1.Research progress in the route of administration and corresponding dosage form of triamcinolone acetonide
Tianjiao SHAO ; Lili JIN ; Shan WANG ; Bohua YAN ; Xinming HU ; Jing GAO
China Pharmacy 2024;35(7):896-900
As a glucocorticoid drug with wide clinical application, triamcinolone acetonide can be administered by multiple routes, such as eye, nose, joint cavity, and skin, for the treatment of various local diseases such as arthritis, macular edema, rhinitis, and urticaria. As a drug with extremely low solubility in water, the dose form of triamcinolone acetonide is closely correlated with administration route and site. The dosage form of triamcinolone acetonide administered via injection(including joint cavity injection, vitreous injection, suprachoroidal injection, intramuscular injection) is mainly suspension, and the representative drugs include Kenalog-40®, Zilretta®, Triesence®, Xipere®, etc.; the dosage forms of nasal mucosal administration are mostly sprays, and the representative drug is Nasacort®; the dosage forms of oral mucosal administration are mostly patches, ointments and creams, and the representative drug is Oracort®; the dosage forms for transdermal administration are mostly ointments, creams and lotions, and the representative drugs include Trianex®, Teva-Triacomb®, etc. At present, the research on dosage forms of triamcinolone acetonide by various administration routes mainly focuses on the construction of delivery carriers, the addition of cosolvents or the use of new delivery tools.
2.Isolation of feline panleukopenia virus from Yanji of China and molecular epidemiology from 2021 to 2022
Haowen XUE ; Chunyi HU ; Haoyuan MA ; Yanhao SONG ; Kunru ZHU ; Jingfeng FU ; Biying MU ; Xu GAO
Journal of Veterinary Science 2023;24(2):e29-
Background:
Feline panleukopenia virus (FPV) is a widespread and highly infectious pathogen in cats with a high mortality rate. Although Yanji has a developed cat breeding industry, the variation of FPV locally is still unclear.
Objectives:
This study aimed to isolate and investigate the epidemiology of FPV in Yanji between 2021 and 2022.
Methods:
A strain of FPV was isolated from F81 cells. Cats suspected of FPV infection (n = 80) between 2021 and 2022 from Yanji were enrolled in this study. The capsid protein 2 (VP2) of FPV was amplified. It was cloned into the pMD-19T vector and transformed into a competent Escherichia coli strain. The positive colonies were analyzed via VP2 Sanger sequencing. A phylogenetic analysis based on a VP2 coding sequence was performed to identify the genetic relationships between the strains.
Results:
An FPV strain named YBYJ-1 was successfully isolated. The virus diameter was approximately 20–24 nm, 50% tissue culture infectious dose = 1 × 10 −4.94 /mL, which caused cytopathic effect in F81 cells. The epidemiological survey from 2021 to 2022 showed that 27 of the 80 samples were FPV-positive. Additionally, three strains positive for CPV-2c were unexpectedly found. Phylogenetic analysis showed that most of the 27 FPV strains belonged to the same group, and no mutations were found in the critical amino acids.
Conclusions
A local FPV strain named YBYJ-1 was successfully isolated. There was no critical mutation in FPV in Yanji, but some cases with CPV-2c infected cats were identified.
3.Versatile flexible micelles integrating mucosal penetration and intestinal targeting for effectively oral delivery of paclitaxel.
Chao LIU ; Wei LIU ; Yanhong LIU ; Hongxia DUAN ; Liqing CHEN ; Xintong ZHANG ; Mingji JIN ; Minhu CUI ; Xiuquan QUAN ; Libin PAN ; Jiachun HU ; Zhonggao GAO ; Yan WANG ; Wei HUANG
Acta Pharmaceutica Sinica B 2023;13(8):3425-3443
The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.
4.Research advances in peptide‒drug conjugates.
Liming GONG ; Heming ZHAO ; Yanhong LIU ; Hao WU ; Chao LIU ; Shuangyan CHANG ; Liqing CHEN ; Mingji JIN ; Qiming WANG ; Zhonggao GAO ; Wei HUANG
Acta Pharmaceutica Sinica B 2023;13(9):3659-3677
Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, linkers and drugs used to construct PDCs, and summarize the clinical applications and challenges of PDC drugs.
5.Preliminary establishment and evaluation of a model for early diagnosis of acute aortic dissection
Ziya XIAO ; Xinyan WANG ; Yong LI ; Yanji GUO ; Lei GAO ; Jiaxing GENG ; Xiangfei LI ; Zhihong LI
Clinical Medicine of China 2022;38(6):533-540
Objective:An early diagnosis model of acute aortic dissection (AAD) was established based on chest pain center database.Methods:The clinical data of patients who attended Chest Pain Center of Department of Emergency in Affiliated Hospital of Jining Medical University of Shandong Province from January 2020 to December 2020 were retrospectively collected. Patients were divided into AAD and non-AAD groups according to whether or not AAD was diagnosed. The clinical related indicators of the two groups were compared. The research indicators with statistical differences between the two groups were included in multivariate Logistic regression analysis, and the early diagnosis of AAD nomogram model was established. The receiver operating characteristic (ROC) curve of the model was used to evaluate the prediction accuracy, and the Homser-Lemeshow statistics were used to test the goodness of fit for the model. A total of 630 patients with chest pain who visited the hospital from January 2021 to March 2021 were also collected for external validation of the model. The t-test of independent samples was used to compare the measurement data of normal distribution, nonparametric test was used to compare the measurement data of skewness distribution, and χ 2 test was used to compare the counting data between groups. Results:A total of 2 738 patients were included, of which 4.09% (112/2 738) were AAD patients. Univariate analysis showed that in AAD group, male morbidity (74.11%(83/112)), hypertension history (70.54%(79/112)), aortic disease history (10.71%(12/112)), family history of aortic disease (4.46%(5/112)), sudden onset of symptoms (76.79%(86/112)), percentage of patients with laceration pain (38.39%(43/112)), patients with back pain (66.07%(74/112)), patients with abdominal pain (16.96%(19/112)), systolic blood pressure ((159.44±30.94) mmHg), bilateral blood pressure/pulse asymmetry (23.21% (26/112)), incidence of complicated neurological signs (7.14%(8/112)) and D-dimer (3.57(2.10, 6.62) mg/L) were significantly higher than those in non-AAD group (59.56%(1 564/2 626), 46.23%(1 214/2 626), 0.23%(6/2 626), 0.08%(2/2 626), 35.99%(945/2 626), 0.08%(2/2 626), 3.08%(81/2 626), 3.81%(100/2 626), (142.46±27.90) mmHg, 0.15%(4/2 626), 0.27%(7/2 626), 0.31(0.20, 0.50) mg/L). Age ((57.95±14.35) years old) and CK-MB (1.50(0.90, 3.25) μg/L) were significantly lower than those in the non-AAD group ((61.94±15.77) years, 2.50(1.24, 4.81) μg/L). The differences were statistically significant (the statistical values were χ 2=9.47, χ 2=25.46, χ 2=180.80, χ 2=81.11, χ 2=76.17, χ 2=975.60, χ 2=798.00, χ 2=44.72, t=6.28, χ 2=527.20, χ 2=93.22, Z=14.09, t=2.61, and Z=3.51, respectively; P values were 0.002, <0.001, <0.001, <0.001, <0.001, <0.001, <0.001, <0.001, <0.001, <0.001, <0.001, <0.001, 0.009, and <0.001, respectively). Multivariate analysis showed that history of hypertension ( OR=3.088, 95% CI:1.294-7.374), history of aortic disease ( OR=20.771, 95% CI:2.132-202.361), family history of aortic disease ( OR=266.425, 95% CI:17.610-4 030.851), sudden onset of symptoms ( OR=3.538, 95% CI:1.643-7.619), laceration pain ( OR=1 771.971, 95% CI:204.048-15 387.935), back pain ( OR=61.550,95% CI:27.987-135.367), abdominal pain ( OR=12.325, 95% CI:4.201-36.161), systolic blood pressure ( OR=1.026, 95% CI:1.013-1.039), bilateral blood pressure/pulse asymmetry ( OR=338.357, 95% CI:60.704-1 885.949) and D-dimer ( OR=1.241, 95% CI:1.176-1.309) were independent factors for the diagnosis of AAD in patients with chest pain (P values were 0.011, 0.009, <0.001, 0.001, <0.001, <0.001, <0.001, <0.001, <0.001, and <0.001, respectively). Furthermore, the nomogram model was constructed. ROC curve analysis showed that the area under the curve was 0.976 ( P<0.01), the specificity was 94.52%, and the sensitivity was 91.96%. The statistics of Homser-lemeshow was used to test the goodness of fit, which shows that the model can be fitted well (χ 2=2.928, P=0.939). The prediction model was verified by external validation data, and the area under the ROC curve was 0.934 ( P<0.01), indicating that the model had good prediction performance. Conclusions:History of hypertension, history of aortic disease, family history of aortic disease, sudden onset of symptoms, laceration pain, back pain, abdominal pain, systolic blood pressure, bilateral blood pressure/pulse asymmetry and D-dimer were independent factors for the diagnosis of AAD in patients with acute chest pain. The AAD early diagnosis nomogram model based on the above factors has good predictive performance.
6.Arterial switch operation: A double cohort study of 20 years’ outcomes of 571 patients in a single center
QU Yanji ; LUO Dandong ; LIU Xiaoqing ; WEN Shusheng ; NIE Zhiqiang ; PANG Chengcheng ; CEN Jianzheng ; XU Gang ; MAI Jinzhuang ; OU Yanqiu ; GAO Xiangmin ; WU Yong ; CHEN Jimei ; ZHUANG Jian
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(02):133-141
Objective To define the patient characteristics and perioperative management, and to define the mortality and its risk factors after arterial switch operation (ASO). Methods We conducted a bidirectional cohort study with 571 consecutive patients undergoing ASO from 1997 to 2016 in our hospital. We enrolled patients who underwent ASO before 2012 retrospectively and after 2012 prospectively and followed up all the patients prospectively. Demographic characteristics, clinical information and mortality of these patients were summarized. Joinpoint regression analysis was used to identify the time trend of the overall mortality. Kaplan-Meier survival analysis was used to evaluate the mid- and long-term survival rate after ASO. Cox proportional hazards regression models were used to explore the potential factors associated with mortality. The cumulative incidence of complications after ASO was predicted using competing risk models. Results Several aspects of patients’ characteristics and perioperative management in our center differed from those in the developed countries. The overall mortality and in-hospital mortality after ASO was 16.3% and 15.1%, respectively. The overall cumulative survival rate at 5, 10 and 15 years after ASO was 83.3%, 82.8% and 82.8%, respectively. A significant decrease of overall mortality from 1997 to 2016 was observed. Independent risk factors of mortality included earlier ASO (1997-2006), single or intramural coronary anatomy and longer cardiopulmonary bypass time. Ten years after ASO, re-intervention, arrhythmia, pulmonary and anastomotic stenosis were the most common complications with a cumulative incidence over 10%. Conclusion Significant improvements in the results of the ASO were observed and the postoperative mortality rate is close to reports from developed countries. Nonetheless, we have identified the need for further improvement in the early and late postoperative periods after ASO. Pulmonary stenosis, anastomotic stenosis and arrhythmia should be paid attention to during the long-term follow-up after ASO.
7.IL-10 promotes ocular neovascularization by regulating macrophages
Ailing SUI ; Ting SU ; Yushuo GAO ; Yanji ZHU ; Bing XIE
Journal of Shanghai Jiaotong University(Medical Science) 2017;37(3):278-287
Objective · To investigate the role of interleukin-10 (IL-10) in regulating ocular neovascularization (NV). Methods · Expression of IL-10 was investigated in mice with oxygen-induced retinopathy (OIR) and transgenic mice with VEGF expression in photoreceptors by immunofluorescence,RT-PCR, and Western blotting. Mice deficient in IL-10 were used to test the effect of IL-10 in retinal, sub-retinal, and choroidal NV. Results · In OIR mice and transgenic mice with VEGF expression in photoreceptors, the staining intensity and mRNA expression of IL-10 were increased. Mice deficient in IL-10 showed a significant reduction in ischemia-induced retinal NV, and choroidal NV at rupture sites in Bruch's membrane. Mice lacking IL-10 showed reduced levels of hypoxia-inducible factor-1α (HIF-1α) and suppression of ischemia-induced expression of VEGF and VEGF receptor 1. Macrophage was regulated and reduced in ischemic retina of mice with IL-10 deficiency. Conclusion · IL-10 stimulates ocular NV through modulation of HIF-1α and its target genes VEGF and VEGF receptor 1. IL-10 promotes ocular NV via macrophage response to retina ischemia.
8.Comparison between Two Surgical Techniques to Repair Total Anomalous Pulmonary Venous Connection Using propensity Scoreanalysis
Xiangmin GAO ; Zhiqiang NIE ; Yanqiu OU ; Biaochuan HE ; Haiyun YUAN ; Yanji QU ; Xiaoqing LIU
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(1):143-150
[Objective]To evaluate the effects of sutureless technique in comparison to conventional techniques for repair of total anomalous pulmonary venous connection(TAPVC)with the method of propensity score analysis.[Methods]From October 2007 to December 2013,179 consecutive patients were enrolled in this study. Patients were operated with sutureless technique(n = 81)or Conventional technique(n=98),and followed up at an interval of 1 month,3 months,6 months and then once a year post-operation. During analysis,three type of propensity-score matching methods,including nearest neighbor caliper matching,Mahalanobis metric matching with propensity score ,optimal full matching were used to create balanced groups of patients receiving each treatment. Surgeons’performance difference was assessed with random frailty proportional hazards models with gamma. Composite endpoints was defined by postoperative death or late death or postoperative pulmonary venous obstruction(PVO),which was evaluated with Kaplan-Meier curve and multivariable Cox proportional hazard model,adjusted by Preoperative-PVO,age,gender,weight and TAPVC type.[Results]Nearest neighbor caliper matching method was the best choice during propensity score analysis. After matching ,sutureless group included 73 patients and Conventional group73 patients. In sutureless group,cardiopulmonary bypass(CPB)time(Z=2.18, P=0.030),cross-clamp time(Z=3.63,P<0.001),rate of composite endpoints(HR 95%CI=0.20(0.06~0.61),P=0.005),late death(HR 95%CI=0.03(0.01~0.55),P=0.017)were significantly better than that in Conventional group. In subgroup analysis ,for patients with pre-PVO,decreased composite endpoints was seen in sutureless group.[Conclusion]Comparison using thepropensity score analysis demonstrated that sutureless strategy for primary repair of TAPVC may associate with decreased mortality rate of post-PVO and CPB time and cross-clamp time.
9.Early-and intermediate-term results of surgical correction in 328 patients with different drainage type of total anoma-lous pulmonary venous connection
Yanqiu OU ; Zhiqiang NIE ; Jian ZHUANG ; Jimei CHEN ; Xiangmin GAO ; Yong WU ; Yanji QU ; Jinzhuang MAI ; Xiaohua LI ; Xiaoqing LIU ; Jianzheng CEN
Chinese Journal of Thoracic and Cardiovascular Surgery 2017;33(1):10-15
Objective This retrospective cohort study aims to evaluate and compare the prognosis of surgical repair for total anomalous pulmonary venous connection(TAPVC) with different drainage type.Methods From January 2006 to Decem-ber 2013, 328 consecutive patients were enrolled in this study .The distribution of the defects was 109 cases with cardiac, 161 with supracardiac, 32 with infracardiac, and 26 with mixed type of the drainage into the systemic circulation .The clinical re-cords of all the patients were reviewed.Studied variables were extracted from the clinical records.Followed-up was conducted at an interval of 1 month, 3 months, 6 months and then once a year post-operation.Prevalence of peri-operative conditions were compared among four different types.Studied endpoints was defined by postoperative total death or pulmonary venous obstruc-tion(PVO), which was evaluated with Kaplan-Meier curve and multivariable Cox proportional hazard model, adjusted by differ-ent surgical strategy, emergency operation, preoperative-PVO, neonates, weight, combing with other complex cardiac defects,NYHA cardiac function, severe pulmonary hypertension and severe tricuspid regurgitation.Results There were significant discrepancyof preoperative conditions among four types of TAPVC.Patients with infracardiac TAPVC presented the most criticalsymptoms and clinical indexes, which included having largest proportion of neonates, preoperative PVO, severe NYHA grading,pulmonary hypertension and tricuspid regurgitation, having lowest body weight at operation and youngest age.The cardiopulmonarybypass time, aortic crossclamp time and mechanical ventilation time were significantly longer in infracadiac and mixedTAPVC comparing to the other two types.For early mortality(death in hospital), infracadiac(9.4%) and mixed(11.5%)TAPVC demonstrated higher rates of death than cardiac(4.6%) and supracardiac(7.5%)TAPVC, although had no statisticalsignificance.For intermediate-term results, mortality in infracadiac(21.9%) and mixed(30.8%) TAPVC were significantlyhigher than cardiac ( 8.3%) and supracardiac (11.8%) TAPVC.Reoperation was more frequently required in mixed(19.2%), then infracadiac(15.6%)TAPVC.Mixed and infracadiac types are independent risk factors for TAPVC prognosis,after adjusting by the confounding factors.Conclusion Mixed and infracadiac types are independent risk factors for postoperativedeath and PVO among TAPVC patients.This study provided evidence for clinical assessment and management strategy fordifferent types of TAPVC.
10. Feasibility of single-staged Han-uvulopalatopharyngoplasty with septoplasty in adults with obstructive sleep apnea-hypopnea syndrome
Shiguo XIU ; Dandan YU ; Yimeng WANG ; Shidan GAO
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2017;52(8):592-596
Objective:
To explore the feasibility and therapeutic effect of single-staged Han-uvulopalatopharyngoplasty with septoplasty in adults with obstructive sleep apnea-hypopnea syndrome.
Methods:
Ninety six cases with OSAHS were diagnosed by polysomnography, and they all had retropalatal obstruction and deviation of nasal septum. Patients were divided into study group(48 cases) and control group(48 cases) randomly. Cases in study group were simultaneously treated with Han-uvulopalatopharyngoplasty and septoplasty, while cases in control group were only treated with Han-uvulopalatopharyngoplasty. U saturation skill and coblation-assisted were applied in Han-uvulopalatopharyngoplasty. And nasal septum suture technique was applied in septoplasty. The observation index included the intranasal changes with acoustic rhinometry, the prevalence of common postoperation complications and curative effects after six months follow-up period. SPSS 18.0 was used for statistical analysis.
Results:
In study group the overall response rate was 83.33%(40/48), while in control group the overall response rate was 62.50%(30/48). There was statistical significance of response rate between test group and control group(χ2=5.275,

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