To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.
Dermatitis, Atopic/drug therapy* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Mice ; Network Pharmacology ; Male ; Female ; Adult ; Receptors, Glucocorticoid/metabolism* ; Disease Models, Animal ; Single-Blind Method ; Middle Aged ; Young Adult

Objective:To analyze the causal relationship between lifestyle-based factors and the occurrence and development of hepatobiliary malignancies by Mendelian randomization study method,and to provide the potential clinical evidence for the prevention and treatment of hepatobiliary malignancies.Methods:The data from large-scale,independent genome-wide association studies(GWAS)were selected,and seven-step inclusion criteria for the instrumental variable screening were set up.The exposure lifestyles included the percentage of carbohydrate intake,percentage of fat intake,percentage of protein intake in the diet,coffee intake,weekly alcohol consumption times,leisure electronic screen exposure time,moderate to vigorous intensity physical activity(MVPA)during leisure time,sedentary behavior at work,age at first smoking,daily smoking quantity,current smoking status,and past smoking status,totaling 12 phenotypes.The primary analysis method used was the random effect model of the inverse variance weighted(IVW)method,and the heterogeneity was detected by Cochrane's Q test and the horizontal pleiotropy was detected by MR-Egger intercept method.Results:The current smoking status was significantly positively correlated with the increasing risk of extrahepatic cholangiocarcinoma(OR=1.607,95%CI:1.113-2.322,P=0.011).Higher coffee intake was causally linked to a higher risk of liver cancer and intrahepatic cholangiocarcinoma(OR=1.000,95%CI:0.999-1.000,P=0.012).In the physical activity,more MVPA was associated with the lower risk of liver cancer and intrahepatic cholangiocarcinoma(OR=0.998,95%CI:0.996-0.999,P=0.002).The Cochrane's Q test results showed that there was mild heterogeneity between MVPA and extrahepatic cholangiocarcinoma(Q=18.354,P=0.049)as well as the percentage of protein intake and intraphepatic cholangiocarainoma(Q=12.715,P=0.026),and the MR-Egger intercept method results showed there was no horizontal pleiotropy.Conclusion:There is a causal relationship between current smoking status and extrahepatic cholangiocarcinoma,and there is a causal relationship between more MVPA and the lower risk of liver cancer and intrahepatic cholangiocarcinoma.Education on smoking and physical activity for the patients may offer potential benefits for the prevention of hepatobiliary malignancies.

Laparoscopic distal pancreatectomy is the conventional treatment for tumors of the pancreatic body or tail.And laparoscopic spleen-preserving distal pancreatectomy has been emphasized because it can preserve the spleen's function and lower the complications following splenectomy.However,the occult onset and complex anatomical location of pancreatic tumors pose a challenge to their diagnosis and spleen-preserving distal pancreatectomy.In recent years,our team has accumulated rich experience in the diagnosis and treatment of pancreatic tumors,and innovatively proposed the"SELECT"concept(S-Single-Operator Cholangiopancreatoscopy,E-ERCP,L-Laparoscopy,E-Endoscopic ultrasound,C-Choledochoscopy/Confocal laser endomicroscopy,T-Traditional Chinese medicine)for diagnosis and treatment.Based on the various characteristics of pancreatic tumors,various endoscopic and laparoscopic techniques are applied,and an optimal combination of various minimally invasive methods is selected.Fully applying the SELECT concept to laparoscopic spleen-preserving distal pancreatectomy is conducive to accurate preoperative diagnosis,accurate intraoperative resection,prediction and treatment of postoperative complications,and one-stop diagnosis and treatment of pancreatic tumors,maximizing patient benefits.

Objective To Establish a loop-mediated isothermal amplification(LAMP)assay for detection of Salmonella in fecal samples of tree shrews, and report the result of preliminary application of this method. Methods LAMP primers were designed and synthesized according to the conserved sequence of Salmonella specific gene invA (invasive protein gene A). To optimize the reaction time and temperature by setting 10 reaction times(24 to 42 min)and temperature(57℃ to 66℃)and tested its specificity and sensitivity. At the same time, a conventional PCR test was performed to verify and compare with the LAMP assay. 91 fecal samples of wild-derived tree shrews were detected by the LAMP assay. Results The experimental condition was confirmed as 62℃ and 34 min. The sensitivity of Salmonella was 3.36×101CFU/mL, which was 10 to 100 times higher than that of conventional PCR assay. In 10 kinds of intestinal bacteria for LAMP amplification,Salmonella enteritidis and Salmonella paratyphi B were positive,the others were negative. Among the 91 samples of tree shrew fecal samples detected by the LAMP assay, the positive detection rate was 20.88%. The LAMP assay can be completed within 40 min, the result can be observed and judged visually by color changes. Conclusions The LAMP assay established in this study is convenient,rapid,sensitive and specific. It can be used as a rapid measure for large-scale detection of Salmonella in feces of tree shrews.

Objective To investigate the risk factors and treatment of local recurrence after Dixon operation of rectal cancer.Methods The clinical data of forty-seven patients who had local recurrence after Dixon operation of rectal cancer in our hospital from January 2011 to December 2013 was analyzed retrospectively.According to literature review,the high risk factors and treatment methods of local recurrence of rectal cancer in China and abroad were analyzed.Results The treatment methods of patients with local recurrence after anterior resection were radical resection,palliative resection and chemotherapy.The prognosis of patients with radical resection whose overall survival time was (38.202±2.411) months,better than that with palliative resection ((24.591±2.150) months),better than that with chemotherapy ((12.833±1.033) months).There was a significant difference in the survival time among the three groups (χ2=30.155,P<0.001).Conclusion Fully understanding of high risk factor can help reduce the probability of local recurrence.For patients with local recurrence of the rectal cancer,radical resection should be performed.In case that radical surgery is not possible,positive treatments should be adopted if the patients are in good physical condition.

Objective To investigate the significance of circulating tumor cells in tumor reflux venous blood in colorectal cancer patients with liver metastasis.Methods Seventy-four patients with colorectal cancer treated in Liaoning Cancer Hospital & Institute from January 2015 to January 2017 were enrolled in this study.The circulating tumor cells were detected by CellSearch system in patients with tumor reflux venous blood to analyze the results of circulating tumor cells and their clinical significance.Results Among the 74 patients with colorectal cancer,there were 24 patients with synchronous liver metastasis and 9 patients with metachronous liver metastasis.The sensitivity of CEA and CA19-9 positive in the detection of colorectal cancer synchronous liver metastasis was 67.9% and 58.6%,respectively.The sensitivity of circulating tumor cells positive detection in tumor reflux venous blood in the diagnosis of synchronous liver metastasis was 60.6%.n patients with metachronous liver metastases,CEA and CA19-9 positive patients were 33.3% and 55.6%,respectively,while CTCs positive patients were 77.8%.Conclusion The detection of circulating tumor cells in tumor reflux venous blood of colorectal cancer not only improves the detection rate,but also may become a predictive factor for metachronous liver metastasis.

Objective To find the key miRNA that relative to peritoneal fibrosis associated with peritoneal dialysis (PD) by microarray technology,and verify its expression in vitro and in vivo.Methods The peritoneal fibrosis mouse model associated with PD were established by intraperitoneal injection of lipopolysaccharide (LPS)+ 4.25％ peritoneal dialysate.The expression of miRNA was detected by microarray in peritoneal tissues.The expression of miRNA profiles between fibrotic and normal peritoneal tissues was compared.The differentially expressed miRNA (miR-200a) was validated by real-time PCR in lager sample size cohorts.The expressions of miR-200a were also detected in the epithelial-mesenchymal transition (EMT) process of human peritoneal mesothelium cells.Results In mice model of PD,peritoneal tissue was markedly thickened and with a massive extracellular matrix accumulation.In contrast with control,the expression level of epithelial marker E-cadherin was significantly decreased,α-SMA,Col-Ⅰ and FN were remarkably increased (P ＜ 0.05).By miRNA microarray analysis,miR-200a was significantly down-regulated (3.31 folds change,P ＜ 0.05) in fibrotic peritoneal tissues.The down-regulated expression level of miR-200a was also validated by realtime PCR in larger cohorts (P ＜ 0.05).Then,the expression level of miR-200a was detected in the EMT process of human peritoneal mesothelium cells.During the process of TGF-β1 induced EMT,miR -200a was significantly down-regulated compared with the control (P ＜ 0.05).Conclusions Downregulated expression of miR-200a was observed both during peritoneal fibrosis and TGF-β 1 induced EMT in vivo and in vitro,suggesting that miR-200a may be involved in the peritoneum fibrosis by regulating the target genes of EMT.

OBJECTIVETo detect structural changes in the brain in fetuses with agenesis of the corpus callosum (ACC) and holoprosencephaly (HPE) in the first trimester.

METHODSThe ultrasound data were analyzed retrospectively in 620 normal singleton fetuses between 11 and 13(+6) gestational weeks, 5 fetuses diagnosed to have ACC, and 13 fetuses with HPE. The midbrain diameter (MD) and falx diameter (FD) were measured and their ratio (MD/FD) was calculated for comparative analysis.

RESULTSNo significant difference was found in the MD, FD, and MD/FD ratio between fetuses with ACC and HPE (P>0.05). Compared to the normal fetuses, all the fetuses with ACC and HPE showed significantly increased mean MD and MD/FD ratio (P<0.05); 4 (80%) fetuses with ACC and 11 (84.6%) with HPE had a reduced FD. All the fetuses with ACC and HPE had MD/FD ratios greater than 1, which were below 1 in all the normal fetuses.

CONCLUSIONIn the first trimester, fetuses with ACC and HPE have measurable abnormalities in the midbrain and falx area of the brain, and these changes, represented by abnormal midsagittal MD, FD and their ratio, can be of value in detecting ACC or HPE in fetuses in the first trimester.

Agenesis of Corpus Callosum ; diagnosis ; Corpus Callosum ; diagnostic imaging ; Female ; Fetus ; Gestational Age ; Humans ; Pregnancy ; Pregnancy Trimester, First ; Retrospective Studies ; Ultrasonography, Prenatal

OBJECTIVETo investigate risk factors associated with lymph node metastasis and prognosis of rectal neuroendocrine tumor (NET).

METHODSClinicopathological data of 69 patients with rectal NET in our department from April 2003 to October 2011 were retrospectively analyzed. Associations of clinicopathological factors with lymph node metastasis and prognosis were examined using univariate and multivariate analysis.

RESULTSOf the 69 patients, 9 cases had lymph node metastasis. The lymph node metastasis was significantly associated with tumor size, T stage and G grade by univariate analysis. Multivariate analysis showed that T stage was the only risk factor associated with lymph node metastasis. The overall 5-year survival rate was 90.3%. Prognosis of rectal NET was significantly associated with tumor size, T stage, N stage, M stage, TNM stage and G grade by univariate analysis. Multivariate analysis showed that M stage was significantly associated with long-term survival in rectal NET patients (P=0.000, HR=2.285, 95%CI:1.484~3.518). There was no significant difference in patients with stage I between local and radical resection, while there were significant differences in those with stage II or higher between the two operations (P=0.046).

CONCLUSIONT stage is associated with lymph node metastasis and both TNM stage and M stage can affect the prognosis of patients with NET, which may be used as potential predictive factors for rectal NET. Local resection should be recommended for patients with stage I and radical resection should be recommended for patients with stage II or higher.

Adult ; Aged ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; diagnosis ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Neuroendocrine Tumors ; diagnosis ; pathology ; Prognosis ; Rectal Neoplasms ; diagnosis ; pathology