Worldwide cohort study of 46, XY differences/disorders of sex development genetic diagnoses: geographic and ethnic differences in variants.

Differences/disorders of sex development (DSDs) in individuals with a 46, XY karyotype are a group of congenital disorders that manifest as male gonadal hypoplasia or abnormalities of the external genitalia. Approximately 50% of patients with 46, XY DSDs cannot obtain a molecular diagnosis. The aims of this paper were to review the most common causative genes and rare genes in patients with 46, XY DSDs, analyze global molecular diagnostic cohorts for the prevalence and geographic distribution of causative genes, and identify the factors affecting cohort detection results. Although the spectrum of genetic variants varies across regions and the severity of the clinical phenotype varies across patients, next-generation sequencing (NGS), the most commonly used detection method, can still reveal genetic variants and aid in diagnosis. A comparison of the detection rates of various sequencing modalities revealed that whole-exome sequencing (WES) facilitates a greater rate of molecular diagnosis of the disease than panel sequencing. Whole-genome sequencing (WGS), third-generation sequencing, and algorithm advancements will contribute to the improvement of detection efficiency. The most commonly mutated genes associated with androgen synthesis and action are AR, SR5A2, and HSD17B3, and the most commonly mutated genes involved in gonadal formation are NR5A1 and MAP3K1. Detection results are affected by differences in enrollment criteria and sequencing technologies.

Efficacy of electroacupuncture stimulating Zusanli (ST36) and Xuanzhong (GB39) on synovial angiogenesis in rats with adjuvant arthritis.

OBJECTIVE: To investigate the efficacy of electroacupuncture (EA) stimulating Zusanli (ST36) and Xuanzhong (GB39) on synovial angiogenesis in rats with adjuvant arthritis (AA). METHODS: AA models were established by bilateral injection of Freund's complete adjuvant (FCA) in male Sprague-Dawley rats. Three days after injection, rats were given EA at Zusanli (ST36) and Xuanzhong (GB39) acupoints, once every other day, for 16 d. The arthritis index score, paw volume, and hematoxylin-eosin (HE) staining was performed for each animal. Angiogenesis marker cluster of differentiation 34 (CD34) expression and synovial cell apoptosis in synovial tissue were observed. The levels of Notch1, hairy and enhancer of split homolog-1 (Hes1), transforming growth factor-beta (TGF-ß) and basic fibroblast growth factor (bFGF) were subsequently detected. RESULTS: We found that EA significantly decreased arthritis index scores, paw volume, and HE staining scores. EA could significantly inhibit the expression of CD34, promoting apoptosis of synovial cells in the joint synovial tissue of AA rats. The expression of Notch1 signaling pathway proteins and mRNAs (Notch1, Hes1, TGF-ß, and bFGF) were markedly downregulated by EA treatment. CONCLUSIONS: These results prove that EA attenuates synovial angiogenesis by inhibiting the Notch1 signaling pathway in AA rat models. Based on our findings, we propose that EA is a promising complementary and alternative therapy in rheumatoid arthritis.

Effect of Tuina along "bladder meridian" alleviating intervertebral disc degeneration by regulating the transforming growth factor-ß1/Smad signaling pathway in a rabbit model.

OBJECTIVE: The aim of this study was to investigate the protective effects of Tuina (a traditional Chinese massage therapy) on intervertebral disc (IVD) degeneration and the regulatory mechanisms of the transforming growth factor-ß1 (TGF-ß1)/small mothers against decapentaplegic (Smad) signaling pathway. METHODS: Thirty New Zealand white rabbits were randomized into five groups: the control group, model group, model + Tuina group (Tuina group), model + TGF-ß1 group (TGF-ß1 group), and model + TGF-ß1 inhibitor SB431542 group (SB431542 group). The model was established by posterolateral annulus fibrosus puncturing (AFP). Recombinant TGF-ß1 and inhibitor SB431542 was injected into the TGF-ß1 group and SB431542 group with a microsyringe, respectively. The rabbits in the Tuina group received Tuina treatment along the bladder meridian for 4 weeks. Magnetic resonance imaging (MRI) was performed on rabbits before AFP and after 4 weeks of intervention. Lumbar IVDs (L2-L3 to L4-L5) were harvested after intervention. Histopathological changes in the IVDs were measured by hematoxylin and eosin (HE) staining. Type I collagen was analyzed by immunohistochemistry detection. The expression level of matrix metalloproteinase-3 (MMP3) was determined by enzyme-linked immunosorbent assay. Cell apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated nick end labeling and Western blotting. Real-time polymerase chain reaction and Western blotting were used to analyze the expression of TGF-ß1 and Smad2/3/4 and a disintegrin and metalloproteinase with thrombospondin motifs 5. RESULTS: Posterolateral AFP induced IVD degeneration in rabbits with histopathological damage and noticeable changes in MRI images. Tuina alleviated histo-pathological changes and reversed the expression of extracellular matrix degeneration-related molecules and apoptosis-related proteins. Furthermore, AFP induced the activation of TGF-ß1 and Smad2/3/4, whereas Tuina therapy markedly reduced the protein expression of Smad2/3 and the gene expression of TGF-ß1 and Smad2/3/4. Additionally, the TGF-ß1/Smad signaling pathway was activated in the TGF-ß1 group, while the TGF-ß1/Smad signaling pathway was inhibited in the SB431542 group. CONCLUSION: Posterolateral AFP induced disc degeneration as determined by MRI assessment and histological analysis. Tuina alleviated disc degeneration, possibly by inhibiting the fibrotic response mediated by the TGF-ß1/Smad pathway, thus alleviating extracellular matrix degeneration and reducing cell apoptosis.

Association between smoking and ankylosing spondylitis: a Mendelian randomization study / 预防医学

Objective@#To evaluate the association of smoking with the risk of ankylosing spondylitis (AS) using a Mendelian randomization (MR) approach.@*Methods@#A total of 16 383 186 AS-associated single nucleotide polymorphisms (SNPs), 378 smoking initiation associated SNPs and 126 lifetime smoking score-associated SNPs were collected from three large-scale genome-wide association studies (GWAS). The association of smoking phenotypes with the risk of AS was examined using inverse-variance weighted (IVW) with AS as a outcome variable, smoking initiation and lifetime smoking score as exposure factors and SNPs with strong associations with smoking as instrumental variables, and sensitivity analyses were performed with maximum likelihood-based method, MR pleiotropy residual sum and outlier (MR-PRESSO) test and MR-Egger regression analysis.@*Results@# A 33.5% increased risk of AS was found among genetically predicted smokers relative to non-smokers (OR=1.335, 95%CI: 1.059-1.682), and an increase in predicted lifetime smoking by per standard deviation resulted in a 101.4% increased risk of AS (OR=2.014, 95%CI: 1.341-3.024). The maximum likelihood-based method and MR-PRESSO test showed consistent correlated effect estimations and MR-Egger regression analysis identified no evidence of pleiotropy.@*Conclusion@#It is genetically predicted that smoking is associated with an increased risk of AS.

CT-Based Radiomics Signature for Preoperative Prediction of Coagulative Necrosis in Clear Cell Renal Cell Carcinoma

Objective@#The presence of coagulative necrosis (CN) in clear cell renal cell carcinoma (ccRCC) indicates a poor prognosis, while the absence of CN indicates a good prognosis. The purpose of this study was to build and validate a radiomics signature based on preoperative CT imaging data to estimate CN status in ccRCC. @*Materials and Methods@#Altogether, 105 patients with pathologically confirmed ccRCC were retrospectively enrolled in this study and then divided into training (n = 72) and validation (n = 33) sets. Thereafter, 385 radiomics features were extracted from the three-dimensional volumes of interest of each tumor, and 10 traditional features were assessed by two experienced radiologists using triple-phase CT-enhanced images. A multivariate logistic regression algorithm was used to build the radiomics score and traditional predictors in the training set, and their performance was assessed and then tested in the validation set. The radiomics signature to distinguish CN status was then developed by incorporating the radiomics score and the selected traditional predictors. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive performance. @*Results@#The area under the ROC curve (AUC) of the radiomics score, which consisted of 7 radiomics features, was 0.855 in the training set and 0.885 in the validation set. The AUC of the traditional predictor, which consisted of 2 traditional features, was 0.843 in the training set and 0.858 in the validation set. The radiomics signature showed the best performance with an AUC of 0.942 in the training set, which was then confirmed with an AUC of 0.969 in the validation set. @*Conclusion@#The CT-based radiomics signature that incorporated radiomics and traditional features has the potential to be used as a non-invasive tool for preoperative prediction of CN in ccRCC.

Treatment of lateral tibial plateau fractures involving posterolateral condyle with double plate fixation via combined anterolateral and posterolateral approaches / 中华创伤骨科杂志

Objective To evaluate the treatment of lateral tibial plateau fractures involving the posterolateral condyle with double plate fixation via the combined anterolateral and posterolateral approaches.Methods From January 2013 to August 2015,12 patients with lateral tibial plateau fracture involving the posterolateral condyle were treated by double plate fixation via the combined anterolateral and posterolateral approaches.They were 8 males and 4 females,with an average age of 36.9 years (range,from 23 to 58 years).According to the Schatzker classification,we had 8 ones of type Ⅱ,3 ones of type Ⅴ and one of type Ⅵ.Firstly,the posterolateral condylar fractures were stabilized temporarily by the Kirschner wire after reduction through the posterolateral approach.Secondly,the lateral tibial plateau fractures were dealt with via the anterolateral approach,and fixated with a proximal tibial locking plate.Finally,a T-shaped plate for the distal radius was used to support the posterolateral condyle.The clinical and radiographic results were evaluated using the Hospital for Special Surgery (HSS) knee score and the Rasmussen Score,respectively.Results The average operative time was 143.3 min (range,from 110 to 210 min);the average intraoperative blood loss was 190.0 mL (range,from 100 to 300 mL).The follow-ups for the 12 cases ranged from 12 to 24 months (average,16.6 months).All the cases obtained clinical healing after 12 to 24 weeks (average,16 weeks).At the last follow-up,the HSS knee-scores ranged from 65 to 98 points (average,84.6 points),giving 7 excellent cases,3 good ones and 2 fair ones.The Rasmussen radiological scores ranged from 13 to 18 points (average,17.1 points),giving 8 excellent and 4 good cases.Conclusions The combined anterolateral and posterolateral approaches can offer excellent exposure for articular reduction and fixation with double plates,achieving satisfactory radiological and functional results in lateral tibial plateau fractures involving the posterolateral condyle.First reduction of the posterior lateral condylar fractures,followed by reduction and fixation of the anterolateral plateau fractures and finally fixation of the lateral condylar fractures,can lead to effectively improved knee function for the patients.

The effects of Bushen-Gufeigao and breathing movements on the patients with COPD of ;lung and kidney yang deficiency TCM pattern / 国际中医中药杂志

Objective Evaluating the effects of Bushen-Gufeigao and breathing movements on the patients with chronic obstructive pulmonary disease of Lung and kidney deficiency TCM pattern. Methods The patients with chronic obstructive pulmonary disease of lung and kidney deficiency TCM pattern were recruited and randomly divided into two groups the treatment group (32 cases) and the control group (34 cases). The control group was treated with the conventional medicine, and the treatment group were added Bufei-Gushengao and breathing movements based on the treatment of control group. Both groups were treated for 1 month. The changes of the clinical symptoms, lung function and frequency of attack and duration of each attack in 10 months after treatment were observed. Results After the treatment, compared with the control group, the TCM patterns scores (5.32 ± 2.67 vs. 9.12 ± 4.11, t=4.424) of the treatment group significantly decreased, while the FVC (3.00 ± 0.49 L vs. 2.71 ± 0.47 L, t=2.408), FEV1 (2.27 ± 0.44 L vs. 1.85 ± 0.54 L, t=3.496), and the percentage of FEV1%(75.62 ± 6.84 vs. 66.86 ± 9.32, t=4.333) increased significantly. In the 10 mouths after the treatment, the treatment group showed significantly fewer patients who had attacked more than 6 times than that in the control group, and the duration of attacks showed significantly fewer minutes in the treatment group than the control group (5.56 ± 1.45 d vs. 8.06 ± 1.80 d, t=6.190). Conclusion Bushen-Gufeigao and breathing movements can effectively improve patient's lung function and symptoms.

The diagnostic value of the early rheumatoid arthritis classification criteria and clinical efficacy of knee arthroscopic synovectomy for early RA / 中国基层医药

Objective To evaluate the diagnostic value of the early rheumatoid arthritis (RA) classification criteria for early RA and to assess the clinical efficacy of knee arthroscopic synovectomy for RA.Methods A total of 62 patients who had arthritic complaints with disease duration less than one year were treated with knee arthroscopic synovectomy.Patients were diagnosed as RA confirmed by changes of synoviomorphous under arthroscopy,synovial biopsy,immunological biochemical laboratory and MRI,and compared with the preoperative ERA diagnosis.The efficacy was assessed at the third months and more than 12 months after operation,including Health Assessment Questionnaire (HAQ),Lysholm score,laboratory parameters of erythrocyte sedi-mentation rate (ESR) and C-reactive protein (CRP).Results The sensitivity and specificity in the early RA classification criteria for RA diagnosis were 81.58％ and 91.67％.38 patients diagnosed as RA and the remaining 24 patients were significantly improved of HAQ,Lysholm score,ESR,CRP compared with preoperation,showed statistical difference (P ＜ 0.01).There were still statistical differences between the follow-up results of the group of patients with RA in different period after operation (P ＜ 0.01).Conclusion The early RA classification criteria is worthy of clinical application,because it has the advantages of simple,practical,and is beneficial to early diagnosis of RA.The early RA patients should be treated with knee arthroscopic synovectomy as far as possible.It can improve not only the knee function,but also the general symptoms,and it can interrupt the RA pathological process,effective maintain curative effect after operation.

Multi-segment transpedicle spinal fixation for thoracolumbar fractures with ankylosing spondylitis:one-year follow-up / 中国组织工程研究

BACKGROUND:Because of osteoporosis, short-segment transpedicular fixation or screw-rod system fixation is prone to screw loosening depending on its poor anti-pul-out strength in patients with thoracolumbar fracture with ankylosing spondylitis. OBJECTIVE:To probe the clinic outcomes of multi-segment transpedicle spinal fixation for thoracolumbar fractures with ankylosing spondylitis. METHODS:Eleven patients with ankylosing spondylitis combined with thoracolumbar fracture in the Fourth Department of Orthopedics, Meizhou Hospital, Sun Yat-sen University, China from January 2009 to December 2012 were selected. Al the patients underwent posterior reduction and multi-segment transpedicle spinal fixation, among whom, six cases were subjected to internal fixation through the pedicle of fractured vertebra. RESULTS AND CONCLUSION:Al of the 11 patients were fol owed up for 13 to 36 months. Solid bone healing was achieved in al of the patients, and there were no complications related to the internal fixation systems such as loosening or breakage. Three cases of spinal cord injury achieved Frankel’s class E from class C recovery. Lumbodorsal pain rate achieved 100%according to the Japanese Orthopaedic Association scoring. Results confirmed that it is effective to treat thoracolumbar fractures with ankylosing spondylitis by posterior reduction and multi-segment transpedicle spinal fixation. Strong internal fixation and fracture union can be achieved by operation.

Preliminary effect of In-Space percataneous interspinous spacer in the treatment of lumbar instability / 中华骨科杂志

Objective To evaluate preliminary effect of In-Space percataneous interspinous spacer in the treatment of lumbar instability.Methods Data of 18 patients who had undergone interspinous spacer implant for lumbar instability from May 2009 to June 2011 were retrospectively analyzed.There were 10 males and 8 female,aged from 39 to 58 years.All patients suffered from varying degrees of lower back pain induced by lumbar hyperextension,as well as radiating and segmental pain of unilateral lower limb.The visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate clinical outcomes.The pre-and postoperative interspinous distance,trailing edge height of intervertebral space,foraminal width,foraminal height,segmental lordotic angle and lumbar range of motion were tested and compared.Results All patients were followed up for 18 to 36 months.The VAS score improved from preoperative 7.9±2.1 to 3.1±1.3 at 6 months postoperatively and 1.5±0.8 at final follow-up.The ODI improved from preoperative 82.1％±13.1％ to 54.7％±14.8％ at 6 months postoperatively and 10.1％±2.5％ at final follow-up.The postoperative interspinous distance,trailing edge height of intervertebral space,foraminal height,foraminal width,segmental lordotic angle and lumbar range of motion were 9.29±1.43 mm,11.28±0.85 mm,21.27±1.01 mm,10.83±0.73 mm,7.62°±0.74° and 6.34°±0.81°,respectively.Wound healed smoothly in all patients,and there were no complications such as spinous process fracture,spinal cord injury,cerebrospinal fluid leakage,device displacement and device dislocation.Conclusion It is easy and safe to use In-Space percataneousinterspinous spacer in the treatment of lumbar instability,and the preliminary effect is satisfactory.

Repair of the soft tissue defect of upper lip with the buccal region of nasolabial groove flap / 中国医师进修杂志

Objective To explore the clinical new ways to repair the soft tissue defect of upper lip.Methods The soft tissue defect of upper lip caused by various reason were repaired with the buccal region of nasolabial groove flap.The size of flap was designed based on the range of soft tissue defect and located in the buccal region along nasolabial groove.The maximum scale of flaps between the length and width were 2∶1 and slit to the SMAS layer.The soft tissue defect of upper lip was repaired by direct vicinity aversion of the flap.The wound after the flap diversion was direct sut in favour of propulsion of the flap and relief the tension of flap pedicle.Results The flaps completely survived in 15 cases without obviously scar accrementition.The cosmetic result were satisfactory.Conclusion The buccal region of nasolabial groove flap is characterized by simple designation,easy dissection,reliable blood supply with the vascular net of fascia without well-known blood vessel damaged and repaired by direct vicinity aversion.Therefore,it is an ideal new method to repair the soft tissue defect of upper lip.

Detection of the expression of alpha3-integrin on hantavirus permissive cells / 中华实验和临床病毒学杂志

<p><b>BACKGROUND</b>To express and purify human alpha3-integrin to serve as the antigen to prepare its antibody and to separate the Vero cell clones without expression of alpha3-integrin.</p><p><b>METHODS</b>The human alpha3-integrin gene was amplified by using RT-PCR, then subcloned into a pQE30 expression vector and expressed in E. coli. The gene expression was confirmed by Western blot assay. Rabbit was inoculated with purified antigen to stimulate the antibody generation. The target Vero cells were separated by negative selection using antibody plus complement mediated cytolysis. The separated cell clones were confirmed by immunofluorescence and Western blot assay.</p><p><b>RESULTS</b>The alpha3- integrin gene was cloned and expressed effetively, Western blot assay revealed that the expressed protein held good immune reactivity. High titer antibody was generated. However the expression of alpha3-integrin was not detected on Vero, VeroE6, Hep-2, 2BS and 293 cells.</p><p><b>CONCLUSIONS</b>The results of the study suggested that hantavirus has other receptors on Vero cells beside alpha 3-integrin.</p>