Objective To study the value of sequential duodenoscopic-laparoscopic treatment in patients with cholelithiasis. Methods Clinical data of 2 248 cases of cholelithiasis treated with sequential duodenoscopic-laparoscopic plan from January 2000 to December 2004 were retrospectively reviewed. Results Duodenoscopy indicated the confirmative diagnosis of gallbladder stones in 1 817 cases and gallbladder stones with associated common bile duct stones in 431 cases. Among 2 021 cases diagnosed as having gallbladder stones by B-ultrasonography: endoscopic retrograde cholangiopancreatography (ERCP) was performed in 690 cases, 213 of which were found having associated common bile duct stones; intraoperative cholangiography (IOC) was conducted in 85 cases, 10 of which were found presenting common bile duct stones; residual stones in the common bile duct after laparoscopic cholecystectomy (LC) were noted in 6 cases which were cured by endoscopic sphincterotomy (EST). Among 227 cases diagnosed as having gallbladder stones combined with common bile duct stones by B-ultrasonography, the diagnosis of common bile duct stones were confirmed by ERCP in 202 cases. Out of the 2 248 cases, 1 817 cases underwent the LC, 395 cases received EST and LC, and 36 cases were given the laparoscopic bile duct exploration (LBDE) (the bile duct was closed by primary suture in 26 cases and a T-tube was left in the bile duct in 10 cases). The 6 cases of residual stones in the bile duct were cured with EST postoperatively. A total of 28 cases required a conversion to open surgery (1.2%), and complications occurred in 52 cases (2.3%). Conclusions Sequential duodenoscopic- laparoscopic treatment for cholelithiasis offers a low residual stone rate and a high success rate.

Objective To study the clinical application of laparoscopic cholecystectomy (LC) combined with intraoperative endoscopic sphincterotomy (IOEST) with the antegrade guidewire technique in the treatment of cholecystocholedocholithiasis.Methods This is a prospective controlled study comparing LC combined with preoperative endoscopic sphincterotomy (POEST) versus LC combined with IOEST in the treatment of cholecystocholedocholithiasis.Patients who were diagnosed to have cholecystocholedocholithiasis from June 2012 to February 2013 in our hospital were divided into the POEST group and the IOEST group.There were 50 patients in each group.The operation time,successful stone-extraction rate,residual stones rate,complication rate,postoperative stay and hospitalization cost between the groups were compared.Results The sex,age,stone size,number of stones and diameter of the common bile duct showed no significant difference between the two groups (P ＞ 0.05).There were no differences between the two groups in surgical time of EST,surgical time of LC combined with EST,successful stone-extraction rate and hospitalization cost (P ＞ 0.05).There were significant differences between the two groups in the residual stones rate,postoperative hyperamylasemia rate,postoperative acute pancreatitis rate and postoperative stay (P ＜0.05).LC combined with IOEST using the antegrade insertion of guidewire technique significantly reduced the residual stones rate (0 vs 8％),postoperative hyperamylasemia rate (4％ vs 18％),postoperative acute pancreatitis rate (0 vs 8％) and postoperative stay.Conclusions LC combined with IOEST using the antegrade guidewire technique could be performed safely when compared with the traditional sequential technique,LC combined with IOEST using the antegrade guidewire technique significantly reduced the postoperative acute pancreatitis rate and the residual stones rate.LC combined with IOEST using the antegrade guidewire technique should be the recommended technique to treat patients with cholecystocholedocholithiasis.

BACKGROUND:Sodium hyaluronate is a polysaccharide polymer biomaterial, which is considered to have a certain effect to repair the cartilage surface, reduce the release of inflammatory mediators, and promote meniscal repair. OBJECTIVE:To observe the therapeutic effect of Fast-Fix combined with sodium hyaluronate in meniscal repair under arthroscope. METHODS:Eighty-six patients with meniscus injury admitted at the Department of Orthopedics, CNPC Central Hospital, from March 2008 to March 2014 were enrol ed in the study. The average age was 25.5 years, and the average duration of disease was 1.5 months. The main clinical manifestations included knee joint pain and swel ing after exercise and positive McMurray signs. The MRI results showed meniscus tear or degeneration. Arthroscopic repairing surgeries were performed with Fast-Fix combined with sodium hyaluronate injection (2.5 mL at the end of surgery), and then sodium hyaluronate was injected intraarticularly at 1, 2, 3 weeks after surgery. Each patient was assessed with Lysholm knee joint score system before and after operation. RESULTS AND CONCLUSION:Eighty-one patients were fol owed up for an average of 1.5 years and five patients were lost to fol ow-up. Joint locking, significant tenderness and movement disorder symptoms disappeared in 79 of 81 patients, and meniscal healing was shown on MRI review within 1 year after surgery;the Lysholm score was higher than 75 points, and the excel ent rate was 98%. Only the remained two patients felt swel ing and tenderness and the movement was slightly restricted when going down or standing up. The Fast-Fix combined with sodium hyaluronate in meniscal repair under arthroscope has good effect and good function of knee joint.

Objective To explore the effects and mechanisms of prostaglandin E2 (PGE2) receptor 1 antagonist (SC-19220) on proliferation,prostaglandin synthase and extracellular regulated protein kinases (ERK) signal pathway induced by transforming growth factor β1(TGF-β1) in glomerular mesangial cells.Methods Mouse glomerular mesangial cells (GMCs) were divided into 5 groups:control group,TGF-β1 (10 μg/L) group,TGF-β1 (10 μg/L) plus SC-19220 group (0.1,0.5,1.0 μmol/L).The proliferation of GMCs was measured by CCK-8.The PGE2 in supernatant was measured by ELISA.The expression of connective tissue growth factor (CTGF),laminin (LN),cyclooxygenase 2(COX2),membrane-bound prostaglandin E2 synthase 1 (mPGES1) protein and mRNA was examined by Westem blotting and real-time quantitative PCR,ERK1/2 or phospho-ERK1/2 was measured by Western blotting as well.Results TGF-β1 induced the proliferation of GMCs and increased the secretion of PGE2.Besides,TGF-β1 significantly up-regulated the expression of CTGF,LN,COX2 and mPGES1 mRNA and protein (P ＜ 0.05),and increased the expression of phospho-ERK1/2 protein (P ＜ 0.05).However,SC-19220 significantly attenuated the changes of above-mentioned parameters and their activities (P ＜ 0.05).All the effects of SC-19220 were in dose-dependent manner.Conclusions SC19220 may reduce TGF-β1-induced cell damage by suppressing the activity of ERK1/2,and feedback inhibition of COX2,mPGES1 and PGE2,thus decreases the expression of LN and CTGF.

Objective To study the effect of maternal subclinical thyroid abnormalities [including subclinical hypothyroidism, hypothyroxinemia and positive anti-thyroid peroxidase antibody (TPOAb) with normal thyroid function] in women during 16-20 weeks of gestation on offspfing's intellectual development and motor function. Methods Sera from 1 268 women during 16-20 weeks of gestation (collected 2 years ago) were obtained and thyroid stimulating hormone (TSH), total thyroxine (TT4), free thyroxine (FT4) and TPOAb levels were measured. Pregnant specific thyroid function reference ranges were used to screen for subclinical hypothyroidism (18 cases), hypothyroxinemia (19 cases) and positive TPOAb (34 cases). From the same cohort, a total of 142 pregnant women who were euthyroid with negative TPOAb were selected as controls (a case: control ratio of 1 : 2). Intellectual and motor development score evaluations were performed in their children at 25-30 months of age. Results In the group of pregnant women with subclinical hypothyroidism, the offspring' s intelligence score was (109.89±13.81) points, which was 8.88 points lower than in the control group (P < 0.01). Similarly, the motor score of the offspring was (108.11±9.93) points, which was 9.98 points lower than in the control group (P < 0.01). In the pregnant women with hypothyroxinemia, the offspring's intelligence score was (112.32±15.10) points, 9.30 points lower than in the control group (P <0.01); the motor score was (112.21±12.26) points, 7.57 points lower than in the control group (P < 0.01). In the pregnant women with positive TPOAb and euthyroid function, the offspring's intelligence score was (112.70±20.64) points, 10.56 points lower than in the control group (P < 0.01); the motor score was (110.64±12.49) points, 9.03 points lower than in the control group (P < 0.01). Conclusion Maternal subclinical thyroid abnormality between 16-20 weeks of gestation adversely may affect offspring intellectual and motor development, suggesting the necessity for screening and treatment of maternal subclinical thyroid abnormality in the early stages of pregnancy.

Objective:To explore the effectiveness of applet-assisted teaching in the pedagogy of stomatology and gain suggestions for the improvement of the applet.Methods:Using digital technology, we built a professional atlas applet for Oral Histopathology that covered a wide range of contents including illustrations, histological slides, schematic diagrams, and hand-drawn pictures of knowledge points. Based on the WeChat platform, the applet had the functions of bilingual (Chinese/English) annotation and real-time interactive communication between teachers and students. Thirty dental students were given quizzes before and after using the atlas applet. The scores were analyzed using the t-test with SPSS 22.0 software. At the same time, 45 students filled a questionnaire after using the applet for one month, which involved comments on the use of the digital atlas, the degree of satisfaction and suggestions for the applet during learning, and suggestions for its co-use by teachers and students in the future. Results:After using the atlas applet to assist with learning, the test scores of the students were improved significantly in all domains. There were significant differences between the test and control groups in the score of completion questions [(17.00±2.61) vs. (15.03±1.85), P<0.05], the score of identification of images [(27.93±5.08) vs. (25.13±3.31), P<0.05], and the total score [(78.77±8.59) vs. (72.90±6.08), P<0.05]. The questionnaire feedback showed that the students were highly satisfied with the atlas applet-assisted learning, the function of teacher-student interaction, and the overall performance of the applet. Conclusion:An atlas is one of the crucial teaching tools of Oral Histopathology for its intuitionistic and realistic presentation of tissue structures, which plays an important role in the theoretical learning process for dental students. The combination of the atlas and electronic media based on portable mobile devices is beneficial for students' understanding of knowledge.

OBJECTIVE To study the pharmacokinetic changes in the plasma and cerebrospinal fluid of bronchial asthma model rats after the complication of Ephedra sinica and Prunus armeniaca. METHODS SD male rats were randomly divided into blank group， model group， E. sinica group （12 g/kg， calculated by raw drug， similarly hereinafter）， P. armeniaca group （6 g/kg） and E. sinica-P. armeniaca drug-pair group （12 g/kg of E. sinica+6 g/kg of P. armeniaca）， with 6 rats in each group. Except for the blank group， the bronchial asthma model was induced by spraying rats in each group with an equal volume mixture of 2% acetylcholine chloride and 0.4% histamine phosphate， once a day， for 7 d. One hour before modeling every time， rats in each group were gavaged with the corresponding drug/normal saline， once a day， for 7 d. After the final administration and provocation of asthma， blood and cerebrospinal fluid collection were performed at different time points. The plasma and cerebrospinal fluid samples were pre-treated （with geranylgeranyl as the internal standard）， and the mass concentrations of ephedrine/pseudoephedrine， methyl ephedrine and amygdalin in both samples were determined by liquid chromatography-tandem mass spectrometry. DAS 2.0 pharmacokinetic software was used to determine the main pharmacokinetic parameters through the non-atrial chamber model and to compare the changes of the pharmacokinetic parameters before and after the combination of the two drugs. RESULTS Compared with E. sinica group， cmax and AUC0-21.33 h （or AUC0-10.67 h） of ephedrine/pseudoephedrine and methyl ephedrine in the plasma and cerebrospinal fluid of rats were significantly reduced in E. sinica-P. armeniaca drug-pair group， while CLZ/F and VZ/F were significantly increased （P＜0.05 or P＜0.01）； tmax of methyl ephedrine in the cerebrospinal fluid was significantly shortened （P＜ 0.05）.Compared with P. armeniaca group， the t1/2 of amygdalin in the plasma of rats in E. sinica-P. armeniaca drug-pair group was significantly shortened， and CLZ/F was significantly increased （P＜0.01）； the tmax of bitter amygdalin in the cerebrospinal fluid was significantly shortened， and the AUC0-10.67 h， CLZ/F， and VZ/F were significantly increased （P＜0.01）. CONCLUSIONS The combination of E. sinica and P. armeniaca accelerates the absorption and elimination of ephedra alkaloids， thus reducing the accumulation of ephedra alkaloids in the bronchial asthma model rats.

Autopsy ; Brain ; metabolism ; pathology ; Gene Expression ; physiology ; Humans ; Transcriptional Activation ; physiology

OBJECTIVE：To provide reference f or the qualit y sta ndard establishment of Amaranthus retroflexus. METHODS ： Taking 7 batches of A. retroflexus medicinal materials as the research object ，the appearance properties of the medicinal materials were investigated ，and the microscopic characteristics of the medicinal powders were observed. TLC method was adopted to qualitatively identify rutin ，valine and leucine in A. retroflexus medicinal materials. According to the relevant methods of the 2015 edition of Chinese Pharmacopoeia （part Ⅳ），water content ，total ash content ，acid-insoluble ash content and water-soluble extract content were determined. HPLC method was used to determine the content of rutin in the medicinal material of A. retroflexus . The determination was performed on Agilent 5 TC-C18（2）column with mobile phase consisted of methanol- 0.3％ phosphoric acid solution（40∶60，V/V），at the flow rate of 1.0 mL/min. The detection wavelength was set at 358 nm，and the column temperature was 30 ℃. The sample size was 10 μL. RESULTS：The appearance and microstructure characteristics of the medicinal materials were consistent with the existing description. The identification results of TLC meth od showed that 7 batches of medicinal materials and each reference substance （rutin，valine，leucine）showed spots of the same color at the same position. The moisture content of 7 batches of A. retroflexus medicinal materials was 7.43％-8.72％，the total ash content was 11.82％-13.78％，the acid-insoluble ash content was 0.15％-0.55％，and the water-soluble extract content was 17.27％-24.74％. The linear range of rutin was 10-200 μg/mL（R 2＝1.000 0）. RSDs of precision test ，stability test （24 h）and repeatability test were all less than 2.0％ （n＝6）. The average recovery rates of rutin were 99.14％，97.98％ and 98.80％ in low ，medium and high concentration of samples，and RSDs were 0.97％，0.95％，0.96％（n＝3）. The contents of rutin in 7 batches of A. retrophylla were 0.314-1.102 mg/g. CONCLUSIONS：In this study ，character observation ，microscopic identification ，moisture content ，total ash content ，acid- insoluble ash content and water-soluble extract content of A. retroflexus are investigated ；TLC method was established for qualitative identification of leucine ，valine and rutin in A. retroflexus ，and the HPLC method was established for content determination of rutin. It provides reference for the quality standard establishment of A. retroflexus .

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone