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Local anesthetic drugs are commonly used to block the conduction function of patient's nerves temporarily for anesthesia during surgery or to provide targeted analgesia after trauma. Compared with general anesthetics, local anesthetics makes less impact on the physiological status and alleviates pain complications in the presence of clear consciousness. However, its clinical application is still limited by its systemic toxicity, as well as toxicity to nerves and muscles, duration of action and lack of penetration. Nanotechnology can help it penetrate the physiological barrier, prolong the time of nerve block, and reduce toxic side effects. In addition, by building a light-responsive release system, local anesthetics can be released on demand, enhancing drug effectiveness and safety. However, in addition to the problems of poor consistency and high production costs, the system of light response release is still limited in application due to the limitation of the depth of penetration of the tissue. According to the current research progress, this paper briefly introduces and analyzes the main dosage forms, hoping to provide new ideas for the responsive release of local anesthetic drugs.
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Proteolysis targeting chimeras (PROTACs) is an innovative technique in targeted protein degradation. PROTACs is a heterobifunctional molecule which can bind to the E3 ligase and target protein to form a ubiquitination complex, resulting in the ubiquitin-proteasome system dependent degradation of target protein. PROTACs has been regarded as the promising method in drug discovery campaign, for its high commonality, potent degradation activity and unique selectivity profile. However, the catalytic mechanism also induces the uncontrollable protein degradation risk. Controllable PROTACs contain the responsive element in the molecular entity. In certain conditions, the element can be triggered to activate or terminate the degradation event. In this review, we will briefly summarize the strategies in controllable PROTACs and describe the representative examples according to the responsive mechanism. We hope this review could provide some insight into the further development of controllable PROTACs.
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Gastric ''inflammation-cancer'' transformation stars from inflammation and ends as gastric cancer （GC）， and the pathogenesis is still unclear. In China， GC features high morbidity and mortality and poor prognosis， influencing the quality of life and physical and mental health of patients. Therefore， it is of great significance to construct the prevention and treatment system for GC. Chronic atrophic gastritis （CAG） plays a key role in the occurrence， development， and outcome of gastric ''inflammation-cancer'' transformation. Modern therapies for CAG generally aim at eliminating causes and alleviating clinical symptoms， which show satisfactory short-term efficacy， but the reverse and recurrence are common. Based on the holistic view， syndrome differentiation-based treatment， and the ''inflammation-cancer'' transformation in modern medicine， traditional Chinese medicine emphasizes both prevention and treatment， with individualized therapies for CAG and GC to control the transformation. According to the pathogenesis of CAG-asthenia in origin and sthenia in superficiality and deficiency-excess in complexity， this study proposed the theory of spleen deficiency and pathogen stagnation in CAG， and believed spleen deficiency， pathogen， and stagnation are respectively the root cause of， the main factor of， and the key to ''inflammation-cancer'' transformation， respectively. Spleen deficiency and pathogen stagnation are closely related to the process of the transformation. For the treatment， the spleen-invigorating and pathogen-eliminating method should be used for invigorating the spleen to consolidate original Qi， improve the blood supply in stomach， and regulate immunity， and eliminating the pathogen to relieve stagnation， reduce the occurrence of non-controllable inflammation， and improve inflammatory micro-environment. As a result， the gastric inflammation is controlled at the early stage and the gastric ''inflammation-cancer'' transformation is blocked. The gastric mucosal lesions are blocked， delayed， or even reversed. This study provides a new idea in clinical diagnosis and treatment of CAG and in the prevention of GC.
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【Objective】 To compare the clinical application value of controllable negative pressure suction outer sheath and ordinary flexible endoscope outer sheath in flexible ureteroscopic lithotripsy with holmium laser in the treatment of renal calculi less than or equal to 2 cm in diameter. 【Methods】 A total of 85 patients with renal calculi were selected and randomly divided into negative pressure group (n=45) and ordinary group (n=40). The operation time, complications, infection indexes 2 h after operation, adverse reactions, treatment efficacy and stone-clearance rate were compared between the two groups. 【Results】 The sheath was successfully implanted and holmium laser lithotripsy was performed in both groups. The negative pressure group had significantly shorter operation time than the ordinary group [(43.3±4.9) min vs. (66.2±5.8) min, P0.05). The increase of infection indexes (procalcitonin and leukocyte) 2 h after operation were significantly lower in the negative pressure group than in the ordinary group (P<0.05). The efficacy in the negative pressure group was 91.11% (41/45) and the stone-clearance rate was 95.56% (43/45), which were significantly better than those in the ordinary group (72.50% (29/40) and 80% (32/40), respectively. The total incidence of adverse reactions such as renal colic, gross hematuria and ureteral stone street was higher in the ordinary group than in the negative pressure group (P<0.05). 【Conclusions】 Controllable negative pressure suction sheath in flexible ureteroscopic lithotripsy is more effective, as the circulation perfusion keeps the operation field clear, reduces the operation time and improves the stone-clearance rate, while the negative pressure suction lowers the pelvis pressure to prevent infectious urine from entering the blood.
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Objective:To evaluate the efficacy and safety of Yang-Monti tube in the operation of bladder controllable outflow tract, and to compare the efficacy of single and double segments Yang-Monti tube in patients with urethral damage.Methods:The clinical data of 27 patients who underwent Yang-Monti tube surgery in West China Hospital of Sichuan University from January 2009 to February 2018 were retrospectively analyzed, including 14 cases of single segment ileum (single segment group) and 13 cases of double segment ileum (double segment group). The age of single-segment group and double-segment group was (56.5±4.3) years and (50.2±6.8) years, respectively ( P=0.220). There were 2/12 and 3/10 males and females, respectively ( P=0.564). The body mass index (BMI) was (19.6±1.3) kg/m2 and (24.2±2.1) kg/m2, respectively ( P<0.001). The disease duration was 6 (3-24) months and 8 (3-48) months, respectively ( P=0.650). The preoperative quality of life (QOL) score was (46.7±1.7) and (45.5±1.7), respectively ( P=0.061). The number of patients with urinary tract infection before operation was 11 and 13, respectively ( P=0.480). In the single-segment group, a 2 cm ileum with mesangial vessels was cut at a distance of about 15 cm from the ileocecal part, and the intestine was cut longitudinally along the direction of the intestinal canal at the opposite mesangial margin. The intestinal piece was wrapped horizontally around the F12 urinary tube and wound into a Yang-Monti tube by intermittent suture with a 3-0 single thread. The bladder wall was cut anterolateral to the top wall of the bladder, about 1 cm in length, and the Yang-Monti tube was anastomosed end-to-end with the mucosal muscularis of the bladder wall. A circular incision with a diameter of about 1 cm was made at the level of the anterior superior iliac spine at the rectus abdominis muscle, and a tunnel was formed by puncture into the abdomen with curved forceps. The Yang-Monti tube was led out of the abdominal wall along the tunnel, and the tube opening was fixed with subcutaneous suture. At the same time, the tube wall was fixed in the peritoneum with 4-0 silk thread. In the double-segment group, two segments of 2 cm ileum were cut, and the intestinal tube was cut longitudes along the direction of the opposite mesangial margin. The intestinal piece was first sutured end to end, and then the tube was coiled and reconstructed to form a Yang-Monti tube with a diameter of 0.6-0.8 cm and a length of about 12 cm. The proximal end of the Yang-Monti tube was directly anastomosed with the mucosal muscle layer of the bladder. The operation time, intraoperative blood loss, postoperative catheterization interval, postoperative single catheterization volume, postoperative complications (bleeding, intestinal obstruction, anastomotic leakage, anastomotic stenosis, stoma infection, urinary tract infection, urinary tract infection) and QOL score were compared between the two groups. Results:The operation was successfully completed in both groups. The operation time of single-segment group and double-segment group were (165.8±17.8) min and (157.54±12.25) min, respectively ( P=0.302), and the intraoperative blood loss was (60.0±20.0) ml and (50.00±25.00) ml, respectively ( P=0.650). The postoperative recovery time was 3 (2-4) d and 3 (2-9) d, respectively ( P=0.790), and the postoperative hospital stay was 12 (9-40) d and 12 (10-32) d, respectively (P=0.259). The postoperative single catheterization volume was (240.4±42.7) ml and (261.5±36.3) ml ( P=0.186), and the postoperative QOL was (22.4±2.7) and (21.5±2.6), respectively ( P=0.325), and there was no significant difference. There were 2 cases of urinary tract infection in the single-segment group, and 1 case of urinary tract infection, postoperative bleeding, and intestinal obstruction in the double-segment group. There was no significant difference between the two groups ( P=0.222). The time interval of catheterization in single-segment group and double-segment group was (2.5±1.0) h and (3.5±1.3) h, respectively, and the difference was statistically significant ( P=0.029). The quality of life score after operation was statistically significant compared with that before operation ( P<0.001), and the incidence of urinary tract infection after operation was also statistically significant compared with that before operation ( P=0.011). Conclusions:Both single segment and double segment ileum Yang-Monti tube surgery are feasible surgical methods for patients with urethral damage. There was no difference in the effects of the two types of surgery, and both may improve the quality of life of patients.The postoperative QOL score could be greatly improved and the incidence of complications was low.
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Cell therapy approaches that employ engineered mammalian cells for on-demand production of therapeutic agents in the patient's body are moving beyond proof-of-concept in translational medicine. The therapeutic cells can be customized to sense user-defined signals, process them, and respond in a programmable and predictable way. In this paper, we introduce the available tools and strategies employed to design therapeutic cells. Then, various approaches to control cell behaviors, including open-loop and closed-loop systems, are discussed. We also highlight therapeutic applications of engineered cells for early diagnosis and treatment of various diseases in the clinic and in experimental disease models. Finally, we consider emerging technologies such as digital devices and their potential for incorporation into future cell-based therapies.
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Animals , Humans , Cell Engineering , Gene Regulatory Networks , Genetic Engineering , Mammals/genetics , Synthetic BiologyABSTRACT
Objective: The purpose of the research was to optimize technology for producing a magneto controllable nanocomposite Ag@Fe3O4 with modern physicochemical and therapeutic requirements using methods of mathematical design of the experiment. Methods: To optimize the synthesis process of the nanocomposite Ag@Fe3O4, the method of factor experiment was used. Mathematical calculations were performed using the STATISTICA 10 StatSoft Inc. system and Excel spreadsheet processor of MS Office 2019 Professional Plus. Results: Based on the study of technological parameters of nanocomposite synthesis Ag@Fe3O4 (16 experiments) a regression equation was obtained: Y = 106.415+0.038X1+4.448Х2+1.806Х3–1.593Х4–18.945Х5–109.980Х6. By the use of this equation the synthesis parameters were optimized with the help of steepest ascent method. It was found that the maximum yield of Ag@Fe3O4 can be achieved under the following conditions: X1 (magnetite synthesis time, min)–40; X2 (glucose content in solution,%)–10; X3 (temperature of the Tollens reaction, °С)–65; X4 (magnetite silver coating time, min)–30; X5 (pH, units)–8.5; X6 (rate of addition of ammonia, mol/min)–0.36. Conclusion: Using mathematical design of the experiment, a technology was developed for producing Ag@Fe3O4 with modern physicochemical and therapeutic requirements.
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Objective To evaluate the surgical outcomes of anterior controllable anteriodisplacement and fusion (ACAF) for the reoperation of the cervical ossification of posterior longitudinal ligament (OPLL). Methods Twelve cervical OPLL patients aged 52-74 (63.92±6.54) years, who had poor curative effect or aggravated symptoms after posterior decompressive surgery, were included in this study, with 7 males and 5 females. All patients underwent reoperation with ACAF between Feb. 2016 and Feb. 2017. The Japanese Orthopaedic Association (JOA) score and visual analogue scale (VAS) were used to evaluate neurological function and pain preoperatively and 3, 6, 12 months postoperatively and at final follow-up. Results The patients were followed up for 9-21 months (average [14.92±3.75] months). The neurological function was recovered to varying degrees after ACAF in all patients. The JOA score was significantly improved from 9.33±1.93 preoperatively to 14.67±2.01 at final follow-up (t=3.184, P<0.05), and the neurological function recovery rate was (71.9±21.8)%. The VAS score was significantly decreased from 5.25±1.42 preoperatively to 0.92±0.83 at final followup (t=4.025, P<0.05). Conclusion The outcomes of ACAF for the reoperation of cervical OPLL are satisfactory. ACAF significantly improves the patients' neurological function, and it is an alternative surgical treatment of the reoperation for cervical OPLL.
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Objective To report a novel technique named anterior controllable antedisplacement and fusion (ACAF) for the treatment of severe ossification of the posterior longitudinal ligament of the cervical spine, which allows for direct decompression of the nerve without resection of the ossification, making up for deficiencies in traditional anterior or posterior decompression. Methods The main surgical procedures of the ACAF included treatment of intervertebral space, removal of the anterior part of vertebrae, installation of titanium plate and interbody fusion cages, bilateral osteotomies of the vertebrae, and antedisplacement of the vertebrae ossification complex. The clinical data of two patients undergoing this surgery for severe ossification of the posterior longitudinal ligament of cervical spine were collected and analyzed. Results ACAF enabled direct decompression of spinal cord and nerve root through antedisplacement of the vertebrae ossification complex. The two patients who underwent ACAF gained satisfactory restoration with decompression of spinal cord and good recovery of neurological function, with no specific complications. Conclusion ACAF surgery takes into account the effectiveness of anterior direct decompression and the safety of posterior indirect decompression. Preliminary results shows that it can be used for severe cervical ossification of the posterior longitudinal ligament.
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Objective To report a novel technique named anterior controllable antedisplacement and fusion (ACAF) for the treatment of severe ossification of the posterior longitudinal ligament of the cervical spine,which allows for direct decompression of the nerve without resection of the ossification,making up for deficiencies in traditional anterior or posterior decompression.Methods The main surgical procedures of the ACAF included treatment of intervertebral space,removal of the anterior part of vertebrae,installation of titanium plate and interbody fusion cages,bilateral osteotomies of the vertebrae,and antedisplacement of the vertebrae ossification complex.The clinical data of two patients undergoing this surgery for severe ossification of the posterior longitudinal ligament of cervical spine were collected and analyzed.Results ACAF enabled direct decompression of spinal cord and nerve root through antedisplacement of the vertebrae ossification complex.The two patients who underwent ACAF gained satisfactory restoration with decompression of spinal cord and good recovery of neurological function,with no specific complications.Conclusion ACAF surgery takes into account the effectiveness of anterior direct decompression and the safety of posterior indirect decompression.Preliminary results shows that it can be used for severe cervical ossification of the posterior longitudinal ligament.
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@#Objective To design and apply a kind of controllable enema input apparatus in patients with spinal cord injury (SCI). Methods 20 SCI patients with chronic constipation were included. Their defecation time, nature of defecation and usage of enema of 5 times of defecation were recorded before and after using the new apparatus. Results There were significant differences in the defecation time, nature of defecation and usage of enema before and after using the new apparatus (P<0.05). Conclusion The application of the new controllable enema input apparatus may shorten the defecation time, improve the nature of defecation, and reduce the usage of enema in SCI patients with chronic constipation.
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To differentiate health responsibilities in different circumstances should judge correctly the principle and conditions of responsibility division .It is deemed that the controllability view of responsibility provides the mor-al basis for health responsibility , which claims that the controllable causality is necessary condition for the judgment of responsibility .The construction of health responsibility is a multi -party participation .In face of the current re-ality of China , must build a diversified responsibility principle system: the responsibility of the government as the leading factor , the family and social responsibility as the backbone , and individual responsibility as base .
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Objective To design and construct a controlled adenovirus vector in degradating by itself after induction for solving the problem of stimulating host immune and producing replication adenovirus and providing a secure exogenous gene vectors for clinical practice. Methods Based on the traditional adenovirus vector AdEasyTM system, we inserted the Cre gene which belongs to Cre-LoxP system into the downstream of Tet-On inducible expression system. Two LoxP sites were inserted into two sides of the shuttle plasmid′s right arm genome. Then, the full-length human insulin gene was inserted HindIII enzyme site. After the recombinant adenovirus infected the rat bone marrow-derived mesenchymal stem cells , fluorescent protein expression and insulin secretion were detected before or after induction by Dox. Results A new controlled recombinant adenovirus vector carrying human insulin gene was constructed successfully, and was named AdEasyN/INS. After the transfection of this new vector into QBI-293A cells and rat bone marrow mesenchymal stem cells , green fluorescent protein could be observed. After induction by Dox, both of the ratio of fluorescent cells/total cell and the levels of insulin significantly decreased. Conclusion Construction and preliminary validation of a controlledrecombinant adenovirus vector carrying human insulin gene is constructed successfully , it could infect rat bone marrow mesenchymal stem cells, and degradate by itself after Dox induction, realize the controllability of exogenous gene carrier.
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Hydrogen sulfide (H2S) is recognized as one of three gasotransmitters together with nitric oxide (NO) and carbon monoxide (CO). As a signaling molecule, H2S plays an important role in physiology and shows great potential in pharmaceutical applications. Along this line, there is a need for the development of H2S prodrugs for various reasons. In this review, we summarize different H2S prodrugs, their chemical properties, and some of their potential therapeutic applications.
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Objective To design and apply a kind of controllable enema input apparatus in patients with spinal cord injury (SCI). Meth-ods 20 SCI patients with chronic constipation were included. Their defecation time, nature of defecation and usage of enema of 5 times of defecation were recorded before and after using the new apparatus. Results There were significant differences in the defecation time, nature of defecation and usage of enema before and after using the new apparatus (P<0.05). Conclusion The application of the new controllable en-ema input apparatus may shorten the defecation time, improve the nature of defecation, and reduce the usage of enema in SCI patients with chronic constipation.
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Objective Observe the clinical effect of the controllable airbag elastic chest strap after the breast cancer operation,studying the clinical value of the controllable airbag elastic chest strap.Methods Between May.2009 and Oct.2012,71 women having surgery for breast cancer at The Affiliated Second Hospital of Nan Hua University Oncology Center.They were to receive either a common thoracic girdle compressed binding(n =35),or the controllable airbag elastic chest strap compressed binding (n =36) at the postoperation.The following complications were evaluated:the incidence of seroma formation and duration,the incidence of skin flap swelling,and the dressing time.Results Thirty-five patients with common thoracic girdle is 14 cases of subcutaneous effusion,fluid rate was 40.0％,the effusion duration 7 to 31 days,an average of 17.6 ±7.3 days,15 cases with skin redness (disc),swelling rate is 42.9％,the average treatment time 18.7 ±3.5 minutes; With the controllable airbag elastic chest strap group of six cases of subcutaneous effusion,fluid rate was 16.7％,the duration of effusion 5-14days,an average of 10.5 ± 3.9 days,skin redness (disc),swelling rate is 13.9％,the average treatment time 12.2 ± 2.4 minutes.Conclusions The controllable airbag elastic chest strap can reduce subcutaneous effusion,reduce skin flapswelling,saving the treatment time,is worth promoting in the clinical medical supplies.
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Objective To explore the application strategies of immunosuppression scheme after different types of liver transplantation for liver diseases. Methods According to the published literatures and the practical experiences in organ transplant center of Tianjin First Center Hospital,the immunosuppression schemes used after liver transplantation,the liver transplantation in patients with hepatitis C or liver cancer,patients after liver re-transplantation or with concurrent infection or with renal injury were summarized,and the spontaneous controllable tolerance (SOT) and the dosage reduction or elimination of immunosuppressor were approached. Results① Dose reduction and combined drugs therapy were the important strategies to adjust immunosuppressor after liver transplantation.②Maintaining low level immunosuppression,avoiding the repeat of cell rejection reaction and actively implementing antiviral therapy could slow down the progress of fibrosis after liver transplantation in HCV patients with recurrent hepatitis.③The induction therapy using anti CD25 monoclonal antibody and based on sirolimus(SRL) maintaining immune inhibition were the related factors to improve the survival rate of liver transplantation in patients with liver cancer. ④ We needed to strengthen the immune inhibitor concentration detection and timely adjust the dosage of calcineurin inhibitors(CNIs)or SRL after liver re-transplantation or when there was infectious complication. In severe cases with infection,we could consider to remove them.⑤We could reduce the progression of renal injury after transplantation by decreasing the CNIs or converting to SRL.⑥Inducing stable and durable immune tolerance and designedly withdrawing the immunosuppressor after liver transplantation in relatively stable patients,we might expect 20% patients achieving SOT. Conclusions The progress of immunosuppression scheme after liver transplantation on the one hand depends on the successive development of new types of immunosuppressor with lower adverse effect, and on the other hand,the more accurate genomics,pharmacogenetics and pharmacokinetic methods for monitoring the transplanted liver damage are necessary. We also need to look for specific immune monitoring methods to accurately assess the effectiveness and toxicity of immunosuppressive agents to gradually withdraw or stop the immunity inhibitors.
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Objective To investigate the effect of the modified and controllable sigmoid colostomy in ostomy operation.Methods Sixty patients were divided into two groups.The control group (30 cases) received extraperitoneal sigrnoid colostomy while the experimental group (30 cases) received modified and controllable sigmoid colostomy.Postoperative complications caused by sigmoid colostomy,artificial anal function,psychological disorder,life quality,and the level of tumor marker between two groups were compared.Results In experimental group,4 patients (13.33％,4/30) at postoperative 6 months and 1 patient (3.33％,1/30) at postoperative 12 months suffered from complications caused by sigmoid colostomy.The incidence rate of complications caused by sigmoid colostomy was higher in control group[30.00％(9/30) and 10.00％(3/30)],but there was no significant difference (P ＞ 0.05).In experimental group,the defecate controllable and times were increased,18 patients (60.00％,18/30) could freedom control defecation,14patients (46.67％,14/30) defecation times ≤3 at postoperative 12 months.But there were 11 patients (36.67％,11/30) and 8 patients (26.67％,8/30) in control group,there was significant difference (P ＜0.05).The rate of human communication disorders,self abasement,anxiety and disappointment in experimental group at postoperative 12 months were significantly lower than those in control group (P ＜ 0.05).The rate of pessimism,loneliness and fear between two groups had no significant difference (P ＞ 0.05).In the evaluation of QLQ-C30 scale,aside from recognition function and financial straits had no significant difference(P ＞ 0.05),others scores in experimental group were significantly better than those in control group (P ＜ 0.05 or ＜ 0.01).In the evaluation of QLQ-C38 scale,the scores in experimental group at postoperative 12 months were significantly better than those in control group (P ＜ 0.01 or ＜ 0.05).At postoperative 12 months,the level of carcinoembryonic antigen,cancer antigen 125 and cancer antigen 199 in experimental group were significantly lower than those in control group (P ＜ 0.05).Conclusion The modified and controllable sigrnoid colostomy has the advantages,less complications,controllable,simple,safe and it is worthy of application more widely in clinical practice.
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44 obstructive sleepapnea-hypopnea syndrome ( OSAHS) patients were Supplemented by an controlla-ble appliance in their intervene treatments. The data of polysomnography ( PSG) , Epworth sleepiness scale( ESS) and quality of life-Quebec sleep questionnaire( QSQ) before and 3 treatment period months after oral appliance were recorded. Correlations between subjective and objective measure before treated with OA and subsequently investi-gate treatment mechanism of oral appliance( OA) . Correlations indexes between before and after 3 treatment with an controllable appliance, and evaluation had statistically significance ( P <0. 05 ) . Absolute correlations between PSG indexes and subjective measures before oral appliance ranged from 0. 321 ~0. 433 , and 3 treatment period months after oral appliance ranged from 0. 306~0. 437 . Both PSG indexes and quality of life improved significantly after oral appliance(P<0. 05).
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Objective:To study the effect of controllable abdominal breath in treatment of migraine.Method:20 patients(10 male,10 female,aged 20-30 years)with migraine according to international diagnostic standard published 1990 were randomly divided into study group and control group.The study group received training of controllable abdominal breath.All subjects were followed for 3 months.Changes of symptoms and hemorhelogy were recorded.Result:Study group improved in both symptom and index of hemorheology after treatment,and the results were better than that of control.Conclusion:Controllable abdominal breath is effective in treatment of migraine.