OBJECTIVE:To investigate the complexation of clonazepam with hydroxypropyl-?-cyclodextrin(HP-?-CD)in aqueous solutions.METHODS:The complexation of clonazepam with(HP-?-CD),the inclusion molar ratio of host and guest molecules and thermodynamic parameters were detected using phase solubility method,equimolar series method,UV absorption spectroscopy etc.RESULTS:The solubility of clonazepam increased linearly with the increase of(HP-?-CD)level in aqueous solutions at different temperatures(25℃,35℃and45℃)and in buffers at different pH values(4.0,6.0and7.0),the phase solubility diagram was classified as type AL.CONCLUSIONS:Under the above research condition,the incl_ usion complexes of clonazepam with(HP-?-CD)can be formed spontaneously at a molar ratio of1∶1.

Objective To evaluate the specific methods and clinical efficacy of docetaxel combined with doxorubicin in the treatment of locally advanced breast cancer and to evaluate its safety.MethodsThe clinical data of 72 pitients with locally advanced breast cancer who were treated in our hospital from July 2012 to July 2016 were retrospectively analyzed.According to the random double blind method,the patients were divided into the control group and the experimental group,with 36 cases in each group.The control group were treated with cyclophosphamide,5-fluorouracil and ammonia armor pterin methotrexate treatment,the experimental group were treated with docetaxel combined with adriamycin treatment,21 days for a cycle,withThe clinical curative effect,toxicity and quality of life were compared between the two groups of patients two cycles of treatment after the completion of the assessment.Results The total remission rate of the experimental group was 75.0％,which was significantly higher than that in control group 41.7％(P<0.05); the main adverse reactions were gastrointestinal reaction and bone marrow suppression,two groups of patients with 0-I,nausea and vomiting,hair loss,diarrhea,fatigue,white blood cell reduction,blood loss,blood loss,heart rate disorders,abnormal liver function and peripheral phlebitis.Two groups were compared.The two groups had no significant difference.Conclusion Docetaxel combined with adriamycin in the treatment of locally advanced breast cancer had definite and toxic and side reaction were slightly in patients can tolerance range,to promote the rehabilitation of patients,improve the quality of life has a very positive significance for popularization and application in the medical practice.

Objective To evaluate the diagnostic value of 2D ultrasound (2DUS)-based composite score method and contrast enhanced ultrasound (CEUS) in differentiation between thyroid microcarcinomas and benign micronodules. Methods A total of 216 consecutive patients with 258 thyroid micronodules underwent 2DUS and CEUS examinations before thyroidectomy from June 2011 to October 2013. The scoring of each nodule was based on five 2DUS features including hypoechogencity, irregular shape, macrocalcification, and taller than wide in shape. Microcalciifcation was assigned as 2 points and the remaining features were assigned as 1 point. A composite score was ifnally given to each thyroid nodule ranging from 0 to 6 points. The sensitivity, specificity and accuracy of diagnosing thyroid microcarcinoma by 2DUS composite score method and CEUS were calculated. Results The histopathologic results of all 258 nodules were acquired, including 125 papillary microcarcinomas and 133 benign micronodules. Each nodule′s 2DUS compostie score was ranging from 0 to 6 points. The area of receiver operating characteristic (ROC) curve of 2DUS in diagnosing thyroid microcarcinoma was 0.81. The 2DUS composite score method predicted the thyroid microcarcinoma with sensitivity of 78.4%(98/125), speciifcity of 72.9%(97/133), accuracy of 75.6%(195/258), when the nodule with a score greater than or equal to 3 points was deifned as malignant. Thyroid micronodules′enhancement pattern were divided into 7 types, including early hypoenhancement, hypoenhancement, isoenhancement, hyperenhancement, local nonenhancement, nonenhancement, and ring margin ring enhancement. CEUS predicted thyroid malignant micronodules with sensitivity of 87.2%(109/125), specificity of 75.9%(101/133), and accuracy of 81.4%(210/258), when early hypoenhancement and hypoenhancement pattern was defined as malignant patterns. There were no differences in sensitivity, specificity, and accuracy between 2DUS cumulative score method and CEUS in diagnosing thyroid microcarcinoma (McNemar test, P=0.099, 0.608, 0.096). Conclusion Early hypoenhancement and hypoenhancement are CEUS characteristic enhancement pattern for thyroid microcarcinoma, CEUS has higher sensitivity, speciifcity in diagnosis than 2DUS composite score method, while there are no statistical differences.

Objective To construct a prostate cancer specific oncolytic adenovirus armed with a fusion protein gene , PSA-IZ-CD40L, and to evaluate its oncolytic efficiency and immune activation ability in vitro.Methods Prostate Specific Antigen (PSA) gene, CD40L-N and CD40L-C genes were obtained from cDNA of LNCaP cells and Jurkat cells using poly-merase chain reaction (PCR) or nested-PCR, respectively.PSA,Linker,CD40L-N and CD40L-C were linked sequentially to generate fusion protein gene PSA-IZ-CD40L (PL) by overlapping PCR.Then, prostate specific oncolytic adenovirus PL-carrying gene, Ad-PL-PPT-E1A,was constructed using the oncolytic adenovirus system , which was based on Adeasy sys-tem.PC3M cells were infected by Ad-PL-PPT-E1A at serial multiplicity of infection (MOI), and the apoptosis was detec-ted by flow cytometry at several time points post-infection.For immune activation detection , PC3M cells were infected with Ad-PL-PPT-E1A at a MOI of 50, and the cell lysate was collected at 48 h post-infection.Peripheral blood mononuclear cells derived (PBMCs) from healthy donors were stimulated by the lysate from PC 3M cells or Ad-PL-PPT-E1A infected PC3M cells before proliferation was assayed using cell counting kit-8 (CCK8).Results Fusion protein gene, PSA-IZ-CD40L, was successfully constructed and cloned into the prostate cancer specific adenovirus to generate Ad -PL-PPT-PL. The expression of E1A and PL protein could be detected by reverse transcription PCR and Western-blotting.Cytopathic effect was observed in PC3M cells infected with Ad-PL-PPT-E1A.Furthermore, the apoptosis rate reached 70.67% ± 2.98%at 48 h post-infection with 200 MOI Ad-PL-PPT-E1A.Compared with the lysate of PC3M cells, that from Ad-PL-PPT-E1A infected cells could promote the proliferation of PBMCs .Conclusion We have constructed a prostate cancer spe-cific oncolytic adenovirus armed can fusion protein gene PL , Ad-PL-PPT-E1A, which could kill PC3M cells effectively and enhance the proliferation of PBMCs in vitro.

Objective To study the effect of heavy ion radiation on proliferation and apoptosis of human peripheral blood derived T lymphocytes and the mechanism .Methods T lymphocytes were isolated from heparinized whole blood samples by density gradient centrifugation using Ficoll before being irradiated with heavy ion beams 12 C.The accumulated absorbed dose (dose-rate values=0.5 Gy/min, and meanLET=29 keV/μm).12 h and 24 h post-infection, total RNA of T lymphocytes was isolated , and the apoptosis related gene expression , including Bcl-2, Bax, Caspase3, Caspase8 and Caspase9, was detected by RT-RT-PCR.24 h and 48 h after irradiation, the proliferation was analyzed by CCK 8 kit.The cell apoptosis was detected by flow cytometry after being labeled with AnnexinV-PE/7-AAD or AnnexinV-FITC/PE.The expression of Bcl-2, Bax and Caspase3 was also assayed by RT-PCR.Results Data showed that heavy ion radiation could inhibit the proliferation of T lymphocytes obviously , and the inhibition ratio in cells that received 2 Gy dose was much high-er than in cells that received 1 Gy dose.Furthermore, heavy ion radiation promoted the apoptosis of T lymphocytes signifi-cantly.The results of RT-PCR showed that the mRNA expression of Bcl-2 was down-regulated in heavy ion radiation T lym-phocytes while the expression of Bax and Caspase 3 was up-regulated.Conclusion Heavy ion radiation can inhibit the pro-liferation and promote the apoptosis of human peripheral blood derived T lymphocytes .

Platelet-activation factor (PAF), one of the potent proinflammatory mediators, is produced from a large range of cells, including polymorphonuclear neutrophils, monocytes, and natural killer cells. To study the role of PAF in the pathogenesis of silicosis, we determined the PAF in silicotic patients and in healthy persons. The results showed that the concentration of PAF in the plasma of silicotic patients was significantly higher than that of healthy persons. Our in vitro experimental results showed that the total numbers of fibroblasts were markedly raised with added PAF from 0 to 1 μ g/ml. Adding 1 μ g/ml PAF significantly increased the total numbers of fibroblasts after culture for 48, 72, 96 hrs. Therefore, we suggest that PAF be possibly involved in the pathogenesis of silicosis. However, the mechanism remains to be further elucidated.
Platelet Activating Factor ; g <3> ; Pathogenesis ; /mL ; Effective

Objective:This study aimed to explore the status of radiological Kashin-Beck disease (KBD) among school-aged children in Chamdo City, Tibet, through a 3-year monitoring survey, providing epidemiological evidence for prevention and control strategies.Methods:The target areas for this study were Luolong, Bianba, and Basu counties in Chamdo City, Tibet Autonomous Region, identified as having the most severe historical cases of KBD. Children aged 7-12 years attending school were enrolled as study subjects. Anteroposterior X-ray films of the right-hand were taken, and radiological diagnoses were made based on the "Diagnosis of Kashin-Beck Disease" criteria (WS/T 207-2010). Two experienced researchers independently reviewed the X-rays, and intra- and inter-group consistency were assessed using weighted Kappa values and percentage agreement. Cross-sectional surveys were conducted in 2017 and 2020 to describe the X-ray detection rates of KBD, and logistic regression analysis was employed to construct a predictive model of risk factors for radiological KBD cases.Results:In 2017, a total of 5,711 children aged 7-12 years in Chamdo City, Tibet, participated in the baseline cross-sectional survey (average age 9.2 years, 48.0% female), with 28 cases of radiological KBD. The age- and gender-standardized prevalence rate was 0.527%. In 2020, 6,771 participants (average age 9.3 years, 49.5% female) underwent a second cross-sectional survey, with 9 cases of radiological KBD and a standardized prevalence rate of 0.134%. Logistic regression analysis indicated that older age [ OR=2.439, 95% CI(1.299, 4.580), P=0.006] and female gender [ OR=8.157, 95% CI(1.016, 65.528), P=0.048] were independent risk factors for radiological KBD cases. Conversely, higher residential altitude, under the premise of Tibet's high altitude, was a protective factor [ OR=0.995, 95% CI(0.990, 0.999), P=0.032). Conclusion:The radiographically positive detection rate of KBD among school-aged children in Chamdo City, Tibet Autonomous Region, is at an extremely low level and showing a declining trend, reaching the historical standard in 2020. Considering the absence of positive signs in affected children, it suggests that local KBD has been effectively eliminated.

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.