1.Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults (version 2023)
Yukun DU ; Dageng HUANG ; Wei TIAN ; Dingjun HAO ; Yongming XI ; Baorong HE ; Bohua CHEN ; Tongwei CHU ; Jian DONG ; Jun DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Yong HAI ; Lijun HE ; Yuan HE ; Dianming JIANG ; Jianyuan JIANG ; Weiqing KONG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Fei LUO ; Jianyi LI ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Jiang SHAO ; Jiwei TIAN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Xiangyang WANG ; Hong XIA ; Jinglong YAN ; Liang YAN ; Wen YUAN ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Xuhui ZHOU ; Mingwei ZHAO
Chinese Journal of Trauma 2023;39(4):299-308
The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.
2.Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF).
Feng XU ; Yuan BIAN ; Guo Qiang ZHANG ; Lu Yao GAO ; Yu Fa LIU ; Tong Xiang LIU ; Gang LI ; Rui Xue SONG ; Li Jun SU ; Yan Ju ZHOU ; Jia Yu CUI ; Xian Liang YAN ; Fang Ming GUO ; Huan Yi ZHANG ; Qing Hui LI ; Min ZHAO ; Li Kun MA ; Bei An YOU ; Ge WANG ; Li KONG ; Jian Liang MA ; Xin Fu ZHOU ; Ze Long CHANG ; Zhen Yu TANG ; Dan Yu YU ; Kai CHENG ; Li XUE ; Xiao LI ; Jiao Jiao PANG ; Jia Li WANG ; Hai Tao ZHANG ; Xue Zhong YU ; Yu Guo CHEN
Chinese Journal of Internal Medicine 2023;62(4):374-383
Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male
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Female
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Humans
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Aged
;
Natriuretic Peptide, Brain
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Simendan/therapeutic use*
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Non-ST Elevated Myocardial Infarction
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Heart Failure/drug therapy*
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Peptide Fragments
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Arrhythmias, Cardiac
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Biomarkers
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Prognosis
3.Clinical efficacy of combined therapy in children with stage 4 neuroblastoma.
Wei-Ling LIANG ; Xiao-Fan YE ; Gong ZHONG ; Jian-Jun CHEN ; Kang-Lin DAI ; Ka Leung Daniel CHEUK ; Shu MO ; Bo-Shen WANG ; Chun-Yu LI ; Xuan-Zhu JIANG ; Zhi-Yuan XU ; Li ZHOU ; Irene CHAN ; Jian-Liang CHEN ; Patrick CHU ; Pui Wah Pamela LEE ; Chi Fung Godfrey CHAN
Chinese Journal of Contemporary Pediatrics 2022;24(7):759-764
OBJECTIVES:
To study the early clinical efficacy of combined therapy of stage 4 neuroblastoma.
METHODS:
A retrospective analysis was performed on the medical data and follow-up data of 14 children with stage 4 neuroblastoma who were diagnosed in Hong Kong University-Shenzhen Hospital from January 2016 to June 2021.
RESULTS:
The median age of onset was 3 years and 7.5 months in these 14 children. Among these children, 9 had positive results of bone marrow biopsy, 4 had N-Myc gene amplification, 13 had an increase in neuron-specific enolase, and 7 had an increase in vanilmandelic acid in urine. Based on the results of pathological examination, differentiated type was observed in 6 children, undifferentiated type in one child, mixed type, in one child and poorly differentiated type in 6 children. Of all the children, 10 received chemotherapy with the N7 regimen (including 2 children receiving arsenic trioxide in addition) and 4 received chemotherapy with the Rapid COJEC regimen. Thirteen children underwent surgery, 14 received hematopoietic stem cell transplantation, and 10 received radiotherapy. A total of 8 children received Ch14.18/CHO immunotherapy, among whom 1 child discontinued due to anaphylactic shock during immunotherapy, and the other 7 children completed Ch14.18/CHO treatment without serious adverse events, among whom 1 child was treated with Lu177 Dotatate 3 times after recurrence and is still undergoing chemotherapy at present. The median follow-up time was 45 months for all the 14 children. Four children experienced recurrence within 2 years, and the 2-year overall survival rate was 100%; 4 children experienced recurrence within 3 years, and 7 achieved disease-free survival within 3 years.
CONCLUSIONS
Multidisciplinary combined therapy is recommended for children with stage 4 neuroblastoma and can help them achieve better survival and prognosis.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Child
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Child, Preschool
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Combined Modality Therapy
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Humans
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Infant
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Neuroblastoma/drug therapy*
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Positron-Emission Tomography
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Radionuclide Imaging
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Retrospective Studies
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Treatment Outcome
4.Survival and disease burden trend analysis of occupational pneumoconiosis from 1963 to 2020 in Shizuishan City.
Yan TONG ; Yun Yan KONG ; Hao BIAN ; Jian Zhong ZHENG ; Yong Jun WU ; Yue ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2022;40(5):341-347
Objective: To understand the survival status and its influencing factors of occupational pneumoconiosis patients in Shizuishan City, and to analyze the disease burden of occupational pneumoconiosis and its trend, so as to provide scientific basis for formulating comprehensive prevention and treatment measures of occupational pneumoconiosis. Methods: A retrospective survey was conducted during July to December 2020 to explore the survival status of occupational pneumoconiosis patients who had been reported from 1963 to 2020 in Shizuishan City. The Kaplan-Meier method and Life-table method were used for survival analysis, and Cox proportional hazards regression model was used to analyze the influencing factors of survival time. The disability adjusted life years (DALY) was applied to analyze the disease burden of occupational pneumoconiosis and its temporal trend. Results: From 1963 to 2020, a total of 3263 cases of occupational pneumoconiosis were reported in Shizuishan City, of which 1467 died, so that the fatality rate was 44.96%. The median survival time was 26.71 years, average age of death was (70.55±10.92) years old. There were significant differences in the survival rates of occupational pneumoconiosis patients among different types, diagnosis age, exposure time, industry, initial diagnosis stage and whether upgraded (P<0.05) . As the survival time increased, the survival rate of patients decreased gradually. When the survival time was ≥50 years, the cumulative survival rate of patients was 4.20%. Cox regression analysis suggested that the type of pneumoconiosis, industry, diagnosis age, exposure time, initial diagnosis stage and whether upgraded were the influencing factors for the survival time of patients with occupational pneumoconiosis (P<0.05) . The total DALY attributable to occupational pneumoconiosis from 1963 to 2020 in Shizuishan City was 48026.65 person years, of which the years of life lost (YLL) was 15155.39 person years, and the average YLL was 10.33 years/person, and the years lost due to disability (YLD) was 32871.26 person years, and the average YLD was 10.07 years/person. The DALY attributed to coal worker's pneumoconiosis and silicosis were 39408.51 person years and 6565.02 person years, respectively, and they accounted for 82.06% and 13.67% of the total disease burden in Shizuishan City, respectively. The DALY caused by occupational pneumoconiosis in the age group of 40-49 years old and the first diagnosis of stage I occupational pneumoconiosis were higher, which were 20899.71 and 36231.97 person years, respectively. The average YLL and average YLD showed a volatility downtrend over time. Conclusion: The disease burden of occupational pneumoconiosis cannot be ignored in Shizuishan City, and timely targeted measures should be taken for key populations and key industries. It is recommended that life-cycle health management and hierarchical medical should be taken to improve the life quality of patients and prolong their lifes.
Adult
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Aged
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Aged, 80 and over
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Anthracosis
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China/epidemiology*
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Coal Mining
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Cost of Illness
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Humans
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Middle Aged
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Pneumoconiosis/epidemiology*
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Retrospective Studies
5.Natural ingredients from Chinese materia medica for pulmonary hypertension.
Jia-Rui ZHANG ; Xuan OUYANG ; Chi HOU ; Qi-Feng YANG ; Yingjun WU ; Wen-Ju LU ; Chun-Li LIU ; Kai YANG ; Nan-Shan ZHONG ; Jian WANG ; Yu-Qin CHEN
Chinese Journal of Natural Medicines (English Ed.) 2021;19(11):801-814
Pulmonary hypertension (PH) is a severe pathophysiological condition characterized by pulmonary artery remodeling and continuous increases in pulmonary artery pressure, which may eventually develop to right heart failure and death. Although newly discovered and incredible treatment strategies in recent years have improved the prognosis of PH, limited types of effective and economical drugs for PH still makes it as a life-threatening disease. Some drugs from Chinese materia medica (CMM) have been traditionally applied in the treatment of lung diseases. Accumulating evidence suggests active pharmaceutical ingredients (APIs) derived from those medicines brings promising future for the prevention and treatment of PH. In this review, we summarized the pharmacological effects of APIs derived from CMM which are potent in treating PH, so as to provide new thoughts for initial drug discovery and identification of potential therapeutic strategies in alternative medicine for PH.
China
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Drugs, Chinese Herbal
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Humans
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Hypertension, Pulmonary/drug therapy*
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Materia Medica
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Medicine, Chinese Traditional
6.Incidence and risk factors of anastomotic leak after transanal total mesorectal excision in China: a retrospective analysis based on national database.
Lei GU ; Yong Bo AN ; Ming Yang REN ; Quan WANG ; Hong Yu ZHANG ; Gang YU ; Jian Zhi CHEN ; Miao WU ; Yi XIAO ; Zhi Cong FU ; Hong ZHANG ; Wei Dong TONG ; Dan MA ; Qing XU ; Hong Wei YAO ; Zhong Tao ZHANG
Chinese Journal of Gastrointestinal Surgery 2021;24(6):505-512
Objective: Transanal total mesorectal excision (taTME) was a very hot topic in the first few years since its appearance, but now more introspections and controversies on this procedure have emerged. One of the reasons why the Norwegian Ministry of Health stopped taTME was the high incidence of postoperative anastomotic leak. In current study, the incidence and risk factors of anastomotic leak after taTME were analyzed based on the data registered in the Chinese taTME Registry Collaborative (CTRC). Methods: A case-control study was carried out. Between November 15, 2017 and December 31, 2020, clinical data of 1668 patients undergoing taTME procedure registered in the CTRC database from 43 domestic centers were collected retrospectively. After excluding 98 cases without anastomosis and 109 cases without complete postoperative complication data, 1461 patients were finally enrolled for analysis. There were 1036 males (70.9%) and 425 females (29.1%) with mean age of (58.2±15.6) years and mean body mass index of (23.6±3.8) kg/m(2). Anastomotic leak was diagnosed and classified according to the International Study Group of Rectal Cancer (ISREC) criteria. The risk factors associated with postoperative anastomotic leak cases were analyzed. The impact of the cumulative number of taTME surgeries in a single center on the incidence of anastomotic leak was evaluated. As for those centers with the number of taTME surgery ≥ 40 cases, incidence of anastomic leak between 20 cases of taTME surgery in the early and later phases was compared. Results: Of 1461 patients undergoing taTME, 103(7.0%) developed anastomotic leak, including 71 (68.9%) males and 32 (31.1%) females with mean age of (59.0±13.9) years and mean body mass index of (24.5±5.7) kg/m(2). The mean distance between anastomosis site and anal verge was (2.6±1.4) cm. Thirty-nine cases (37.9%) were classified as ISREC grade A, 30 cases (29.1%) as grade B and 34 cases (33.0%) as grade C. Anastomotic leak occurred in 89 cases (7.0%,89/1263) in the laparoscopic taTME group and 14 cases (7.1%, 14/198) in the pure taTME group. Multivariate analysis showed that hand-sewn anastomosis (P=0.004) and the absence of defunctioning stoma (P=0.013) were independently associated with anastomotic leak after taTME. In the 16 centers (37.2%) which performed ≥ 30 taTME surgeries with cumulative number of 1317 taTME surgeries, 86 cases developed anastomotic leak (6.5%, 86/1317). And in the 27 centers which performed less than 30 taTME surgeries with cumulative number of 144 taTME surgeries, 17 cases developed anastomotic leak (11.8%, 17/144). There was significant difference between two kinds of center (χ(2)=5.513, P=0.019). Thirteen centers performed ≥ 40 taTME surgeries. In the early phase (the first 20 cases in each center), 29 cases (11.2%, 29/260) developed anastomotic leak, and in the later phase, 12 cases (4.6%, 12/260) developed anastomotic leak. The difference between the early phase and the later phase was statistically significant (χ(2)=7.652, P=0.006). Conclusion: The incidence of anastomotic leak after taTME may be reduced by using stapler and defunctioning stoma, or by accumulating experience.
Adult
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Aged
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Anastomotic Leak/etiology*
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Case-Control Studies
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China/epidemiology*
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Female
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Humans
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Incidence
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Laparoscopy
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Male
;
Middle Aged
;
Postoperative Complications/epidemiology*
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Rectal Neoplasms/surgery*
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Rectum/surgery*
;
Retrospective Studies
;
Risk Factors
7.A comparison between endoscopic CO2 laser cauterization and open neck surgery in the treatment of congenital piriform fistula.
Shu Ling HUANG ; Liang Si CHEN ; Mi Mi XU ; Xi Xiang GONG ; Bei ZHANG ; Lu LIANG ; Xiao Li SHENG ; Jian Dong ZHAN ; Xiao Ning LUO ; Zhong Ming LU ; Si Yi ZHANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2021;56(6):619-625
Objective: To compare the efficacy, advantages and disadvantages of endoscopic CO2 laser cauterization (ECLC) and open neck surgery in the treatment of congenital pyriform sinus fistula (CPSF). Methods: From September 2014 to March 2017, 80 cases with confirmed diagnosis of CPSF received initial treatment at Guangdong Provincial People's Hospital were prospectively analyzed, including 34 males and 46 females, aged 18 to 672 (194.17±141.18) months. They were consecutively divided into endoscopic group and open-surgery group, with 40 cases in each group. Both groups of patients received surgical treatment under general anesthesia. The endoscopic group was treated by endoscopic CO2 laser cauterization, and the open-surgery group underwent the following surgery: first, we performed suspension laryngoscopy examination to confirm the presence of fistula in the bottom of the piriform fossa, then open-neck resection of congenital piriform sinus fistula with recurrent laryngeal nerve and/or lateral branch of superior laryngeal nerve anatomy plus partial thyroidectomy were performed. The data between the two groups were compared, including the operative time, intraoperative blood loss, postoperative pain, average length of stay, neck cosmetic scores, complications and cure rates. All patients were followed up in outpatient clinics. Statistical analysis was performed using SPSS 20.0 software. P<0.05 indicates that the difference is statistically significant. Results: All patients were successfully completed the operation. The operative time, intraoperative blood loss, postoperative pain and average length of hospital stay in the endoscopic group were significantly less than those in the open group [(27.4±5.5) min to (105.8±52.5) min, (0.6±0.5) ml to (33.6±41.5) ml, (1.7±0.9) points to (4.6±0.7) points, (5.9±2.9)d to(8.9±3.3)d, t values were-9.400, -5.031, -16.199, -4.293, P values were all<0.01]; The neck cosmetic score in the endoscopy group was significantly greater than that of the open group [(9.9±0.4) against (5.8±0.9) points, t=25.847, P<0.01]. Compared with the open group (15.0%, 6/40), the complication rate of the endoscopic group (7.5%, 3/40) was not statistically significant (χ²=0.50, P>0.05). Three months after the first treatment, the cure rate in the endoscopic group (82.5%, 33/40) was significantly lower than that in the open-neck group (100.0%, 40/40), χ²=5.64, P<0.05. The follow-up time was 12 months after the last treatment. Eighty cases were followed up and none was lost to follow-up. During the follow-up period, the cure rate of the endoscopy group (97.5%, 39/40) was compared with that of the open group (100.0%, 40/40), and the difference was not statistically significant. Conclusions: In the treatment of CPSF, the two-surgical method each has their advantages. Compared with open-neck surgery, ECLC is simpler, repeatable. ECLC has shorter time in operation and hospital stay, less complications, and less postoperative pain and more precise cosmetic results. It could be preferred for the initial treatment of CPSF and relapsed cases after cauterization. But subject to relatively low cure rate of one-time cauterization and uncertain long-term efficacy, it cannot completely replace the open-neck surgery at present.
Carbon Dioxide
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Cautery
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Endoscopy
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Female
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Fistula/surgery*
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Humans
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Lasers, Gas/therapeutic use*
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Male
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Pyriform Sinus/surgery*
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Retrospective Studies
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Treatment Outcome
8.Modified Zhibai Dihuang pill, a traditional Chinese medicine formula, on steroid withdrawal in systemic lupus erythematosus: A systematic review and meta-analysis.
Liang DAI ; Ka Kei CHAN ; Jian-Chun MAO ; Yu TIAN ; Jun-Hua GU ; Jun ZHOU ; Linda L D ZHONG
Journal of Integrative Medicine 2020;18(6):478-491
BACKGROUND:
Zhibai Dihuang pill (ZBDH), a Chinese herbal formula, has been widely used as an adjunctive therapy to help reduce the patient's steroid dose and maintain low disease activity in systemic lupus erythematosus (SLE).
OBJECTIVE:
This systematic review evaluates the therapeutic effect of modified ZBDH in reducing steroid use in patients with SLE.
SEARCH STRATEGY:
A systematic literature search was carried out using seven databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese VIP Information and Wanfang Database, from their inception to June 1st, 2019. The search terms included "systemic lupus erythematosus," "Chinese medicine" and "clinical trial," and their synonyms. Subject headings matching the above terms were also used.
INCLUSION CRITERIA:
This meta-analysis included randomized controlled trials that evaluated the reduction of steroid dose in patients with SLE. Traditional Chinese medicine (TCM) formulas in experimental group should be prescribed based on ZBDH and used as adjunctive therapy and the comparator should contain steroids.
DATA EXTRACTION AND ANALYSIS:
Two authors independently conducted database search, study selection, data extraction and quality assessment. The extracted information contained study design, sample size, recruitment mode, diagnostic criteria, inclusion and exclusion criteria, participant characteristics, TCM patterns, TCM formulas and treatment outcomes. The primary outcome was the change of steroid dose. Secondary outcomes included SLE Disease Activity Index (SLEDAI), biomarkers of disease activity and clinical response rate. STATA 15.0 was used to analyze the pooled effects reported as weighted mean difference (WMD) or odds ratio, with a 95% confidence interval (CI).
RESULTS:
In total, 20 trials involving 1470 SLE patients were included. The pooled result showed that modified ZBDH taken in combination with standard care led to a larger reduction in steroid dose, compared to standard care alone (WMD: 3.79; 95% CI: 2.58-5.01; P < 0.001). Favorable outcomes were also seen in secondary outcome criteria, such as SLEDAI and complement 3. The modified ZBDH treatments were well tolerated without increasing adverse effects.
CONCLUSION
The systematic review provided preliminary evidence supporting the use of ZBDH as a co-therapy to aid steroid dose reduction in patients with SLE. However, more rigorous studies should be conducted to validate these findings, and explore the mechanisms of ZBDH's relevant bioactive constituents.
9.The efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation: a randomized, controlled, multi-center clinical trial with 2 years’ follow-up
Hao YU ; Kaiwen LI ; Hailong HU ; Xiang LI ; Nan LIU ; Jian ZHANG ; Xudong YAO ; Xiaodong ZHANG ; Wei LI ; Liqun ZHOU ; Xiangbo KONG ; Jinjian YANG ; Youhan CAO ; Junli WEI ; Jiacun CHEN ; Zhaoyang WU ; Dongwen WANG ; Xuhui ZHANG ; Jinkai SHAO ; Qingwen LI ; Huiqing ZHANG ; Xiaolin WANG ; Shaozhong WEI ; Ye TIAN ; Tie ZHONG ; Hongshun MA ; Kun LI ; Benkang SHI ; Jin YANG ; Yuhua QIAO ; Hongxing HUANG ; Liming LI ; Zhimin WANG ; Jianhua TIAN ; Tianxin LIN ; Jian HUANG
Chinese Journal of Urology 2020;41(10):724-730
Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.
10.The role of tyrosine phosphatase Shp2 in spermatogonial differentiation and spermatocyte meiosis.
Yang LI ; Wen-Sheng LIU ; Jia YI ; Shuang-Bo KONG ; Jian-Cheng DING ; Yi-Nan ZHAO ; Ying-Pu TIAN ; Gen-Sheng FENG ; Chao-Jun LI ; Wen LIU ; Hai-Bin WANG ; Zhong-Xian LU
Asian Journal of Andrology 2020;22(1):79-87
The transition from spermatogonia to spermatocytes and the initiation of meiosis are key steps in spermatogenesis and are precisely regulated by a plethora of proteins. However, the underlying molecular mechanism remains largely unknown. Here, we report that Src homology domain tyrosine phosphatase 2 (Shp2; encoded by the protein tyrosine phosphatase, nonreceptor type 11 [Ptpn11] gene) is abundant in spermatogonia but markedly decreases in meiotic spermatocytes. Conditional knockout of Shp2 in spermatogonia in mice using stimulated by retinoic acid gene 8 (Stra8)-cre enhanced spermatogonial differentiation and disturbed the meiotic process. Depletion of Shp2 in spermatogonia caused many meiotic spermatocytes to die; moreover, the surviving spermatocytes reached the leptotene stage early at postnatal day 9 (PN9) and the pachytene stage at PN11-13. In preleptotene spermatocytes, Shp2 deletion disrupted the expression of meiotic genes, such as disrupted meiotic cDNA 1 (Dmc1), DNA repair recombinase rad51 (Rad51), and structural maintenance of chromosome 3 (Smc3), and these deficiencies interrupted spermatocyte meiosis. In GC-1 cells cultured in vitro, Shp2 knockdown suppressed the retinoic acid (RA)-induced phosphorylation of extracellular-regulated protein kinase (Erk) and protein kinase B (Akt/PKB) and the expression of target genes such as synaptonemal complex protein 3 (Sycp3) and Dmc1. Together, these data suggest that Shp2 plays a crucial role in spermatogenesis by governing the transition from spermatogonia to spermatocytes and by mediating meiotic progression through regulating gene transcription, thus providing a potential treatment target for male infertility.
Animals
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Cell Cycle Proteins/genetics*
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Cell Line
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Cell Survival
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Chondroitin Sulfate Proteoglycans/genetics*
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Chromosomal Proteins, Non-Histone/genetics*
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Gene Expression Regulation
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Gene Knockdown Techniques
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Infertility, Male
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Male
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Meiosis/genetics*
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Mice
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Mice, Knockout
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Mice, Transgenic
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Phosphate-Binding Proteins/genetics*
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Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics*
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Rad51 Recombinase/genetics*
;
Real-Time Polymerase Chain Reaction
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Spermatocytes/metabolism*
;
Spermatogenesis/genetics*
;
Spermatogonia/metabolism*

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