OBJECTIVE:To prepare Baicalin proliposomes (PBA) containing sodium deoxycholate (SD) with optimized for-mulation,and to study pharmacokinetics of it in rats in vivo. METHODS:PBA were prepared by spray drying method. Response surface method based on Box-behnken design was adopted to optimize the formulation of PBA with the amount of HSPC,cholester-ol and SD as factors using entrapment efficiency of PBA as index. The particle size,morphology,leakage rate and stability of the optimal PBA were evaluated along with the pharmacokinetics of it(compared to raw materials)in rats after ig administration of 15 mg/kg. RESULTS:The optimal formulation of PBA was that the amounts of baicalin,HSPC,cholesterol and SD were 100,214, 68 and 53 mg,respectively;the predicted and practical values of entrapment efficiency were 86.42% and 84.32%,respectively, and particle size of the optimal PBA was 358.4 nm. The leakage rate of reconstituted liposomes was low and the stability of PBA was good. Compared with baicalin raw material,t1/2,tmax,MRT,cmax and AUC0-t of PBA were all increased significantly(P<0.05 or P<0.01 or P<0.001). CONCLUSIONS:PBA were prepared successfully using the spray drying method. This method is simple and easy,and the optimized formulation is feasible and can improve the oral bioavailability of baicalin.

Objective To observe the changes of the peripheral blood T helper (Th)17 cells/regulatory T cells (Treg) ratio in patients with anti‐tuberculosis drug‐induced liver injury ,and to explore the relationship between Th17/Treg ratio and liver function . Methods Ninety inpatients with the diagnosis of secondary pulmonary tuberculosis (TB) from Affiliated Hospital of Zunyi Medical College from Feb .2013 to Mar .2015 were included in this study .All these patients had normal base line liver function .After 2 weeks of anti‐TB chemotherapy ,21 patients with alanine transaminase (ALT) and/or aspartate aminotransferase (AST) ≥2 × upper limit of normal (ULN) were defined as TB with liver injure group ,the other 69 patients with ALT and/or AST<2 × ULN were defined as TB with non‐liver injured group .Before treatment and two weeks after anti‐TB therapy ,the peripheral blood Th17/Treg ratios and liver functions of all patients in both groups were detected in order to compare the changes of Th17/Treg ratios pre and post anti‐TB chemotherapy and to explore the relationship between Th17/Treg ratio and ALT/AST levels .Student′s t test was used for statistical analysis ,and Pearson correlation analysis was used for correlation test .Results Before treatment ,there was no statistical significance of Th17 ,Treg and Th17/Treg ratio between groups (P> 0 .05) .The Th17 levels in TB with liver injured group ([2 .522 ± 0 .388]/mL vs [2 .075 ± 0 .369]/mL ,t=3 .633 ,P<0 .01) and TB with non‐liver injured group ([2 .326 ± 0 .348]/mL vs [1 .929 ± 0 .402]/mL ,t= 6 .468 , P< 0 .01) ,and Th17/Treg ratios in both groups(0.618±0.104vs0.489±0.107,t=3.553,P<0.01 ;0.554±0.108vs0.450±0.098,t=6 .353 ,P<0 .01) were all increased after anti‐TB chemotherapy ,with statistically significant differences . However ,there was no statistical significance of Treg levels pre and post anti‐treatment in both groups (both P>0 .05) .The Th17 level and Th17/Treg ratio in TB with liver injured group were significantly higher than those in TB with non‐liver injured group (t= 2 .203 , P< 0 .05 and t= 2 .345 , P< 0 .05 , respectively) .In liver injured group ,the Th17/Treg ratio was positively correlated with ALT level (r=0 .849 ,P=0 .044) ,but not with AST level (P>0 .05) .Conclusion The changes of Th17/Treg ratio are related with anti‐TB drug‐induced liver injury in patients with secondary pulmonary tuberculosis .

Objective To explore the relationship between serum levels of interferon-inducible protein-10 (IP-10), interferon-γ (IFN-γ) and hepatic inflammatory reaction, disease progression in patients with severe hepatitis B (SHB). Methods Sera of 40 patients with SHB at time of admission,at the beginning of single plasma exchange (PE), at time of PE completion and 5 days after PE. The SHB patients were divided into improved group and aggravated group. And 20 patients with chronic hepatitis B (CHB) and 20 healthy controls were enrolled in this study. Serum levels of IP-10, IFN-γand tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA). Results The serum levels of IP-10 in patients with SHB and CHB on admission were (683.6 174.6)ng/L and (216.1 102.9)ng/L, respectively, which were notably higher than those in healthy controls [(107.6 55.8)ng/L F=9.036, both P＜0. 01],and those in patients with SHB was significantly higher than that in patients with CHB (P＜0. 01). The serum level of IFN-γ in patients with SHB and CHB on admission were (19. 8 8. 8) ng/L and (16. 7 7. 8) ng/L,respectively, which were significantly higher than those in healthy controls [(2.6 1.2) ng/L F=9. 288, both P＜0. 01]. The serum level of IP-10 and IFN-γ were both positively correlated with TNF α (r=0. 366 and r=0. 365, respectively;P＜0.05) and both negatively correlated with prothrombinase activity (r=-0.401 and r=-0.350, respectively;P＜0.05), but not correlated with serum total bilirubin(r=0. 223 and r=0. 219, respectively;P＞0.05). The serum level of IP-10 and IFN-γ were positively correlated ( r= 0. 602 ; P= 0. 000 ). On day 5 after PE, serum level of IP-10 in patients with SHB was significantly decreased compared with that'in patients before PE (t= 8. 947, P＜0.01 in improved group;t=4. 121, P＜0.05 in aggravated group) and that in aggravated group was significantly higher than improved group (t=7.862, P＜0.01). But serum level of IFN-γ was not decreased significantly (t=0. 491, P＞0.05). Conclusions IP-10 and IFN-γ are involved in the hepatic immunopathological mechanism. Serum level of IP-10 is correlated with the severity of hepatic inflammatory injury and IP-10 could reflect the progression and development of disease in patients with SHB.

Objective To evaluate the application value of denaturing high-performance liquid chromatography (DHPLC) as a rapid gene typing tool for β thalassemia. Methods 226 suspicious samples were screened with MCV, RDW, erythrocytcte agility and hemoglobin electrophoresis. The final diagnosis ofβ thalassemia genotype was made by DHPLC and PCR-reverse dot blot (PCR-RDB). Results Sixty-nine samples (30. 5% ) were eventually diagnosed as βthalassemia by PCR-RDB. The genotyping results for βthalassemia identified by DHPLC were complete agreement with genotyping results by PCR-RDB. We found 37 cases of CD41/CD42 ( - TCTT) frame shift mutation(54% ) ; 12 cases of IVS - Ⅱ - 654 (C→T) insertion mutation( 17% ) ;10 cases of TATA - 28 (A→G) transcription mutation ( 15% ) ;5 cases of CD17 (A→T)nonsense mutation ( 7% ) ; 5 cases of CD71/CD72 ( + A) frame shift mutation (7%). Conclusion The DHPLC is a rapid, sensitive , efficient and highly accurate assay in the diagnosis of β-thalassemia.

OBJECTIVETo observe the clinical efficacy of shensong yangxin capsule (SYC) on ventricular premature beat (VPB) differentiated in TCM as palpitation of Qi-yin deficiency syndrome or Xin collateral stagnation syndrome, and cardiovascular autonomic nervous function in patients with coronary heart disease (CHD).

METHODSThe randomized, double-blind, parallel contrast method was adopted, patients were randomly assigned by 3:1 ratio into two groups. One hundred and sixty-five patients in SYC treated group and 56 in the control group (treated with Xinlvning tablet), and the therapeutic course for both groups was 4 weeks.

RESULTSThe clinical efficacy on VPB and in improving TCM syndromes was better in SYC group than that in the control group (P < 0.01). After treatment, the heart rate variability (HRV) and QT dispersion in the two groups were improved in a certain degree. The changes of SDNN, SDANN, SDNN Index and PNN50 in the two groups were significantly different (P < 0.05, P < 0.01), the efficacy in the treated group was superior to that in the control group.

CONCLUSIONSYC has definite effect on VPB and TCM Syndromes, it can obviously meliorate the activity of cardiovascular autonomic nervous system in the patients with CHD.

Adult ; Aged ; Autonomic Nervous System ; drug effects ; physiopathology ; Capsules ; Coronary Disease ; complications ; drug therapy ; Double-Blind Method ; Drug Administration Schedule ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heart ; innervation ; Humans ; Male ; Middle Aged ; Phytotherapy ; Ventricular Premature Complexes ; drug therapy ; etiology

As one of the main forms of the medical alliance, the specialty alliance functions as a service carrier for hierarchical medical service and resources integration in the region. The authors introduced the exploration and practice of the West China Women′s and Children′s Alliance, the first pediatric specialty alliance in Sichuan, established by the West China Second Hospital of Sichuan University. Based on family doctor contracted services, the West China Women′s and Children′s Alliance took such measures as differentiated functional positioning, assessment of certified physicians, continuous online quality control, construction of referral platforms, and innovative payment mechanisms. Such efforts effectively integrated the three stages of pre-hospital " preventive care" , in-hospital " disease diagnosis and treatment" , and post-hospital " follow-up management" , exploring the homogenization of medical services within the alliance, and forming a pediatric closed-loop health management system, hence improving the primary medical services.

Aspergillosis ; Humans ; Mucor ; Mucormycosis/drug therapy*

ObjectiveTo confirm the clinical efficacy and safety of Yishen Yangxin Anshen tablets in the treatment of insomnia （heart-blood deficiency and kidney-essence insufficiency syndrome）. MethodA randomized block， double-blind， placebo-controlled， multi-center clinical trial design method was adopted， and a total of 480 patients with insomnia due to deficiency of heart blood and insufficiency of kidney essence （treatment group-control group 3∶1） from seven hospitals （Guang'anmen Hospital， China Academy of Chinese Medical Sciences， The First Clinical Hospital， Jilin Province Academy of Traditional Chinese Medicine（TCM）， The Second Affiliated Hospital of Liaoning University of TCM， The First Affiliated Hospital of Henan University of Chinese Medicine， Henan Province Hospital of TCM， Hebei General Hospital， The First Hospital of Hunan University of Chinese Medicine） were enrolled. The treatment group was given Yishen Yangxin Anshen tablets and the control group received placebo tablets （4 tablets/time， 3 times/day， 4 weeks of administration， 4 weeks of follow-up after drug withdrawal）. The sleep dysfunction rating scale （SDRS） score， pittsburgh sleep quality index （PSQI） score， TCM， polysomnography （PSG） indicators from four hospital （Guang'anmen Hospital， China Academy of Chinese Medical Sciences， Henan Province Hospital of TCM， Hebei General Hospital， The First Hospital of Hunan University of Chinese Medicine）， and other efficacy indicators were compared between the two groups before and after treatment. Through general physical examination， laboratory examination， and observation of adverse events， the safety of the drugs was evaluated. ResultThe baseline indexes of the two groups showed no significant difference and thus the two groups were comparable. After treatment， the total score of SDRS in the treatment group was lower than that in the control group （P<0.01）. After drug withdrawal for 4 weeks， the total score of SDRS demonstrated no significant change in the treatment group as compared with that at the end of treatment， indicating that the rebound change of curative effect was not obvious. After treatment， the total score of PSQI in the treatment group decreased as compared with that in the control group （P<0.01）， and the change of total score of PSQI in the treatment group was statistically significant （P<0.05） after drug withdrawal for 4 weeks but small， indicating that the rebound change of curative effect was not obvious. After treatment， the total effective rate about the TCM symptoms in the treatment group was higher than that in the control group （χ²=137.521，P<0.01）. After treatment， the disappearance rates of single indexes in the treatment group， such as difficulty in falling asleep， easily waking up after sleeping， early awakening， short sleep time， dreamfulness， palpitation， forgetfulness， dizziness， mental fatigue， and weakness of waist and knee， increased compared with those in the control group （P<0.01）. After treatment， the treatment group demonstrated fewer awaking times （AT）， longer total sleep time （TST）， lower ATA/TST ratio， and higher sleep efficiency （%） than the control group （P<0.05）. No abnormal value or aggravation related to drugs was observed in either group. The incidence of adverse events in the treatment group and the control group was 5.57% and 8.40% respectively. No serious adverse events or adverse events leading to withdrawal happened in either group. ConclusionYishen Yangxin Anshen tablets is effective and safe for patients with insomnia of deficiency of heart-blood and insufficiency of kidney-essence.

Objective: To retrospectively analyze the distribution of non-fermentative bacteria causing bloodstream infection in hospitalized patients in Sichuan Province and their drug susceptibility to common antibiotics for better understanding their epidemiological characteristics. Methods: From January 1, 2015 to December 31, 2017, all of the non-fermentative bacteria isolated from patients with bloodstream infection in nine hospitals in Sichuan Province were collected. Species distribution and drug resistance test results were retrospectively analyzed. Results: A total of 6 291 strains of pathogenic bacteria were isolated, including 3 674 strains of gram-negative bacteria (58.4%) and 2 617 strains of gram-positive bacteria (41.6%). The gram-positive bacteria were 1 895 strains of Staphylococcus (30.1%), 372 strains of Streptococcus (5.9%), 317 strains of Enterococcus (5.1%) and 33 strains of other gram-positive bacteria (0.5%). The gram-negative bacteria were 3 191 Enterobacteriaceae strains (50.7%), 389 non-fermentative strains (6.2%) and 94 other gram-negative strains (1.5%). The isolated non-fermentative bacteria were mainly Pseudomonas aeruginosa (136 strains, 35.0%), Acinetobacter baumannii (126 strains, 32.0%) and Stenotrophomonas maltophilia (33 strains, 8.5%). There were 167 (42.9%), 112 (28.8%) and 82 (21.1%) non-fermentative bacteria isolated in internal medicine departments, ICUs and surgery departments, respectively. The drug resistance rates of Pseudomonas aeruginosa to cefepime, ciprofloxacin and gentamicin were 16.5%, 10.7% and 9.9%, respectively. Carbapenems-resistant Pseudomonas aeruginosa (CR-PA) accounted for 13.6%. No polymyxin-resistant Pseudomonas aeruginosa was found. The resistance rates of Acinetobacter baumannii to all antibiotics were over 30% except for minocycline and polymyxin and 75.7% of carbapenem-resistant Acinetobacter baumannii (CR-AB) were isolated. The drug resistance rates to levofloxacin, trimethoprim/sulfamethoxazole and ceftazidime were 0%, 0% and 37.0% in Stenotrophomonas maltophilia isolates and 10.5%, 4.2% and 19% in Burkholderia cepacia isolates, respectively. Conclusions Non-fermentative bacteria causing 6.2% of bloodstream infection in Sichuan, mainly by Pseudomonas aeruginosa and Acinetobacter baumannii. There were significant differences in the isolation rate of non-fermentative bacteria in different departments and most of the strains were isolated in internal medicine departments. The detection rate of Acinetobacter baumannii with multiple drug resistance was high, while other non-fermentative bacteria had good sensitivity to antibiotics.

Bone remodelling keeps going through the lifespan of human by bone formation and bone resorption. In the craniofacial region, mandibles act as the main force for biting and chewing, and also become susceptible to a common bone-loss disease, namely, apical periodontitis, once infected dental pulp is not treated timely, during which bone resorption occurs from the apical foramen to the apical bone area. Although conventional root canal treatment (RCT) can remove the most of the infection, chronical apical periodontitis due to incomplete removal of dental pulp and subsequent microleakage will become refractory and more challenging, and this process has scarcely been specifically studied as a bone remodelling issue in rat models. Therefore, to study chronical and refractory apical periodontitis owing to incomplete cleaning of infected dental pulp and microleackage in vivo, we establish a modified rat model of gradually progressive apical periodontitis by sealing residual necrotic dental pulp and introducing limited saliva, which simulates gradually progressive apical periodontitis, as observed in the clinical treatment of chronical and refractory apical periodontitis. We show that bone-loss is inevitable and progressive in this case of apical periodontitis, which confirms again that complete and sound root canal treatment is crucial to halt the progression of chronical and refractory apical periodontitis and promote bone formation. Interestingly, bone remodelling was enhanced at the initial stage of apical periodontitis in this model while reduced with a high osteoblast number afterwards, as shown by the time course study of the modified model. Suggesting that the pathological apical microenvironment reserve its hard tissue formation ability to some degree but in a disturbed manner. Hopefully, our findings can provide insights for future bone regenerative treatment for apical periodontitis-associated bone loss.