Objective To compare effectiveness between the modified and traditional pressure-overload myocardial hypertrophy(POMH) model by abdominal aorta coarctation (AAC) method. Methods Totally 45 rats were divided into three groups(n = 15 per group), sham group, traditional group, and modified group. In the traditional group, the diameter ol the abdominal aorta was narrowed to 0. 70 mm through a midline incision for 4 weeks; in the modified group, the diameter of the abdominal aorta was narrowed above the left kidney to 0. 45 mm for 1 week, and then the narrowing was lifted postoperatively. The cardiac index, heart weight (HW) /body weight (BW) and left ventricular index, left ventricular weight (LVW)/BW were measured from the heart specimens, and the cross-sectional area of cardiac myocytes, myocardial collagen area, and myocardial collagen area Iraction were measured in the pathological sections by HE staining and Masson staining. Results Compared with the sham group, the differences in end-systolic interventricular septum thickness (IVSs), left ventricular end-systolic posterior wall thickness (LVPWs), HW/BW, LVW/BW, cardiomyocyte cross-sectional area, myocardial collagen area, myocardial collagen area fraction, and brain natriuretic peptide (BNP) expression levels were statistically significant (P<0. 05) in the modilied and traditional groups of rats. The differences in these indices were not statistically significant between the modified and traditional groups (P>0. 05). Conclusion The modified abdominal aortic constriction method used in this experiment is time-saving, stable, homogeneous and easy to replicate, and is a more ideal approach to establish a rat model of POMH.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective:To investigate the safety and efficacy of MR-guided focused ultrasound surgery (MRgFUS) in treating localized prostate cancer.Methods:Six patients with localized prostate cancer who underwent MRgFUS treatment from August 2020 to September 2021 in Beijing Hospital were prospectively enrolled in this study. The patients were all over 18 years old, with an average age of (68±10) years, and had not received any prior treatment for prostate cancer. Pretreatment pelvic MR and CT scans were performed to determine the region of treatment (ROT). Different urinary catheterization measures were given based on the location of the lesion. Under general anesthesia, the lesions were treated by MRgFUS using a specialized rectal ultrasound transducer on the treatment bed. The patients were followed up at 1, 3, and 6 months after treatment and annually thereafter. During follow-up, prostate-specific antigen (PSA) levels, pelvic MR scans, International Prostate Symptom Score (IPSS), International Index of Erectile Function-15 (IIEF-15) scores, and adverse events were assessed.Results:(1) All six patients underwent MRgFUS treatment for six lesions, with an average duration of (126±56) minutes, an average number of (7.3±3.2) focal ultrasound pulses per lesion, and an average non-perfusion volume of (3.8±1.1) cm 3, which covered the entire treatment target area. No treatment-related adverse events were reported. (2) The PSA levels at baseline, 1, 3, 6, and 12 months after treatment were (6.6±0.8), (3.6±1.3), (3.4±3.0), (2.5±1.7), and (2.3±1.8) ng/ml, respectively. PSA levels increased in 2 out of 6 patients during follow-up, and pelvic MR scan revealed recurrent lesions, while PSA levels continued to decrease in the remaining 4 patients, and pelvic MR scan were normal. (3) The IPSS scores at baseline, 1, and 3 months after treatment were 13.0 (4.0, 16.0), 10.0 (4.0, 12.0), and 5.0 (3.0, 6.0) points, respectively. For the three sexually active patients, the IIEF-15 scores at baseline were 40, 51, and 14 points, respectively, and IIEF-15 at 1 month after treatment were 9, 8, and 14 points, respectively, and at 3 months after treatment were 9, 66 and 26 points, respectively. (4) One patient was diagnosed with recurrence 10 months after treatment, and another patient was found to have a new lesion 6 months after treatment. Conclusions:MRgFUS might be a safe, non-invasive, and effective treatment for localized prostate cancer, but regular follow-up is vital for detecting tumor recurrence.

To investigate the factors affecting the sperm retrieval rate of microdissection testicular sperm extraction (micro-TESE) in patients with nonmosaic Klinefelter syndrome (KS), 64 patients with nonmosaic KS who underwent micro-TESE in the Center for Reproductive Medicine of Peking University Third Hospital (Beijing, China) between January 2016 and December 2017 were included in the study. Data on medical history, physical examination and laboratory examination results, and micro-TESE outcomes were collected. Patients were divided into two groups according to micro-TESE outcomes. The following factors were compared between the two groups by the Mann‒Whitney U test or Student's t-test based on the distribution (nonnormal or normal) of the factors: age, testicular size, follicle-stimulating hormone level, luteinizing hormone level, testosterone level, and anti-Müllerian hormone level. The overall success rate of sperm retrieval was 50.0%. Correlation analysis showed that testicular volume was positively correlated with testosterone level. Using a logistic regression model, age and anti-Müllerian hormone levels were found to be better predictors for the sperm retrieval rate than the other parameters.
Humans ; Male ; Sperm Retrieval ; Klinefelter Syndrome ; Microdissection ; Anti-Mullerian Hormone ; Semen ; Testis ; Spermatozoa ; Testosterone ; Azoospermia ; Retrospective Studies

Mutations of the X-linked methyl-CpG-binding protein 2 (MECP2) gene in humans are responsible for most cases of Rett syndrome (RTT), an X-linked progressive neurological disorder. While genome-wide screens in clinical trials have revealed several putative RTT-associated mutations in MECP2, their causal relevance regarding the functional regulation of MeCP2 at the etiologic sites at the protein level requires more evidence. In this study, we demonstrated that MeCP2 was dynamically modified by O-linked-β-N-acetylglucosamine (O-GlcNAc) at threonine 203 (T203), an etiologic site in RTT patients. Disruption of the O-GlcNAcylation of MeCP2 specifically at T203 impaired dendrite development and spine maturation in cultured hippocampal neurons, and disrupted neuronal migration, dendritic spine morphogenesis, and caused dysfunction of synaptic transmission in the developing and juvenile mouse cerebral cortex. Mechanistically, genetic disruption of O-GlcNAcylation at T203 on MeCP2 decreased the neuronal activity-induced induction of Bdnf transcription. Our study highlights the critical role of MeCP2 T203 O-GlcNAcylation in neural development and synaptic transmission potentially via brain-derived neurotrophic factor.
Animals ; Humans ; Methyl-CpG-Binding Protein 2/metabolism* ; Mice ; Neurodevelopmental Disorders/genetics* ; Rett Syndrome/genetics* ; Synaptic Transmission ; Threonine

ObjectiveThe purpose of this study was to explore the difference in expression of gene between the osteosarcoma metastasis and primary specimens through NGS detection， in order to find the molecular mechanism of inducing osteosarcoma occurrence and metastasis. MethodsNext generation sequencing （NGS） was used to detect the tumor tissue samples of paired primary and metastatic lesions in 12 patients with metastasis， including 9 pairs of Panel detection （678 genes） and 3 pairs of whole exon detection （WES）. Copy number variation was detected by Excavator. DNA mutations were detected by Lumpy fusion， and RNA mutations were detected with Defuse + Star fusion. The distribution of mutations was shown by Circos. Metascape was used to analyze the enrichment of Go and KEGG signal pathways of differential genes. Pyclone+Citup/LICHEE was used for clonal evolution analysis. ResultsThe most frequent gene mutation mode of osteosarcoma was gene amplification， high-frequency mutation genes were FLCN（37.5%），GID4（37.5%），TP53（33.3%），ATRX（25%），CALR（25%），CCND3（25%），CCNE1（25%），NOCR1（25%），TFEB（25%），VEGFA（25%）， and the mutation frequency of cell cycle pathway was the highest. KT1， PLCG2 and EGFR were closely related to the metastasis of osteosarcoma. The frequency of tumor mutation burden （TMB） in metastatic lesions was significantly higher than primary lesions （P = 0.013）. Three patients detected by WES showed linear clonal evolution， suggesting that the mutations of osteosarcoma metastasis genes may be accumulated sequentially. We identified new candidate genes that may play an important role in the progression of osteosarcoma， including PLCG2， MYO15A and PEX6. ConclusionsThe most frequent gene mutation pattern of osteosarcoma occurrence and metastasis is gene amplification， and the frequency of tumor mutation burden （TMB） in metastatic lesions is significantly higher than that in primary lesions. There is an interrelated linear gene clonal evolution in patients with metastasis. This study suggests that PLCG2， MYO15A and PEX6 may play an important role in the progression of osteosarcoma.

OBJECTIVE: To investigate the damaging of human umbilical vein endothelial cells (HUVEC) induced by antiplatelet integrin β3 antibodies in vitro. METHODS: The serum from 36 chronic ITP patients were collected, flow cytometry and monoclonal antibody specific immobilization of platelet antigen (MAIPA) assay were used to collect antiplatelet integrin β3 antibodies from the serum of the patients. After HUVEC were treated by ITP patient serum (PS) containing anti-integrin β3 antibodies, the cell damage was detected by Lactate dehydrogenase (LDH) assay, cell apoptosis was detected by flow cytometry, the expression of apoptosis-related gene Bax was detected by Reverse transcription-Quantitative real-time PCR (RT-qPCR), and expression of Apoptosis-related signaling pathway protein Akt and related protein Bax were detected by Western blot. HUVEC were treated by PS combined with Akt activator SC79, the cells damage were detected by LDH assay, apoptosis of the cells were detected by flow cytometry, the expression of apoptosis-related gene Bax was detected by RT-qPCR. RESULTS: Among 36 cases of serum from the chronic ITP patients, 5 patients' serum containing anti-integrin β3 antibodies were collected. After HUVEC was treated by PS, the viability of LDH was significant increased（P<0.05）, so as for the apoptosis of the cells（P<0.05）, the expression of gene and protein of Bax was increased up-regulated（P<0.05）, the protein expression of pAkt was down-regulated（P<0.05）. Comparing with HUVEC cultured with PS alone, the viability of LDH of HUVEC treated by PS combined with SC79 was significantly reduced（P<0.05）, so as for the apoptosis of the cells（P<0.05）, and gene expression of Bax was significantly decreased（P<0.05）. CONCLUSION Anti-integrin β3 serum can cause the damage and apoptosis of HUVEC through Akt signaling pathway，the apoptotic effects of anti-integrin β3 antibodies to HUVEC was effectively reversed by SC79.
Apoptosis ; Cells, Cultured ; Human Umbilical Vein Endothelial Cells ; Humans ; Integrin beta3 ; Signal Transduction

OBJECTIVE: To explore clinical and radiographic effects of percutaneous pie-crusting deep medial collateral ligament release in patients with posterior horn tear of medial meniscus combined with tight medial compartment. METHODS: From January 2012 to December 2016, 35 patients with medial meniscus posterior horn injury were treated with percutaneous pie crusting deep medial collateral ligament release technique, including 21 males and 14 females, aged from 21 to 55 years old with an average of (39.1±6.5) years old. Degree of meniscus extrusion were recorded before and 24 months after operation. The knee valgus stress test was performed to evaluate stability of medial collateral ligament, and compared difference between healthy and affected side. Lysholm and IKDC functional scores were compared before and 24 months after operation. RESULTS: All patients were followed up from 27 to 60 months with an average of (36.7±6.8) months. All patients were underwent operation, the wound healed well without complications. Operative time ranged from 0.5 to 1.2 h with an average of (0.8±0.4) h. Nineteen patients were performed partial meniscectomy, 16 patients were performed repair suture. Convex of meniscus before operation was (1.5±0.7) mm, and (1.7±0.4) mm after operation;had no statistical difference( CONCLUSION For patients with medial meniscus tear of posterior horn combined with tight medial compartment, percutaneous pie-crusting deep medial collateralligament release could improve medial compartment space, and Knee valgus instability and meniscus extrusion are not affected.
Adult ; Arthroscopy ; Collateral Ligaments ; Female ; Humans ; Joint Instability ; Knee Joint/surgery* ; Male ; Menisci, Tibial/surgery* ; Middle Aged ; Young Adult

Many studies have shown that microRNAs (miRNAs) play vital roles during the spermatogenesis. However, little is known about the altered miRNA profiles of testicular tissues in nonobstructive azoospermia (NOA). Using microarray technology, the miRNA expression profiles of testicular biopsies from patients with NOA and of normal testicular tissues were determined. Bioinformatics analyses were conducted to predict the enriched biological processes and functions of identified miRNAs. The microarray data were validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), the results of which were then validated with a larger sample size. Correlations between the miRNA expression levels and clinical characteristics were analyzed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic ability of miRNAs for azoospermia. Hierarchical clustering showed that 129 miRNAs were significantly differentially expressed between the NOA and control groups. Bioinformatics analysis indicated that the differentially expressed miRNAs were involved in spermatogenesis, cell cycle, and mitotic prometaphase. In the subsequent qRT-PCR assays, the selected miRNA expression levels were consistent with the microarray results, and similar validated results were obtained with a larger sample size. Some clinical characteristics were significantly associated with the expression of certain miRNAs. In particular, we identified a combination of two miRNAs (miR-10b-3p and miR-34b-5p) that could serve as a predictive biomarker of azoospermia. This study provides altered miRNA profiles of testicular biopsies from NOA patients and examines the roles of miRNAs in spermatogenesis. These profiles may be useful for predicting and diagnosing the presence of testicular sperm in individuals with azoospermia.
Adult ; Azoospermia/genetics* ; Biopsy ; Cluster Analysis ; Computational Biology ; Follicle Stimulating Hormone/metabolism* ; Gene Expression Profiling ; Humans ; Luteinizing Hormone/metabolism* ; Male ; MicroRNAs/metabolism* ; Reverse Transcriptase Polymerase Chain Reaction ; Spermatogenesis/genetics* ; Testis/metabolism* ; Testosterone/metabolism* ; Tissue Array Analysis

OBJECTIVE: To explore the application accuracy of virtual preoperative plan after the condylectomy via intraoral approach under computer assisted surgical navigation, and to analyze the location and cause of the surgical deviation to provide reference for the surgical procedure improvement in the future. METHODS: In the study, 23 cases with condylar hypertrophy (11 with condylar osteochondroma and 12 with condylar benign hypertrophy) in Department of Oral and Maxilloficial Surgery, Peking University School and Hospital of Atomatology from December 2012 to December 2016 were treated by condylectomy via intraoral approach under computer assisted surgical navigation. The patient's spiral CT data were imported into ProPlan software before operation, and the affected mandibular ramus was reconstructed three-dimensionally. The condylar osteotomy line was designed according to the lesion range, and the preoperative design model was generated and introduced into the BrainLab navigation system. Under the guidance of computer navigation, the intraoral approach was used to complete the condylar resection according to the preoperative design of the osteotomy line. Cranial spiral CT of the craniofacial region was taken within one week after operation. three-dimensional reconstruction of the mandibular ramus at the condylectomy side was performed, and the condylar section was divided into six segments (anterolateral, anterior, anteromedial, posteromedial, posterior, and posterolateral) and the corresponding regional measurement points P1 to P6 were defined. Then the preoperative virtual model and the postoperative actual model were matched by Geomagic studio 12.0 to compare the differences and to analyze the accuracy of the operation. RESULTS: All the patients had successfully accomplished the operation and obtained satisfactory results. Postoperative CT showed that the condyle lesion was completely resected, and the condylar osteotomy line was basically consistent with the surgical design. No tumor recurrence or temporomandibular joint ankylosis during the follow-up period. The postoperative accuracy analysis of the condylar resection showed that the confidence intervals measured by the six groups of P1 to P6 were (-2.26 mm, -1.89 mm), (-2.30 mm, -1.45 mm), (-3.37 mm, -2.91 mm), (-2.83 mm, -1.75 mm), (-1.13 mm, 0.99 mm), and(-1.17 mm, 0.17 mm), where P3 group was different from the other 5 groups. There was no significant difference between the P5 and P6 groups and the difference between the other four groups was statistically significant. CONCLUSION Under the guidance of computer navigation, the intraoral approach can be performed more accurately. The surgical deviation of each part of the osteotomy surface is mainly due to excessive resection. The anterior medial area of the anterior medial condyle represents the most excessive resection. The posterior and posterior lateral measurement points represent the posterior condylar area. The average deviation is not large, but the fluctuation of the deviation value is larger than that of the other four groups. The accuracy of computer-assisted subtotal resection has yet to be improved.
Humans ; Mandibular Condyle ; Mandibular Neoplasms ; Neoplasm Recurrence, Local ; Osteochondroma ; Osteotomy ; Tomography, X-Ray Computed