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Objective To explore the effect of activation of mammalian target of rapmycin complex 2(mTORC2)/Akt signaling pathway on dopaminergic neurons and behavior in 6-hydroxydopamine (6-OHDA) model mice and its possible mechanism. Methods Selecting 36 mice which The Nestin-CreERTM and ROSA26-LacZ reporter genes were detected at the same time in 3-month-old male C57BL/6J mice weighing 20-25 g divideng them into 4 gruops, NS+ corn oil group, 6-OHDA+corn oil group, 6-OHDA+PP242 group and 6-OHDA+A-443654 group, and 6-OHDA was injected into the right striatum of the brain to replicate the Parkinson’s disease (PD) model of mice, and then daily intraperitoneal injection of mTORC2/Akt signaling pathway agonist A-443654 or inhibitor PP242. Serum interleukin-1β (IL-1β) and tumor necrosis factor-α(TNF-α)levels were measured by enzyme-linked immunosorbent assay. Immunohistochemistry and immunofluorescence staining were performed to investigate the change of microglia, dopaminergic neurons as well as neural progenitor cells (NPCs). Western blotting was used to detect the expression of related protein of mTORC2/Akt signaling pathway including rictor, p-Akt and regulated in development and DNA dgmage responses 1(REDD1) and the interaction between them were verified by immunoprecipitation. Finally, the behavioral performance of each group of mice was observed. Results With the activation of microglia and the increase of inflammatory factors in PD model mice, the number of dopaminergic neurons in the substantia nigra(SN) decreased significantly, and the motor function of the mice was impaired, but the number of NPCs increased significantly compared with the control mice, mTORC2/Akt signaling pathway related protein expression was also significantly up-regulated. A-443654 treatment further up-regulated the expression of these proteins, meanwhile the indicators mentioned above were ameliorated. However, the inhibitor PP242 treatment group showed completely opposite result with the agonist group. Conclusion A-443654 can promote the proliferation of NPCs and the number of new-born dopaminergic neurons by up-regulating related proteins of mTORC2/Akt signaling pathway, and reducing the activation of microglia and the level of inflammation factors, which ultimately lead to the amelioration of SN-striatal dopaminergic neurons and behavioral performance in PD model mice.
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The incidence of portal vein tumor thrombus (PVTT) in patients with hepato-cellular carcinoma (HCC) is high and the prognosis is poor. The treatment mode of HCC+PVTT is changing to multidisciplinary comprehensive treatment. The authors make a deep investigation on the occurrence basis, classification, surgical treatment indication, postoperative adjuvant treatment and preoperative conversion treatment plan of HCC+PVTT, in order to provide reference for the diagnosis and treatment of this disease.
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Objective To explore the effect of recombination signal binding protein for immunoglobulin Kappa J region (RBP-Jκ) on the proliferation and differentiation of CD133￣positive ependymal cells and its possible mechanism. Methods RBP-Jκ in CD133-positive ependymal cells of lateral ventricle was interfered with siRNA in the fetuses of embryos which were isolated from 12-day pregnant Institute of Cancer Research(ICR) mouse (3 mice) and knocked out in CD133-CreER
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Objective To clarify the protective effect of allopregnanolone (APα) on cell line SH-SY5Y damaged by 6-hydroxydopamine (6-OHDA) and its possible molecular mechanism. Methods 6-OHDA, APα, γ-aminobutyric acid A receptor (GABAAR) antagonist, voltage-gated L-type Ca2
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The coronavirus disease 2019 (COVID-19) outbreak is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world, which has posed a great threat to global public health security. Angiotensin converting enzyme 2 (ACE2) has been identified as the major functional receptor of SARS-CoV-2, which plays an essential role in mediating virus invasion into host cells. Thus, an in-depth understanding of the recent progress of ACE2, its relationship with the virus and related drugs is of great significance for the prevention and treatment of COVID-19. Here, from the aspects of structure, expression and function, this article reviews the latest research progress of ACE2 and SARS-CoV-2. Meanwhile, this article also summarizes the mechanism of ACE2-mediated virus invasion and ACE2-related drugs, which will provide theoretical reference for viral prevention and treatment.
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[ Abstract] Objective To investigate the effects of allopregnanolone (APα) on the dopaminergic neurons in substantia nigra, striatal dopaminergic neural fibers and behavioral performance in Parkinson’ s disease (PD) model mice, as well as its possible molecular mechanisms. Methods C57BL / 6 adult male mice with 20-25 g at 3-month old (n = 90) were successively injected with 6-hydroxydopamine (6-OHDA) to generate a PD animal model. APα and its receptor γ-aminobutyric acid A receptor (GABAAR) antagonist—bicuculline (Bic) were successively injected. ELISA was used to detect the APα or dopamine concentration in the serum, cerebral cortex and striatum. The number of tyrosine hydroxylase (TH) in the substantia nigra (SN) and striatal dopaminergic neural projections were examined by immunohistochemical staining. The expression levels of GABAAR in membrane fractions and Ca
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Objective To observe the influence of Qileng Decoction on the level of serum visfatin and the degree of carotid atherosclerosis in patients with acute atherosclerotic cerebral infarction(AACI). Methods One hundred and eighty AACI patients were classified into non-AACI control group (group A;N = 30), stable carotid atherosclerotic plaques group(group B;N = 75)and unstable carotid atherosclerotic plaques group(group C;N= 75)according to the results of carotid color ultrasonography. The serum visfatin level of the three groups was detected at the time of AACI attack. Group B and group C were separately randomized into conventional treatment subgroup (N = 37)and Qileng Decoction subgroup (N = 38). The conventional treatment subgroup was given basic therapy for AACI including nutrition support and symptomatic treatment , and Qileng Decoction subgroup was treated with Qileng Decoction (mainly composed of Radix Astragali,Rhizoma Sparganii, Fructus Mori,Radix Trichosanthis, Rhizoma Curcumae,Hirudo,and Fructus Aurantii)orally on the basis of treatment for the conventional treatment group. Before treatment and 15,90 and 180 days after treatment,we detected the level of serum visfatin,and measured the carotid intima-media thickness(IMT)and plaque scores(PS). Results (1)At the time of AACI attack,serum visfatin level of group B and group C was significantly higher than that of group A,and the level of serum visfatin of group C was significantly higher than that of group B,the difference being significant (P < 0.05). After treatment,serum visfatin over-expression was improved in both conventional treatment subgroup and Qileng Decoction subgroup of groups B and C at various time points (P< 0.05 compared with that before treatment), and the improvement in Qileng Decoction subgroup was superior to that in conventional treatment subgroup (P < 0.05). (2)At the end of treatment, IMT was improved in conventional treatment subgroup and Qileng Decoction subgroup of groups B and C (P < 0.05 compared with that before treatment), and the improvement in Qileng Decoction subgroup was superior to that in conventional treatment subgroup (P < 0.05). (3) The total effective rate for PS improvement of conventional treatment subgroup in groups B and C was 74.3％,68.6％ respectively,and that of Qileng Decoction subgroup in groups B and C was 94.4％, 91.7％ respectively, indicating that Qileng Decoction subgroup had better effect on improving PS than conventional treatment subgroup(P < 0.05). Conclusion Qileng Decoction exerts certain effect on regulating the over-expression of serum visfatin and improving the degree of carotid atherosclerosis in AACI patients.
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Myocardial fibrosis (MF) is an important pathological process of cardiac remodeling in patients with heart failure; however its etiology has not been clear. It has been known that the angiotensin II type 1 receptor autoantibody (AT1-AA) is present in patients with heart failure, but it is unclear whether this antibody directly causes MF. In this study, we investigated the role of AT1-AA in MF and its effects on cardiac fibroblasts (CFs). The AT1-AA positive rat model was established by active immunization method, and the measurement of indexes were made in the 8th week after active immunity. The results of heart echocardiography showed that the cardiac systolic and diastolic functions of AT1-AA positive rats were impaired with reduced left ventricular wall thickness and enlarged heart chambers. HE staining results showed that the myocardial fibers were disorganized and ruptured, and Masson staining revealed that the area of collagen fibers around the myocardium and coronary arteries was significantly increased in AT1-AA positive group compared with that of the control group (P < 0.05). Moreover, primary CFs isolated from neonatal rats were cultured and treated with AT1-AA for 48 h. CCK-8 and immunofluorescence staining results showed that AT1-AA enhanced proliferation rate of CFs (P < 0.001), and Western blot results showed that AT1-AA significantly increased expressions of collagen I (Col I), Col III, matrix metalloproteinase-2 (MMP-2) and MMP-9 in CFs (all P < 0.05). Taken together, these results suggest that AT1-AA may induce MF and cardiac dysfunction via activating CFs.
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<p><b>OBJECTIVE</b>To evaluate the application of CT scan in diagnosis of pathological types and origins of metastatic ovarian tumors.</p><p><b>METHODS</b>Clinical data, histopathological results and CT images of 43 patients with pathologically-proved metastatic ovarian tumor were retrospectively analyzed. Diagnostic values of CT imaging for pathological type and origin of metastatic ovarian tumors were evaluated.</p><p><b>RESULTS</b>The pathological types of metastatic ovarian tumor were related to the size of the lesion (<0.01), while not related to the sites of lesion (unilateral or bilateral), the cystic-solid and mixed lesions with or without separation (all>0.05). Metastatic ovarian tumors of colorectal origin were usually unilateral lesions, and showed cystic or cystic-solid masses, while those of gastric origin were usually bilateral lesions, and showed solid or solid-based masses.</p><p><b>CONCLUSIONS</b>CT imaging may be of value in diagnosis of pathological types and origin of metastatic ovarian tumor.</p>
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Objective To explore the feeling of parents of children with strabismus. Methods A semi-structured interview was conducted among 20 parents of children with strabismus. The data were analyzed based on Colaizzi phenomenotogical research methods. Result The parents' feeling was classified into 4 themes:negative emotional experience, parent-child relationship disorder, social communication disorders, and lack of support system. Conclusion According to the parents' real experience and feelings, medical staffs should pay attention to parents' psychological conditions, giving them necessary knowledge and psychological nursing so as to reduce the parents' psychological tension, improve the quality of life and promote the recovery after surgery.
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Objective To investigate the changes of TLR4 and nuclear factor kappa B(NF-κB) levels in peripheral blood mononuclear cells(PBMC) of the patients with ulcerative colitis(UC) and its possible pathogenesis mechanism.Methods In our hospital from January 2014 to January 2015,30 cases of UC were selected as the observation group,and other 10 individuals undergoing healthy physical examination in this hospital were selected as the control group.Flow cytometry was used to detect the positive expression rate of TLR4 on surface of peripheral blood CD14+ mononuclear cells.The levels of TLR4,MyD88,NF-κB(P65)mRNA expression were detected by RT-PCR.Western blot was adopted to detect the levels of TLR4,MyD88,NF-κB(P65) protein.Results The positive expression rate of TLR4 on the surface of peripheral blood CD14+ mononuclear cells in the observation group was significantly higher than that in the control group(P＜0.05);the levels of TLR4,MyD88 and NF-κB(P65) B mRNA and protein in the control group were significantly lower than those in the observation group(P＜0.05);the levels of TLR4,MyD88 and NF-κB(P65) protein were positively correlated with the severity of UC.Conclusion The levels of TLR4 and NF-κB in PBMC of the patients with UC are significantly increased,clinic can judge the UC development degree by detecting TLR4 and NF-κB levels.
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<p><b>OBJECTIVE</b>To investigate the effects of interim hemodialysis (HD) on survival and clinical outcomes in patients with maintenance peritoneal dialysis (PD).</p><p><b>METHODS</b>The clinical data of 908 patients undergoing maintenance PD from January 2010 to December 2014 registered in Zhejiang Dialysis Regisration System were retrospectively analyzed. Among all PD patients, 176 cases received interim HD for less than 3 months, and then transferred to PD (transfer group) and 732 cases had initial PD (non-transfer group). The demographic parameters, biochemical data, comorbidity, details of peritonitis and transplantation were documented. Survival curves were made by the Kaplan-Meier method; univariate and multivariate analyses were performed with Cox proportional hazard regression model to identify risk factors of mortality.</p><p><b>RESULTS</b>Compared with patients in transfer group, patients in non-transfer group had significantly higher serum albumin and total Kt/V levels. The survival rate was significantly higher in non-transfer group, but there was no significant difference in technique survival between two groups. After multivariable adjustment, initial dialysis modality (HR=1.60, 95% CI: 1.01~2.56), age (HR=1.07, 95% CI:1.05~1.09) and serum albumin (HR=0.96, 95% CI: 0.93~0.99) and Charslon comorbidity index (HR=2.54, 95% CI:1.63~3.94) were independent factors for long-term survival.</p><p><b>CONCLUSION</b>Patients who transfer to PD after interim HD have lower survival rate than patients who start with and are maintained on PD. HD is an independent risk factor for PD patients, therefore, patients with PD should be well informed and educated with dialysis protocols.</p>
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Humans , Kidney Failure, Chronic , Mortality , Therapeutics , Peritoneal Dialysis , Proportional Hazards Models , Renal Dialysis , Retrospective Studies , Risk Factors , Survival RateABSTRACT
Retrospective analyses were conducted for the clinical data of two cases with pseudoMeigs' syndrome at our hospital.Both had respiratory symptoms,such as cough and dyspnea.Radiological examinations revealed ascites,pleural effusion and pelvic mass.The definite pathological diagnosis was pelvic malignant tumor.After surgical tumor removal,ascites and pleural effusion disappeared without recurrence.Along with reviewed cases from PubMed in the last decade,a total of 49 cases had pseudoMeigs' syndrome.The age range was 11-73 years.Their clinical manifestations include dyspnea (78％),abdominal distension (69％),cough (14％),abdominal pain (12％),fatigue (10％),weight loss (6％) chest pain (4％),fever (4％),abdominal mass (4％),and oliguria (2％).CA125 was commonly elevated.The primary tumors in pelvic cavity accounted for 78％.And ovarian metastasis from colon cancer was one of the most common in metastatic tumor.
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Objective To investigate the pathological findings and diagnosis value of CT and MRI in detec-tion of primary centralnervous system lymphoma (PCNSL)so as to improve diagnostic accuracy of the condition. Methods The results of CT and MRI for 32 patients with PCNSL were analyzed retrospectively,and the results were compared with the finally obtained surgical-pathological examination.Results Of 32 cases,the foci were single in 29 cases and multiple in 4 cases,and there were 41 foci in total.Most foci were located near the surface or middle line of brain.On CT scan appearances,most foci were hyperdensity or slightly hyperdensity masses with the well definite margin,on MRI,it showed low signal of T1 -weighted imaging (T1 WI)and slightly increased non-uniform signal of T2 -weighted imaging (T2 WI).All the foci were equally and markedly enhanced after enhancement.The diagnostic coincident rate of combination diagnosis (93.8%)was significantly higher than that of CT (71.9%)and MRI (75.0%)(χ2 =7.234 6,P=0.003 2;χ2 =6.953 8,P=0.003 7).Conclusion CT,MRI have characteristic mani-festation for PCNSL,and according to the manifestation of CT,MRI,predilection site,mass effect,and combined with pathological examination,which can effectively improve the sensitivity and accuracy of diagnosis.
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<p><b>BACKGROUND</b>High peritoneal transport status was previously thought to be a poor prognostic factor in peritoneal dialysis (PD) patients. However, its effect on diabetic nephropathy PD patients is unclear in consideration of the adverse impact of diabetes itself. The purpose of this study was to investigate the influence of peritoneal transport characteristics on nutritional status and clinical outcome in diabetic nephropathy patients on PD.</p><p><b>METHODS</b>One hundred and two diabetic nephropathy patients on PD were enrolled in this observational cohort study. According to the initial peritoneal equilibration test result, patients were divided into two groups: Higher transport group (HT, including high and high average transport) and lower transport group (LT, including low and low-average transport). Demographic characteristics, biochemical data, dialysis adequacy, and nutritional status were evaluated. Clinical outcomes were compared. Risk factors for death-censored technique failure and mortality were analyzed.</p><p><b>RESULTS</b>Compared with LT group (n = 37), serum albumin was significantly lower and the incidence of malnutrition by subjective global assessment was significantly higher in HT group (n = 65) (P < 0.05). Kaplan-Meier analyses showed that death-censored technique failure and mortality were significantly increased in HT group compared with that in LT group. On multivariate Cox analyses, higher peritoneal transport status and lower residual renal function (RRF) were independent predictors of death-censored technique failure when adjusted for serum albumin and total weekly urea clearance (Kt/V). Independent predictors of mortality were advanced age, anemia, hypoalbuminemia, and lower RRF, but not higher peritoneal transport status.</p><p><b>CONCLUSIONS</b>Higher peritoneal transport status has an adverse influence on nutrition for diabetic nephropathy patients on PD. Higher peritoneal transport status is a significant independent risk factor for death-censored technique failure, but not for mortality in diabetic nephropathy patients on PD.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Biological Transport , Cohort Studies , Diabetic Nephropathies , Metabolism , Therapeutics , Kidney , Metabolism , Pathology , Nutritional Status , Peritoneal DialysisABSTRACT
Objective To investigate the efficacy of prostaglandin E1 administered via the pulmonary artery for treatment of pulmonary hypertension in patients.Methods Thirty ASA Ⅱ or Ⅲ patients undergoing offpump coronary artery bypass grafting complicated with pulmonary hypertension,with pulmonary arterial systolic pressure (PASP) ＞ 40 mm Hg,were randomly divided into 2 groups (n =15 each):administration via the central vein group (group C) and administration via the pulmonary artery group (group P).Anesthesia was induced with midazolam,etomidate,cisatracurium and sufentanil.The patients were tracheal intubated and mechanically ventilated.Swan-Ganz catheter was placed via the right internal jugular vein for monitoring of hemodynamic parameters after induction of anesthesia.The central vein and pulmonary artery were cannulated for infusion of prostaglandin E1.Prostaglandin E1 was infused at a rate of 20-50 ng· kg-1 · min-1 starting from the end of skin incision until PASP was decreased to 20-30 mm Hg.Heart rate (HR),mean arterial pressure (MAP),central venous pressure (CVP),PASP,pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) were recorded at 5 rain before administration (To) and 5 min after administration (T1).The pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) were calculated.The amount of prostaglandin E1 consumed was recorded.Results Compared with group C,the amount of prostaglandin E1 consumed was significantly reduced,PASP and PVR were decreased at T1,while MAP and SVR were increased at T1 in group P(P ＜ 0.05).Conclusion Administration via the pulmonary artery can increase the potency of prostaglandin E1 for treatment of pulmonary hypertension and exerts no influence on the systemic hemodynamics.
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Objective To investigate the possible role of X-box binding protein (XBP1) expression at mRNA level in the hepatocarcinogenesis. Methods The expression of XBP1 at mRNA level was determined with RT-PCR method in liver carcinoma (42 cases), liver tissue adjacent to carcinoma (15 cases) and normal liver tissue (15 cases). XBP1 mRNA relative expression level was obtained by comparing with GAPDH mRNA level. The correlation between XBP1 expression and clinicopathological features of liver carcinoma were respectively analyzed. Results RT-PCR results showed that the expression of XBP1 mRNA in liver carcinoma cases (0.4396 ±0.0241) was significantly higher that that of liver tissues adjacent to carcinoma (0.4152±0.0252) and normal liver tissue (0.4095 ±0.0149), (F =12.79,P =0.001). No significant differences in the expression of XBP1 were found among different age and sex of the patients, different location, histological types, grade and metastatic status in liver carcinoma (P >0.05). Conclusion Increased expression of XBP1 mRNA is found in liver carcinoma but no correlation could be seen between XBP1 expression and clinicopathological features, which XBP1 is involved in the hepatocarcinogenesis.
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Objective To evaluate the cardioprotective effect of dexmedetomidine in patients undergoing off-pump coronary artery bypass grafting. Methods Forty-six ASA Ⅱ or Ⅲ patients aged 37-64 yr weighing 54-81 kg undergoing off-pump coronary artery bypass grafting were randomized into 2 groups ( n = 23 each): control group (group C) and dexmedetomidine group (group D) . Dexmedetomidine was infused at 0.5 μg·kg-1·h-1 starting after induction of anesthesia until the end of operation in group D. Radial artery was cannulated and Swan-Ganz catheter placed via right internal jugular vein. HR, MAP, mean pulmonary arterial pressure, pulmonary capilary wedge pressure, central venous pressure, and cardiac output were recorded and stroke volume index, left and right ventricular stroke work index, systemic vascular resistance and pulmonary vascular resistance were calculated at the beginning of operation (T1 ), immediately (T2 ) and at 30 min after reestablishment of coronary blood flow (T3 ) and the end of operation (T4 ) . Venous blood samples were taken before induction of anesthesia (T0 , baseline) , at T4 and 4 h (T5 ) and 24 h (T6 ) after operation for determination of plasma concentration of cardiac troponin I by ELISA. Results Stroke volume index and left ventricular stroke work index were significantly higher at T4 while systemic vascular resistance was lower at T34 in group D than in group C. Plasma cardiac troponin Ⅰ concentration was significantly lower at T6 in group D than in group C. Conclusion Dexmedetomidine infusion at 0.5 μg ·kg-1·h-1 during operation can protect myocardium in patients undergoing off-pump coronary artery bypass grafting.
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ObjectiveTo investigate the effects of dexmedetomidine on cerebral oxygen and glucose metabolism in patients undergoing mitral valve replacement under cardiopulmonary bypass (CPB).Methods Fiftyeight ASA Ⅱ or Ⅲ patients of both sexes aged 32-64 yr weighing 52-90 kg undergoing mitral valve replacement were randomly divided into 2 groups (n =29 each): control group (group C) and dexmedetomidine group (group D).Dexmedetomidine was infused iv at 0.5 μg· kg- 1 · h- 1 starting after tracheal intubation until the end of operation in group D,while in group C equal volume of normal saline was infused instead of dexmedetomidine.Blood samples were collected from radial artery and jugular venous bulb for blood gas analysis and determination of glucose and lactate concentrations before CPB (T1,nasopharyngeal temperature =36 ℃ ),during CPB (T2,nasopharyngeal temperature =30 ℃ ),immediately and 30 min after restoration of spontaneous heart beat ( T3,T4 ).Arterial O2 content ( CaO2 ),arteriovenous O2 content difference ( Da-jvO2 ),cerebral extraction of O2 ( CEO2 ),arteriovenous glucose and lactate content differences (Da-jvGlu and Da-jvLac) were calculated.ResultsThe Da-jvO2 and CEO2 were significantly decreased at T2 in group D as compared with group C.There was no significant difference in CaO2,Da-jvGlu and Da-jvLac between the 2 groups.ConclusionDexmedetomidine can reduce cerebral O2 metabolism and help maintain the balance between cerebral O2 supply and demand but has no effect on cerebral glucose metabolism in patients undergoing mitral valve replacement under CPB.
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<p><b>OBJECTIVE</b>Dominant disease menu of mental and behavioral disorder of acupuncture therapy was summarized and obtained in this article.</p><p><b>METHODS</b>Literatures on clinical treatment of mental and behavioral disorder with acupuncture were picked up from CBMdisc and CNKI during 1978 to 2007. Types of mental and behavioral disorder and report frequency of each disease treated with acupuncture were counted. And dominant diseases which were favorable to be treated with acupuncture were acquired through analysis and inductive method.</p><p><b>RESULTS</b>Twenty-nine diseases of mental and behavioral disorder are favorable to be treated with acupuncture which were mentioned in totally 1967 related documents. It is found that the number of reports of sleep disorder, depression, hysteria aphronesia, dementia and sexual disorder are ranked as the top five.</p><p><b>CONCLUSION</b>It is concluded that the preponderant diseases of mental and behavioral disorder treated by acupuncture are dementia, withdrawal syndrome, mental retardation, obsessive-compulsive disorder, sleep disorder, gastrointestinal neurosis (gastrointestinal disorders), depression, alcoholism and globus hystericus.</p>