice were sacrificed after 6 weeks. HE staining and picrosirius red staining were used to observe liver histopathology and collagen deposition; immunohistochemistry was used to measure the expressions of α-smooth muscle actin (α-SMA) and fibrinogen; quantitative real-time PCR was used to measure the mRNA expression of hypoxia-inducible factor 1α (HIF-1α) and type Ⅰ collagen (collagen 1), and Western blot was used to measure the relative protein expression levels of HIF-1α, vascular endothelial growth factor (VEGF), fibrinogen, α-SMA, and collagen 1. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Pathological staining showed that compared with the SHAM group, the BCS group had significant liver fibrosis, disordered arrangement of hepatocytes near the central vein, sinusoidal expansion with red blood cell deposition and a small amount of inflammatory cell infiltration, and collagen deposition. The BCS group had significant increases in the mRNA expression levels of HIF-1α and collagen 1 and the protein expression levels of α-SMA, collagen 1, HIF-1α, VEGF, and fibrinogen (all P < 0.05); compared with the BCS group, the BCS+M group had significant alleviation of liver fibrosis, red blood cell deposition, and collagen deposition and significant reductions in the mRNA expression levels of HIF-1α and collagen 1 and the protein expression levels of α-SMA, collagen 1, HIF-1α, VEGF, and fibrinogen (all P < 0.05). Conclusion Metformin can improve congestive liver fibrosis caused by Budd-Chiari syndrome, possibly by reducing microthrombus in hepatic sinusoid and inhibiting the HIF-1α/VEGF pathway.

ObjectiveTo systematically and objectively characterize the pharmacological effects of Fufang Biejia Ruangan pills （FBRP） in the intervention of alcoholic liver disease （ALD） using acute and chronic ALD mouse models and to elucidate its molecular mechanisms. MethodFifty SPF-grade male BALB/c mice were randomly divided into the normal group， model group， and FBRP low-， medium-， and high-dose groups （9.6， 19.2， 38.4 mg·kg^-1）. Except for the normal group， the remaining groups were given 56° white wine by gavage to establish the acute ALD model， with samples collected after 4 weeks. Thirty SPF-grade male C57BL/6N mice were randomly divided into the normal group， model group， and FBRP medium-dose group （19.2 mg·kg^-1）. The chronic ALD mouse model was established using the Lieber-DeCarli method over a 10-week period. Inflammatory markers in liver tissues were assessed using hematoxylin-eosin （HE）， Sirius Red， oil red O staining， and enzyme-linked immunosorbent assay （ELISA）. Intoxication behaviors of each group were objectively evaluated through sobering-up time， net-catching， and pole-climbing tests. Further bioinformatics analyses based on clinical transcriptomic data were conducted to identify key targets and molecular mechanisms of FBRP in alleviating ALD through liver-brain dialogue， with experimental validation by ELISA， Western blot， and immunohistochemical staining. ResultCompared with the normal group, the levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） in liver tissues of mice in the acute and chronic ALD model groups were significantly increased （P<0.05）. Compared with the model group， the levels of AST and ALT in liver tissue of mice in FBRP groups were significantly decreased （P<0.05）. Compared with the normal group， the time of grasping the net and climbing the pole in the acute ALD model group was significantly decreased within 4 weeks （P<0.01）. Compared with the model group， the grasping and climbing time of FBRP high dose groups increased significantly within 4 weeks （P<0.05）. Compared with the normal group， the expression of high mobility group protein B1 （HMGB1） protein in liver tissue and prefrontal lobe tissue of mice in the chronic ALD model group was significantly increased （P<0.01）. Compared with the model group， the expression of HMGB1 protein in FBRP medium dose group was significantly decreased （P<0.05，P<0.01）. Compared with the normal group， the expression of brain-derived neurotrophic factor （BDNF） protein and the release of γ-aminobutyric acid （GABA） in the prefrontal cortex of the model group were significantly decreased （P<0.01）. Compared with the model group, the expression of BDNF protein and the release of GABA in the FBRP medium dose group were significantly increased （P<0.05）. ConclusionThis study revealed that FBRP improved key pathological changes in ALD by modulating liver-brain dialogue mediated by the HMGB1-BDNF axis. These findings provide experimental evidence for the clinical use of FBRP in treating ALD and offer new insights for the development of ALD therapeutic agents.