1.Coronary artery perforation after using shockwave balloon during percutaneous coronary intervention treatment:a case report
Chen-Ji XU ; Fei LI ; Fa ZHENG ; Bin ZHANG ; Feng-Xia QU ; Jian-Meng WANG ; Ya-Qun ZHOU ; Xian-Liang LI ; Song-Tao WANG ; Yan SHAO ; Chang-Hong LU
Chinese Journal of Interventional Cardiology 2024;32(7):405-408
Coronary perforation is when a contrast agent or blood flows outside a blood vessel through a tear in a coronary artery.In this case,we reported a case of percutaneous coronary intervention for coronary calcified lesions,which led to iatrogenic coronary perforation and cardiac tamponade after the use of Shockwave balloon to treat intracoronary calcified nodules,and the management of PCI-related CAP was systematically reviewed through the literature.
2.Chemical constituents from salt-processed Citri Reticulatae Semen and their antioxidant activities
Xing YANG ; Zhang-Xian CHEN ; Yi-Mou WANG ; Xu-Li DENG ; Hong-Chuan ZHANG ; Rui YIN ; Wei-Mao DONG ; Hong-Ping HE ; Fa-Wu DONG
Chinese Traditional Patent Medicine 2024;46(7):2259-2265
AIM To study the chemical constituents from salt-processed Citri Reticulatae Semen and their antioxidant activities.METHODS The 85% ethanol extract from salt-processed Citri Reticulatae Semen was isolated and purified by silica gel,D101 macroporous resins,MCI,ODS,Sephadex LH-20 and semi-prepative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their antioxidant activities in vitro of the ethanol extract of Citri Reticulatae Semen,salt-processed Citri Reticulatae Semen and all the obtained compounds were evaluated by DPPH and ABTS+assay.RESULTS Sixteen compounds were isolated and identified as limonin(1),obacunone(2),nomilin(3),deacetyl nomilin(4),kaempferol(5),nobiletin(6),diosmetin(7),isosakuranetin(8),hesperetin(9),epicatechin(10),trans-p-menthane-1α,2β,8-triol(11),byakangelicin(12),vanillin(13),p-coumaric acid(14),4-[(1-ethoxy-2-hydroxy)ethyl]phenol(15),catechol(16).Compound 10 showed strong DPPH free radical scavenging activity,with an IC50 value of(0.015±0.001)μmol/mL,and strong ABTS+radical scavenging activity,with an IC50 value of(0.010±0.005)μmol/mL.CONCLUSION Compounds 8,11,15-16 are isolated from genus Citrus for the first time,5,12,14 are obtained from Citri Reticulatae Semen for the first time.Compound 10 shows obvious antioxidant activities.After salt roasting,the antioxidant activity of the ethanol extract of Citri Reticulatae Semen is enhanced.
3.Comparison of distribution of eight components from Liangxue Tuizi Mixture between normal and Henoch-Schonlein purpura rats.
Li-Ling SI ; Lu NIU ; Xiao-Yan WANG ; Hui ZHANG ; Ming-Liang ZHANG ; Shuang XU ; Xian-Qing REN ; Jin-Fa TANG ; Wei-Xia LI
China Journal of Chinese Materia Medica 2023;48(21):5915-5931
This study used UPLC-TQ-MS technology to replicate a Henoch-Schonlein purpura(HSP) model in rats by administering warm drugs by gavage and injecting ovalbumin with Freund's complete adjuvant emulsion. The distribution differences and characteristics of eight major components(ferulic acid, caffeic acid, neochlorogenic acid, cryptochlorogenic acid, benzoyl oxypaeoniflorin, tracheloside, loganin, and paeoniflorin) in rat liver, lung, heart, spleen, and kidney tissues were determined after oral administration of the Liangxue Tuizi Mixture at a dose of 42 g·kg~(-1) in both normal physiological and HSP states at 0.5, 1, 2, 6, and 12 hours. The results showed that the distribution patterns of the eight components of Liangxue Tuizi Mixture in the tissues of normal and HSP model rats were different. The main component, paeoniflorin, in Moutan Cortex and Paeoniae Radix Alba had higher content in all tissues. The eight components were predominantly distributed in the liver, lung, and kidney tissues, followed by spleen and heart tissues.
Rats
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Animals
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IgA Vasculitis/drug therapy*
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Monoterpenes
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Administration, Oral
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Liquid Chromatography-Mass Spectrometry
4.Potential components and mechanism of Liangxue Tuezi Mixture in treating Henoch-Schönlein purpura based on network pharmacology and metabolomics.
Wei-Xia LI ; Shuang XU ; Yu-Long CHEN ; Xiao-Yan WANG ; Hui ZHANG ; Ming-Liang ZHANG ; Wen-Juan NI ; Xian-Qing REN ; Jin-Fa TANG
China Journal of Chinese Materia Medica 2023;48(12):3327-3344
Ultra-performance liquid chromatography-quadrupole time of fight/mass spectrometry(UPLC-Q-TOF-MS) and UNIFI were employed to rapidly determine the content of the components in Liangxue Tuizi Mixture. The targets of the active components and Henoch-Schönlein purpura(HSP) were obtained from SwissTargetPrediction, Online Mendelian Inheritance in Man(OMIM), and GeneCards. A "component-target-disease" network and a protein-protein interaction(PPI) network were constructed. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the targets by Omishare. The interactions between the potential active components and the core targets were verified by molecular docking. Furthermore, rats were randomly assigned into a normal group, a model group, and low-, medium-, and high-dose Liangxue Tuizi Mixture groups. Non-targeted metabolomics was employed to screen the differential metabolites in the serum, analyze possible metabolic pathways, and construct the "component-target-differential metabolite" network. A total of 45 components of Liangxue Tuizi Mixture were identified, and 145 potential targets for the treatment of HSP were predicted. The main signaling pathways enriched included resistance to epidermal growth factor receptor tyrosine kinase inhibitors, phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT), and T cell receptor. The results of molecular docking showed that the active components in Liangxue Tuizi Mixture had strong binding ability with the key target proteins. A total of 13 differential metabolites in the serum were screened out, which shared 27 common targets with active components. The progression of HSP was related to metabolic abnormalities of glycerophospholipid and sphingolipid. The results indicate that the components in Liangxue Tuizi Mixture mainly treats HSP by regulating inflammation and immunity, providing a scientific basis for rational drug use in clinical practice.
Animals
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Rats
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IgA Vasculitis/drug therapy*
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Network Pharmacology
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Molecular Docking Simulation
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Phosphatidylinositol 3-Kinases
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Metabolomics
5.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
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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
6.A multi-center retrospective study of perioperative chemotherapy for gastric cancer based on real-world data.
Xue Wei DING ; Zhi Chao ZHENG ; Qun ZHAO ; Gang ZHAI ; Han LIANG ; Xin WU ; Zheng Gang ZHU ; Hai Jiang WANG ; Qing Si HE ; Xian Li HE ; Yi An DU ; Lu Chuan CHEN ; Ya Wei HUA ; Chang Ming HUANG ; Ying Wei XUE ; Ye ZHOU ; Yan Bing ZHOU ; Dan WU ; Xue Dong FANG ; You Guo DAI ; Hong Wei ZHANG ; Jia Qing CAO ; Le Ping LI ; Jie CHAI ; Kai Xiong TAO ; Guo Li LI ; Zhi Gang JIE ; Jie GE ; Zhong Fa XU ; Wen Bin ZHANG ; Qi Yun LI ; Ping ZHAO ; Zhi Qiang MA ; Zhi Long YAN ; Guo Liang ZHENG ; Yang YAN ; Xiao Long TANG ; Xiang ZHOU
Chinese Journal of Gastrointestinal Surgery 2021;24(5):403-412
Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant
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Female
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Gastrectomy
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Humans
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Male
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Neoadjuvant Therapy
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Neoplasm Staging
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Prognosis
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Retrospective Studies
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Stomach Neoplasms/surgery*
7. Clinical significance of laparoscopic extraperitoneal abdominal para-aortic lymphadenectomy
Jian-fa LAN ; Dian-chao LIN ; Ya-yun XU ; Rong JIAO ; Qiu-ying HONG ; Ya-xian WANG ; Jin-na JIANG ; Qiong-hua CHEN
Chinese Journal of Practical Gynecology and Obstetrics 2019;35(12):1379-1383
OBJECTIVE: To evaluate the clinical significance of laparoscopic extraperitoneal para-aortic lmphadenectomy(PAL)in high para-aortic lymphadenectomy.METHODS: A non-randomized controlled method was used to analyze the clinical data of laparoscopic extraperitoneal PAL in 35 patients(extraperitoneal group)and laparoscopic transabdominal PAL in 40 patients(transabdominal group)in the Gynecological Department of the First Affiliated Hospital of Xiamen University from March 2018 to April 2019.RESULTS: All the 35 cases of laparoscopic extraperitoneal PAL reached the level of renal vein.Endometrial cancer accounted for the largest proportion,with an average age of 47.57 years and an average body mass index of 23.77.The average operation time was 109 minutes in the first 6 cases and 74.73 minutes in the other 29 cases.The amount of hemorrhage was 15.19 mL,and the average number of para-aortic lymph nodes(PALN)resected was 17.87.There were 5 cases of positive PALN metastasis,and the average gastrointestinal recovery time was13.43 hours.The average postoperative pelvic drainage was 76.57 hours and the average postoperative hospital stay was8.24 days.Intraoperative and postoperative complications included 1 case of inferior vena cava rupture,1 case of chyle leakage,and 1 case of vulvar edema.None of the 40 cases of laparoscopic transabdominal PAL reached the level of renal vein,and endometrial cancer accounted for the largest proportion,with the average age of 46.78 years and the average body mass index of 24.03.The average operation time was 90.55 min;the average intraoperative blood loss was 67.40 mL The average number of para-aortic lymph nodes was 3.30.There was one case of PALN metastasis.The average gastrointestinal recovery time was 22.35 hours,and the average postoperative pelvic drainage time was 75.75 hours.The average length of hospital stay was 8.90 days.There were 2 cases of rupture of the inferior mesenteric artery,3 cases of chyle leakage,and 2 cases of vulvar edema.The number of PALN resection,intraoperative blood loss,and operation time in the extraperitoneal group were not related to the body mass index,but the number of PALN in obese patients in the laparoscopic transabdominal group was significantly reduced,the operation time was longer,the intraoperative blood loss was more,and postoperative gastrointestinal recovery time is longer(P<0.05).CONCLUSION: Laparoscopic extraperitoneal PAL can solve the problems of laparoscopic transabdominal PAL lymph node resection,which is difficult to reach the level of renal vein,intraoperative intestinal tube interference,and the number of lymph nodes resected.It is especially suitable for obese patients.Laparoscopic extra-peritoneal high-grade PAL is safe,feasible,and recommended.
8.Re-operation treatment in uremic patients complicated with persistent secondary hyperparathyroidism after parathyroidectomy with autotransplantation.
Shao Jun BO ; Xian Fa XU ; Chuan Ya QIU ; Tian Tian WANG ; Yu Dong NING ; Hong Yue LI
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2018;32(2):142-147
To analyze the clinical profile and therapeutic effect of re-operation treatment in uremic patients complicated with persistent secondary hyperparathyroidism(SHPT)after parathyroidectomy with autotransplantation.Twelve persistent SHPT patients who were treated with reoperation of paramyroidectomy(PTX)were enrolled in this study during the period from Jan 2014 to Jul 2017 in our hospital.We evaluated the location of the remaining parathyroid glands by ultrasonography,dual-phase 99 Tcm-sestamibi scintigraphy,CT and MR imaging of the neck before the operation.We resected the parathyroid gland tissue in situ,and the ectopic parathyroid glands hiding in thymus,mediastinal,tracheal esophageal groove,thyroid gland and other locations in the neck.During the surgery,nanocarbon imaging was used to help identify the parathyroid gland and parathyroid hormone assay(IOPTH)was measured at the end of the surgery.We observed the changes of clinical symptoms after the surgery and collected blood parameters including serum intact aramyroidhomone(i-PTH),calcium(Ca),phosphoms(P),calcium and phosphorus product before and after surgery.Complications and failure were also analyzed.All the 12 patients underwented successful operation.The postoperative pathological results were hyperplastic parathyroid glands tissue.22 parathyroid glands were resected,among which 14 were located at the neck in situ,8 were ectopic,i.e.,located at thymus in 4 cases,superior mediastinum in 2 cases and thyroid parenchyma in 2 cases.The clinical symptoms were significantly improved including osteoarthritis,skin itching and limb weakness.The levels of serum iPTH,calcium,phosphorus and calcium and phosphorus product were significantly lower than those before operation(<0.05).Ten patients presented hypocalcemia after surgery and the level of calcium returned to normal after supplement of calcium.Temporary injury of laryngeal nerve was found in4 cases,but there was no patient with transient bucking,dyspnea or death.No recurrence was found during 1 year follow-up.It was very important to locate the residual parathyroid gland accurately with a variety of imaging methods in uremic patients complicated with persistent or recurrent SHPT when they needed re-operation.Surgeons should explorate ectopic parathyroid gland according to the concept of the superior mediastinum dissection and the central compartment neck dissection.Meanwhile,the use of nanocarbon assisted parathyroid gland negative imaging and rapid IOPTH can significantly improve the success rate of surgery and reduce surgical complications.
Humans
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Hyperparathyroidism, Secondary
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complications
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surgery
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Parathyroid Glands
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Parathyroid Hormone
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Parathyroidectomy
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Reoperation
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Transplantation, Autologous
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Uremia
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complications
9.Absorption of irrigation fluid occurs during 1470 nm diode laser vaporization of the prostate
Fa-You ZHOU ; Shu-Xian ZHANG ; Yun-Wu WANG ; Wei PENG ; Xiao-Yi ZHANG ; Wei XU ; Jun-Ya SHEN ; Yi-Long WU ; Jiu-De ZHENG ; Pan GAO
China Journal of Endoscopy 2018;24(1):80-83
Objective To investigate and evaluate the effects and safety of the operationabsorption of irrigation fluid occurs during 1470 nm diode laser vaporization of the prostate by ethano. Methods We retrospectively analyzed the clinical data about 32 cases of BPH treated by 1470 nm diode laser vaporization from May 2016 to December 2016 intraoperative use of isotonic saline contains 1.0% ethanol as perfusion fluid, monitor the patients' breath ethanol concentration, calculation of perfusion fluid absorption. Results All the operations were successfully completed, the average operation time was (57.6 ± 32.9) min, the average perfusion fluid volume was (21.5 ± 9.9) L, only 5 cases detected perfusion fluid absorption, the average absorptive amount was (156.8 ± 111.7) ml. During operation, all the patients with stable breathing, circulation, no alcohol poisoning symptoms, no bleeding, capsular perforation, cardiorespiratory failure occurred. All the 32 cases patients were followed up for 3 months, which revealed a significant improvement in dysuresia, no severe complications such as urethrostenosis, urinary incontinence, secondary hemorrhage were noted. Conclusion Fluid absorption little occurs during 1470 nm diode laser vaporization, it is safe and effective in treatment of benign prostatic hyperplasia.
10.The Effect of PCDH15 Gene Variations on the Risk of Noise-induced Hearing Loss in a Chinese Population.
Xiang Rong XU ; Jing Jing WANG ; Qiu Yue YANG ; Jie JIAO ; Li Hua HE ; Shan Fa YU ; Gui Zhen GU ; Guo Shun CHEN ; Wen Hui ZHOU ; Hui WU ; Yan Hong LI ; Huan Ling ZHANG ; Zeng Rui ZHANG ; Xian Ning JIN
Biomedical and Environmental Sciences 2017;30(2):143-146
Noise-induced hearing loss (NIHL) is a complex disease caused by interactions between environmental and genetic factors. This study investigated whether genetic variability in protocadherin related 15 (PCDH15) underlies an increased susceptibility to the development of NIHL in a Chinese population. The results showed that compared with the TT genotype of rs11004085, CT/CC genotypes were associated with an increased risk of NIHL [adjusted odds ratio (OR) = 2.64; 95% confidence interval (CI): 1.14-6.11, P = 0.024]. Additionally, significant interactions between the rs11004085 and rs978842 genetic variations and noise exposure were observed in the high-level exposure groups (P < 0.05). Furthermore, the risk haplotype TAGCC was observed when combined with higher levels of noise exposure (P < 0.05). Thus, our study confirms that genetic variations in PCDH15 modify the susceptibility to NIHL development in humans.
Cadherins
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genetics
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China
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Genetic Predisposition to Disease
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Genetic Variation
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Hearing Loss, Noise-Induced
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epidemiology
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genetics
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Humans
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Risk Factors

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