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1.
Cancer Research on Prevention and Treatment ; (12): 452-457, 2023.
Article in Chinese | WPRIM | ID: wpr-986215

ABSTRACT

Targeted therapy has brought revolutionary breakthroughs for radioiodine-refractory differentiated thyroid cancer. New targeted drugs have prolonged the survival of patients with advanced differentiated thyroid cancer. Multiple tyrosine kinase inhibitors, represented by sorafenib and lenvatinib, have remarkably improved the progression-free survival of patients. Novel tyrosine kinase inhibitors targeting BRAF and RET mutation have also achieved remarkable curative effects, greatly enriching the treatment methods for thyroid cancer. This article reviews the latest research progress on targeted therapy in radioiodine-refractory differentiated thyroid cancer.

2.
International Journal of Traditional Chinese Medicine ; (6): 1049-1053, 2020.
Article in Chinese | WPRIM | ID: wpr-863723

ABSTRACT

With the rapid development of science and technology, more creative methods have been applied to the inheritance mode of traditional Chinese medicine, such as studying the inheritance process of famous doctorsin an objective and rigorous way. The bottleneck of information transmission from famous doctors is to collect data, process data, apply algorithms, analyze and summarize data. The integration of artificial intelligence and big data deep learning algorithm knowledge mapping technology and other technical methods has brought technological innovation for the inheritance of famous doctors. With such development, the team of the research center of TCM grand health intelligence, Institute of Information on Chinese Medicine, China Academy of Chinese Medical Science, has carried out a series of professional application system research in the field of traditional Chinese medicine, centering on the planning and inheritance of famous doctors. We developed the ancient and modern medical case cloud platform, medical big data analysis platform, cloud medical APP, and famous doctor inheritance workstation. In such way, the problems were solved of low efficiency of medical case collection and the lack of objective data support and information barriers in the experience summary of famous doctors. The artificial intelligence techniques are to promote the inheritance of famous doctors' experience and improve the teaching ability and efficiency.

3.
International Journal of Traditional Chinese Medicine ; (6): 1008-1013, 2020.
Article in Chinese | WPRIM | ID: wpr-863722

ABSTRACT

Objective:To analyze the medication rules of modern physicians on treating depression syndrome, so as to provide reference for clinical treatment of depression syndrome.Methods:We collect and sort out the modern medical records of depression syndrome in the cloud platform of ancient and modern medical records (v1.5) and the modern medical records' database of famous doctors, and search CNKI, Chongqing VIP and Wanfang databases for the modern depression medical cases from journals during database establishment time to October 1, 2018. We extracted traditional Chinese medicine prescription data in the medical records, and applied the ancient and modern medical records cloud platform (v 1.5) to standardize the acquired TCM data, and integrate data mining function for frequency statistics, cluster analysis, association analysis and complex network analysis to obtain the high frequency of drugs' attributes, classification, and common drug pairs and core prescriptions of modern doctors. Results:After screening, a total of 1 984 cases were included, 3 618 cases were diagnosed, and 3 089 pieces of data of TCM prescriptions were included. A total of 1 458 medicines were involved, and the total frequency of medication was 39 634. The high frequency medicines were: Bupleurum chinense (1 546 times), Poria cocos (1 210 times), Angelica sinensis (1 167 times), Paeonia lactiflora (1 109 times) and Tulip (1 091 times). The commonly used Chinese medicines were mainly warm, flat, bitter and bitter, mostly attributed to the four meridians of spleen, lung, liver and heart. Commonly used medicines were Radix Paeoniae Alba- Bupleurum, Radix Angelicae- Bupleurum, Radix Bupleurum- Tulip, Radix Angelicae- Paeoniae Alba, Radix Angelicae- Paeoniae Alba- Bupleurum, etc. The core prescriptions were Suanzaoren Decoction, Chaihu- Shugan San and Erchen Decoction. Conclusions:Modern physicians' treating principles for depression syndrome is soothing liver and regulating qi, invigorating spleen and nourishing heart, emphasizing qi and blood, harmonizing liver, spleen and heart, and linking TCM pathogeneses.

4.
Chinese Journal of General Surgery ; (12): 393-397, 2018.
Article in Chinese | WPRIM | ID: wpr-710555

ABSTRACT

Objective To evaluate the change of clinicopathological features and prognosis of papillary thyroid cancer over a 15-year period.Methods The clinicopathological features and outcomes of papillary thyroid cancer patients were analyzed in three groups according to the time of diagnosis:group Ⅰ (1997-2001),group Ⅱ (2002-2006),and group Ⅲ (2007-2011).Results As time advanced,the average age of papillary thyroid cancer patients increased,tumor stage,like size,extrathyroid invasion and lymph node metastasis decreased dramatically (P < 0.01).The percentage of multifocality and bilaterality increased.The long-term follow up data (median follow up time was 6.6 years),indicated that the 15-year over all survival was 97.8% and the 15-year disease-free survival was 90.2%.Tumor ≥3 cm,bilaterality,extrathyroid invasion,lymph node metastasis and AJCC stage were correlated with tumor recurrence.By multivariate COX-regression analysis only lymph node metastasis and bilaterality were independent risk factors.Conclusion The clinicopathological features of papillary thyroid cancer changed over 15 years,with the percentage of early-staged patients increased.Lymph node metastasis and bilaterality are two risk factors for tumor recurrence.

5.
Chinese Journal of Postgraduates of Medicine ; (36): 248-252, 2018.
Article in Chinese | WPRIM | ID: wpr-700201

ABSTRACT

Objective To compare the efficacy of percutaneous transforaminal endoscopic discectomy with minimally invasive ozone therapy in the treatment of lumbar disc herniation combined with lumbar canal stenosis. Methods The clinical data of 90 patients with lumbar disc herniation combined with lumbar canal stenosis from May 2015 to May 2017 were analyzed retrospectively. The patients were divided into 2 groups according to the method of operation, control group (45 patients received minimally invasive ozone therapy), and observation group (45 patients received percutaneous transforaminal endoscopic discectomy). The basic surgical conditions, visual analog score (VAS), Oswestry dysfunction index (ODI), Japanese Orthopedic Association (JOA) score and efficacy were compared between 2 groups.Results The operation time in observation group was significantly longer than that in control group:(81.93 ± 17.02)min vs.(42.41 ± 15.69)min,postoperative hospitalization time was significantly shorter than that in control group: (1.27 ± 1.05) d vs. (4.29 ± 2.03) d, and there were statistical differences(t=-9.571 and 3.742,P<0.01).The VAS 1 week and 1 month after operation in observation group was significantly lower than that in control group:(4.29 ± 1.39)scores vs.(5.91 ± 1.51) scores and(2.53 ± 0.69)scores vs.(3.25 ± 0.94)scores,and there was statistical difference(P<0.01 or<0.05).The ODI and JOA score 3 months after operation in observation group were significantly better than those in control group: (13.24 ± 5.86) scores vs. (27.83 ± 8.91) scores and (24.24 ± 3.09) scores vs. (20.95 ± 6.25) scores, and there were statistical differences (P<0.01). The eligible rate in observation group was significantly higher than that in control group: 86.67%(39/45)vs.68.89%(31/45),and there was statistical difference(χ2=4.114,P<0.05).Conclusions Percutaneous transforaminal endoscopic discectomy compared with minimally invasive ozone therapy for lumbar disc herniation combined with lumbar canal stenosis is more effective,with shorter postoperative length of stay,more obvious pain relief and more quick lumbar function recovery after operation.

6.
World Science and Technology-Modernization of Traditional Chinese Medicine ; (12): 2262-2268, 2018.
Article in Chinese | WPRIM | ID: wpr-752196

ABSTRACT

Objective: To research the medication regularity of Chinese medicine on treating urinary tract infection based on the Ancient and Modern Consilia Cloud Platform to provide references for clinical treatment of urinary tract infection.Methods: The Ancient and Modern Consilia Cloud Platform was used to screen the consilia of Traditional Chinese Medicine for the treatment of urinary tract infection, the materials mainly come from books, journal articles, famous medical studios in the modern Chinese medicine case database. Screening, cleaning, standardizing consilia, and the standardized consilia database was set up. Statistical analysis, cluster analysis and complex networks were used to analysed the core prescription, the herb medicine frequency, the herb medicine four gas, the herb medicine five flavors, the herb medicine channel tropism and other regularity of Chinese medicine treatment of urinary tract infection, and displayed visually. Results: A total of 501 prescriptions were included, a total of 245 herb medicine were involved, and liquorice, poria, dianthus superbus and rehmannia were used more frequently. The tastes are cold, neutral, sweet taste, and bitter taste. Their channel tropisms mainly belong to lung and liver. The core prescriptions are based on Bazhengsan and Zhibaidihuangwan. Conclusion: Heat, dampness and diuretic herbs are used in the treatment of urinary tract infections in Chinese medicine, and nourishing yin and kidney, and relieving the stagnation of liver at the same time.Asthenic and sthenia syndrome, appearance and essence are also taken into account.

7.
Chinese Journal of Surgery ; (12): 528-531, 2017.
Article in Chinese | WPRIM | ID: wpr-808983

ABSTRACT

Objective@#To discuss the impact of updated definition and classification system of pancreatic fistula published in 2016 on the postoperative classification of pancreatic fistula.@*Methods@#Retrospective analysis was made on patients who underwent pancreatic surgery at ward 1 in Department of General Surgery, Peking Union Medical College Hospital from January 2015 to December 2016.A total of 408 patients were included in this retrospective study, male/female was 184/224, aged from 9 to 81 years with mean age of 51.6 years.One hundred and fifty-two cases were performed pancreaticoduodenectomy, 125 cases for distal pancreatectomy, 43 cases for spleen preservation distal pancreatectomy, 61 cases for partital pancreatectomy or enucleation, 8 cases for middle pancreatectomy, 6 cases for pancreaticojejunostomy and 13 cases for other procedures.Clinical data including postoperative drainage fluid volume, amylase concentration, duration of hospitalization and drainage were obtained, revaluated and re-analyzed, classified grounded on 2005 edition and 2016 edition, respectively.t-test was adopted for data analysis.@*Results@#According to the previous standards, the incident rate of pancreatic fistula was 57.4%, and the incident rate of B-level plus C-level pancreatic fistula was 35.8%, which decreased to 13.7% based on 2016 edition.Nine patients who received percutaneous puncture or endoscopic drainage was regraded from C-level to B-level. The average duration of postoperative hospitalization of patients without pancreatic fistula was (12.5±6.0)days, demonstrating no significant difference compared to (14.1±7.7)days, duration of postoperative hospitalization of A-level(under 2005 edition of criteria) pancreatic fistula group(t=1.66, P=0.09) and (12.4±6.1)days, duration of postoperative hospitalization of biochemical leakage group(t=0.14, P=0.89). Nevertheless, there was statistical significant difference between the average postoperative duration of hospitalization(30.7±16.9) days of B-level(under 2016 criteria) pancreatic fistula patients and pancreatic fistula-free patients as well as the biochemical leakage group patients (t=7.10, 7.13; both P<0.01).@*Conclusions@#Based on the new diagnostic criteria, the incidence of postoperative pancreatic fistula decreased dramatically.New classification system downgraded part of cases graded C-level pancreatic fistula to B-level and some B-level to biochemical fistula.The new diagnostic classification and criteria facilitated clinical practice, accomplished better conformity to clinical reality and potentially enacted clinical outcome.

8.
Journal of Medical Postgraduates ; (12): 355-359, 2017.
Article in Chinese | WPRIM | ID: wpr-512207

ABSTRACT

Objective The expression of chemokine C-X-C motif ligand 13 (CXCL13) within liver in primary biliary cholangitis (PBC) patients is significantly increased, but its origin and mechanism is not clear yet.The study aimed to investigate the expression of CXCL13 in the liver of mice through establishing a mouse model of PBC.Methods C57BL/6 mice were randomly divided into experiment group (n=20) control group(n=10).The mice in the experimental group were intraperitoneally injected with polyriboinosinic polyribocytidylic acid (Poly I:C) while the mice in control group were injected with PBS of the same volume.The level of serum AMA was quantified by ELISA and intrahepatic inflammatory cells were assessed by HE staining.Kupffer cells, liver sinusoidal endothelial cells, and infiltrating lymphocytes in the liver of mice were collected by in situ perfusion enzyme digestion and magnetic bead separation methods.The transcriptional level of intrahepatic CXCL13 in liver tissues and cell subpopulations were detected by qPCR.Results The serum AMA titers of the mice in experiment group increased gradually with the prolonging of modeling time and the positive rates at the 4th, 8th, and 12th week after the first injection of Poly I:C were 5.9%, 52.9% and 76.5% respectively.While the serum AMA titers of the mice in control group were at a lower level through the modeling process, with only 2 mice presenting a little higher level above positive cutoff value at the 12th week.The results of HE staining in liver tissues of both groups showed that there were a great amount of intensely infiltrating inflammatory cells in the mice of experimental group while no inflammatory cell infiltration were found in the mice of control group.The separation purity of Kupffer cells and liver sinusoidal endothelial cells in the mice of experiment group tested by flow cytometry were 76%-80%, 68%-72% respectively.Compared with the CXCL13 mRNA level in Kupffer cells [2.34(0.22-8.64)], the expression levels in liver sinusoidal endothelial cells and infiltrating lymphocytes declined[0.27(0.03-1.64), 0.05(0-0.22), P<0.05].Conclusion The chemokine CXCL13 is predominantly produced by Kupffer cells in the liver of PBC mice established by Poly I:C injection.

9.
Chinese Journal of Biochemical Pharmaceutics ; (6): 385-387, 2017.
Article in Chinese | WPRIM | ID: wpr-511731

ABSTRACT

Objective To study the the overall effect of methotrexate combined with multi-glycosides of tripterygium wilfordii on the clinical intervention of rheumatoid arthritis.Methods In Changxing county people's hospital,96 cases with rheumatoid arthritis were selected as the research object,which were randomly divided into the the control group and the study group,48 cases in each group.On the basis of the basic treatment in the two groups,the control group were given methotrexate,the experimental group were given methotrexate combined with multi-glycosides of tripterygium wilfordii.3 months after treatment,the clinical symptoms,the laboratory index and assessment of disease activity by physicians and patients were evaluated.The drug safety was observed.Results Before treatment,The clinical symptoms,laboratory index and physician and assessment of disease activity by physicians and patients showed no significant differences between the two groups.All the indexes in the two groups after treatment were improved(P<0.05).Compared with the control group,all the indexes in the study group were better(P<0.05).There were 4 cases(8.3%)gastrointestinal adverse reaction in the control group and 6(12.5%)in the study group.There was no significant difference about adverse reaction between the two groups.Conclusion It can obtain satisfactory overall effect that methotrexate combined with multi-glycosides of tripterygium wilfordii on the clinical intervention of rheumatoid arthritis which is safty.The joint pain,swelling and other symptoms and inflammatory index were significantly improved.It is worthy of clinical application.

10.
Journal of Clinical Hepatology ; (12): 1858-1862, 2016.
Article in Chinese | WPRIM | ID: wpr-778417

ABSTRACT

Host immune response is a double-edged sword and participates in liver injury and viral control in patients with HBV infection. Antiviral therapy with nucleos(t)ide analogues and interferon may improve prognosis through regulating host immune response. This article describes the role of host immune response in chronic HBV infection and its features during antiviral therapy and emphasizes the importance of host immune reconstruction in sustained control of HBV infection.

11.
Chinese Journal of Hepatology ; (12): 340-343, 2014.
Article in Chinese | WPRIM | ID: wpr-314047

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the association between the PNPLA3 rs738409 polymorphism and chronic hepatitis B (CH[B) in a Han Chinese population residing in Qingdao.</p><p><b>METHODS</b>Peripheral blood samples were collected from 185 CHB patients and 164 healthy controls and subjected to polymerase chain reaction (PCR) and DNA sequencing to determine the PNPLA3 genotypes. The relative risk of the rs738409 polymorphism for CHB was estimated by calculating the odds ratio (OR) and 95% confidence interval.</p><p><b>RESULTS</b>The rs738409 G allele frequency was significantly different between the CHB and control groups (31.9% vs.21.9% respectively, P less than 0.05). Compared to he rs738409 C allele, the G allele was associated with an increased risk of developing CHB (OR =1.67, 95% CI:1.18-2.34, P =0.003). Logistic regression model analysis, with adjustment for confounding factors, indicated that carriers of the PNPLA3 rs738409 GG + GC genotype had increased risk of CHB than carriers of the CC genotype (OR =1.76 ,95% CI:1.14-2.71, P =0.011).</p><p><b>CONCLUSION</b>Qingdao Han Chinese who are carriers of the rs738409 G allele are at increased risk of CHB.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Asian People , Genetics , Case-Control Studies , China , Epidemiology , Gene Frequency , Genetic Predisposition to Disease , Genotype , Hepatitis B, Chronic , Epidemiology , Genetics , Lipase , Genetics , Membrane Proteins , Genetics , Polymorphism, Single Nucleotide , Risk Factors
12.
Chinese Journal of Surgery ; (12): 682-685, 2014.
Article in Chinese | WPRIM | ID: wpr-336697

ABSTRACT

<p><b>OBJECTIVES</b>To evaluate the safety and effectiveness of open preperitoneal herniorraphy comparing with traditional Lichtenstein tension-free herniorraphy on the surgical treatment of inguinal hernia.</p><p><b>METHODS</b>The clinical data of 249 patients with inguinal hernia admitted from October 2008 to December 2013 were reviewed retrospectively.Eighty-three patients received preperitoneal herniorraphy (preperitoneal group), there were 76 male and 7 female patients with a mean age of (70 ± 10) years.One hundred and seventy-three patients underwent Lichtenstein procedure (Lichtenstein group), there were 162 male and 11 femal patients with a mean age of (60 ± 16) years. The peri-operative performance, recurrence rate and postoperative morbidities of the patients underwent preperitoneal herniorraphy and traditional Lichtenstein herniorraphy were analyzed.</p><p><b>RESULTS</b>The operation time of the preperitoneal group (60 ± 11) minutes was significantly shorter than the Lichtenstein group (63 ± 8) minutes (t = -2.16, P = 0.032). The preperitoneal group showed significantly earlier out-of-bed activity ((6.2 ± 1.8) hours) than the Lichtenstein group ((15.0 ± 2.8) hours) (t = -13.2, P = 0.000). The visual analogue scale score on 24 hours postoperative was also lower in the preperitoneal group (4.0 ± 0.9) than in the Lichtenstein group (4.6 ± 1.4) (t = -4.11, P = 0.000). The two groups had no significant difference on the cost. There was one incision infection in preperitoneal group (1.20%).Four fat liquefaction (2.31%) and one patch rejection (0.58%) were found in Lichtenstein group. The incidence of complication of the two groups had no significant difference (P > 0.05). All the patients were followed up for 6 to 36 months, and there was no recurrence among all these patients.</p><p><b>CONCLUSIONS</b>There is no significant difference on the safety and effectiveness between preperitoneal herniorraphy and traditional Lichtenstein procedure on inguinal hernia.Open preperitoneal herniorraphy and can be applied for surgical treatment of recurrent or femoral hernia.</p>


Subject(s)
Aged , Female , Humans , Male , Middle Aged , Hernia, Inguinal , General Surgery , Operative Time , Recurrence , Retrospective Studies , Surgical Mesh
13.
Chinese Journal of General Surgery ; (12): 378-381, 2013.
Article in Chinese | WPRIM | ID: wpr-435031

ABSTRACT

Objective To investigate BRAFV600E mutation and sodium iodide symporter (NIS) expression and its clinical significance in papillary thyroid carcinomas (PTC).Methods BRAFV600E mutation was evaluated by direct sequencing and BRAFV600E mutation was determined in 40 cases of PTC.NIS expression was examined by means of immunohistochemistry.The relationship between BRAFV600E mutation and the clinicopathologic features of PTC was analyzed.The relationship between NIS expression and BRAFV600E mutation in PTC was analyzed.Results Positive BRAFV600E mutation was determined in 23 of 40 cases of PTC (57.5%),whereas positive NIS expression was showed in 7 of 40 cases (12.5%).BRAFV600E mutation was associated with extrathyroid invasion and a high risk of disease recurrence in PTC (P < 0.05).Positive NIS expression was found in only one of 23 cases of PTC with BRAFV600E mutation,and positive NIS expression was associated with a statistically significant lower BRAFV600E mutation in PTC (P =0.011).Conclusions BRAFV600E mutation might be associated with higher aggressiveness,higher disease recurrence and a poorer prognosis.Lower NIS expression may be responsible for poor 131I uptake in

14.
Chinese Journal of Endocrinology and Metabolism ; (12): 404-407, 2012.
Article in Chinese | WPRIM | ID: wpr-425906

ABSTRACT

The expression of Rap1 GAP protein was detected in 69 cases of papillary thyroid carcinoma and adjacent normal thyroid tissues with immunohistochemistry method.Methylation of Rapl GAP gene was analyzed by methylation-specific-PCR (MSP) in these tissues.The immunohistochemistry results indicated that the Rap1GAP protein was down-regulated in tumor tissues of 54 ( 78% ) cases compared with normal thyroid tissues.Statistical analysis demonstrated that the decreased level of Rap1 GAP protein expression was significantly correlated with the tumor stage T according to American Joint Committee on Cancer ( AJCC,P =0.043 ).The MSP results demonstrated that 46 cases of Rap1GAP gene methylation were detected in 54 cases with down-regulated expression of Rap1GAP (66.7%),but only 1 case of methylation was found in 15 cases without obvious change of Rap1GAP expression (6.67%),showing significant difference ( P<0.01 ).There was no methylation in normal thyroid tissues.These results suggest that raised methylation of promoter region may contribute to the low expression of Rap1GAP protein in papillary thyroid carcinoma.

15.
Chinese Journal of General Surgery ; (12): 581-583, 2008.
Article in Chinese | WPRIM | ID: wpr-399032

ABSTRACT

Objective To investigate the clinicopathologic features and treatment of thyroid microcarcinoma (TMC). Methods From January 1997 to December 2006,311 patients who underwent surgery and defined as TMC(tumor size≤1 cm)were enrolled. Results TMC was identified incidentally by frozen pathologic examination on thyroidectomy specimens in tentative benign goiters in 181 patients; another 130 patients with clinically detectable primary tumors or suspected nodal metastases were grouped to as clinically overt TMC. The clinically overt TMC had a higher incidence of bilateral multifocal tumors (18.5%vs.9.4%,P=0.03),and cervical lymph node metastases(27.7%vs.10.5%,P=0.000)than that in clinically occult TMC group. Conclusion TMC may vary considerably in clinical and biologic behaviors between these two subtypes: clinically overt and occult. Lobectomy for single lesion, total or near total thyroidectomy for multifocal with central compartment nodal dissection should be performed, lateral nodal dissection was not carried out unless US or physical examination detected nodal metastases. Lobetomy, subtotal or more limited thyroidectomy for occult TMC, diagnosed incidentally following thyroid surgery for initially tentative benign thyroid disease, could all be treatment of choice depending on the preference of surgeons.

16.
Basic & Clinical Medicine ; (12)2006.
Article in Chinese | WPRIM | ID: wpr-586264

ABSTRACT

Objective To observe the levels of cAMP and adenylyl cyclase(AC) in hippocampus of mice with vascular dementia(VD) and the effect of Dihydroergocriptine(DHE),and to explore the molecular pathogenesis of VD.Methods The mice were subjected for ischemia-reperfusion three times on bilateral common carotid arteries by knots to establish models of VD and the changes of learning and memory were tested on d29/d30 after operation.DHE was administrated to another group of mice,which was taken as treatment group.The cAMP level was evaluated by the radioimmunoassay;AC mRNA positive neurons of hippocampus CA1 area were examined through in-situ hybridization.Results Compared with shamed-operation group,the learning and memory of model group was worse(P

17.
Chinese Journal of Geriatrics ; (12)2001.
Article in Chinese | WPRIM | ID: wpr-539236

ABSTRACT

Objective To investigate the calcium signal transduction pathway in hippocampal neurons of mice with vascular dementia (VaD) and the intervention effect of dihydroergocriptine (DHE). Methods The mice were subjected for ischemia-reperfusion repeatedly on bilateral common carotid arteries by knots to establish the VaD models. Animals with sham-operation were taken as control group. The treating group was administered with DHE after the establishment of VaD model. The behavior changes were observed through the step-down avoidance test and water maze test on the 29th and 30th days after operation. The resting 〔Ca 2+〕 i level of hippocampal neurons was evaluated by laser scanning confocal microscopy. RT-PCR technique was used to measure mRNA expression of CaM an CaMPKⅡ in hippocampal neurons. Results The resting 〔Ca 2+〕 i level in model group(43.50?3.00) was significantly higher than those in the sham-operation group (25.50?3.50) (P

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