Systemic juvenile idiopathic arthritis (sJIA) is a special type of JIA. It is an inflammatory condition characterized by fever, lymphadenopathy, arthritis, rash and serositis. It is the most acute and severe type,which has a disproportionately high morbidity compared with other subtypes. In sJIA, systemic inflammation has been associated with dysregulation of the innate immune system, suggesting that it is an autoinflammatory disorder. Dysregulation of the innate immune system in sJIA results in increased production of inflammatory cytokines, leading to the distinctive clinical features of the disease. IL-1 and IL-6 play a major role in the pathogenesis of sJIA and treatment with IL-1 and IL-6 inhibitors has shown to be highly effective.
Objective To investigate effect of Qindan particles on acute physiological change in rats under heatstroke, and to explore its mechanism. Methods Male anesthetized Sprague Dawley rats were randomly divided into normal control group, model control group, Qindan low-dose group, Qindan middle dose group and Qindan high-dose group. The model control group and Qindan groups were orally administered with vehicle (0.9% sodium chloride solution) or Qindan 10, 20 and 40 g·kg-1 for 30 days, respectively, followed by exposure to heat (42 ℃ for 75 min) before recovery at room temperature (RT, 24 ℃). The normal control group rats were treated with vehicle and were kept at room temperature. Core body temperature (Tc), heart rate (HR), mean arterial pressure (MAP) and systolic arterial blood pressure (SAP) were monitored. After the thermal damage, blood was collected immediately and the serum superoxide dismutase (SOD), malondialdehyde (MDA), total nitric oxide synthase (TNOS), induce nitric oxide synthase (iNOS) levels were detected. Part of the rats recovered at room temperature, and the time of death was observed. Observation of liver tissue pathological changes was carried out also. Results The Tc, MDA and iNOS in heatstroke model control group rats were (41.05±0.30) ℃, (11.66±2.25) μmol·L-1, (23.66±2.05) U·L-1, respectively, significantly higher than those of normal control group. The level of serum SOD was (291.22±51.17) U·mL-1, significantly lower than that of normal control group. After 60 min, the values of HR, MAP and SAP were maxed at (474.13±18.40) beat·min-1, (138.35±6.51) mmHg, and (187.12±7.85) mmHg, significantly higher than those of normal control group. After 75 min, the indexes fell rapidly to (309.58±22.47) beat·min-1, (104.11±4.26) mmHg, and (140.46±6.74) mmHg, respectively. The levels of Tc, MDA, iNOS fell to (39.94±0.17) ℃, (7.90±1.57) μmol·L-1, (17.20±1.57) U·L-1 and SOD rose to (373.51±38.78) U·mL-1 in Qindan particles high-dose group. After 75 min, the values of HR, MAP and SAP rose to (409.58±22.50) beat·min-1, (124.11±7.26) mmHg and (172.85±4.09) mmHg. Conclusion Qindan particles can delay the onset of heatstroke and reduce the thermal damage, playing a protective role in rats under heat stress. This protective effect may be related to relieving oxidative stress reactions.
Objective To investigate the impact of Galectin-3 (Gal-3) on cisplatin sensitivity of epithelial ovarian cancer (EOC) cell lines and the associated mechanisms. Methods SKOV3 and OVCAR3 cells were transfected with siRNA and negative control sequences respectively to down-regulate Gal-3. Gal-3 was up-regulated by transfection of plasmid containing Gal-3 sequences and blank control plasmid into SKOV3 and OVCAR3 cells. Western blotting was used to detect the protein expression levels of Caspase-3 and BCL-2. After treatment with gradient concentration of cisplatin for 48 h, CCK-8 kits were used to detect the proliferation and flow cytometry was used to detect the apoptosis in EOC cell lines. Results After siRNA-mediated knockdown of Gal-3, the protein expression level of casepase-3 was increased while BCL-2 was decreased. The cell proliferation of the siRNA group was significantly lower than that of the control group (P<0.05). The apoptosis of the siRNA group was significantly higher than that of the control group (P<0.05). After plasmid-mediated up-regulation of Gal-3, the protein expression level of casepase-3 was decreased while BCL-2 was increased. The cell proliferation of the siRNA group was significantly higher than that of the control group (P<0.05). The apoptosis of the siRNA group was significantly lower than that of the control group (P<0.05). Conclusion Down-regulation of the expression of Gal-3 would increase the sensitivity to cisplatin in EOC cell lines, while up-regulation of the expression of Gal-3 would decrease the sensitivity to cisplatin in EOC cell lines. New drugs targeting Gal-3 are expected to become effective therapies for platinum-resistant EOCs.
Objective To investigate the effects of minocycline on the expression of matrix metalloproteinases-9 (MMP-9) and the permeability of blood brain barrier in ischemic cortex of rats after cerebral ischemia reperfusion, and to explore the potential mechanism. Methods Thirty male Sprageue-Dawley rats were randomly divided into 3 groups: sham group, model control group and minocycline group (n=10 each group).The ischemia/reperfusion injury (IRI) model was induced by ligation with nylon monofilament.At 24 h after IRI, the permeability of blood brain barrier (BBB) in peri-infarct region was evaluated by Evans Blue (EB) test.Expression of MMP-9, claudin-5 and phospholylated p38 mitogen-activated protein kinase (MAPK) were detected by Western blotting. Results Compared to the sham group, the BBB permeability was markedly increased [(4.55±0.69) μg·g-1 vs.(0.55±0.08) μg·g-1, P<0.05], the expression of MMP-9 (1.18±0.12 vs.0.15±0.02) and phospholylated p38 protein (0.67±0.07 vs.0.11±0.02) were significantly increased (P<0.05), and the expression of claudin-5was decreased in the model control group (P<0.05).Compared to model control group, minocycline significantly alleviated BBB breakdown [(2.82±0.46) μg·g-1 vs.(4.55±0.69) μg·g-1], downregulated MMP-9 (0.77±0.06 vs.1.18±0.12) and phospholylated p38 protein expression (0.36±0.04 vs.0.67±0.07), promoted claudin-5 protein expression (P<0.05). Conclusion These results indicate that minocycline attenuates BBB disruption after IRI by regulating the expression of MMP-9 and claudin-5 protein, inhibition of p38 pathway may be involved in its neuroprotective effect.
Objective To investigate growth inhibition and apoptosis induction of Shenmai injection on human glioma cells SHG-44 in vivo and in vitro. Methods Cells were cultivated in vitro, SHG-44 cells in culture medium were treated with 10, 20, 40, 80, 160 and 320 μg·mL-1Shenmai injection, respectively, the inhibitory rate of the cells was measured by MTT assay after 48, 72 and 96 h respectively. Annexin V-FITC/PI was utilized to measure the apoptosis; SHG-44 cells were seeded in BALB/C-nu mice, the tumor-bearing nude mice were divided into 5 groups randomly: model control group, cisplatin group, Shenmai injection (20, 40, 80 mg·kg-1) groups. The mice were intraperitoneally injected daily. General activity and food intake in nude mice were observed, after 12 days. The tumor weight was determined, and the tumor-inhibition rate was calculated. The content of gene protein Caspase-9, Caspase-12, Fas and Survivin were detected by immunohistochemistry. Results Shenmai injection inhibited the proliferation of SHG-44 cells in vitro at six doses, which was concentration- and time-dependent. At a dosage range of 20-80 μmol·L-1 in cultured cells, the apoptosis rates was elevated, Shenmai intraperitoneal injection inhibited the tumor growth of tumor-bearing nude mice, improved the level of Caspase-9, Caspase-12 and Fas, and decreased the level of Survivin. Conclusion Shenmai injection can inhibit proliferation of SHG-44 cells in vitro and in vivo, and induce its apoptosis. The mechanism may be related to the level of Caspase-9, Caspase-12, Fas and Survivin.
Objective To evaluate the clinical efficacy of compound lidocaine cream in the treatment of hormone dependent dermatitis (HDD) and the effect on serum IL-17, IL-22 and IL-23 expression levels and its clinical significance. Methods Treatment group (34 cases) of HDD were coated with compound lidocaine cream, and control group (34 cases) were coated with heparin sodium ointment. The two groups were both treated for 8 weeks, and the illness scores before the treatment, and after 1, 2, 4, 8 weeks of the treatment and 2 weeks after the 8-week-long treatment were recorded respectively, and then the clinical efficacy was evaluated. In addition, 30 healthy volunteers were chosen as health control group, IL-17, IL-22 and IL-23 levels in the peripheral blood of healthy control group and two groups of patients before and after the treatment and 2 weeks after the treatment were detected by double antibody enzyme linked immunosorbent assay (ELISA). Results After 1 week of the treatment and 2 weeks after the treatment, the illness scores of patients were significantly decreased, and the difference was statistically significant as compared with that before treatment (P<0.05 or P<0.01). After 2 weeks of the treatment and 2 weeks after the treatment, as compared with the illness scores of the control group, the difference was statistically significant (P<0.05 or P<0.01). The effective rate of the treatment group (91.18%) was significantly higher than that of the control group (61.76%,P<0.01). Before treatment, the expression levels of IL-17, IL-22 and IL-23 were not statistically significantly different between the treatment group and the control group (P>0.05), but they were significantly higher than those of the healthy control group (P<0.01). After the treatment and 2 weeks after the treatment: 3 indexes of the treatment group were significantly lower than those before treatment [IL-17: (19.61±3.85), (20.05±3.63) pg·mL-1vs. (41.36±6.19) pg·mL-1, P<0.01; IL-22: (33.07±4.67), (33.18±4.36) pg·mL-1vs. (35.64±5.78) pg·mL-1, P<0.05; IL-23: (24.56±3.71), (24.95±3.45) pg·mL-1 vs. (54.97±8.19) pg·mL-1, P<0.01]; 2 indexes of the control group were significantly lower than those before the treatment [IL-17: (37.83±5.07), (38.32±5.21) pg·mL-1 vs. (40.77±6.45) pg·mL-1, P<0.05; IL-23: (51.86±6.22), (52.14±6.70) pg·mL-1 vs. (55.46±7.81) pg·mL-1, P<0.05]; the 3 indexes of the treatment group were significantly different as compared with the control group (P<0.05 or P<0.01); IL-17, IL-22, IL-23 levels of the treatment group and IL-17, IL-23 levels of the control group had a significant positive correlation with the disease scores. Conclusion Compound lidocaine cream is effective in treating HDD, perhaps by down-regulating the expression levels of Th17-related cytokines (IL-17, IL-22 and IL-23) in serum of patients.
Objective To compare the respiratory depression and anesthesia effects of remifentanil combined with propofol or etomidate by target controlled infusion in patients undergoing bronehoscopy. Methods Seventy-five patients (ASAⅡ or Ⅲ grade) selectively undergoing bronchoscopy were randomly divided into etomidate group (n=37) and propofol group (n=38). Propofol group was treated by propofol combined with remifentanil; etomidate group was treated with combination of etomidate and remifentanil. The arterial blood gas analysis indexes (including PaCO2 and PaO2) before and after 15 min of the treatment, operation time, recovery time and the incidence rate of apnea, hypotension, hypoxidosis, tachycardia, myoclonus, injection pain, nausea, and vomiting of patients were recorded and compared between the 2 groups. Results In the propofol group, the PaCO2/PaO2 15 min after insertion of bronehoscopy was significantly higher/lower than that before anesthesia, the incidence of hypotension and injection pain of etomidate group was significantly lower than that of propofol group, but the recovery time was significantly longer and incidence of myoclonus, nausea and vomiting of etomidate group was significantly higher than those of propofol group, with statistically significant differences (all P<0.05). Conclusion Target controlled infusion of remifentanil combined with propofol exerts stronger respiratory inhibition on patients than remifentanil combined with etomidate, but it can shorten recovery time, reduce the incidence of nausea and vomiting, myoclonus, and get better anesthetic effects.
Objective To screen the formulation and preparation process of 10-hydroxycamptothecin nanocrystals and study the possibility of industrialization. Methods The particle size, drug loading, and placement stability were used as the main indices to evaluate the preparation method, stabilizers, and technological parameters of 10-hydroxycamptothecin nanocrystals in single factor screening. The reproducibility of preparation process and the properties of nanocrystals were investigated after industrial scale-up. Results The optimal preparation process of 10-hydroxycamptothecin nanocrystals was determined: the stabilizer was poloxamer188(0.8%), the proportion of drug and stabilizer was 3∶1 (m/m), and the preparation method was alkali-soluble and acid precipitation method combined with high pressure homogenization, homogenization process was 2×105 kPa, and the number of cycles was 8; the acid precipitation process was applied, and the stabilizer was added after homogenization. When the preparing process was scaled up to 1 000.0 mg 10-hydroxycamptothecin, the loss rate of 10-hydroxycamptothecin was 12.6%. The resultant particle size of 10-hydroxycamptothecin nanocrystals was (141.0±0.4) nm, the polydispersity index was 0.14±0.02, and the zeta potential was (-26.0±1.1) mV. The IC50 values of 10-HCPT injection and nanocrystals against BGC cell were (1.98±0.18) and (1.05±0.21) μg·mL-1, respectively, and against the HCT-8 cell IC50 values were (2.93±0.56) and (0.87±0.16) μg·mL-1, respectively. The inhibition effect was increased by 2.37 times in the nanocrystals group than in the injection group. The 10-hydroxycamptothecin nanocrystals could be directly reconstituted after lyophilization and it was stable in plasma. The physical and chemical properties of freeze-dried powder were stable within two months. Conclusion After screening the formulation and preparation process, 10-hydroxycamptothecin nanocrystals, which have high drug loading (75%), small particle size (<150 nm) and can be directly reconstituted, were obtained. The preparation method was simple and convenient with good reproducibility, and it is expected to achieve industrialization.
Objective To study polymorphism of the newest emergency contraceptive ulipristal acetate and find preponderant pharmaceutical polymorphs which are efficient in the clinical medication. Methods Five non-solvates forms and six solvates forms of ulipristal acetate were obtained through physical or chemical methods. These polymorphs were characterized by X-ray powder diffraction analysis (PXRD), thermogravimetric analysis (TG), differential scanning calorimetry (DSC) and infrared absorption spectroscopy (IR). Furthermore, a variety of experiments on influence factors were used to research the stability and transformation laws of the eleven polymorphs. Results This article demonstrated that ulipristal acetate had polymorphism and the polymorphs could be identified by kinds of detection methods. Eleven crystal forms of ulipristal acetate were discovered and 5 of them were found for the first time. Conclusion This research elucidates composition of a variety of crystal material, preparation methods, stability, solubility and laws of crystal transformation and provides scientific basic data for choice of preponderant pharmaceutical polymorphs. At the same time, the information lays the foundation for increasing drug quality, ensuring clinical quality, and drafting quality control standard of polymorph drugs.
Objective To optimize homogenate extraction process of Forsythia suspensa. Methods With the content of phillyrin serving as the index, the homogenate extraction process of phillyrin was optimized by orthogonal design, in which the ethanol concentration, ratio of solid to liquid and extracting time were selected as affecting factors.And the transfer rates of the polysaccharide in the dregs from homogenate extracting process and ethanol refluxing process were compared. Results The optimum conditions of the homogenate extraction were as follows: 10 times amount of 70% ethanol and 1 minute for each extraction with voltage of 120 V.The content of phillyrin extracted by the optimum process of homogenate extraction was 4.50 mg·g-1, and 4.06 mg·g-1 by ethanol refluxing method.The extraction rate of the polysaccharide from the dregs in the two processes was 2.16% and 1.51%, respectively. Conclusion Both the content of phillyrin and the extraction rate of polysaccharide from the dregs are higher in homogenate extraction than in refluxing extraction.
Objective To establish an HPLC method for determining the vitamin C content in the vinpocetine injection. Methods The chromatographic column was the InertSustain-C18 (4.6 mm×250 mm, 5 μm), with the mobile phase of acetonitrile-0.2 mol·L-1 ammonium acetate solution (60:40), the flow rate was 1 mL·min-1, the column temperature was 30 ℃, and the detection wavelength was 280 nm. Results The calibration curves of vitamin C showed a good linear relationship over the range of 2.5-125.0 μg·mL-1, r=0.999 7.The average recovery of vitamin C was 101.61% and RSD was 1.18% (n=9). Conclusion This method is accurate, sensitive, reproducible, and can be used for the determination of the vitamin C content in vinpocetine injection.
Objective To optimize the formula of lansoprazole enteric-coated pellets-type tablets and evaluate the quality. Methods Orthogonal L9 (34) test was designed to optimize the prescription.UV spectrophotometry was used to detect dissolution of lansoprazole enteric-coated pellets-type tablets and HPLC method was established for determination of lansoprazole and the related substances. Results The optimized prescription was 35% of lansoprazole pellets, 35% of cross-linked povidone, 9% of lactose, 9% of starch, 11.5% of povidone K30 (10% ethanol solution), 0.5% of magnesium stearate.The test showed that disintegration time was less than 60 s.The accumulated release of the pellets and the tablets in hydrochloric acid (pH 1.2) within 2 h were less than 7%, while in phosphate buffer (pH 6.8) within 45 min were over 80%. Conclusion The optimal prescription is feasible.The enteric-coated tablets conform to the quality standard in the Chinese Pharmacopoeia 2010 edition.
Objective To investigate the distribution of CYP3A4 -392A>G, SLCO1B1 388A>G and 521T>C in Bai population of Yunnan province. Methods The genotypes of CYP3A4 -392A>G, SLCO1B1 388A>G and 521T>C were detected in 94 healthy individuals of Bai by PCR-direct sequencing. Haplotypes of SLCO1B1 were inferred with the PHASE software version 2.1. Results The variant allele frequency of CYP3A4 -392A>G was zero in 94 healthy individuals of Bai. The genotype frequencies of SLCO1B1 388A>G were 3.3% (AA), 32.2% (AG), and 64.5% (GG), respectively, and the variant allele frequency was 80.6% in 90 healthy individuals of Bai. The genotype frequencies of SLCO1B1 521T>C were 91.5% (TT), 7.4% (TC) and 1.1% (CC), respectively, and the variant allele frequency was 4.8% in 94 healthy individuals of Bai. SLCO1B1*1a, *1b and *15 haplotypes were observed in Bai population, and the frequencies of them were 19.4%, 75.6% and 5.0%, respectively. Conclusion CYP3A4 -392A>G mutant is rare in Bai population of Yunnan province. The distribution of SLCO1B1 gene polymorphism is characteristic in Bai population of Yunnan province. The variant allele frequency of SLCO1B1 388A>G is very high, the variant allele frequency of SLCO1B1 521T>C is very low, and SLCO1B1*1a, *1b and *15 haplotypes can be observed.
Objective To explore the effect of probiotics combined with early enteral nutrition on clinical outcome of severe traumatic brain injury patients. Methods PubMed, Embase, the Cochrane Library, CBM, CNKI and VIP were searched to indentify randomized controlled trails (RCTs) concerning probiotics combined with early enteral nutrition in treatment of severe traumatic brain injury patients.Methodological quality of included studies was evaluated, and data were analyzed with The Cochrane Collaboration's soft ware RevMan 5.2.0. Results Seven prospective RCTs met the criteria.Meta analysis showed that probiotics combined with early enteral nutrition could shorten the length of ICU stay [MD=-4.73, 95%CI=(-6.45,-3.00), P<0.000 01], reduce mortality rates [RR=0.44, 95%CI=0.30,0.66, P<0.0001], reduce overall infection rates [RR=0.52, 95%CI=(0.39,0.68), P<0.000 1]. Conclusion Probiotics combined with early enteral nutrition could improve the clinical outcomes of severe brain injury patients.
Objective To improve the understanding of treatment with streptococcus a group for injection (SAGI) for neonatal congenital chylothorax. Methods The therapeutic effect of intrapleural injection of SAGI in two newborn infants with congenital chylothorax was analyzed and the literatures was reviewed from Wanfang and PubMed database until June 2015. Finally 38 articles were screened including 18 articles of neonatal and fetal chylothorax treated with intrapleural injection of SAGI, and a total of 87 cases of congenital chylothorax. The clinical data and the newborn's therapeutic response to SAGI of 87 cases and the 2 cases in this study were summarized. Results Two cases of full term were diagnosed of newborn congenital chylothorax according to pleural puncture and respectively admitted to the hospital on the 24th and 1st day after birth .The therapeutic response was not good through the chest drainage or diet treatment, then pleurodesis by intrapleural injection of SAGI was applied on the 20th day and 5th day after admission, respectively and chylous fluid was reduced sharply, finally the patients were recovered and discharged from the hospital. Totally, 80 cases out of the 89 cases were antenatally treated with pleurodesis with SAGI for congenital chylothorax, and 18 cases had gene mutation related diseases or abnormal chromosome karyotype. Intrauterine death occurred in 14 cases and 2 cases of abnormal chromosome karyotype died less than one year old after successful treatment about chylothorax. Twenty-three cases were partially effectively treated, while 41 cases had obvious curative effect. In the other 7 cases of neonatal chylothorax, the treatment efficacy of SAGI after conservative treatment or octreotide administration after birth was remarkable. In this paper, congenital chylothorax in the two cases achieved rapid and effective control due to chest drainage, diet control and combination with SAGI. Conclusion That SAGI should be considered as a therapeutic option for neonatal chylothorax, and its earlier usage may bring with expectation of the quick reduction of the chylous fluid, early removal of the chest tube, less risk of complication related to infection and less time of fasting and hospitalization.
Objective To enhance the standardization and information management of narcotics in our hospital and effectively improve the safety, traceability and rationality of drug use. Methods The function and application of narcotics management based on closed-loop management system were introduced. Then the results were evaluated by comparing the related indexes before and after its application. Results Drug use index (DUI) of narcotics was no more than 1 before and after the management system was implemented. However, the value of DUI was higher than before. The unqualified rates of narcotic prescriptions decreased from (4.82±1.38) % to 0 and turnover days of medicine inventory declined from 17.20±2.16 to 8.38±0.44. The differences were statistically significant (both P<0.05). Average work time of the administrator was reduced by 53.7% from 35.4 min to 16.4 min per day. Conclusion By the use of narcotics management system, the supervision level, safety and traceability of narcotics use can be improved and the human cost can be reduced. Finally, it effectively promotes the rational use of narcotics.