OBJECTIVE: To study the association between the expression of the MDR3 gene and the pathogenesis of parenteral nutrition-associated cholestasis (PNAC) in preterm infants. METHODS: Among the preterm infants who were admitted to the hospital from June 2011 to November 2017 and received parenteral nutrition for more than 14 days, 80 who did not develop PNAC were enrolled as non-PNAC group, and 76 who developed PNAC were enrolled as PNAC group. On days 1, 14, 30, 60 and 90 after birth, serum hepatobiliary biochemical parameters [alanine aminotransferase (ALT), total bilirubin (TBil), direct bilirubin (DBil), total bile acid (TBA) and gamma-glutamyl transpeptidase (γ-GT)], fibrosis indices [hyaluronic acid, laminin, procollagen III N-terminal peptide and type IV collagen] and clinical manifestations were observed. Real-time quantitative PCR was used to measure the mRNA expression of MDR3 in both groups, and the correlation between the mRNA expression of MDR3 and serum hepatobiliary biochemical parameters was analyzed. RESULTS: In the PNAC group, serum levels of hepatobiliary biochemical parameters and fibrosis indices increased on day 14 after birth and reached the peak on day 30 after birth, followed by a reduction on day 60 after birth. On days 14, 30, 60 and 90 after birth, the PNAC group had significantly higher serum levels of hepatobiliary biochemical parameters and fibrosis indices than the non-PNAC group (P<0.05). The PNAC group had higher relative mRNA expression of MDR3 in peripheral blood cells than the non-PNAC group (P<0.05). In the PNAC group, the relative mRNA expression of MDR3 in peripheral blood cells was negatively correlated with serum levels of hepatobiliary biochemical parameters (ALT, TBil, DBil, TBA and γ-GT) (P<0.001). CONCLUSIONS High mRNA expression of MDR3 in preterm infants may be associated with the development of PNAC, and further studies are needed to identify the mechanism.
ATP Binding Cassette Transporter, Subfamily B ; genetics ; Cholestasis ; genetics ; Humans ; Infant, Newborn ; Infant, Premature ; Parenteral Nutrition ; RNA, Messenger

Aneurysm, Dissecting ; diagnostic imaging ; surgery ; Aortic Aneurysm, Thoracic ; diagnostic imaging ; surgery ; Cardiopulmonary Bypass ; Computed Tomography Angiography ; Humans ; Male ; Middle Aged

BACKGROUND: With the popularity of laparoscopic cholecystectomy, common bile duct injury has been reported more frequently. There is no perfect method for repairing porcine biliary segmental defects.METHODS: After the decellularization of human arterial blood vessels, the cells were cultured with GFP⁺ (carry green fluorescent protein) porcine bile duct epithelial cells. The growth and proliferation of porcine bile duct epithelial cells on the human acellular arterial matrix (HAAM) were observed by hematoxylin-eosin (HE) staining, electron microscopy, and immunofluorescence. Then, the recellularized human acellular arterial matrix (RHAAM) was used to repair biliary segmental defects in the pig. The feasibility of it was detected by magnetic resonance cholangiopancreatography, liver function and blood routine changes, HE staining, immunofluorescence, real-time quantitative PCR (RT-qPCR), and western blot.RESULTS: After 4 weeks (w) of co-culture of HAAM and GFP? porcine bile duct epithelial cells, GFP⁺ porcine bile duct epithelial cells grew stably, proliferated, and fused on HAAM. Bile was successfully drained into the duodenum without bile leakage or biliary obstruction. Immunofluorescence detection showed that GFP-positive bile duct cells could still be detected after GFP-containing bile duct cells were implanted into the acellular arterial matrix for 8 w. The implanted bile duct cells can successfully resist bile invasion and protect the acellular arterial matrix until the newborn bile duct is formed.CONCLUSION: The RHAAM can be used to repair biliary segmental defects in pigs, which provides a new idea for the clinical treatment of common bile duct injury.
Bile ; Bile Ducts ; Blood Vessels ; Blotting, Western ; Cholangiopancreatography, Magnetic Resonance ; Cholecystectomy, Laparoscopic ; Coculture Techniques ; Common Bile Duct ; Duodenum ; Epithelial Cells ; Fluorescent Antibody Technique ; Humans ; Infant, Newborn ; Liver ; Methods ; Microscopy, Electron ; Polymerase Chain Reaction ; Swine ; Tissue Engineering

Background: Elderly patients with diffuse large B-cell lymphoma (DLBCL) have a worse prognosis than younger patients, and the optimal treatment strategy for this group remains controversial. We conducted a retrospective analysis to investigate the clinical features and outcomes of elderly patients (>60 years) and to assess the impact of clinical and molecular factors on outcome in this age group. Methods: From April 2006 to December 2012, a total of 349 elderly patients with DLBCL from the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College were included in this analysis. Patients were further divided into two age groups (61–69 years and ≥70 years). We compared clinical characteristics and outcomes between groups. Results: Of 349 total patients, 204 (58.5%) were aged 61 to 69 years, and 145 (41.5%) patients were aged 70 years or older. Except for the Eastern Cooperative Oncology Group performance status, clinical characteristics were comparable between the two groups. With a median follow-up of 82 (range, 1–129) months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 51.9% and 45.8%, respectively. The 5-year OS rates for patients aged 61 to 69 years and those over 70 years were 58.3% and 42.8% (P = 0.007), respectively, and the 5-year PFS rates were 51.0% and 38.6% (P = 0.034). Treatment regimens including rituximab provided a higher 5-year OS rate (63.1% vs. 37.1%, P < 0.001) and PFS rate (56.6% vs. 31.8%, P < 0.001) than chemotherapy alone. For patients aged 61 to 69 years, chemotherapy plus rituximab resulted in a higher 5-year OS rate (66.7% vs. 46.4%, P = 0.002) and PFS rate (60.0% vs. 38.1%, P = 0.002) than chemotherapy alone. For patients aged ≥70 years, there was a marked survival advantage in patients who received chemotherapy plus rituximab (5-year OS rate: 57.7% vs. 25.4%, P < 0.001; 5-year PFS rate: 51.3% vs. 23.9%, P < 0.001) compared with that seen in those who received chemotherapy alone. Multivariate analysis established that stage III/IV disease, elevated lactate dehydrogenase (LDH), initial treatment, and chemotherapy with rituximab were independent risk factors for 5-year OS, and stage III/IV disease, elevated LDH, and chemotherapy with rituximab were independent risk factors for 5-year PFS for elderly patients with DLBCL. Conclusions In comparison to patients aged 61 to 69 years, those aged ≥70 years have poorer survival. Prolonged survival is obtainable with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-like in elderly Chinese patients in all age groups, indicating that the R-CHOP-like regimen should be considered for this population, even for those aged 70 years or older.

Objective To investigate the influence of body mass index(BMI) on the prognosis of patients who had received elective PCI.Methods The study population consisted of 2964 consecutive patients with electivePCIs performed between July 2009 and September 2011. The patients were divided into three groups based on their preoperative BMI levels:the normal group( BMI<24.0 kg/m2,n=810); the overweight group( 24.0 kg/m2≤BMI<28.0 kg/m2,n=1454) and the obese group(BMI≥28.0 kg/m2,n=700). We examined the association between baseline BMI levels and postoperative mortality through a mean(571.5±130.8)days of follow up.Results Patients with high BMI had a higher percentage of comorbidities compared with the normal BMI group. The results of multivariate Cox regression analysis revealed that preoperative BMI was inversely associated with mortality after adjustment for other factors (HR 0.896,95％ CI 0.821-0.977,P=0.031). Compared with the obese group, the hazard ratios for risk of mortality in the overweight and the normal groups were 1.908(95％CI 0.689-5.291,P=0.213) and 2.241(95％CI 1.154-4.350,P=0.017).Conclusions For patients undergoing elective PCI, individuals with obesity and overweight had the better prognosis than those with normal BMI.

Objective:To provide experimental evidences for choosing murine models in the pathogenesis research of thymic impairment induced by viral infection,we compared the impacts of polycytidylic acid(Poly(I:C)) and dexamethasone(DEX) on the thymic morphology and thymic output function,and explored the implication of RLR signaling pathway.Methods: 24 male C57BL/6 mice were randomly assigned into three groups and treated with Poly(I:C),DEX,or saline respectively.Thereafter,their thymic morphology,pathological changes,thymic index,and thymic pathology were examined.Their contents of T-cell receptor excision circles (TRECs) and proportions of the naive CD4+T cell in the peripheral blood were determined to evaluate their thymic output function.The expression levels of thymic RLR/MAVS/IFN-α/β signaling pathway and IL-1β were also measured.Results: Both Poly (I:C) and DEX treatment caused thymic atrophy in appearance and structural destruction under the microscope inspection,and DEX treatment did much more severe damage,especially to the thymic cortex.TRECs decreased significantly in both groups.The proportions of na?ve/memory CD4+T cell subsets remained stable,though total CD4+T cell decreased in DEX group,while the proportion of na?ve CD4+T cell in Poly (I:C) group increased significantly.The expression of RIG-Ⅰ,MDA5,LGP2,and IFN-α/β were up-regulated in DEX group, while it remained unchanged in Poly (I:C) group.Conclusion:Both Poly (I:C) and DEX induced thymic atrophy and the impaired thymic output function.Nevertheless,the expression of RLR-IFN signaling pathway up-regulated more significantly in DEX group instead of in Poly (I:C) group.These results implied the existence of different pathological manifestations and mechanisms underlying the impaired thymic function in different animal models,as well as impact on na?ve/memory CD4+T cell proportions.Our research provides references for choosing animal models in the basic research and drug development for viral infection induced thymic atrophy based on the RLR signaling pathway.

Objective To investigate the variation of renal pelvic pressure during percutaneous nephrolithotomy (PCNL) via standard nephrostomy tract and explore its influence on renal function. Methods 156 patients with renal calculi were selected for PCNL in standard-tract. The patients were divided into normal, mild hydronephrosis, moderate hydronephrosis groups according to the image by color Doppler ultrasonograph. A transurethral 6F ureteral catheter was inserted into renal pelvis and connected to the pressure monitering system before PCNL. During the operations, all the nephrostomy tracts were dilated to F24 size after successful puncture. Energy used was pneumatic and ultrasound lithotripsy. Renal function of the patients was evaluated with glomerular filtration rate (GFR) determined by 99mTc-DTPA dynamic renal imaging before and one week after PCNL. Data were analyzed by SPSS 19.0 software. Results The stone clearance rate was 75.0％ in one-session procedure. Severe complications did not occur during the operation, such as hemorrhage needing nephrectomy and abdominal organ injury or pneumothorax. There were no statistically significant differences between normal and mild hydronephrosis groups for the variation of renal pelvic pressure during preoperative versus intraoperative PCNL (P > 0.05). The renal pelvic pressure was significantly higher during operation than those of preoperation in moderate hydronephrosis group (P < 0.05), and it was greater than those of normal and mild hydronephrosis groups during operation (P < 0.05). Renal pelvic pressure generally remained lower than a level to 30.00 mmHg. There were no significant differences of preoperative and postoperative glomerular filtration rate in all the groups (P > 0.05). Conclusions There were no significant differences on the renal pelvic pressure in normal group and mild hydronephrosis group during operation via standard nephrostomy tract. It should be careful to maintain the lower intrapelvic pressure in order to avoid reflux and infection in moderate hydronephrosis group. Percutaneous nephrolithotomy via standard- tract does not cause significant effects on glomerular filtration rate during the perioperative period of PCNL .

Objective To investigate the effects of peritoneal lavage and dialysis by flexible endoscope in patients with early phase severe acute pancreatitis (SAP) complicated with intra-abdominal hypertension (IAH)/abdominal compartment syndrome (ACS). Methods 32 patients with early phase SAP complicated with IAH/ACS were received peritoneal lavage and dialysis by flexible endoscope in base of routine treatment. The release time of peritoneal irritation sign, the duration of intra-abdominal hypertension (IAP), bowel sound, APACHE-II scores and prognosis of the patients were evaluated. The levels of TNF-α and IL-6 in serum, also, the concentrations of TNF-α, IL-6 and amylase in ascites/peritoneal lavage fluid were measured. Results 30 patients were all cured after treatment, with an average hospital stay of (16.53 ± 5.30) d, and, 2 patients underwent surgical treatment. The difference between before and after treatment was significance in peritoneal irritation sign scores, bowel sound, IAP and APACHE-II scores of the patients (P < 0.05). The levels of testing items in serum and ascites/peritoneal lavage fluid were decreased significantly during peritoneal lavage and dialysis. Conclusion Continuous peritoneal lavage and dialysis by flexible endoscope is a safe and effective method for patients with SAP complicated with IAH/ACS, especially in the early stage of disease.

OBJECTIVESTo investigate the mechanism of Liuwei Dihuang Pill (, LDP) in treating postmenopausal osteoporosis (PMOP) with Shen (Kidney) yin deficiency.

METHODSIn this study, 205 cases of PMOP were divided into the PMOP Shen-yin deficiency group (Group A), PMOP Shen-yang deficiency group (Group B), PMOP without Shen deficiency group (Group C), and control group (Group N). Real-time polymerase chain reaction (RT-PCR) and Western blot techniques were used to observe the effects of LDP treatment on the cardiotrophin-like cytokine factor 1 (CLCF1), ankyrin repeat and SOCS box containing 1 (ASB1), and prokineticin 2 (PROK2) genes and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway.

RESULTSThe mRNA (P<0.05) and protein (P<0.01) expression levels of the CLCF1 gene in Group A were significantly lower than the corresponding levels in Group N. After LDP treatment for 3 months, the mRNA expression levels of the CLCF1 gene were obviously up-regulated (P<0.01). After 6-month treatment, the expression levels of CLCF1 mRNA and protein were significantly up-regulated (both P<0.01), and the average bone density of the top femur had significantly increased (P<0.05). In vitro, CLCF1 overexpression resulted in a significant increase in the total protein and phosphorylated protein levels of JAK2 and STAT3.

CONCLUSIONSThe CLCF1 gene is an important gene associated with PMOP Shen-yin deficiency and the therapeutic effects of LDP may be mediated by up-regulation of CLCF1 gene expression and activation of the JAK/STAT signaling pathway.

Cytokines ; genetics ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gene Expression Regulation ; Humans ; Janus Kinases ; metabolism ; Middle Aged ; Osteoporosis, Postmenopausal ; drug therapy ; genetics ; RNA, Messenger ; genetics ; metabolism ; STAT Transcription Factors ; metabolism ; Signal Transduction ; Up-Regulation ; Yin Deficiency ; drug therapy ; genetics

OBJECTIVETo investigate the possible mechanism of San-Cao Granule (SCG, ) mediating antiliver fibrosis.

METHODSA total of 60 male Sprague-Dawley rats were randomly divided into the normal control group, porcine serum-treated group, ursodesoxycholic acid (UDCA, 60 mg/kg), SCG (3.6 g/kg) group, SCG (1.8 g/kg) group and SCG (0.9 g/kg) group, with 10 rats in each group. Liver fibrosis was induced with porcine serum by intraperitoneal injection for 8 weeks, except for the normal control group. Then, the rats in the three SCG-treated groups and UDCA group were administered SCG and UDCA respectively for 4 weeks. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), albumin (ALB), total bilirubin (TBIL), hyaluronic acid (HA), laminin (LN), and type IV collagen (IVC) were examined using commercial kits and hepatic histopathology was examined with hematoxylin and eosin and Masson staining. Moreover, the protein expression levels of high mobility group box-1 protein (HMGB1), transforming growth factor β1 (TGF-β1), phosphorylated mothers against decapentaplegic homolog 3 (p-Smad3), Smad7, toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-kappa B (NF-κB) and α-smooth muscle actin (α-SMA) were determined by western blot, immunohistochemistry and real time quantitative-reverse transcription polymerase.

RESULTSBoth SCG (3.6 and 1.8 g/kg) and UDCA significantly ameliorated the liver fibrosis induced by porcine serum as indicated by retarding the serum levels increasing of ALT, AST, TBIL, HA, LN and IVC and preventing the serum level reducing of ALB compared with the model group (all P<0.01). Meanwhile, the collagen deposition was attenuated by SCG and UDCA treatment. Furthermore, SCG markedly reduced the expressions of HMGB1, TGF-β1, p-Smad3, TLR4, MyD88, NF-κB and α-SMA, and enhanced the expression of the Smad7 compared with the model group (all P<0.01).

CONCLUSIONSCG ameliorates hepatic fibrosis possibly through inhibiting HMGB1, TLR4/NF-κB and TGF-β1/Smad signaling pathway.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; HMGB1 Protein ; metabolism ; Liver ; drug effects ; metabolism ; pathology ; Liver Cirrhosis ; drug therapy ; metabolism ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Smad Proteins ; metabolism