1.Key techniques for granulation and flavor masking of innovative Chinese medicinal preparations for children: a review.
Chen-Hui WU ; Yan-Jun YANG ; Mao-Mao ZHU ; Bing YANG ; Jun LIU ; Jing ZHAO ; Xiao-Bin JIA ; Liang FENG
China Journal of Chinese Materia Medica 2022;47(21):5708-5716
There are many kinds of pharmaceutical preparations for children in China, which are generally divided into oral solid preparations and oral liquid preparations. Solid preparations, such as microtablets, pellets, dispersible tablets, and fine granules, have become the development trend of pediatric drugs. Liquid preparations mainly include syrup, suspension, oral solution, and drops. The poor taste and the treatment of drugs in children of different ages are the key factors affecting the efficacy, safety, and compliance of pediatric drugs. To reduce the risk caused by the fluctuation of blood concentration and improve the oral compliance of pediatric drugs, it is urgent to develop new techniques for granulation and flavor maskingto improve the poor taste of solid preparations. For liquid pre-parations with poor taste, the flavor correction technique should be used. This paper summarized the new pharmaceutical techniques for granulation and flavor masking, and it was found that sustained/controlled-releasegranules, fine granules, and chewing solid mini-tablets became the mainstream of oral solid preparations for children. Generally, multiparticle preparation, coating, microencapsulation, and other granulating techniques were involved in these preparations. Granulation and flavor masking are closely related and synergetic. Flavor masking techniques mask the bitter taste of Chinese medicine from four aspects, including confusing the brain taste, changing the compounds, reducing the exposure of bitter molecules to bitter receptors in the mouth, and numbing the taste cells to increase the threshold of bitter perception. At present, the main drugs for children on the market mainly inhibit the oral release of bitter drugs.
Child
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Humans
;
Chemistry, Pharmaceutical/methods*
;
Administration, Oral
;
Tablets
;
Taste
;
China
2.Pharmacodynamic substances and mechanism of action of Xiaoer Chiqiao Qingre Granules in treatment of acute upper respiratory tract infection in children.
Guan-Zheng LU ; Yan-Jun YANG ; Mao-Mao ZHU ; Jun LIU ; Jing ZHAO ; Xiao-Bin JIA ; Xiang-Jun ZHU ; Liang FENG
China Journal of Chinese Materia Medica 2022;47(21):5717-5734
This study aimed to forecast the main active components of Xiaoer Chiqiao Qingre Granules(XECQ) in the treatment of children with acute upper respiratory tract infection by UPLC-MS, network pharmacology, molecular docking and cell biology, and explore the mechanism of action, so as to provide certain reference for the research on its pharmacodynamics substances and mechanism of action. The main chemical components of XECQ were comprehensively analyzed by UPLC-Q-TOF-MS combined with UNIFI platform. According to the MS1 and MS2 data of XECQ, comparison and identification were carried out in combination with reference substances and reference articles. On this basis, the chemical components of XECQ were targeted and enriched by network pharmacology, to screen the main pharmacodynamic substances of XECQ in the treatment of acute upper respiratory tract infection in children and discuss the mechanism of action. In addition, the binding degree of core targets and main active components was verified by molecular docking. The results revealed that 202 compounds were identified from XECQ, among which 22 were the main active components, including obovatol, dihydroartemisinin, and longikaurin A. Enrichment analysis of the key target pathways showed that XECQ played its role in the treatment of children with acute upper respiratory tract infection mainly by regulating PI3K/Akt signaling pathway and MAPK signaling pathway. In the experimental verification by Western Blot(WB), it was found that XECQ significantly inhibited the expression of PI3K and Akt, which was consistent with the prediction results of network pharmacology. In conclusion, the potential pharmacodynamic substances of XECQ were obovatol, dihydroartemisinin, longikaurin A and other 19 active components. It treated children with acute upper respiratory tract infection by regulating the PI3K/Akt signaling pathway.
Child
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Humans
;
Chromatography, Liquid
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Molecular Docking Simulation
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Phosphatidylinositol 3-Kinases/genetics*
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Proto-Oncogene Proteins c-akt
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Tandem Mass Spectrometry
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Respiratory Tract Infections/drug therapy*
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Artemisinins
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Drugs, Chinese Herbal/pharmacology*
3.Digestive properties of flavonoid components in Xiaoer Chiqiao Qingre Granules in simulated infant gastrointestinal environment.
Bin-Bin ZHOU ; Yan-Jun YANG ; Mao-Mao ZHU ; Bing YANG ; Wei-Kun MA ; Xiang-Jun ZHU ; Jun LIU ; Jing ZHAO ; Liang FENG ; Xiao-Bin JIA
China Journal of Chinese Materia Medica 2022;47(21):5735-5745
This study aimed to elucidate the digestive characteristics of flavonoid components in Xiaoer Chiqiao Qingre Granules(XECQ) in the gastrointestinal environment of infants. An in vitro model was established to simulate the gastric and intestinal environment of infants. UPLC was used to analyze the content change of flavonoid components in XECQ, and their overall content was integrated through the mass fraction weight coefficient method. UPLC-Q-TOF-MS was employed to determine the digestive products of flavonoid components in gastrointestinal fluids and their metabolic pathways. The results showed that in the process of digestion, 11 digestion products were generated by oxidation, reduction, deglycosylation, methylation and other phase Ⅰ metabolism. From flavonoid content and component changes, it was found that the flavonoid components in XECQ were relatively stable in the gastric fluid, while their content in the intestinal fluid was first increased and then maintained stable. This was mainly because flavonoid components were released from proteins, polysaccharides and other macromolecular substances during gastrointestinal digestion. In addition, phase Ⅰ metabolism occurred, but with relatively low metabolic rate, resulting in their stable content. This study preliminarily explored the digestive characteristics of flavonoid components in XECQ in the infant gastrointestinal environment, which laid a foundation for further studying the absorption, transport and metabolism of pharmacodynamics components in XECQ, and facilitated the study of the biopharmaceutical pro-perties of pediatric Chinese medicine.
Infant
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Humans
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Child
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Flavonoids/metabolism*
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Gastrointestinal Tract
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Intestines
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Drugs, Chinese Herbal/metabolism*
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Chromatography, High Pressure Liquid
4.Optimization and evaluation of Xiaoer Pudilan Xiaoyan Syrup based on characterization of material properties.
Xuan LI ; Ke DING ; Dang YANG ; Meng-Hua JIANG ; Chao LI ; Fa-Gen ZHU ; Jian-Guo SHAO ; E SUN ; Liang FENG ; Xiao-Bin JIA
China Journal of Chinese Materia Medica 2022;47(21):5746-5756
According to the taste analysis of Pudilan Xiaoyan Oral Liquid, the unpleasant taste of the oral liquid is mainly caused by the inherent taste of Chinese medicine and the taste introduced in the preparation process, which leads to its unpopularity among children. Therefore, aiming at the special children patient group, Xiaoer Pudilan Xiaoyan Syrup was developed via technology optimization and dosage form improvement to improve the unpleasant taste and enhance the medication compliance among children. Based on the material properties of Pudilan Xiaoyan Oral Liquid and Xiaoer Pudilan Xiaoyan Syrup extracts, the authors compared the properties(pH, density, turbidity, viscosity, chromaticity, particle size), taste, content of five quality markers and in vivo pharmacokinetic characteristics of these two preparations, to evaluate the suitability of Xiaoer Pudilan Xiaoyan Syrup. The results showed that compared with those of Pudilan Xiaoyan Oral Liquid, the pH, density, turbidity, viscosity and chromaticity of Xiaoer Pudilan Xiaoyan Syrup were significantly changed, and the unpleasant taste was reduced by 26%; the transfer rate of the main active ingredients chicoric acid was increased, while the transfer rate of baicalin had small difference from that of the oral liquid. In addition, pharmacokinetics revealed that the total absorption amount of baicalin in vivo was higher, and the time to peak T_(max) of baicalin and oroxindin in the syrup and the mean residence time MRT_(last )of corynoline in vivo were significantly prolonged. The absorption degree of Xiaoer Pudilan Xiaoyan Syrup and Pudilan Xiaoyan Oral Liquid in the body was the same: baicalin>oroxindin>corynoline. The new dosage form process was simpler than that of the original dosage form, safe, environmentally friendly, reasonable and feasible, meeting the mass production demand. This provided a basis for the reasonable and scientific optimization of Xiaoer Pudilan Xiaoyan Syrup, and also laid a foundation for its further safe and rational use, so as to expand the clinical application in children.
Child
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Humans
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Drugs, Chinese Herbal
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Glucuronates
5.Phenylethanoid glycosides in Xiaoer Chiqiao Qingre Granules and its metabolic transformation in vitro and in vivo.
Ling WEN ; Mao-Mao ZHU ; Yan-Jun YANG ; Xiang-Jun ZHU ; Jun LIU ; Jing ZHAO ; Liang FENG ; Xiao-Bin JIA
China Journal of Chinese Materia Medica 2022;47(21):5775-5788
To clarify the metabolic transformation mechanism of phenylethanoid glycosides in Xiaoer Chiqiao Qingre Granules in vivo, this study extracted and separated the phenylethanoid glycosides in Xiaoer Chiqiao Qingre Granules. Based on UPLC-Q-TOF-MS/MS technology, the retention time and primary and secondary mass spectrometry information were analyzed by UNIFI software, and 11 phenylethanoid glycosides in Xiaoer Chiqiao Qingre Granules were preliminarily identified. Sixty-nine metabolites related to phenylethanoid glycosides were identified from the plasma samples of juvenile rats after administration of Xiaoer Chiqiao Qingre Granules. In addition, this study simulated the transformation system of intestinal flora in children, and discussed the metabolic effects of intestinal flora on the representative components forsythoside A, forsythoside E, and salidroside of phenylethanoid glycosides. The model of gastrointestinal heat retention in children with food accumulation was established to study the differential metabolites of phenylethanoid glycosides. Through the comparative analysis of the representative components absorbed in blood and the intestinal floral transformation products, it was found that the main metabolic pathways of phenylethanoid glycosides were dehydrogenation, oxidation, acetylation, sulfation, and glucuronidation. The findings of this study revealed the transformation law of phenylethanoid glycosides in the gastrointestinal tract. Through the preliminary discussion of the pharmacological mechanism, this study provides references for further clarifying the pharmacodynamic material basis of Xiaoer Chiqiao Qingre Granules and exploring the pediatric Chinese medicine compound.
Rats
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Animals
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Tandem Mass Spectrometry/methods*
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Chromatography, High Pressure Liquid/methods*
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Glycosides/analysis*
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Drugs, Chinese Herbal/chemistry*
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Gastrointestinal Microbiome
6.Association between metabolic risk factors and the hepatitis B reactivation of inactive HBsAg carriers in Jiangsu province: a cohort study.
Jian Fang XU ; Jie JIANG ; Li YANG ; Jiao QIAN ; Han WANG ; Hai Ming CHEN ; Hong Jian LIU ; Ci SONG ; Xin XU ; Feng Cai ZHU ; Li Guo ZHU ; Xiang Jun ZHAI
Chinese Journal of Epidemiology 2022;43(8):1301-1308
Objective: To analyze the impact of metabolic risk factors on the epidemiological characteristics of the reactivation of inactive HBsAg carriers (IHC) and provide effective intervention measures to standardize the management of chronic hepatitis B infections. Methods: Based on the chronic hepatitis B infection cohort established in 2010 in Jiangsu province, six follow-up visits from 2012 to 2020 were conducted to analyze the characteristics and influencing factors of the hepatitis B reactivation of IHC and the impact of metabolic risk factors, including obesity, high blood pressure, diabetes and hyperglycemia. Results: From 2012 to 2020, 2 527 IHC and 17 730 person-years were observed during a median follow-up period of 7.0 person-years. Ninety-eight cases of hepatitis B reactivation, with a cumulative reaction rate, was 3.9%, and the incidence density was 5.53/1 000 person-years. Multivariate Cox proportional risk regression analysis showed that age and baseline HBV DNA were independent risk factors of HBV reactivation. Compared with the patients ≥60 years, 40-49 age group (aHR=2.16, 95%CI:1.20-3.90) and 20-29 age group (aHR=5.48, 95%CI:2.07-14.48) were significantly associated with hepatitis B reactivation. Compared with the HBV DNA negative patients at baseline, the risk of hepatitis B reactivation was higher in the group with low HBV DNA level 100-1 999 IU/ml (aHR=1.67, 95%CI:1.11-2.52). Stratification analysis results showed that compared with those without metabolic risk factors, in the ≥50 age group, patients with ≥2 metabolic risk factors showed adjusted HR of 2.73 (95%CI:1.08-6.96). Conclusions: The risk of hepatitis B being reactive is the persistent existence of IHC in communities in Jiangsu province, especially young adults, low-level HBV DNA carriers, and IHC with ≥2 metabolic risk factors. Follow-up for these IHC should be strengthened to reduce the risk of disease progression by antiviral treatment at the right time.
Cohort Studies
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DNA, Viral
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Hepatitis B/epidemiology*
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Hepatitis B Surface Antigens
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Hepatitis B virus/genetics*
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Hepatitis B, Chronic/epidemiology*
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Humans
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Risk Factors
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Young Adult
7.Status of diagnosis and management of acute appendicitis in 2017: a national multi-center retrospective study.
Jie WU ; Xinjian XU ; Hao XU ; Gang MA ; Chi MA ; Xiaocheng ZHU ; Zeqiang REN ; Xudong WU ; Xudong WU ; Yingjie CHEN ; Yanhong WENG ; Liping HU ; Fei CHEN ; Yonggan JIANG ; Hongbin LIU ; Ming WANG ; Zhenhua YANG ; Xiong YU ; Liang LI ; Xinzeng ZHANG ; Zhigang YAO ; Wei LI ; Jianjun MIAO ; Liguang YANG ; Hui CAO ; Fan CHEN ; Jianjun WU ; Shichen WANG ; Dongzhu ZENG ; Jun ZHANG ; Yongqing HE ; Jianliang CAO ; Wenxing ZHOU ; Zhilong JIANG ; Dongming ZHANG ; Jianwei ZHU ; Wenming YUE ; Yongxi ZHANG ; Junling HOU ; Fei ZHONG ; Junwei WANG ; Chang CAI ; Hongyan LI ; Weishun LIAO ; Haiyang ZHANG ; Getu ZHAORI ; Qinjie LIU ; Zhiwei WANG ; Canwen CHEN ; Jianan REN
Chinese Journal of Gastrointestinal Surgery 2019;22(1):49-58
OBJECTIVE:
To analyze the current status of diagnosis and management of acute appendicitis (AA) in China.
METHODS:
Questionnaire survey was used to retrospectively collect data of hospitalized patients with AA from 43 medical centers nationwide in 2017 (Sort by number of cases provided: Jinling Hospital of Medical School of Nanjing University, The First Affiliated Hospital of Xinjiang Medical University, Lu'an People's Hospital, Tengzhou Central People's Hospital, Dalian Central Hospital, The Affiliated Hospital of Xuzhou Medical University, Dongying People's Hospital, Jinjiang Hospital of Traditional Chinese Medicine, Huangshan Shoukang Hospital, Xuyi People's Hospital, Nanjing Jiangbei People's Hospital, Lanzhou 940th Hospital of PLA, Heze Municipal Hospital, The First College of Clinical Medical Science of China Three Gorges University, Affiliated Jiujiang Hospital of Nanchang University, The Second People's Hospital of Hefei, Affiliated Central Hospital of Shandong Zaozhuang Mining Group, The Third People's Hospital of Kunshan City, Xuzhou First People's Hospital, The 81st Group Army Hospital of PLA, Linyi Central Hospital, The General Hospital of Huainan Eastern Hospital Group, The 908th Hospital of PLA, Liyang People's Hospital, The 901th Hospital of Joint Logistic Support Force, The Third Affiliated Hospital of Chongqing Medical University, The Fourth Hospital of Jilin University, Harbin Acheng District People's Hospital, The First Affiliated Hospital of Zhengzhou University, Nanjing Luhe People's Hospital, Taixing Municipal People's Hospital, Baotou Central Hospital, The Affiliated Hospital of Nantong University, Linyi People's Hospital, The 72st Group Army Hospital of PLA, Zaozhuang Municipal Hospital, People's Hospital of Dayu County, Taixing City Hospital of Traditional Chinese Medicine, Suzhou Municipal Hospital, Beijing Guang'anmen Hospital, Langxi County Hospital of Traditional Chinese Medicine, Nanyang Central Hospital, The Affiliated People's Hospital of Inner Mongolia Medical University).The diagnosis and management of AA were analyzed through unified summary. Different centers collected and summarized their data in 2017 and sent back the questionnaires for summary.
RESULTS:
A total of 8 766 AA patients were enrolled from 43 medical centers, including 4 711 males (53.7%) with median age of 39 years and 958 (10.9%) patients over 65 years old. Of 8 776 patients, 5 677 cases (64.6%) received one or more imaging examinations, and the other 3 099 (35.4%) did not receive any imaging examination. A total of 1 858 (21.2%) cases received medical treatment, mainly a combination of nitroimidazoles (1 107 cases, 59.8%) doublet regimen, followed by a single-agent regimen of non-nitroimidazoles (451 cases, 24.4%), a nitroimidazole-free doublet regimen (134 cases, 7.2%), a triple regimen of combined nitroimidazoles (116 cases, 6.3%), nitroimidazole alone (39 cases, 2.1%) and nitroimidazole-free triple regimen (3 cases, 0.2%). Of the 6 908 patients (78.8%) who underwent surgery, 4 319 (62.5%) underwent laparoscopic appendectomy and 2589 (37.5%) underwent open surgery. Ratio of laparotomy was higher in those patients under 16 years old (392 cases) or over 65 years old (258 cases) [15.1%(392/2 589) and 10.0%(258/2 589), respectively, compared with 8.5%(367/4 316) and 8.0%(347/4 316) in the same age group for laparoscopic surgery, χ²=91.415, P<0.001; χ²=15.915,P<0.001]. Patients with complicated appendicitis had higher ratio of undergoing open surgery as compared to those undergoing laparoscopic surgery [26.7%(692/2 589) vs. 15.6%(672/4 316), χ²=125.726, P<0.001].The cure rates of laparoscopic and open surgery were 100.0% and 99.8%(2 585/2 589) respectively without significant difference (P=0.206). Postoperative complication rates were 4.5%(121/2 589) and 4.7%(196/4 316) respectively, and the difference was not statistically significant (χ²=0.065, P=0.799). The incidence of surgical site infection was lower (0.6% vs. 1.7%, χ²=17.315, P<0.001), and hospital stay was shorter [6(4-7) days vs. 6(5-8) days, U=4 384 348.0, P<0.001] in the laparoscopic surgery group, while hospitalization cost was higher (median 12 527 yuan vs. 9 342 yuan, U=2 586 809.0, P<0.001).
CONCLUSIONS
The diagnosis of acute appendicitis is still clinically based, supplemented by imaging examination. Appendectomy is still the most effective treatment at present. Laparoscopic appendectomy has become the main treatment strategy, but anti-infective drugs are also very effective.
Acute Disease
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Adolescent
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Adult
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Aged
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Anti-Bacterial Agents
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therapeutic use
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Appendectomy
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Appendicitis
;
diagnosis
;
therapy
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China
;
Female
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Health Care Surveys
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Humans
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Laparoscopy
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Male
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Middle Aged
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Retrospective Studies
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Treatment Outcome
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Young Adult
8.Copy number variants of ABCF1, IL17REL, and FCGR3A are associated with the risk of gout.
Zheng DONG ; Yuan LI ; Jingru ZHOU ; Shuai JIANG ; Yi WANG ; Yulin CHEN ; Dongbao ZHAO ; Chengde YANG ; Qiaoxia QIAN ; Yanyun MA ; Hongjun HE ; Hengdong JI ; Yajun YANG ; Xiaofeng WANG ; Xia XU ; Yafei PANG ; Hejian ZOU ; Li JIN ; Feng ZHANG ; Jiucun WANG
Protein & Cell 2017;8(6):467-470
9.A retrospective cohort comparison of esophageal carcinoma between thoracoscopic and laparoscopic esophagectomy and open esophagectomy.
Jun YANG ; Email: 496827756@QQ.COM. ; Bihong LYU ; Weidong ZHU ; Jianzhong CHEN ; Jianming HE ; Shaowen TANG
Chinese Journal of Surgery 2015;53(5):378-381
OBJECTIVETo study the efficacy and safety of thoracoscopic and laparoscopic esophagectomy for esophageal carcinoma.
METHODSBased on hospitalization data from March 2011 to March 2014, 62 cases of esophageal carcinoma treated with thoracoscopic and laparoscopic esophagectomy (minimally invasive group, with 45 male patients) and other 62 cases treated with open esophagectomy (open esophagectomy group, with 45 male patients) were analyzed in a retrospective cohort. The mean age of two groups were (62±9) years and (62±8) years, respectively. Quantitative data were analyzed using t-test, whereas qualitative variables were tested with χ2 test. There were no significant difference in age, tumor location, pathological type, tumor staging between two groups (P>0.05). Perioperative data and three-year clinic outcome were collected. The three-year survival curve were calculated with the Kaplan-Meier method and compared by the log-rank test between the two groups.
RESULTSCompared with open esophagectomy group, minimally invasive group has less amount of bleeding during operations ((231±40) ml vs. (302±37) ml, t=4.63, P=0.000), pleural drainage after operations ((490±41) ml vs. (1 090±43) ml, t=-79.59, P=0.000), and postoperative hospital stay ((16±4) days vs. (17±4) days, t=-2.61, P=0.010). Meanwhile, minimally invasive group has more operation time ((272±39) minutes vs. (242±45) minutes, t=3.97, P=0.000) and total and thoracic cavity retrieved lymph nodes (30±5 vs. 28±4, t=2.39, P=0.018; 15±4 vs. 14±3, t=2.59, P=0.011). Nineteen and 31 patients had postoperative complications and statistical significance difference was found between two groups (χ2=4.83, P=0.028). The three-year survival rate was 73.2% in minimally invasive group and 71.4% in open esophagectomy group. There was no significance difference between two groups (χ2=0.170, P>0.05).
CONCLUSIONThoracoscopic and laparoscopic esophagectomy had the advantages of amount of bleeding, postoperative hospital stay and complications, and had the same three-year survival rate with open esophagectomy.
Aged ; Carcinoma ; surgery ; Esophageal Neoplasms ; surgery ; Esophagectomy ; methods ; Humans ; Laparoscopy ; Length of Stay ; Lymph Node Excision ; Lymph Nodes ; Male ; Middle Aged ; Neoplasm Staging ; Operative Time ; Postoperative Complications ; Retrospective Studies
10.Influence of the therapy of calcitriol combined with prolonged hemodialysis on refractory secondary hyperparathyroidism in maintenance hemodialysis patients
Jie WANG ; Youcai ZHANG ; Yanxia JIANG ; Taixing YANG
Chinese Journal of Postgraduates of Medicine 2014;37(22):58-60
Objective To observe the influence of calcitriol combined with prolonged hemodialysis on parathyroid hormone (PTH),phosphorus and calcium in maintenance hemodialysis patients with refractory secondary hyperparathyroidism.Methods Twenty-two maintenance hemodialysis patients received prolonged hemodialysis (3 times per week and 6 hours each session) and therapy with calcitriol (3 times per week and 1 μ g each time) for 3 months.The levels of serum PTH,calcium and phosphorus of these patients were recorded before and after treatment.Results Compared with that before treatment,the level of serum PTH and phosphorus was decreased significantly[(484.21 ± 230.18) nmol/L vs.(750.53 ± 327.41) nmol/L,(1.49 ±0.27) mmol/L vs.(2.37 ±0.76) mmol/L],but calcium was increased after treatment [(2.35 ±0.32) mmol/L vs.(1.81 ±0.53) mmol/L],and there was significant difference (P <0.05).Conclusions The treatment of calcitriol combined with prolonged hemodialysis not only effectively clear phosphorus and PTH but also increase calcium in maintenance hemodialysis patients.The therapeutic schedule is good to maintenance hemodialysis patients with refractory secondary hyperparathyroidism.

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