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Objective:To investigate the evaluation efficacy and predictive prognostic value of alpha-fetoprotein (AFP) response in tyrosine kinase inhibitors (TKIs) in combination with PD-1 inhibitors (α-PD-1) for intermediate-to-advanced hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 205 patients with intermediate-to-advanced HCC who were admitted to 9 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from March 2020 to July 2022 were collected. There were 178 males and 27 females, aged (52±12)years. Based on AFP response at 6-8 weeks after treatment, patients were divided into the AFP response group (AFP level decreased by ≥50% compared to baseline) and the AFP no response group (AFP level decreased by <50% compared to baseline). Observation indicators: (1) AFP response evaluation of anti-tumor efficacy; (2) comparison of patient prognosis; (3) analysis of factors affecting patient prognosis. Measurement data with normal distrubution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) and M( Q1, Q3). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and the Log-Rank test was used for survival analysis. The COX proportional risk model was used for univariate analysis and the COX stepwise regression model was used for multivariate analysis. Results:(1) AFP response evaluation of anti-tumor efficacy. Before treatment, all 205 patients were positive of AFP, with a baseline AFP level of 1 560(219,3 400)μg/L. All 205 patients were treated with TKIs in combination with α-PD-1, and the AFP level was 776(66,2 000)μg/L after 6 to 8 weeks of treatment. Of the 205 patients, 88 cases were classified as AFP response and 117 cases were classified as AFP no response. According to the response evaluation criteria in solid tumors version 1.1, the objective response rate (ORR) and disease control rate (DCR) were 42.05%(37/88) and 94.32%(83/88) in patients of the AFP response group and 16.24% (19/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=16.846, 25.950, P<0.05). According to the modified response evaluation criteria in solid tumors, the ORR and DCR were 69.32% (61/88) and 94.32% (83/88) in patients of the AFP response group and 33.33% (39/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=26.030, 25.950, P<0.05). (2) Comparison of patient prognosis. All 205 patients were followed up for 12.4(range, 2.4-34.0)months after treatment. The median progression free survival time and total survival time were 5.5 months and 17.8 months, respectively. The 1-year, 2-year progression free survival rates were 20.8% and 7.2%, and the 1-year, 2-year overall survival rates were 68.7% and 31.5%, respectively. The median progression free survival time, 1-year and 2-year progression free survival rates were 9.7 months, 39.6% and 14.2% in patients of the AFP response group and 3.7 months, 7.8% and 2.0% in patients of the AFP no response group, showing a significant difference in progression free survival between them ( χ2=43.154, P<0.05). The median overall survival time, 1-year and 2-year overall survival rates were not reached, 85.2% and 56.3% in patients of the AFP response group and 14.6 months, 56.3% and 14.5% in patients of the AFP no response group, showing a significant difference in overall survival between them ( χ2=33.899, P<0.05). (3) Analysis of factors affecting patient prognosis. Results of multivariate analysis showed that invasion of large blood vessels, extrahepatic metastasis, combined hepatic artery intervention therapy, and AFP response were independent factors influencing progression free survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio=1.474, 1.584, 0.631, 0.367, 95% confidence interval as 1.069-2.033, 1.159-2.167, 0.446-0.893, 0.261-0.516, P<0.05), and Eastern Cooperative Oncology Group score, invasion of large blood vessels, extrahepatic metastasis, and AFP response were independent factors influencing overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio= 1.347, 1.914, 1.673, 0.312, 95% confidence interval as 1.041-1.742, 1.293-2.833, 1.141-2.454, 0.197-0.492, P<0.05). Conclusions:AFP response at 6-8 weeks after treatment can effectively evaluate anti-tumor efficacy of TKIs in combination with α-PD-1 for intermediate-to-advanced HCC. AFP response is the independent factor influencing progression free survival and overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1.
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Objective:To investigate the changes in IL-35 expression in patients with type 1 diabetes mellitus (T1DM) and to analyze the role of IL-35 in regulating Th9 cells.Methods:Thirty-one T1DM patients and 13 controls were enrolled. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated. The levels of IL-35 and IL-9 in plasma were measured by ELISA. The expression of IL-35 subunits, EBI3 and IL-12p35, as well as Th9 transcription factor PU.1 at mRNA level was detected by real-time PCR. The percentages of Th9 cells were measured by flow cytometry. Changes in cell proliferation, the percentage of Th9 cells, PU.1 expression at mRNA level and IL-9 secretion were detected after stimulating PBMCs from T1DM patients and controls with recombinant human IL-35. CD4 + CCR4 -CCR6 -CXCR3 - cells and CD8 + T cells were isolated from PBMCs of 11 T1DM patients. CD4 + CCR4 -CCR6 -CXCR3 - cells were first stimulated with recombinant human IL-35 and then co-cultured with CD8 + T cells. IFN-γ and TNF-α in the culture supernatants were measured by ELISA. Perforin and granzyme B secretion was measured by enzyme-linked immunospot assay. Student′s t-test, paired t-test or LSD- t test was used for statistical analysis. Results:Plasma IL-35 level was lower in T1DM patients than in controls [(67.13±9.94) pg/ml vs (97.77±23.61) pg/ml, P<0.000 1]. Compared with controls, T1DM patients had decreased expression of EBI3 and IL-12p35 at mRNA level in PBMCs ( P<0.000 1). The percentage of Th9 cells, PU.1 expression at mRNA level and plasma IL-9 level were increased in T1DM patients as compared with those in controls [(3.47±0.99)% vs (2.76±0.75)%, P=0.029; P<0.000 1; (99.08±11.85) pg/ml vs (86.38±12.72) pg/ml, P=0.002 8]. IL-35 had no significant influence on the proliferation of PBMCs from both T1DM patients and controls ( P>0.05). The percentage of Th9 cells and PU.1 expression at mRNA level in PBMCs from T1DM patients were down-regulated in response to IL-35 stimulation ( P<0.01), while no significant difference was observed in the control group ( P>0.05). IL-9 secretion by PBMCs was down-regulated in response to IL-35 stimulation in both T1DM and control groups ( P<0.01). CD4 + CCR4 -CCR6 -CXCR3 - cells promoted the secretion of IFN-γ, TNF-α, perforin and granzyme B by CD8 + T cells from T1DM patients ( P<0.05), but the effects could be inhibited by IL-35 ( P<0.05). Conclusions:Decreased IL-35 in T1DM patients could not exert effective immunosuppressive activity, leading to the enhancement of Th9 cell activity and inflammatory injury.
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Objective:To evaluate the diagnostic value of 11C-choline PET/CT brain imaging for localization of epileptogenic foci in hippocampal sclerosis-refractory temporal lobe epilepsy (HS-RTLE), and compare it with 18F-FDG and 11C-flumazeni (FMZ) PET/CT. Methods:From March 2017 and June 2020, a total of 62 patients (39 males, 23 females, age (30.3±11.2) years) with pathologically confirmed HS-RTLE in General Hospital of Northern Theater Command were retrospectively analyzed. All patients were preoperatively treated with multiple radionuclide ( 18F-FDG, 11C-FMZ, 11C-choline) PET/CT brain imaging. 11C-choline PET imaging was used to acquire dynamic imaging data and time-activity curve (TAC) of 11C-choline in bilateral hippocampal regions were drawn. With postoperative pathology as the " gold standard" , the positive detection rates and localization diagnostic efficacies of three radionuclide imaging agents for epileptogenic foci were analyzed. Then a prospective study including 46 patients (27 males, 19 females; age (32.9±11.9) years; between May 2019 and August 2020; General Hospital of Northern Theater Command) with drug-refractory epilepsy caused by clinically suspected hippocampal sclerosis was performed. The examination method was the same as that of retrospective study. Using intracranial electrode implantation or postoperative pathology as " gold standard" , the diagnostic efficacy of 11C-choline TAC for localization of epileptogenic foci was verified, and ROC curve was drawn to evaluate the diagnostic value of three imaging agents for HS-RTLE epileptogenic foci. χ 2 test and Fisher exact probability method, Delong test were used to analyze the data. Results:In the retrospective study, the positive detection rate of 18F-FDG PET/CT was higher than that of 11C-choline PET/CT (100%(62/62) vs 85.48%(53/62); P=0.003), and the localization accuracies of 11C-choline and 11C-FMZ PET/CT were both higher than that of 18F-FDG PET/CT (100%(53/53), 96.61%(57/59) vs 33.87%(21/62); both P<0.001). In the prospective study, 25 of 46 patients were diagnosed as HS-RTLE and 21 were non-HS induced epilepsy. The specificities of 11C-choline, 11C-FMZ and 18F-FDG PET/CT were 100%(21/21), 90.48%(19/21), 33.33%(7/21), respectively. The AUCs of 11C-choline and 11C-FMZ PET/CT were significantly higher than that of 18F-FDG PET/CT (0.920, 0.912, 0.627; z values: 4.93, 5.16, both P<0.01). Conclusions:11C-choline PET/CT can be used in the preoperative localization of epileptic foci. Compared with 18F-FDG and 11C-FMZ PET/CT, the specificity of 11C-choline PET/CT is higher, and the negative imaging of 11C-choline is more significant for exclusion.
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Objective:To explore the effect of recombinant human syntaxin-4(STX4) on lipopolysaccharide(LPS)-induced injury in islet β-cells(INS-1).Methods:Pancreatic islet β-cells(INS-1) were divided into Control (blank control), LPS (LPS treatment), LPS+ NC (transfection of negative control vector, LPS treatment), and LPS+ STX4 (transfection of pcDNA-STX4, LPS treatment) groups. RT-qPCR and Western blot were used to detect STX4 mRNA and protein expression, flow cytometry to detect apoptosis, DCFHDA method to detect reactive oxygen species(ROS) level, xanthine oxidation method to detect superoxide orgotein dismutase(SOD) level, colorimetric method to detect glutathione peroxidase(GSH-Px) level, ammonium molybdate colorimetric method to detect catalase(CAT) level, thiobarbituric acid method to detect malonaldehyde(MDA) level, ELISA method to detect the level of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and insulin secretion levels under glucose conditions secreted by cells, Western blot method to detect Cleared Caspase-3, Bcl-2 Associated X Protein(Bax), p65 protein expression. After treatment with NF-κB signaling pathway activator, STX4 up-regulated islet β-cell INS-1 was given LPS stimulation, and the same method was used to measure apoptosis, ROS, SOD, GSH-Px, CAT, MDA levels and secreted IL-1β, TNF-α, insulin levels and Cleaved Caspase-3, Bax, p65 protein levels.Results:Compared with the Control group, the expression of STX4 mRNA and protein in islet β cells of the LPS group decreased, the apoptosis rate, ROS level, and MDA levels increased, and the levels of SOD, GSH-Px, and CAT decreased, the levels of IL-1β, TNF-α increased, the level of insulin secreted by the cells decreased, and the expression levels of Cleaved Caspase-3, Bax, and p65 also increased. NF-κB pathway activator treatment reversed the effect of up-regulated STX4 on islet β-cell apoptosis, ROS, SOD, GSH-Px, CAT, MDA levels and secreted IL-1β, TNF-α levels, and Cleaved Caspase-3 , Bax and p65 protein levels.Conclusion:Up-regulation of STX4 alleviated LPS-induced islet β cell oxidative damage, apoptosis and inflammatory factor release. The underlying mechanism might be related to the inhibition of activated NF-κB signaling pathway.
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Objective:To analyze the clinical value of serum 2019 novel coronavirus (2019-nCoV) immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies in the diagnosis of COVID-19.Methods:A total of 116 patients diagnosed with NCP in the First Affiliated Hospital of Hunan University of Chinese Medicine and the First Affiliated Hospital of Xiamen University were enrolled from January to February 2020 as the disease group. A total of 134 cases, including 84 non-NCP inpatients and 50 healthy individuals served as the control group. Serum samples from all subjects were collected. A fully-automated chemiluminescence immunoassay analyzer was used to detect the concentration of 2019-nCoV IgM and IgG antibodies in serum. The sensitivity and specificity of the 2019-nCoV IgM and IgG antibody single test and combined detection were compared using the χ 2 test. χ 2 test and Wilcoxon′s rank sum test were used to compare the positive rates and concentrations of IgM and IgG antibodies in NCP patients before and after their 2019-nCoV nucleic acid tests turning negative, respectively. The change trend of 2019-nCoV antibody concentration in the process of NCP patients was analyzed by Wilcoxon′s rank sum test. Results:The sensitivity of 2019-nCoV IgG (90.5%, 105/116) was higher than that of 2019-nCoV IgM (75.9%, 88/116), the difference was statistically significant (χ 2=8.91, P<0.05); The specificity of 2019-nCoV IgG (99.3%,133/134) was higher than that of 2019-nCoV IgM (94.0%, 126/134), the difference was statistically significant (χ 2=5.63, P<0.05). The sensitivity (89.7%,87/97) of 2019-nCoV IgM combined with IgG was higher than that of 2019-nCoV IgM, the difference was statistically significant (χ 2=6.89, P<0.05). The specificity (100%, 125/125) of 2019-nCoV IgM combined with IgG was higher than that of 2019-nCoV IgM, the difference was statistically significant (χ 2=7.70, P<0.05). After 2019-nCoV nucleic acid test converted to negative, the positive rate (9/17) and concentration [13.0 (4.9, 24.7) AU/ml] of serum 2019-nCoV IgM antibody were significantly lower than those when the nucleic acid test was positive, positive rate (15/17) and concentration [29.5 (14.0, 61.3) AU/ml], respectively (χ 2=5.10, Z=-3.195, both P<0.05). In the course of NCP, patients′ serum samples were collected from the first day of diagnosis to every three days, three times in total. The first 2019-nCoV IgM and IgG antibody concentrations [19.4 (12.4, 63.7) AU/ml, 105.8 (74.8, 126.1) AU/ml, respectively] were significantly higher than the second concentrations [15.8 (7.1, 40.3)AU/ml, 80.5 (66.7, 105.9) AU/ml], Z were-2.897,-3.179, both P<0.05. Conclusions:2019-nCoV IgG antibody has a good application value in the diagnosis of NCP. The concentration of 2019-nCoV IgM antibody has a certain correlation with the detection of 2019-nCoV nucleic acid. The combination of 2019-nCoV IgM and IgG antibodies with 2019-nCoV nucleic acid test may be the best laboratory index for the diagnosis of NCP at present.
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Objective To explore the relationship between fibroblast growth factor 21(FGF21) and islet β cell function in pregnant women with different glucose tolerance status.Methods A total of 441 pregnant women were selected in this study from our hospital.Their 50 g GCT at 24~28 gestational weeks were all positive.One week later,all the subjects were treated with 75 g OGTT,and divided into three groups according to their test results:GDM group (n=228),GIGT group (n=112) and GNGT group (n=91).Serum FGF21 level was tested by ELISA.Islet β cell function was evaluated by HOMA-IR,ISI-Matsuda,HOMA-IS,Stumvoll first,second phase secretion and ISSI.The correlation between FGF21 and islet β cell function was evaluated by Pearson correlation analysis.Results (1) BMI,0 h,1 h,2 h,3 hPG and 1 h,2 h,3 hIns were higher in GDM group and GIGT group than in GNGT group,and highest in GDM group (P0.05).(3)Pearson correlation analysis showed that FGF21 was positively correlated with HOMA-IR(r=0.255,P=0.030) and was negatively correlated with ISI-Matsuda,HOMA-β,Stumvoll first,second phase secretion and ISSI(r=-0.289,-0.256,-0.224,-0.230,-0.277,P=0.019,0.037,0.045,0.040,0.023).Conclusion Along with the worsening of glucose metabolic damage,the FGF21 level is increased gradually.FGF21 is related to islet β cell function,and may enroll in the occurrence and development of GDM.
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Objective To investigates the role of duodenum and bile duct preserving pancreatic head resection (DBPPHR) in treatment of benign or low-grade malignant diseases located in the head of pancreas.Methods The clinical data of 31 patients who underwent DBPPHR between April 2012 to May 2016 in Zhejiang Provincial People's Hospital and Zhangzhou Municipal Hospital of Fujian Province were analyzed retrospectively.Results Of the 31 patients,4 patients underwent laparoscopic DBPPHR.One patient in the open group was converted to pancreaticoduodenectomy.For the open group,the mean operation time was (165.3 ±63.6) min;the mean estimated blood loss was (258.1 ± 156.9) ml;and the mean postoperative stay was (11.7 ± 6.3) days.The postoperative complications included 1 reoperation due to postoperative bleeding,1 bile leakage and 13 patients developed grade A pancreatic fistula (48.2%).For the laparoscopic group,the mean operation time was 350.0 (280.0 ~ 450.0) min;the mean estimated blood loss was 425.0 (250.0 ~600.0) ml;and the mean postoperative stay was 14 days.Three patients developed postoperative pancreatic fistula (grade A).The pathological diagnosis were:12 patients with pancreatolithiasis,8 patients with serous cystadenoma,4 patients with branched intraductal papillary mucinous neoplasm,5 patients with neuroendocrine tumor and 2 patients with mucinous cystadenoma.The follow-up period was 1 ~ 48 month,and there was no patient with diabetes or diarrhea.Conclusions DBPPHR was safe and efficacious.It is less invasive to treat benign or low-grade malignant diseases located in the head of pancreas.
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Objective To investigate the improvement of ischemic hypoxic injury of brain after the transplantation of bone marrow mesenchymal stem cells (BMSCs).Methods Rats were randomly (random number) divided into sham operation group,cardiac arrest group and BMSCs treatment group (n =10 in each group).The model of cardiac arrest was induced by asphyxia.One hour after restoration of spontaneous circulation (ROSC),green fluorescent protein labeled BMSCs were transplanted via tail vein injection.At 3 and 7 days after transplantation,frozen sections of hippocampus was stained with hematoxylin-eosin (HE).The rest of brain tissue was weighed by an electronic balance.Brain water content (%) was calculated as (wet weight-dry weight) / wet weight × 100%.Results ①BMSCs were observed in hippocampus at 3 and 7 days after transplantation under fluorescent microscopy.②Compared with sham operation group and BMSCs treatment group,brain water content in cardiac arrest group was higher (all P < 0.05).HE staining results showed that BMSCs transplantation could lessen hypoxia ischemia damage on brain.Conclusions BMSCs reduced the neurons damage induced by cardiac arrest and promoted neurological function recovery.
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Objective To investigate the expressions of spleen tyrosine kinase (Syk), c-Jun amino terminal kinase (JNK) and nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in the heart tissue in SD rat model of diabetic cardiomyopathy, and to explore the relationship between Syk, JNK and NLRP3. Methods Clean male SD rats were randomly divided into the control (Ctrl) group and diabetic cardiomyopathy model (DCM) group. Rats of DCM group were treated with a single intraperitoneal injection of streptozotocin (STZ), while rats of Ctrl group were injected with the same dose of citrate buffer. The random blood glucose level and body weight were monitored every week until 20 weeks after STZ or citrate buffer injection, then all the rats were killed and their hearts were obtained. Rat H 9c2 cardiomyocytes were randomly divided into normal glucose treatment (NG) group, high glucose treatment (HG) group, Syk inhibitor control (BAY) group and Syk inhibitor high glucose (HG+BAY) group. The Syk and JNK phosphorylations and NLRP3 protein expression were detected by Western blot assay in the heart tissue of SD rats and H9c2 cardiomyocytes. The NLRP3, cysteine-containing aspartate specific protease 1(caspase-1) and interleukin (IL)-1β expressions at mRNA level were detected by reverse transcription-polymerase chain reaction (RT-PCR). Results The random blood glucose level was significantly increased (P<0.05) and the body weight was significantly decreased (P<0.05) in DCM group compared with those of Ctrl group. The expressions of cardiac p-Syk, p-JNK and NLRP3 at protein level were significantly increased in DCM group compared with those of Ctrl group (P<0.05). Furthermore, the mRNA levels of NLRP3, caspase-1 and IL-1β were significantly up-regulated (P < 0.05). BAY treatment significantly inhibited the high glucose-induced NLRP3, caspase-1 and IL-1β mRNA expressions and p-JNK, NLRP3 protein expressions in H9c2 cardiomyocytes (P < 0.05). Conclusion JNK phosphorylation and NLRP3 inflammasome activation induced by Syk play an important role in the pathogenesis of diabetic cardiomyopathy.
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Objective To explore the feasibility of laparoscopic surgery in the treatment of pediatric periappendicural abscess.Methods A total of 22 cases of pediatric periappendicural abscess were treated with laparoscopic surgery from April 2013 to May 2016.In the operation, we performed the separation from the side of the abdominal wall and abscess adhesion, and then lifted the abscess for blunt separation into the abscess cavity.After the management of appendix stump, the abdominal cavity was washed and a peritoneal drainage tube was placed.Results Laparoscopic appendectomy was performed successfully in all the cases.No conversion to open laparotomy was needed.The operation time was (65.3±8.2) min, the intraoperative blood loss was (10.5±4.2) ml, and the postoperative hospitalization was (6.5±1.4) days.Follow-ups for 6-24 months (mean, 12 months) in the 22 cases found no complications, such as abdominal abscess, stump fistula, stump appendicitis or adhesive ileus.Conclusion The application of laparoscopic surgery in the treatment of pediatric periappendicural abscess is feasible and safe.
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Objective To summarize the diagnosis and surgical therapeutic experience of functional insulinoma.Methods The clinical materials of 21 cases of functional insulinoma confirmed by pathologic examination from Jul.2006 to Aug.2016 were analyzed retrospectively.Results All patients showed signs of Whipple's triad.19.0% of them were misdiagnosed at the first visit.Before surgery,insulin to glucose ratio(IRI/G)was calculated in all patients,which in 21 cases (100%) was higher than 0.3.The accuracy of preoperative tumor localization,detected by ultrasonography,CT and MRI,was 38.1%,91.67% and 77.78%,respectively.Intraoperative ultrasound (IOUS) plus palpation was able to localize tumor in 100% of the cases.All of the 21 cases were solitary,among which 1 case was malignant insulinoma which was diagnosed with the left lateral lobe metastasis (4.8%).All the 21 cases underwent surgery,among whom 8 cases (38.1%)underwent laparoscopic resection.There were 4 cases (19.0%) of pancreatic fistula.Conclusions IRI/G higher than 0.3 can be used as the main evidence for diagnosis of insulinoma in clinically suspected patients.Multislice spiral CT is the first choice for preoperative localization of insulinoma.The significance of intraoperative ultrasound localization should be paid more attention.Surgical management of insulinomas is considered to be the only curative method.Precise localization,minimally invasive surgery and damage control treatment will be the development trend in the future.
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This paper made an intensive study on existing problems of the current public hospital cost accounting system and proposed amendments by sorting out cost accounting′s content and related concepts.The application value of this paper is,on one hand,to provide a reference for the formulation of cost and expense standards in government accounting standards,and on the other hand,to better its cost accounting method,and to lay system foundation for increasing accuracy efficiency and timeliness of cost accounting.And corresponding proposals were offered to make public hospitals′cost accounting results better applied in hospital management,government pricing and social insurance payment.
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Inflammatory bowel disease (IBD) could lead to the complexity of intra-abdominal pathology and patients' malnutrition,which might greatly increase the risk of operation.Laparoscopic minimally invasive surgery is playing an important role in the treatment of IBD,with the advantages of faster postoperative recovery,shorter duration of hospital stay and lower incidence of postoperative complications.And some new techniques for IBD have been reported in the western countries,such as single-incision laparoscopic surgery,natural orifice transluminal endoscopic surgery,robot-assisted laparoscopic surgery and so on.However,the new techniques are not widely used in China,and it is necessary to carry out a series of clinical practices,which should be carefully selected for IBD patients undergoing minimally invasive surgery.
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Objective To explore the protective effect and possible mechanism of bone marrow mesenchymal stem cells (BMSCs) on pulmonary fibrosis induced by paraquat (PQ) in rats.Methods A total of 54 male SD rats were randomly (random number) divided into 3 groups (n =18 in each).Group A (normal control group),group B [PQ + phosphate buffer solution (PBS)],group C (PQ + BMSCs group).Rats in group B and C were induced to get pulmonary fibrosis by intragastric administration of PQ in a dosage of 120 mg/kg.In addition,BMSCs was given to rats in group C by injection in a dose of 1 × 106/mL via the vena caudalis,whereas an equal volume of PBS (1 mL) was given to rats in group B by injection instead.The survival rats in each groups were sacrificed separately at 7 days,14 days and 28 days after administration of PQ.The lower lobe of left lung were taken to observe histopathological changes with HE staining and Masson staining,and the pulmonary fibrosis was scored by using the Szapiel classification of alveolitis.At the same time,the lower lobe of right lung was harvested to detect the hydroxyproline (HYP),TGF-β1 and HGF in lung tissue by using immunohistochemistry.Results The pathological changes in lung tissue of rats were inflammatory change in alveoli space filled with massive amount of exudate obviously in group B at 7 days after exposure to PQ,but in group C,the inflammatory changes were much milder than those in group B.The exudation and edema in lunge alveoli were mitigated in group B at 14 days after exposure to PQ,but pulmonary interstitial fibers were increased.The degree of pulmonary interstitial fibrosis in group C was milder than that in group B.In group B,there were obvious pathological changes including destroyed alveoli septum,enlarged alveoli,thickened alveoli septum and the deposition of collagen fibers,disarranged alveolar structure at 28 days after exposure to PQ.The deposition off collagen fiber was slighter with well observed basic alveolar structure in group C than that in group B.The levels of HYP in lung tissue at different intervals in B group were escalating with time after exposure to PQ,and reached a peak at 28 day,which were significantly higher than those in group A (P < 0.01).The levels of HYP in lung tissue at different intervals in C group were increasing with time after exposure to PQ,and reached a peak at 28 day,which were significantly lower than those in group B (P < 0.01).The levels of TGF-β1 from different intervals in B group were increased greatly with wider distribution over large portion of lung structure than those in group A,and reached a peak at 7 days,then declined with time,which were significantly higher than those in group A (P < 0.05).The levels of TGF-β1 at different intervals in group C were significantly lower than those in group B (P < 0.05).The levels of HGF at different intervals in B group increased with time,but there was no significant difference among those at different intervals (P >0.05).The levels of HGF at different intervals in group B were little bit higher than those in group A,but there was no significant difference between them (P > 0.05).The levels of HGF at different intervals in group C increased with time with significant differences among different intervals (P < 0.05).The levels of HGF at 3 intervals in group C were significantly different from those of group A and group B group (P <0.05).Conclusions BMSCs can alleviate pulmonary fibrosis induced by PQ,and increase the survival rate,which may be attributed to decreasing the level of TGF-β1 and increasing the level of HGF.
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Objective:To investigate the efficacy and safety of insulin glarsine combined with sitagliptin in elderly type 2 diabetic patients whose blood glucose levels were inadequately controlled by oral anti-diabetic drugs ( OAD) . Methods: In the open-labeled, randomized and parallel study, 98patients (≥60 years) were randomly divided into two groups: insulin glargine/sitagliptin combina-tion group (n=52, the observation group ) and insulin Aspart 30 injection group (n=46, the control group). The dose was adjusted according to the blood glucose. The fasting blood glucose (FBG), 2h postprandial blood glucose (2hPBG), glycosylated hemoglobin (HbA1c), the incidence of hypoglycemia and body mass index (BMI) after the 12-week treatment were compared between the two groups. Results:The fasting glucose and the incidence of hypoglycemia in the observation group were lower than those in the control group (P0. 05). Conclusion:The treatment of insulin glargine combined with sitagliptin is safe, effective and convenient in elderly type 2 diabetes patients with poor glycemic control. By diabetic education, the lower incidence of hypoglycemia treatment will be a better choice for elderly type 2 diabetic patients.
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Objective To investigate the effects of monocyte CD141 and platelet CD36 on peripheral vascular endothelial function (VEF) in patients with hypothyroidism (PWH). Methods The number of mono-cyte CD141and platelet CD36 from 52 patients wtih PWH and 40 healthy persons (control group) was calculated by flow cytometry. VEF was detected in terms of brachial artery flow-mediated dilatation (FMD) using Doppler ultrasonography. The differences of expressions of monocyte CD141 and platelet CD36 were compared between the two groups, so was FMD. The association of monocyte CD141 and platelet CD36 with FMD (%) was analyzed by Pearson analysis. Results Expression of monocyte CD141 (%) was significantly higher in the PWH group than in the control group (21.79 ± 9.45 vs. 18.84 ± 9.64, P < 0.001), so was expression of platelet CD36 (%) (34.26 ± 10.23 vs. 28.65 ± 9.53, P < 0.001). FMD% was lower in the PWH group than in the control group (8.65 ± 1.97 vs. 11.25 ± 2.72, P < 0.001). CD141 was negatively correlated with FMD% (r = -0.657, P < 0.01), so was CD36 (r = -0.557, P < 0.01). Conclusions Both monocyte CD141 and platelet CD36 are significantly higher in the PWH group than in the control group. CD141 and platelet CD36 are negatively related with VEF.
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EZH2 is over-expressed in human colon cancer and is closely associated with tumor proliferation, metastasis and poor prognosis. Targeting and inhibiting EZH2 may be an effective therapeutic strategy for colon cancer. 3-Deazaneplanocin A (DZNep), as an EZH2 inhibitor, can suppress cancer cell growth. However, the anti-cancer role of DZNep in colon cancer cells has been rarely studied. In this study, we demonstrate that DZNep can inhibit the growth and survival of colon cancer HCT116 cells by inducing cellular senescence and apoptosis. The study provides a novel view of anti-cancer mechanisms of DZNep in human colon cancer cells.
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Objective:To explore the wound-healing effect and the anti-inflammatory activity of the aqueous extracts from the fresh roots and rhizomes of A. calamus. Methods: The image analysis techniques and the histological analysis were used to determine the wound-healing effect in the excised wound test, and the real-time RT-PCR techniques was used to evaluate the anti-inflammatory activi-ty in the lipopolysaccharide-induced RAW 264. 7 cells test. Results:The aqueous extracts were given 3 times a day since the model was established. The skin wound area was reduced significantly in the aqueous extracts group when compared with that in the control group since the 3rd day, the wound area in the aqueous extracts group was only 15% of that in the control group on the 13th day, and the wound-healing rate was enhanced significantly by the extracts. Moreover, the mRNA expressions of the inflammatory mediators such as TNF-α, IL-1β and IL-6 in the inflammatory RAW 264. 7 cells induced by lipopolysaccharide were inhibited effectively by the ex-tracts in a dose-dependant manner. Conclusion:The results indicate that the aqueous extracts from the fresh roots and rhizomes of A. calamus have significant wound-healing activity in animal excised wound model and anti-inflammatory activity in vitro.
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Objective To study the relationship between Miao drum and hypertension in the Miao women of the countryside . Methods A survey of blood pressure measurement and questionnaire investigation were conducted among 1 069 Miao females ,by using cluster multistage sampling in countryside of Hunan ,Hubei ,Chongqing ,and Guizhou .A case-control analysis for 226 cases with new diagnosed hypertension and 226 controls with normal blood pressure .Results Among 1 069 sample ,the standardized prevalence rate of hypertemion was 24 .5% .There were significant differences in the prevalence rates of hypertension between the different age groups(χ2 =174 .46 ,P<0 .01) .The single factor logistic regression analysis(OR=0 .383 ,95% CI:0 .262-0 .558)and multi-conditional logistic regression analysis(OR=0 .379 ,95% CI:0 .255-0 .565)showed that Miao drum was probably protective factor for hypertension in the Miao women of the countryside .Conclusion Miao drum was probably protective factor for hyperten-sion in the Miao women of the countryside in Hunan ,Hubei ,Chongqing ,and Guizhou .Long-term adherence to participate in miao drum exercise may prevent high blood pressure .