ABSTRACT
The need for long-term treatments of chronic diseases has motivated the widespread development of long-acting parenteral formulations (LAPFs) with the aim of improving drug pharmacokinetics and therapeutic efficacy. LAPFs have been proven to extend the half-life of therapeutics, as well as to improve patient adherence; consequently, this enhances the outcome of therapy positively. Over past decades, considerable progress has been made in designing effective LAPFs in both preclinical and clinical settings. Here we review the latest advances of LAPFs in preclinical and clinical stages, focusing on the strategies and underlying mechanisms for achieving long acting. Existing strategies are classified into manipulation of
ABSTRACT
Drug delivery systems (DDS) are defined as methods by which drugs are delivered to desired tissues, organs, cells and subcellular organs for drug release and absorption through a variety of drug carriers. Its usual purpose to improve the pharmacological activities of therapeutic drugs and to overcome problems such as limited solubility, drug aggregation, low bioavailability, poor biodistribution, lack of selectivity, or to reduce the side effects of therapeutic drugs. During 2015-2018, significant progress in the research on drug delivery systems has been achieved along with advances in related fields, such as pharmaceutical sciences, material sciences and biomedical sciences. This review provides a concise overview of current progress in this research area through its focus on the delivery strategies, construction techniques and specific examples. It is a valuable reference for pharmaceutical scientists who want to learn more about the design of drug delivery systems.
ABSTRACT
Objective To evaluate the clinical value of recombinant major surface glycoprotein C(Msg C)consensus antigen of Pneumocystis jirovecii in serological diagnosis of Pneumocystis pneumonia(PCP), and explore serological diagnosis for PCP. Methods ELISA method was established for testing IgM antibody of Pneumocystis jirovecii Msg C consensus antigen. Serum antiMsg C consensus antigen IgM antibody and(1, 3)-β-D glucan were determined in 48 patients at high risk of PCP and 51 healthy subjects. The results of ELISA and(1, 3)-β-D glucan assay were compared with the results of PCR in bronchoalveolar lavage fluid. Results In a total of 99 specimens, Msg C consensus antigen IgM antibody detection(28.3％, 28/99)showed similar positive rate as(1, 3)-β-D glucan assay(25.3％, 25/99)(P>0.05). For the 48 patients at high risk of PCP, the positive rate of Msg C consensus antigen IgM antibody and(1, 3)-β-D glucan assay was 35.4％(17/48)and 33.3％(16/48), respectively(P>0.05). The two methods showed 67.7％ agreement in testing 99 specimens and 52.1％ agreement in testing 48 high-risk specimens. The bronchial lavage fluid samples of 48 patients at high risk were also tested by PCR. The result was positive in 15 cases(31.3％), showing no significant difference from Msg C consensus antigen IgM antibody test(P=0.665). The agreement between Msg C consensus antigen IgM antibody test and PCR was 58.3％. The agreement with PCR result increased to 84.0％ in the 25 specimens with the same result by two serological methods.When taking the positive result of either serological method as reference, serological method can detect majority of the PCR positive cases(86.7％, 13/15). Conclusions IgM antibody against Msg C consensus antigen in combination with serological marker(1, 3)-β-D glucan is valuable for PCP diagnosis. Further examination such as lower respiratory tract specimen PCR and conventional cytology should be carried out to confirm the diagnosis when both IgM antibody against Msg C consensus antigen and(1, 3)-β-D glucan are positive.
ABSTRACT
Objective To investigate the predictive role of the intraoperative amylase ( IOA ) from pancreatic stump for postoperative pancreatic fistula. Methods The clinical data of 26 patients who received distal pancreatectomy ( DP) and central pancreatectomy ( CP) in the Shanghai Ruijin Hospital from June 2017 to July 2018 were retrospectively analyzed. IOA and peri-operative potential clinical factors associated with pancreatic fistula were analyzed. Receiver operating characteristics ( ROC) curve was drawn to evaluate the diagnostic efficacy of IOA from pancreatic stump in predicting postoperative pancreatic fistula, and the sensitivity and specificity were calculated. Results Of 26 patients, 19 patients underwent DP and 7 patients underwent CP. 9 patients (34.6％,9/26)had class A pancreatic fistula (biochemical leak) and 11 patients (42. 3％,11/26) had class B pancreatic fistula after surgery, and no class C pancreatic fistula occurred. Univariate analysis showed that IOA from pancreatic stump in clinically relevant pancreatic fistula group was higher than that in clinically irrelevant pancreatic fistula group(7971. 82 ± 4387. 98 vs 1589. 20 ± 1405. 00, P=0. 001). Area under the curve ( AUC) of IOA in predicting the development of clinically relevant pancreatic fistula after surgery was 0. 921 and 95％ confidential interval was 0. 807-1. 000. The optimal cut-off value was 3622 U/L , and the sensitivity and specificity were 90. 9％ and 86. 7％. Conclusions IOA from pancreatic stump could serve as a clinical indicator for predicting the occurrence of postoperative pancreatic fistula.
ABSTRACT
Objective To investigate the mechanism of TNF-related apoptosis-inducing ligand (TRAIL) promoting apoptosis of pancreatic cancer cells SW1990, Patu8988 and BxPC3. Methods Three kinds of pancreatic cancer cells SW1990, Patu8988 and BxPC3 were transfected with the pCA13 plasmid carrying TRAIL gene ( pCA13 TRAIL group) and the blank plasmid control ( pCA13 group) , respectively. The expression of TRAIL mRNA in transfected cells was detected by RT-PCR, and the expression of TRAIL protein was detected by Western blot. The apoptosis rate and expression of TRAIL receptor R1 and R2 were detected by flow cytometry. Apoptosis was detected by TUNEL and Hoechst double staining, and observed by electron microscopy. The expression of caspase-3 in transfected cells was detected by immunohistochemistry. Results SW1990, Patu8988 and BxPC3 cells can expresse TRAIL mRNA and protein within 24 h after transfection. The apoptotic rate at 24 h after transfection was (27. 30 ± 5. 14)％, (13. 52 ± 0. 95)％ and (31. 40 ± 8. 70)％,respectively, which was higher than that of pCA13 group [(10. 58 ± 1. 88)％,(8. 42 ± 0. 46)％ and (16.11 ±1.66)％], respectively. The expression rates of TRAIL-R1 were (61.37 ± 3.05)％,(42.10 ± 5. 11)％ and (36. 64 ± 4. 84)％, respectively, and the expression rates of TRAIL-R2 were (36. 20 ± 4. 83)％,(37. 26 ± 8. 46)％ and (24. 32 ± 3. 71)％, respectively,which were higher than those of pCA13 group except PATU8988 cells. Positivity rates of caspase-3 were ( 14. 64 ± 5. 35 )％, ( 9. 92 ± 5. 50 )％ and (16. 12 ± 6. 74)％, which were obviously higher than ( 3. 01 ± 1. 50 )％, ( 1. 75 ± 0. 50 )％ and ( 3. 79 ± 1. 58)％ in pCA13 group,and the differences were statistically significant(P<0. 05). Conclusions TRAIL could up-regulate the expression of TRAIL R1 and R2 in multiple pancreatic cancer cell lines in vitro, and thus promote cell apoptosis.
ABSTRACT
Chronic inflammatory response often involves in the progression of disease in all organ system.While inflammation has been a highlight topic of study in many decades for patho-genesis or identifying drug targets to disease-associated inflam-mation.In this paper,the main fundamental research areas of projects funded by NSFC on inflammation during 2010 ~2015 are reviewed.The features and research types of projects are an-alyzed.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of the serum of rats fed with Shenkang pill in regulating monocyte chemoattractant protein 1 (MCP-1) expression induced by advanced oxidation protein products (AOPP) in mouse podocyte clone 5 (MPC5) and explore the underlying mechanism.</p><p><b>METHODS</b>MPC5 cultured in vitro were incubated for different time lengths in the presence of different concentrations of serum of rats medicated with Shenkang pill, and the cell proliferation was assessed using MTT assay. In MPC5 treated with AOPP prior to exposure to the rat serum, the changes in the protein expressions of p38MAPK and IκBα were examined with Western blotting, NF-κB p65 nuclear translocation was analyzed with immunofluorescence assay, and MCP-1 expression in the supernatant was determined using ELISA kits.</p><p><b>RESULTS</b>The medicated rat serum time- and concentration-dependently promoted the proliferation of MPC5, with the optimal serum concentration of 5% and incubation time of 24 h. AOPP significantly increased MCP-1 expression in the cell supernatant in a time-and concentration-dependent manner; pretreatment with SB203580 (a p38 inhibitor) or parthenolide (a NF-κB inhibitor) significantly decreased MCP-1 expression, and treatment with the medicated serum significantly decreased AOPP-induced MCP-1 expression. AOPP concentration-dependently increased the protein expression of P-p38 but decreased that of IκBα. Both the medicated serum and SB203580 increased IκBα protein in AOPP-induced cells, but the effect was more obvious with the medicated serum. The medicated serum also decreased NF-κB p65 nuclear translocation in AOPP-induced MPC5.</p><p><b>CONCLUSION</b>Shenkang pill-medicated serum can decrease AOPP-induced expression of MPC-1 in MPC5 by regulating p38MAPK/NF-κB to mediate its anti-inflammatory effect. This finding provides a new theoretical basis for the application of Shenkang pill to treat diabetic nephropathy.</p>
Subject(s)
Animals , Mice , Rats , Advanced Oxidation Protein Products , Pharmacology , Cell Line , Cell Proliferation , Chemokine CCL2 , Metabolism , Down-Regulation , Drugs, Chinese Herbal , Pharmacology , I-kappa B Proteins , Metabolism , Imidazoles , NF-KappaB Inhibitor alpha , Pyridines , Serum , Chemistry , Sesquiterpenes , Transcription Factor RelA , Metabolism , p38 Mitogen-Activated Protein Kinases , MetabolismABSTRACT
BACKGROUND:Treatment methods for high anal fistula include fistula removal, incision and thread drawing, selective mucosal flap displacement, fibrin glue closure, fistula liagtion between sphincter, most of which show many advantages, including long-term healing, a low success rate, high recurrence rate, and high postoperative complication rate. OBJECTIVE:To observe the clinical effect of acelular extracelular matrix in the treatment of high anal fistula, and to explore a minimaly invasive treatment for high anal fistula. METHODS: Totaly 100 cases of high anal fistula were randomly divided into treatment group and control group, 50 cases in each group. Treatment group were treated with alogenic acelular extracelular matrix, and control group were treated with traditional low incision with high thread-drawing. Then, we observed and compared the operation time, bleeding volume, postoperative pain score (visual analog scale score), postoperative pain duration, anal incontinence severity score (Wexner score), wound healing time, one-stage success rate, cure rate, recurrence rate. RESULTS AND CONCLUSION: Compared with the control group, the treatment group showed lower scores in the operation time, bleeding volume, wound healing time, visual analog scale score, postoperative pain duration, and anal incontinence severity score (P short course of treatment, high cure rate and has no damage to the anal function and appearance.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the effects of parthenolide (PTL) on high glucose-stimulated cell proliferation, NF-κB activation and monocyte chemoattractant protein-1 (MCP-1) expression in rat mesangial cells (MCs).</p><p><b>METHODS</b>MCs were cultured in normal glucose (5.6 mmol/L), high glucose (30 mmol/L), or high glucose with PTL. MTT assay was used to detect the cell proliferation. MCP-1 content in the supernatant was measured by ELISA, and the level of IκBα was detected by Western blotting to reflect NF-κB activity. EMSA method was used to measure the activation of NF-κB.</p><p><b>RESULTS</b>MC proliferation, MCP-1 expression and NF-κB activation were significantly enhanced and the expression of NF-κB-binding protein IκBα was obviously reduced in cells cultured in high glucose. Application of PTL obviously abolished the effects of high glucose.</p><p><b>CONCLUSION</b>PTL can suppress high glucose-stimulated NF-κB activation and MCP-1 expression in rat MC. These data provide a theoretical basis for the clinical application of PTL in prevention and control of diabetic nephropathy.</p>
Subject(s)
Animals , Rats , Anti-Inflammatory Agents, Non-Steroidal , Pharmacology , Asteraceae , Chemistry , Cell Proliferation , Cells, Cultured , Chemokine CCL2 , Metabolism , Dose-Response Relationship, Drug , Glucose , Pharmacology , I-kappa B Proteins , Metabolism , Mesangial Cells , Cell Biology , Metabolism , NF-KappaB Inhibitor alpha , NF-kappa B , Metabolism , Plants, Medicinal , Chemistry , Sesquiterpenes , PharmacologyABSTRACT
Objective To determine the effect of ABCC4 gene silencing on cell proliferation and cell cycle in human pancreatic cancer cell lines PANC1 and BxPC-3.Methods PANC1 and BxPC-3 pancreatic cancer cells were transfected with a lentivirus expressing an ABCCA short hairpin RNA (shRNA).ABCC4 mRNA and protein expression of transfected cells was determined by RT-PCR and Western blot,colony formation ability was measured by colony assay,and cell cycle change was investigated by the flow cytometric analysis.Results Lentivirus expressing an ABCC4 short hairpin RNA (shRNA) was successfully established.After transfection with shRNA lentivirus,ABCC4 mRNA and protein expression were significantly inhibited (0.28 ±0.01 vs 1.00 ±0.03,0.22 ±0.02 vs 1.00 ±0.03,P ＜0.05).Colony formation ability was significantly decreased (4 vs 65,P ＜0.05),and cell cycle was significantly blocked at G1 phase [(54.98 ±1.78) ％ vs (42.93 ± 0.88) ％,(68.55 ± 0.75) ％ vs (54.76 ± 0.29) ％].Conclusions ABCC4 gene silencing can significantly inhibit cell proliferation of human pancreatic cancer cell lines PANC1 and BxPC-3,and block the cells at G1 phase.
ABSTRACT
Objective By analyzing the clinical and pathological characteristics of small intestinal neoplasms of patients presenting at our hospital,this study was to improve our cognition of this disease and the prognosis.Methods We collected and reviewed the medical records of 121 patients suffering from small intestinal neoplasms,who underwent surgery at Ruijin hospital from January 2003 to June 2009.Diagnosis was confirmed by pathological examination,and patients were followed-up.Results Intestinal hemorrhage,anemia and abdominal pain were the three main symptoms for all patients.CT,and gastrointestinal endoscopy were valuable for the diagnosis of small intestine neoplasms.Compared with open surgery,laparoscopic procedures can shorten the operation time and the postoperative length of hospital stay.Conclusions Surgical procedure is the key treatment for patients with small intestinal neoplasms.Long term follow-up plays important role in the detection of other synchronous or metachronous gastrointestinal tumors and improves the prognosis.
ABSTRACT
Objective To investigate the etiology of acute recurrent pancreatitis (ACP) and de-termine how to further enhance its level of treatment.Methods The clinical data of 33 patients with ACP treated in Ruijin Hospital from 2003 to 2007 were retrospectively analyzed.Results Of the 33 patients with an average age of 55 (22-86), 18 (55%) were male and 15 (45%) female.ACP occurred once in 26 patients, twice in 4 and 3 times in 3.The disease appeared whithin 1 year in 29 patients, 1-2 years in 2, 2-3 years in 1 and 3 years in 1 after being dischared from hospital.For its etiology, it was of biliary origin in 29 patients, hyperlipidemia in 1, pancreatic tumor in 1 and unknow reasons in 2.Twenty-four patients were treated with operation or endoscopy.Two patients died and the mortali-ty was 9.1%.Conclusion ACP is mainly due to biliary origin in China.Operative intervention at an appropriate opportunity can effectively reduce the recurrence of biliary-origin pancreatitis.
ABSTRACT
Objective: To investigate the causes and management of enteral feeding intolerance in patients with severe acute pancreatitis (SAP). Methods: The clinical data were retrospectively analyzed of 128 SAP patients who underwent enteral feeding treatment during the period from January 2006 to January 2008. Results: The rate of enteral feeding intolerance was significantly higher in the group of patients who didn' t use Flocare 800 pump, single-use enteral feeding tube and heater (10/50 or 20.0%) than that in the group of patients who used Flocare 800 pump, single-use enteral feeding tube and heater (5/78 or 6.4%). Conclusion: The possible risk factors of enteral feeding intolerance may be transfusional speed, temperature and concentration of nutritional fluid. Severity of acute pancreatitis is another important factor. Intestinal dysfunction should be noticed during the enteral nutritional support.
ABSTRACT
Objective To investigate the characteristics of intestinal microflora and its effect on fecal secretory immunoglobulin A (sIgA) in the elderly. Methods All 104 cases were assigned to two groups: the control group (healthy adults, age<60 years ,n=36) and the elderly group (healthy elderly persons, age ≥60 years, n=68). Feces samples of all cases were cultured under both aerobic and anaerobic conditions for the 6 bacteria (4 kinds of anaerobes and 2 kinds of aerobes) and the yeasts. The ratio of bifidobaeterium to Enterobacteria (the ratio of B/E) was calculated, which reflected personal colonization resistance. The fecal sIgA was also measured. Results Compared with control group, the number of fecal bifidobacterium and the ratio of B/E were significantly decreased in elderly group[(9.1±1.1)vs. (10.2±0.8)lgCFU/g,P<0. 01 ;(1. 02±0.14) vs. (1.24± 0. 18), P < 0. 01], and the number of enterobacteria and peptostreptococcus was significantly increased in elderly group [(9.2±1.3) vs. (8. 2±0.7) lgCFU/g, P < 0. 05 ; (8. 5 ±1.4) vs. (7.1 ± 1.6)lgCFU/g, P<0. 05]. The fecal slgA was much lower than that in control group [(652.9± 184.3) vs. (793. 5±150. 3)μg/ml, P<0. 05]. Moreover, the quantity change of bifidobacterium was correlated with the concentration of fecal sIgA(r=0. 562, P<0. 01). Conclusions The number of fecal bifidobacterium is significantly decreased, while the number of enterobacteria and peptostreptococcus is significantly increased in elderly persons. The colonization resistance is significantly decreased and the intestinal immuno-barrier function is injuried in elderly persons, which have influenced the intestinal microflora.
ABSTRACT
Objective To describe the clinical and pathological features and survival of juvenile patients with pancreatic carcinoma ( age ≤ 40 years old ) and to explore whether pancreatic carcinoma in young patients was a particular subtype. Methods As a case control study, the clinical data and follow-up data of sporadic 29 cases diagnosed as juvenile pancreatic carcinoma in Ruijin hospital from January, 2000 to December, 2007 were analyzed and compared with randomly selected 89 cases of senile eases (age≥ 61 years old) with pancreatic carcinoma. Results The percentage of juvenile pancreatic carcinoma was 3.6% (29/811 ) and the male/female ratio was 2.5: 1. The incidence rate of abdominal pain was significantly higher in the juvenile patients than in the senile patients (72.4% vs 48.3% , P < 0.05 ) ;the incidence of malnutrition was significantly lower in juvenile patients than that in senile patients ( 13.8% vs 38.0%, P <0.05 ) ;and the rate of patients with advanced stage disease ( Ⅲ～Ⅳ ) was significantly higher in juvenile patients than in senile patients (69.0% vs 55. 1%, P < 0.05). The percentage of radical operation in juvenile patients was not statistically different from that in senile patients ( 34.5% vs 30.34%, P > 0.05 ), and analysis using the Kaplan-Meier method and log-rank test revealed no significant difference in overall survival between the two groups ( median survival time : 7.0 vs 8.0 months, P > 0.05 ). Conclusions The age onset of the pancreatic carcinoma tended to be younger. The predominant clinical manifestations of juvenile pancreatic carcinoma were abdominal pain or back pain. Juvenile pancreatic carcinoma may be a particular subtype of pancreatic cancer.
ABSTRACT
Objective To investigate the incidence, consequence and short-term prognosis of noninflammatory ascitic bacterial translocation (BT) in cirrhotic patients. Methods A set of universal primers was designed based on the conservative regions in bacterial 16S ribosomal RNA (16S rRNA) genes. Eighty-seven ascitie and/or serum samples from cirrhotic patients were amplified using PCR, and bacterial DNA was detected as molecular marker of BT. The corresponding bacteria were identified by nucleotide sequencing of purified PCR products. All patients were followed up of six months. The outcome of the patients were observed and bacterial DNA in ascites were detected again in some patients. Results Among 87 cirrhotic patients, bacterial DNA was positive in 33 aseites and 12 serum samples with E. coli in predominant. The bacterial DNA identification indicated that similarity of 99% between the sequence was found in both ascites and blood from one patients. Six months later, the bacterial DNA in ascites was dynamically changed. The variables correlatied with prognosis of the patients were liver function and BT. Conclusions Non-inflammatory BT is a dynamic process in cirrhotic patients, which may either lead to infection or be eliminated by the host. Liver function and the incidence of BT can influence the short-time prognosis of cirrhotic patients.
ABSTRACT
Objective To investigate the appropriate method in diagnosing precursor lesions of pancreatic cancer and its treatment. Methods From Jan. 2006 to Dec. 2007, 92 cases were operated for pancreatic neoplasms. Among them 7 cases had pancreatic precursors. The mucinous cystic neoplasm was found in 1 case, intraductal papillary mucinous neoplasm(IPMN) in 2 cases, endocrine tumor in 1 case and pancreatic intraepithelial neoplasia (PanIN) in 3 cases. CA19-9 level was tested by immunoflucence assay. All of the 7 patients were examined by CT. Endoscopic ultrasound(EUS) and endoscopic retrograde cholangio-pancreatography examinations were performed on 1 and 2 patients respectively. Results There was neither specific symptom related to these precursors nor any evidence of mass as revealed by CT or ultrasound. But dilatation and stricture of pancreatic duct were found in PanIN patients, and cystic dilatation of pancreatic duct in pancreatic head was present more in IPMN patients. For cystic neoplasms in pancreatic body and tail, they were commonly solid and isolated. CA19-9 level was slightly elevated in some patients but with no diagnostic value. Surgical resection was done with excellent result. Conclusion For the suspected pancreatic precursors, aggressive diagnostic approach and surgical resection will be the best option and can further prevent cancer development.