[Advancements in virtual screening techniques for study of enzyme inhibitor compounds].

Enzymes are closely associated with the onset and progression of numerous diseases, making enzymes a primary target in innovative drug development. However, the challenge remains in identifying compounds that exhibit potent inhibitory effects on the target enzymes. With the continuous expansion of the total number of natural products and increasing difficulty in isolating and enriching new compounds, traditional high-throughput screening methods are finding it increasingly challenging to meet the demands of new drug development. Virtual screening, characterized by its high efficiency and low cost, has gradually become an indispensable technology in drug development. It represents a prominent example of the integration of artificial intelligence with biopharmaceuticals and is an inevitable trend in the rapid development of innovative drug screening in the future. Therefore, this article primarily focused on systematically reviewing the recent applications of virtual screening technology in the development of enzyme inhibitors and explored the prospects and advantages of using this technology in developing new drugs, aiming to provide essential theoretical insights and references for the application of related technologies in the field of new drug development.

Retrosplenial Cortex Effects Contextual Fear Formation Relying on Dysgranular Constituent in Rats.

Animal contextual fear conditioning (CFC) models are the most-studied forms used to explore the neural substances of posttraumatic stress disorder (PTSD). In addition to the well-recognized hippocampal-amygdalar system, the retrosplenial cortex (RSC) is getting more and more attention due to substantial involvement in CFC, but with a poor understanding of the specific roles of its two major constituents-dysgranular (RSCd) and granular (RSCg). The current study sought to identify their roles and underlying brain network mechanisms during the encoding processing of the rat CFC model. Rats with pharmacologically inactivated RSCd, RSCg, and corresponding controls underwent contextual fear conditioning. [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scanning was performed for each animal. The 5-h and 24-h retrieval were followed to test the formation of contextual memory. Graph theoretic tools were used to identify the brain metabolic network involved in encoding phase, and changes of nodal (brain region) properties linked, respectively, to disturbed RSCd and RSCg were analyzed. Impaired retrieval occurred in disturbed RSCd animals, not in RSCg ones. The RSC, hippocampus (Hip), amygdala (Amy), piriform cortex (Pir), and visual cortex (VC) are hub nodes of the brain-wide network for contextual fear memory encoding in rats. Nodal degree and efficiency of hippocampus and its connectivity with amygdala, Pir, and VC were decreased in rats with disturbed RSCd, while not in those with suppressed RSCg. The RSC plays its role in contextual fear memory encoding mainly relying on its RSCd part, whose condition would influence the activity of the hippocampal-amygdalar system.

Bone metastasis of esophageal carcinoma diagnosed as a first primary tumor: a population-based study.

Background: This study aimed to explore predictors of bone metastasis (BM) of esophageal carcinoma (EC) and factors affecting the prognosis of EC with BM (ECBM). Methods: We retrospectively studied the data of EC patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. Logistic regression analysis was used to analyze the risk factors of BM. Cox regression and Fine and Gray's competing risk regression were performed to identify prognostic factors associated with all-cause and cancer-specific death, respectively. The Kaplan-Meier method was used to assess survival. Results: After exclusion, 8,916 patients were eligible, of whom 462 (5.2%) had ECBM. Independent risk factors of BM were age <65 years, male sex, stage T1, advanced N stage, and non-bone organ metastases. For EC, the median survival time (MST) was 17 months, and the 3- and 5-year survival rates were 31.6% and 23.3%, respectively; meanwhile, for BM, the MST was 5 months, and the 3- and 5-year survival rates were 2% and 1%, respectively. Adenocarcinoma, stage T2, the absence of non-bone organ metastases, and combined radiotherapy and chemotherapy were associated with a reduced risk of all-cause death in ECBM patients. Stage T2, the absence of non-bone organ metastases, and combined radiotherapy and chemotherapy were associated with a decreased risk of cancer-specific death in ECBM patients. Conclusions: Although rare, BM severely impairs the prognosis of EC. BM predictors and factors influencing the prognosis of ECBM may help distinguish high-risk patients with BM and assess survival in ECBM patients.

Cox-maze III procedure for atrial fibrillation during valve surgery: a single institution experience.

OBJECTIVES: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in patients with heart valve disease. Our aim was to summarize our experience and evaluate the efficacy and safety of the Cox maze III procedure combined with valve surgery in patients with AF. METHODS: A retrospective, observational analysis was performed for all consecutive patients underwent maze III procedure combined with valve surgery between October 2015 and June 2019. In this trial, we used a monopolar radiofrequency (RF) ablation in addition to cut and sew technique to treat AF. RESULTS: 66 patients (37 female, 56.1%) with persistent or long-lasting persistent AF associated with valve disease were identified. The mean age was 54.2 ± 8.4 years (range, 30 to 73 years). Overall hospital mortality was 3.0%. The duration of cardiopulmonary bypass and aortic cross clamping was 175.4 ± 32.9 and 115.6 ± 22.8 min respectively. The first 24 h drainage was 488.6 ± 293.3 ml. The postoperative hospital stay was 14.8 ± 8.3 days. The postoperative incidence of permanent pacemaker implantation, reoperation for bleeding, renal failure required hemodialysis, and stroke was 4.5, 1.5, 4.5% and 0 respectively. The frequency of sinus rhythm was 91.7, 93.1, 94.7, 93.3 and 89.5% at 1, 3, 6, 12, and 24 months respectively. CONCLUSIONS: The Cox-Maze III procedure is safe in the surgical treatment of AF associated with valve disease, and efficacious for sinus rhythm maintenance, with low morbidity and mortality.

The clinicopathologic features and prognosis of esophageal neuroendocrine carcinomas: a single-center study of 53 resection cases.

BACKGROUND: Esophageal neuroendocrine carcinomas (NECs) are exceedingly rare and poorly understood. The aims of the retrospective study were to delineate the clinicopathologic features and prognosis of patients with the disease. METHODS: We performed a retrospective study containing 53 patients of esophageal NECs in our center from 2002 through 2018. Patients were assigned to the pure esophageal NECs group and the esophageal NECs mixed with squamous carcinoma and/or esophageal adenocarcinoma (MiNECs) group. Demographic, clinical, pathologic and prognostic factors were recorded and analyzed. RESULTS: Of the 53 patients, elderly male patients were predominant. Dysphagia was the most common symptom (45/53, 84.9%). Most tumors were centered in the middle esophagus (36/53,67.9%).Ulcerated appearance was frequently seen in the pure NECs (56.8%), and the tumors in the MiNECs group mostly represented elevated types (57.9%). Synaptophysin (38/45, 84.4%), chromogranin A (21/38, 55.3%) and CD56(23/27, 85.2%) have been proven to be positive markers for NECs. Most patients (46/53, 86.8%) received surgery combined with chemotherapy. Though the pathologic stages were alike (P = 0.129), the median survival time was 3.53 years for the pure NECs group and 7 years for the MiNECs group. In multivariate analysis, pathologic stage (RR = 1.938, P = 0.045) and age (RR = 2.410, P = 0.028) were independent prognostic factors for patients with MiNECs. The prognosis of patients with pure NECs was independent from any factors. CONCLUSIONS: Careful endoscopic examination could help distinguish pure NECs from MiNECs. NECs were aggressive, but a relative better prognosis for patients with MiNECs. Surgery should be performed if applicable, and chemotherapy might be helpful.

[Clinical application evaluation and revision suggestions of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for community acquired pneumonia].

To clarify the clinical application of the group standard (T/CACM 1035-2017) of the Chinese Society of Traditional Chinese Medicine (TCM), the clinical practice guideline on traditional chinese medicine therapy alone or combined with community acquired pneumonia, and to understand the clinical applicability of the Guideline. The clinical workers trained in terms of the Guideline in hospitals at all levels in China were selected as the research objects. A total of 494 questionnaires on application evaluation and 511 questionnaires on applicability evaluation were collected to construct the database of the post-effect evaluation of the Guideline. Excel software was used for statistical analysis. The overall evaluation of the Guideline was 92.31%, 91.06%, 87.45% respectively in efficacy, safety and economy. The Guideline was well used in clinical application, and 99.41% of the patients were willing to follow the recommended scheme. The agreed ratio in rationality evaluation was 97.98%, 92.37%, 94.53% and 92.71% in treatment rules, syndrome differentiation and classification, prevention of complications, and rehabilitation method. The effective rate of the prescriptions recommended in the Guideline was all above 65%. More than 80% of the prescriptions were Tanreqing Injection, Yinqiao Powder, Qingjin Huatan Decoction, Maxing Shigan Decoction, Shengmai San and Shashen Maidong Decoction. Adverse reactions, unknown active components and economy of Chinese patent medicines were the important factors affecting drug use and efficacy, providing a clinical basis for updating and revising the standard.

[Literature study on prevention and treatment of community acquired pneumonia by traditional Chinese medicine].

Among the literatures of the prevention and treatment of community-acquired pneumonia (CAP) published in recent years, there were 16 kinds of classic prescription, including 52 RCTs about Maxingshigan Decoction, 21Chinese patent medicines. There are eight kinds of indications for the drug specification, among which the literatures of Tan Reqing injection accounted for the most about 136 RCTs; There were literatures about non-drug treatment, including： acupuncture, Chinese medicine paste, enema, Chinese medicine ionization, Chinese medicine fumigation, bamboo cans and so on. In this study, author has analysed the classic prescription, Chinese patent medicine and non-drug therapy referring to advantages and disadvantages of CAP, which could be used to treat virus infection instead of antibiotic therapy. Based on antibiotic therapy, Chinese medicine treatment could increase synergistic interaction while decrease the antibiotic side-effects. In addition, Chinese medicine could perform synergistic interaction in CAP every period, which resulted from classified analysis of basic studies about Chinese medicine treatment in CPA. This study is aimed to provides an important basis for clarifying the direction of scientific research.

[Methodological quality assessment of community-acquired pneumonia clinical practice guidelines in China based on AGREE â ¡ tool].

This study is aimed to identify and assess the methodological quality of community-acquired pneumonia (CAP) clinical practice guidelines (CPG) in China by using AGREE Ⅱ tool. CNKI, SinoMed, Wanfang, and VIP Chinese databases from database establishment to March 2017 were searched by manual retrieval to collect all the clinical practice guidelines prepared by various associations or organizations, then AGREE Ⅱtool was used to assess them. Data in each CPG were analyzed in terms of six domains, including scope and purpose, participants, rigor, clarity and readability, applicability and editorial independence. A total of 4 CPGs were included. The results showed that the scope and purpose scored 45.8%; the clarity of expression scored 44.75%; the participants scored 31.9%; the rigor scored 18.98%; the applicability scored 7%; and finally the editorial independence scored 1%. It is concluded that the quality of applicability and the editorial independence should attained paid more attention in future development or updating of the guidelines. In addition to strengthening the compliance with international general principles, we should also pay attention to the characteristics of traditional Chinese medicine treatment, especially the related evidences as complementary and alternative treatment for western intervention measures.

Effect of PPM1H on malignant phenotype of human pancreatic cancer cells.

The objective of this study was to investigate the effect of silencing gene protein phosphatase 1H (PPM1H) on malignant phenotype of human pancreatic cancer cell line BxPC-3. In order to explore the function of PPM1H in pancreatic cancer cells, real-time PCR and western blotting were used to detect the expression of PPM1H in different pancreatic cancer cell lines. Human pancreatic cancer cell line BxPC-3 was treated with 10 ng/ml TGF-ß1 and 200 ng/ml BMP2 for 72 h, respectively, and the mRNA and protein expression levels of PPM1H and EMT-related markers (E-cadherin, vimentin) were detected by real-time PCR and western blotting, respectively. Using exogenous RNA interference technology to silence the PPM1H gene, the expression of PPM1H and EMT-related markers at mRNA and protein levels were detected by real-time PCR and western blotting. The cell migration and invasion were measured using Transwell assays. Finally, cell counting kit-8 (CCK-8) and flow cytometry were used to determine the effect of PPM1H on cell proliferation and apoptosis of BxPC-3 cells. The expression levels of PPM1H in all of the examined pancreatic cancer cell lines (BxPC-3, MIA-PACA2, PANC-1, SW1990, PANC-03.27) were lower than that of normal pancreatic ductal epithelial cells (HPDE6-C7) at both mRNA and protein levels. Both TGF-ß1 and BMP2 treatment induced EMT and downregulation of PPM1H in BxPC-3 cells. By using RNA interference to transiently knock down PPM1H expression in BxPC-3 cells, we found that the expression of E-cadherin was downregulated while vimentin was up-regulated. The data suggested that silencing PPM1H gene can induce EMT in BxPC-3 cells. In addition, Transwell migration assays showed that silencing PPM1H gene can promote the invasion and metastasis of BxPC-3 cells. Cell proliferation and apotosis detection demonstrated that silencing PPM1H gene can promote the proliferation and inhibit apoptosis of BxPC-3 cells. In conclusion, PPM1H is aberrantly expressed in human pancreatic cancer cell lines and can be downregulated when EMT is induced by cytokine stimulation. Silencing PPM1H gene can induce EMT in BxPC-3 cells, and promote the invasion and metastasis of BxPC-3 cells. Moreover, silencing PPM1H gene can promote the proliferation and inhibit apoptosis of BxPC-3 cells. PPM1H may be a new tumor-suppressor factor for pancreatic cancer and provides new insight into molecular targets for gene therapy of pancreatic cancer.

Diagnostic and therapeutic value of computed tomography guided coil placement after digital subtraction angiography guided video-assisted thoracoscopic surgery resection for solitary pulmonary nodules.

BACKGROUND: With the widespread use of general health examinations, the detection rate of pulmonary nodules has increased; however, locating the pulmonary nodules is still a challenge. METHODS: We reviewed cases that underwent computed tomography (CT)-guided coil localization followed by real-time digital subtraction angiography (DSA)-guided accurate resection of solitary pulmonary nodules (SPNs) using video-assisted thoracoscopic surgery (VATS) at our hospital, and we evaluated the clinical value. From September 2011 to October 2014, 116 cases with SPNs were treated in our unit. The lesion was preoperatively localized using coil placement under CT guidance, and the patients were subsequently transferred to the hybrid operating room. VATS wedge resection with real-time DSA guidance was performed, and further processing was conducted in accordance with the intraoperative pathological diagnosis for these lesions. RESULTS: Coil localization, which averaged 15.30±3.20 min, was successful in all patients (100%), while VATS wedge resection took 24.20±12.10 min and lobectomy or segmentectomy took 88.8±36 min. The pathological results revealed malignant lesions in 61 cases and benign lesions in 55 cases. CONCLUSIONS: Preoperative CT-guided coil localization for SPNs had a high accuracy with no serious complications. Following real-time DSA-guided VATS resection, the lesions could be accurately removed with a cutting edge distance of >2 cm to the lesion, which may help diagnose and treat the SPN simultaneously.

Associations of C1q/TNF-Related Protein-9 Levels in Serum and Epicardial Adipose Tissue with Coronary Atherosclerosis in Humans.

OBJECTIVE: To investigate the correlation of CTRP9 with coronary atherosclerosis. METHODS: Coronary angiography confirmed CAD in 241 patients (62 received CABG) and non-CAD in 121 (55 received valve replacement). RESULTS: Serum levels of LDL-C, CRP, TNF-α, IL-6, and leptin in CAD patients were significantly higher than those in non-CAD patients (P < 0.05), but APN and CTRP9 were lower (P < 0.05). Serum levels of CTRP9 and APN were negatively related to BMI, HOMA-IR, TNF-α, IL-6, and leptin but positively to HDL-C (P < 0.05) in CAD patients. After adjustment of APN, CTRP9 was still related to the above parameters. Serum CTRP9 was a protective factor of CAD (P < 0.05). When compared with non-CAD patients, leptin mRNA expression increased dramatically, while CTRP9 mRNA expression reduced markedly in epicardial adipose tissue of CAD patients (P < 0.05). The leptin expression and macrophage count in CAD group were significantly higher than in non-CAD group, but CAD patients had a markedly lower CTRP9 expression (P < 0.05). CONCLUSIONS: Circulating and coronary CTRP9 plays an important role in the inflammation and coronary atherosclerosis of CAD patients. Serum CTRP9 is an independent protective factor of CAD.

Graft pathology at the time of harvest: impact on long-term survival / Patologia do enxerto no momento da coleta: impacto na sobrevida a longo prazo

Objective: This study aims to present the graft pathology at the time of harvest and its impact on long-term survival. Methods: The remnants of the bypass grafts from 66 consecutive patients with coronary artery disease receiving a coronary artery bypass grafting were investigated pathologically, and pertinent predictive risk factors and survival were analyzed. Results: Medial degenerative changes with or without intimal proliferation were present in 36.8%, 37.8% and 35.6% of left internal mammary artery (IMA), radial artery and saphenous vein grafts. There were 2 (3.0%) hospital deaths and 9 (14.1%) late deaths. Multinomial logistic regression revealed left IMA pathological changes, dyslipidemia, history of percutaneous transluminal coronary angioplasty/stent deployment and Y-graft were significant predictive risk factors negatively influencing the patients’ long-term survival. Kaplan-Meier survival analysis revealed that the long-term survival of patients with left IMA pathological changes were significantly reduced compared with those without (74.1% vs. 91.4%, P=0.002); whereas no differences were noted in long-term survivals between patients with and without pathological changes of the radial arterial or saphenous vein grafts. Conclusion: Pathological changes may be seen in the bypass graft at the time of harvest. The subtle ultrastructural modifications and the expressions of vascular tone regulators might be responsible for late graft patency. The pathological changes of the left IMA at the time of harvest rather than those of the radial artery or saphenous vein graft affect significantly longterm survival. Non-traumatic maneuver of left IMA harvest, well-controlled dyslipidemia and avoidance of using composite grafts can be helpful in maintaining the architecture of the grafts. .

Objetivo: Este estudo tem como objetivo apresentar a patologia do enxerto no momento da coleta e do impacto na sobrevida a longo prazo. Métodos: Os remanescentes de pontes de safena de 66 pacientes consecutivos com doença arterial coronária que receberam uma cirurgia de revascularização coronariana foram investigados patologicamente, e os fatores de risco preditivos e a sobrevivência foram analisados. Resultados: Alterações degenerativas da artéria medial, com ou sem proliferação da íntima estavam presentes em 36,8%, 37,8% e 35,6% de pontes da artéria torácica interna esquerda (ATIE), artéria radial e veia safena. Houve dois (3,0%) óbitos hospitalares e nove (14,1%) óbitos tardios. A regressão logística multinomial revelou que alterações patológicas na ATIE, dislipidemia, história de angioplastia/stent implantação coronariana transluminal percutânea e Y-enxerto foram significativos fatores de risco preditivos que influenciam negativamente a sobrevivência a longo prazo dos pacientes. Análise de sobrevida de Kaplan- Meier revelou que a sobrevivência a longo prazo de pacientes com alterações patológicas da ATIE foi significativamente reduzida em comparação com aqueles sem (74,1% vs. 91,4%, P=0,002), considerando que não foram observadas diferenças na sobrevivência de longo prazo entre pacientes com e sem alterações patológicas dos enxertos da artéria radial ou de veia safena. Conclusão: As alterações patológicas podem se desenvolver na revascularização no momento da coleta. As modificações ultraestruturais sutis e as expressões de reguladores do tônus vascular podem ser responsáveis pela patência tardia do enxerto. As alterações patológicas da ATIE no momento da coleta, em vez do enxerto da artéria radial ou da veia safena, podem afetar significativamente a sobrevida de longo prazo. Manobra não traumática da ATIE na coleta, bom controle da dislipidemia e para evitar uso de enxertos compostos pode ser útil na manutenção da arquitetura dos enxertos. .

Safety and efficacy of endoscopic retrograde cholangiopancreatography for common bile duct stones in liver cirrhotic patients.

In order to investigate the safety and efficacy of endoscopic retrograde cholangiopancreatograpy (ERCP) in liver cirrhosis patients with common bile duct stones, we retrospectively analyzed data of 46 common bile duct stones patients with liver cirrhosis who underwent ERCP between 2000 and 2008. There were 12 cases of Child-Pugh A, 26 cases of Child-Pugh B, and 8 cases of Child-Pugh C. 100 common bile duct stones patients without liver cirrhosis were randomly selected. All the patients were subjected to ERCP for biliary stones extraction. The rates of bile duct clearance and complications were compared between cirrhotic and non-cirrhotic patients. The success rate of selective biliary cannulation was 95.6% in liver cirrhotic patients versus 97% in non-cirrhotic patients (P>0.05). The bile duct clearance rate was 87% in cirrhotic patients versus 96% in non-cirrhotic patients, but the difference was not statistically significant. Two liver cirrhotic patients (4.35%, 2/46) who were scored Child-Pugh C had hematemesis and melena 24 h after ERCP. The hemorrhage rate after ERCP in non-cirrhotic patients was 3%. The hemorrhage rate associated with ERCP in Child-Pugh C patients was significantly higher (25%, 2/8) than that (3%, 3/100) in non-cirrhotic patients (P<0.01%). There was no significant difference between these two groups in the rate of post-ERCP pancreatitis (PEP) and cholangitis. ERCP is safe and effective for Child-Pugh A and B cirrhotic patients with common bile duct stones. Hemorrhage risk in ERCP is higher in Child-Pugh C patients.

Doxycycline attenuates acute lung injury following cardiopulmonary bypass: involvement of matrix metalloproteinases.

Acute lung injury (ALI) was one of the major complications after cardiopulmonary bypass (CPB). Matrix metalloproteinases (MMPs) play an important role in ALI following CPB. In this study, we investigated the effects of doxycycline (DOX), a potent MMP inhibitor, on MMP-9 and ALI in the rat model of CPB. 48 adult male Sprague-Dawley rats were randomized into four groups: group I (Control group, underwent cannulation + heparinization only); group II (CPB group, underwent 60-minutes of normothermic CPB); group III (Low-dose treatment group, underwent 60-minutes of normothermic CPB with DOX gavage 30 mg/kg ×1 week ahead of CPB); and group IV (High-dose treatment group, underwent 60-minutes of normothermic CPB with DOX gavage 60 mg/kg ×1 week ahead of CPB). The effects of doxycycline on ALI were determined by measuring the lung Wet/Dry ratio, the inflammation of bronchoalveolar lavage fluid (BALF) and the ultrastructural changes of the lungs. The role of doxycycline on MMP-9 was assessed by the plasma concentration, the activity and the expression in lung tissue. Our results demonstrated that the lung Wet/Dry weight ratio and the inflammatory mediators (TNF-α, IL-1ß) in BALF were decreased significantly with doxycycline treatment. The lung damages were attenuated by doxycycline. The levels of plasma concentration, the activity and the expression of MMP-9 in lung tissue were suppressed with doxycycline and the effects were dose dependent. Doxycycline could suppress the expression of MMP-9 and cytokines, and improve the ALI following CPB.

Graft pathology at the time of harvest: impact on long-term survival.

OBJECTIVE: This study aims to present the graft pathology at the time of harvest and its impact on long-term survival. METHODS: The remnants of the bypass grafts from 66 consecutive patients with coronary artery disease receiving a coronary artery bypass grafting were investigated pathologically, and pertinent predictive risk factors and survival were analyzed. RESULTS: Medial degenerative changes with or without intimal proliferation were present in 36.8%, 37.8% and 35.6% of left internal mammary artery (IMA), radial artery and saphenous vein grafts. There were 2 (3.0%) hospital deaths and 9 (14.1%) late deaths. Multinomial logistic regression revealed left IMA pathological changes, dyslipidemia, history of percutaneous transluminal coronary angioplasty/stent deployment and Y-graft were significant predictive risk factors negatively influencing the patients' long-term survival. Kaplan-Meier survival analysis revealed that the long-term survival of patients with left IMA pathological changes were significantly reduced compared with those without (74.1% vs. 91.4%, P=0.002); whereas no differences were noted in long-term survivals between patients with and without pathological changes of the radial arterial or saphenous vein grafts. CONCLUSION: Pathological changes may be seen in the bypass graft at the time of harvest. The subtle ultrastructural modifications and the expressions of vascular tone regulators might be responsible for late graft patency. The pathological changes of the left IMA at the time of harvest rather than those of the radial artery or saphenous vein graft affect significantly longterm survival. Non-traumatic maneuver of left IMA harvest, well-controlled dyslipidemia and avoidance of using composite grafts can be helpful in maintaining the architecture of the grafts.

Evaluation of a new method for placing nasojejunal feeding tubes.

AIM: To compare fluoroscopic, endoscopic and guide wire assistance with ultraslim gastroscopy for placement of nasojejunal feeding tubes. METHODS: The information regarding nasojejunal tube placement procedures was retrieved using the gastrointestinal tract database at Tongji Hospital affiliated to Tongji Medical College. Records from 81 patients who underwent nasojejunal tubes placement by different techniques between 2004 and 2011 were reviewed for procedure success and tube-related outcomes. RESULTS: Nasojejunal feeding tubes were successfully placed in 78 (96.3%) of 81 patients. The success rate by fluoroscopy was 92% (23 of 25), by endoscopic technique 96.3% (26 of 27), and by guide wire assistance (whether via transnasal or transoral insertion) 100% (23/23, 6/6). The average time for successful placement was 14.9 ± 2.9 min for fluoroscopic placement, 14.8 ± 4.9 min for endoscopic placement, 11.1 ± 2.2 min for guide wire assistance with transnasal gastroscopic placement, and 14.7 ± 1.2 min for transoral gastroscopic placement. Statistically, the duration for the third method was significantly different (P < 0.05) compared with the other three methods. Transnasal placement over a guidewire was significantly faster (P < 0.05) than any of the other approaches. CONCLUSION: Guide wire assistance with transnasal insertion of nasojejunal feeding tubes represents a safe, quick and effective method for providing enteral nutrition.

Response gene to complement-32 enhances metastatic phenotype by mediating transforming growth factor beta-induced epithelial-mesenchymal transition in human pancreatic cancer cell line BxPC-3.

BACKGROUND: Response gene to complement-32 (RGC-32) is comprehensively expressed in many kinds of tissues and has been reported to be expressed abnormally in different kinds of human tumors. However, the role of RGC-32 in cancer remains controversial and no reports have described the effect of RGC-32 in pancreatic cancer. The present study investigated the expression of RGC-32 in pancreatic cancer tissues and explored the role of RGC-32 in transforming growth factor-beta (TGF-ß)-induced epithelial-mesenchymal transition (EMT) in human pancreatic cancer cell line BxPC-3. METHODS: Immunohistochemical staining of RGC-32 and E-cadherin was performed on specimens from 42 patients with pancreatic cancer, 12 with chronic pancreatitis and 8 with normal pancreas. To evaluate the role of RGC-32 in TGF-ß-induced EMT in pancreatic cancer cells, BxPC-3 cells were treated with TGF-ß1, and RGC-32 siRNA silencing and gene overexpression were performed as well. The mRNA expression and protein expression of RGC-32 and EMT markers such E-cadherin and vimentin were determined by quantitative reverse transcription-PCR (qRT-PCR) and western blot respectively. Finally, migration ability of BxPC-3 cells treated with TGF-ß and RGC-32 siRNA transfection was examined by transwell cell migration assay. RESULTS: We found stronger expression of RGC-32 and higher abnormal expression rate of E-cadherin in pancreatic cancer tissues than those in chronic pancreatitis tissues and normal pancreatic tissues. Immunohistochemical analysis revealed that both RGC-32 positive expression and E-cadherin abnormal expression in pancreatic cancer were correlated with lymph node metastasis and TNM staging. In addition, a significant and positive correlation was found between positive expression of RGC-32 and abnormal expression of E-cadherin. Furthermore, in vitro, we found sustained TGF-ß stimuli induced EMT and up-regulated RGC-32 expression in BxPC-3 cells. By means of siRNA silencing and gene overexpression, we further demonstrated that RGC-32 mediated TGF-ß-induced EMT and migration in BxPC-3 cells. CONCLUSIONS: The results above indicated that RGC-32 might be a novel metastasis promoting gene in pancreatic cancer and it enhances metastatic phenotype by mediating TGF-ß-induced EMT in human pancreatic cancer cell line BxPC-3.

A method for generating image-derived input function in quantitative 18F-FDG PET study based on the monotonicity of the input and output function curve.

OBJECTIVE: A method of defining the image-derived input function (IDIF) was introduced and evaluated for the quantification of the regional cerebral metabolic rate of glucose in PET studies. METHODS: The voxels in the brain vasculature are extracted on the basis of the different monotonicities between the input and the output function curves. Time activity curves (TACs) of such voxels are averaged to obtain the uncorrected TAC of the brain vasculature. The IDIF was obtained from the raw TAC after correcting for the partial volume and spillover effects by an empirical formula in conjunction with a single blood sample and the TAC of the brain tissue. Data from 16 patients were used to test the proposed method. The Patlak approach is used to calculate the net fluoro-2-deoxyglucose clearance with plasma-derived input function and our generated IDIF, respectively. RESULTS: The net fluoro-2-deoxyglucose clearances calculated with the IDIF generated by our approach are not only highly correlated (correlation coefficients close to 1) to, but also highly comparable (regression slopes close to 1 and intercepts close to 0) with those calculated with plasma-derived input function. CONCLUSION: The method used in the present work is feasible and accurate.

Transforming growth factor-ß/Smad signaling function in the aortopathies.

OBJECTIVES: Transforming growth factor (TGF)-ß/Smad signaling pathway in aortic dissection patients and normal subjects has not been previously described. The present study was designed to evaluate the TGF-ß/Smad signaling expressions in the patients with acute type A aortic dissection in comparison with those in the patients with thoracic aortic aneurysm and with coronary artery disease, and (or) the healthy subjects. METHODS: Consecutive surgical patients for acute type A aortic dissection (20 patients), aortic aneurysm (nine patients) or coronary artery disease (20 patients) were selected into this study. Blood samples (4 ml) were obtained from the right radial arterial indwelling catheter after systemic heparinization prior to the start of cardiopulmonary bypass in the operating room. Twenty-one young healthy volunteers without underlying health issues who donated forearm venous blood samples (4 ml) were taken as control. The surgical specimens of the aortic tissues were obtained immediately after they were severed during the operations of the replacement of the aorta in the patients with aortic dissection or aortic aneurysm. In patients receiving coronary artery bypass grafting, the tiny aortic tissues were taken when the punch holes of the proximal anastomosis on the anterior wall of the ascending aorta were made. The aortic tissues were for RNA, protein, or supernatant preparations until detection of TGF-ß1 mRNA by quantitative real-time reverse transcription polymerase chain reaction, of TGF-ß1, TGF-ß receptor I, Smad2/3, Smad4 and Smad7 by Western blot, and of TGF-ß1 by enzyme-linked immunosorbent assay, respectively. In particular, the linear correlations of the relative grayscales between different proteins of each group, and those correlations between the quantitative TGF-ß1 by enzyme-linked immunosorbent assay and the time interval from the onset to surgery or the maximal dimensions of the aorta of the aortic dissection group were assessed. RESULTS: Quantitative real-time reverse transcription polymerase chain reaction showed that TGF-ß1 mRNA were upregulated in all surgical groups (1.59 ± 0.33 vs. 1.45 ± 0.34 vs. 1.48 ± 0.48, P > 0.05). Western blot revealed that the expressions of TGF-ß1, TGF-ß receptor I, Smad2/3, Smad4 and Smad7 were positive in the aortic tissues of all three investigated groups. Of the quantitative relative grayscales, a significant reverse correlation was noted between TGF-ß1 and Smad2/3 (Y = -0.8552X + 1.6417, r = -0.759, P < 0.0001), and a close direct correlation between Smad4 and Smad7 (Y = 0.5905X + 0.2805, r = 0.781, P < 0.0001) in the Aortic Dissection Group. In the Aortic Aneurysm Group, Smad4 and Smad7 were also closely correlated (Y = 0.5228X + 0.1642, r = 0.727, P = 0.026), and in the Coronary Artery Disease Group, TGF-ß1 and Smad7 were much significantly correlated (Y = 0.5301X + 0.5758, r = 0.917, P = 0.004). By enzyme-linked immunosorbent assay, TGF-ß1 level of the aortic tissue was lower in the aortic dissection than in the aortic aneurysm and coronary artery disease groups with no statistical significance (319.52 ± 129.21 pg/mg protein vs. 324.09 ± 49.70 pg/mg protein vs. 304.15 ± 29.39 pg/mg protein, P > 0.05). The plasma TGF-ß1 levels were 1158.30 ± 11.54 pg/ ml, 1170.27 ± 8.26 pg/ml, 1225.00 ± 174.42 pg/mL and 1160.25 ± 13.01 pg/mL in the four groups, respectively, showing significant intergroup differences (P < 0.05). No significant correlation was found between the aortic or plasma TGF-ß1 levels and the time interval from the onset to surgery or the maximal dimensions of the aorta in the patients of the aortic dissection group. CONCLUSIONS: Aortic dissection, aortic aneurysm and atheroslerosis might be associated with an enhanced TGF ß/Smad signaling function, with aortic dissection exhibiting a less prominent upregulation. It might have implications for downstream signal activation presumably translating into matrix degradation in the condition of aortic dissection in comparison to matrix deposition in aortic aneurysm and coronary artery disease.