Factors influencing the sperm retrieval rate of microdissection testicular sperm extraction in patients with nonmosaic Klinefelter syndrome / 亚洲男科学杂志(英文版)

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.

Treatment response of a two-dose regimen of dose-adjusted inotuzumab ozogamicin in relapsed/refractory B-cell acute lymphoblastic leukemia / 中华血液学杂志

Objective: To observe the treatment response of a two-dose regimen of inotuzumab ozogamicin (inotuzumab), a monoclonal antibody targeting CD22, for patients with heavily treated relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), including those failed or relapsed after chimeric antigen receptor (CAR) -T-cell therapy. Methods: Pediatric and adult patients who received two doses of inotuzumab and who were evaluated after inotuzumab treatment were included. Antibody infusions were performed between March 2020 and September 2022. All patients expressed CD22 antigen as detected by flow cytometry (>80% leukemic cells displaying CD22) before treatment. For adults, the maximum dosage per administration was 1 mg (with a total of two administrations). For children, the maximum dosage per administration was 0.85 mg/m(2) (no more than 1 mg/dose; total of two administrations). The total dosage administered to each patient was less than the standard dosage of 1.8 mg/m(2). Results: Twenty-one patients with R/R B-ALL were included, including five children (<18 years old) and sixteen adults. Seventeen patients presented with 5.0% -99.0% leukemic blasts in the bone marrow/peripheral blood or with extramedullary disease, and four patients were minimal residual disease (MRD) -positive. Fourteen patients underwent both CD19 and CD22 CAR-T-cell therapy, four underwent CD19 CAR-T-cell therapy, and three underwent blinatumomab therapy. Eleven patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). After inotuzumab treatment, 14 of 21 patients (66.7% ) achieved a complete response (CR, one was MRD-positive CR), and all four MRD-positive patients turned MRD-negative. Four of six patients who failed recent CD22 CAR-T-cell therapy achieved a CR after subsequent inotuzumab treatment. Seven patients (33.3% ) demonstrated no response. Grade 1-3 hepatotoxicity occurred in five patients (23.8% ), one child with no response experienced hepatic veno-occlusive disease (HVOD) during salvage transplantation and recovered completely. Conclusion: For patients with heavily treated R/R B-ALL, including those who had undergone allo-HSCT and CD19/CD22 CAR-T-cell therapy, the two-dose regimen of inotuzumab resulted in a CR rate of 66.7%, and the frequency of hepatotoxicity and HVOD was low.

Clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection with fresh or cryopreserved sperm in patients with nonobstructive azoospermia / 亚洲男科学杂志(英文版)

We performed this study to evaluate the clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection (micro-TESE-ICSI) treatment that used fresh or cryopreserved sperm in patients with nonobstructive azoospermia (NOA). A total of 338 NOA patients with 344 consecutive cycles received treatment in the reproductive medicine center of Peking University Third Hospital in Beijing, China, from January 2014 to December 2017. Fresh oocytes and fresh sperm were used in 222 patients with 234 cycles (Group A). Fresh oocytes and cryopreserved sperm were used in 116 patients with 110 cycles (Group B). We compared patient characteristics, embryonic development, and pregnancy outcomes between Groups A and B. There was no statistical difference in the patient characteristics, and no differences were observed with fertilization or quality embryo rates between Groups A and B. The rates of clinical pregnancy and live birth were both higher for Group A than those for Group B (both P < 0.05). In conclusion, fresh testicular sperm appears to produce better ICSI outcomes than cryopreserved testicular sperm in patients with NOA.

Sperm retrieval rates and clinical outcomes for patients with different causes of azoospermia who undergo microdissection testicular sperm extraction-intracytoplasmic sperm injection / 亚洲男科学杂志(英文版)

The aim of our study was to compare the sperm retrieval rates (SRRs) and clinical outcomes of patients with different causes of azoospermia who underwent microdissection testicular sperm extraction-intracytoplasmic sperm injection (micro-TESE-ICSI). We conducted a retrospective study at the Reproductive Medicine Center of Peking University Third Hospital in Beijing, China, from January 2014 to December 2017. This study examined 769 patients with nonobstructive azoospermia who underwent 347 cycles of micro-TESE-ICSI. Patients with azoospermia were classified into Group A (Klinefelter syndrome, n = 284, 125 cycles), Group B (azoospermia Y chromosome factor c [AZFc] microdeletion, n = 91, 64 cycles), Group C (cryptorchidism, n = 52, 39 cycles), Group D (previous mumps and bilateral orchitis, n = 23, 23 cycles), and Group E (idiopathic azoospermia, n = 319, 96 cycles). Clinical characteristics, SRR, embryonic development, and pregnancy outcomes of the patients were compared between all groups. Patients in Group D had the highest and most successful SRR. The average SRR for all patients was 46.0%. The rates of clinical pregnancy, implantation, and live birth in Group D were 78.3%, 65.0%, and 74.0%, respectively, which were higher than those in all other groups (P 0.05). Patients with orchitis had the highest SRR and best clinical outcomes. Although AZFc microdeletion patients had a higher SRR, their clinical outcomes were worse.

Cut-off values of lesion and vessel quantitative flow ratio in de novo coronary lesion post-drug-coated balloon therapy predicting vessel restenosis at mid-term follow-up / 中华医学杂志(英文版)

BACKGROUND@#Drug-coated balloons (DCBs) have emerged as potential alternatives to drug-eluting stents in specific lesion subsets for de novo coronary lesions. Quantitative flow ratio (QFR) is a method based on the three-dimensional quantitative coronary angiography and contrast flow velocity during coronary angiography (CAG), obviating the need for an invasive fractional flow reserve procedural. This study aimed to assess the serial angiographic changes of de novo lesions post-DCB therapy and further explore the cut-off values of lesion and vessel QFR, which predict vessel restenosis (diameter stenosis [DS] ≥50%) at mid-term follow-up.@*METHODS@#The data of patients who underwent DCB therapy between January 2014 and December 2019 from the multicenter hospital were retrospectively collected for QFR analysis. From their QFR performances, which were analyzed by CAG images at follow-up, we divided them into two groups: group A, showing target vessel DS ≥50%, and group B, showing target vessel DS <50%. The median follow-up time was 287 days in group A and 227 days in group B. We compared the clinical characteristics, parameters during DCB therapy, and QFR performances, which were analyzed by CAG images between the two groups, in need to explore the cut-off value of lesion/vessel QFR which can predict vessel restenosis. Student's t test was used for the comparison of normally distributed continuous data, Mann-Whitney U test for the comparison of non-normally distributed continuous data, and receiver operating characteristic (ROC) curves for the evaluation of QFR performance which can predict vessel restenosis (DS ≥50%) at mid-term follow-up using the area under the curve (AUC).@*RESULTS@#A total of 112 patients with 112 target vessels were enrolled in this study. Group A had 41 patients, while group B had 71. Vessel QFR and lesion QFR were lower in group A than in group B post-DCB therapy, and the cut-off values of lesion QFR and vessel QFR in the ROC analysis to predict target vessel DS ≥50% post-DCB therapy were 0.905 (AUC, 0.741 [95% confidence interval, CI: 0.645, 0.837]; sensitivity, 0.817; specificity, 0.561; P < 0.001) and 0.890 (AUC, 0.796 [95% CI: 0.709, 0.882]; sensitivity, 0.746; specificity, 0.780; P < 0.001).@*CONCLUSIONS@#The cut-off values of lesion QFR and vessel QFR can assist in predicting the angiographic changes post-DCB therapy. When lesion/vessel QFR values are <0.905/0.890 post-DCB therapy, a higher risk of vessel restenosis is potentially predicted at follow-up.

Anterior thalamic nuclei deep brain stimulation inhibits mossy fiber sprouting via 3',5'-cyclic adenosine monophosphate/protein kinase A signaling pathway in a chronic epileptic monkey model / 中华医学杂志(英文版)

BACKGROUND@#Anterior thalamic nuclei (ATN) deep brain stimulation (DBS) is an effective method of controlling epilepsy, especially temporal lobe epilepsy. Mossy fiber sprouting (MFS) plays an indispensable role in the pathogenesis and progression of epilepsy, but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown. This study aimed to investigate the effect of ATN-DBS on MFS, as well as potential signaling pathways by a kainic acid (KA)-induced epileptic model.@*METHODS@#Twenty-four rhesus monkeys were randomly assigned to control, epilepsy (EP), EP-sham-DBS, and EP-DBS groups. KA was injected to establish the chronic epileptic model. The left ATN was implanted with a DBS lead and stimulated for 8 weeks. Enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus. One-way analysis of variance, followed by the Tukey post hoc correction, was used to analyze the statistical significance of differences among multiple groups.@*RESULTS@#ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy. The number of ectopic granule cells was reduced in monkeys that received ATN stimulation (P < 0.0001). Levels of 3',5'-cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the hippocampus, together with Akt phosphorylation, were noticeably reduced in monkeys that received ATN stimulation (P = 0.0030 and P = 0.0001, respectively). ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions (all P < 0.0001).@*CONCLUSION@#ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells, which may be associated with the reduced MFS in chronic epilepsy. The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.

Lignans with NO inhibitory activity from Tinospora sinensis / 中国天然药物

Two new lignan glucosides, tinsinlignans A and B (1 and 2), two new oxyneolignans, tinsinlignans C and D (3 and 4), along with one known analogue (5), were isolated from the stems of Tinospora sinensis. The structures of the new compounds were elucidated based on analysis of spectroscopic data, and the absolute configuration of 1 was determined through electronic circular dichroism (ECD) calculation based on the time-dependent density functional theory (TD-DFT). Compounds 1-4 were evaluated for their inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells and compounds 1 and 2 exhibited moderate inhibitory activities with IC

Research progress of the relationship between endothelial progenitor cells and cardiovascular complications in diabetes / 医学研究生学报

70% to 80% of people with diabetes died from cardiovascular complications, which had become the leading cause of death in diabetic patients. Cardiovascular complications in diabetic patients are mainly associated with vascular endothelial dysfunction and poor neovascularization. Its important influencing factors are changes in the number of endothelial progenitor cells and dysfunction. Hyperglycemia in diabetic patients can cause endothelial progenitor cell dysfunction, inhibit its proliferation ability, angiogenesis ability and paracrine effect. In order to provide research ideas for the prevention and treatment of cardiovascular complications in diabetic patients, this article aims to review the relevant mechanism of the effect of hyperglycemia on the number and function of endothelial progenitor cells in patients with diabetes, and the application of endothelial progenitor cells in the treatment of diabetic cardiovascular disease.

MiR-218 Targeting Bmi-1 Inhibits Proliferation of Acute Promyelocytic Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To explore the molecular mechanism by which miR-218 targeting Bmi-1 inhibits the proliferation of acute promyelocytic leukemia (APL) cells.@*METHODS@#APL cell line HL-60 was transfected by miR-218 and RNA-negative control sequences, respectively. The expression of miR-218 in cells was detected by real-time fluorescence quantitative PCR. The effect of transfected miR-218 on the proliferation of APL cells was detected by MTT assay. Cell apoptosis was detected by flow cytometry. The regulation effect of miR-218 on Bmi-1 expression was determined by Western blot. The correlation of miR-218 expressions with Bmi-1 was analyzed by Spearman test. The targeted relationship between miR-218 and Bmi-1 was verified by luciferase assay.@*RESULTS@#MTT assay showed that the proliferation of HL-60 cells in vitro was inhibited by high expression miR-218 significantly. Flow cytometry showed that the G1 and G2 phase cells increased while the S phase cells decreased after transfected by miR-218. Western blot showed that the level of Bmi-1 protein in HL-60 cells decreased significantly after transfection of miR-218 (P＜0.05). Spearman correlation analysis showed that the mRNA level of miR-218 negatively correlated with the protein content of Bmi-1 (r=-0.326, P＜0.01). Luciferase assay indicated that Bmi-1 could targeted on miR-218 directly.@*CONCLUSION@#miR-218 can inhibit the proliferation, metastasis and invasion of APL cells, which can be related with the down-regulated of Bmi-1.

Altered microRNA profiles of testicular biopsies from patients with nonobstructive azoospermia / 亚洲男科学杂志(英文版)

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.

Transurethral seminal vesiculoscopy in treatment of oligoasthenozoospermia secondary incomplete ejaculatory duct obstruction: A report of 8 cases / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the utility of transurethral seminal vesiculoscopy with a slender ureteroscope in the treatment of severe oligoasthenozoospermia secondary incomplete ejaculatory duct obstruction (EDO).@*METHODS@#From March 2018 to September 2018, the clinical data of 8 patients with severe oligoasthenozoospermia secondary incomplete EDO treated by the technique of transurethral seminal vesiculoscopy in the Peking University Third Hospital Reproductive Center were analyzed. Preoperative routine included semen analysis, hormone determination, transrectal ultrasonography, pelvic magne-tic resonance examination and other examinations. All the patients were diagnosed with severe oligoasthenozoospermia secondary to incomplete EDO. All the patients were operated by the same surgeon with multiple cases of experience in transurethral surgery, and 1 year follow-up was conducted to evaluate the surgical effect.@*RESULTS@#The average age of the 8 patients was 29 years, and the average operation time was 32 min. Preoperative transrectal ultrasound indicated 6 cases of ejaculatory duct cyst or Mullerian cyst, 1 case of prostate calcification and bilateral seminal vesicle dilatation. The average maximum transverse diameter of the right seminal vesicle in pelvic MRI was 33.60 mm (24.63-42.28 mm), the average maximum transverse diameter of the left seminal vesicle was 32.85 mm (25.91-44.89 mm), the ave-rage maximum antero-posterior diameter was 27.99 mm (21.36-33.12 mm), the average maximum width of the seminal vesicle duct was 10.53 mm (5.93-19.39 mm). There were 5 cases of ejaculatory duct cyst, 2 cases of seminal vesicle hemorrhage, and 1 case of Mullerian cyst. The semen volume [(2.64±0.80) mL], the sperm concentration [(49.76±8.50)×106/mL], and the motility (grade a+b) [(25.76±6.48)%] in postoperation were significantly higher than those in preoperation [(1.46±0.50) mL, (28.78±5.17)×106/mL, and (2.88±0.93)%, P < 0.05]. Two patients conceived naturally during the follow-up of 6 months after surgery. There were no severe complications, such as retrograde ejaculation, urinary incontinence or rectal injury.@*CONCLUSION@#The technique of transurethral seminal vesiculoscopy is safe and effective for treating severe oligoasthenozoospermia secondary to incomplete EDO. However, due to the small sample size of this study, short follow-up time, and the uncertainty in seminal vesicle surgery, it still needs to be further confirmed by long-term follow-up studies with large samples.

Computed tomography-magnetic resonance imaging fusion-guided iodine-125 seed implantation for single malignant brain tumor: Feasibility and safety

Background: To investigate the feasibility and safety of computed tomography-magnetic resonance imaging (CT-MRI) fusion-guided iodine-125 seed implantation for a single malignant brain tumor. Methods: From November 2015 to October 2016, 12 patients with a single malignant brain tumor were treated with permanent iodine-125 seeds implantation. CT-MRI fusion images were used to make the preoperative treatment plan, intraoperative dose optimization, postoperative verification, and tumor response follow-up. The dosimetry parameters of CT-MRI image fusion plans were compared between preprocedures and postprocedures, including plan target volume, V100 (the percentage of the target volume covered by the prescription dose [PD]), D90 (the dose that covers 90% of the target volume), and V200 (the percentage volume of the brain tumor receiving 200% of the PD). Adverse events were graded by the Common Terminology Criteria for Adverse Events. Clinical and radiological follow-ups were performed at a 3-month interval. Results: All the interstitial implantations were completed successfully under the guidance of CT-MRI image fusion. The dosimetry parameters of CT-MRI image fusion postplans did not differ significantly from those of preplans (P > 0.05). No higher than Grade 2 adverse events were observed during the follow-up. Tumor control was achieved in 10 of 12 patients (83.33%). The median overall survival time was 15.05 ± 3.35 months (95% confidence interval 12.99–17.26). Conclusions: CT-MRI image fusion is feasible for the design, optimization, and verification of treatment planning. CT-MRI fusion-based brachytherapy may improve dosimetry of brain tumor while sparing the normal structures, potentially impacting disease control, treatment-related toxicity, and long-term survival

Mechanisms and Components Identification of Naoxintong Intestinal Absorption Liquid Protecting Cardiac Injury Induced by H2O2 / 中国实验方剂学杂志

Objective: Intestinal absorption liquid as medicine carriers, one or more kinds of traditional Chinese medicine protecting cardiac injury in Naoxintong capsule will be found through separation and combination of prescription. This study also can expand protecting mechanisms of Naoxintong capsule. Method: Naoxintong intestinal absorption liquids of single, combination and total prescription were prepared. H9c2 cell line exposed to H2O2 was established. Cell survival rate was determined with methyl thiazolyl tetrazolium(MTT). Cell apoptosis rate was examined by Annexin Ⅴ-FITC/PI staining with a flow cytometer. Aquaporin1(AQP1) expression was detected by Western blot. One or more kinds of traditional Chinese medicine in Naoxintong capsule which exerted protective effect from cardiac injury were screened through separation and combination of prescription. Result: As compared with control group, the protein expression level of AQP1 was significantly increased(PPPPPPConclusion: Naoxintong capsule acts as a protective role in myocardial injury through decreasing AQP1 expression and inhibiting cell apoptosis. Salviae Miltiorrhizae Radix et Rhizoma, Pheretima, Scorpio are important components in Naoxintong capsule.

Bioinformatics Screening of Key Genes and Candidate Therapeutic Drugs of Osteoarthritis / 中国实验方剂学杂志

Objective: To explore the key genes and potential therapeutic drugs for osteoarthritis (OA) by bioinformatics.Method: The microarray data GSE55235 was downloaded from the data platform of gene expression omnibus (GEO) and the differentially expressed genes were screened by R language software (3.5.0).Then,the differentially expressed genes were subjected to gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis with David online database.The protein-protein interaction was analyzed by String 10.5 online database and visual editing was analyzed by Cytoscape v3.6.1 software.Subnetwork module analysis was utilized by MCODE plugin to screen the core genes in the process of OA.Finally,small molecule drugs with potential treatment for OA were analyzed by connectivity map (CMap) database.Result: A total of 556 differentially expressed genes were screened,among which 252 were up-regulated and 304 were down-regulated.These genes were mainly involved in extracellular matrix (ECM) organization,inflammatory response,cell adhesion,immune response,collagen binding,etc.The analysis of KEGG pathway showed that differential genes were mainly involved in ECM-receptor interaction,phosphatidylinositol 3 kinase-protein kinase B (PI3K/Akt) signaling pathway and osteoclast differentiation.Some genes,such as interleukin-6(IL-6),JUN,vascular endothelial growth factor α(VEGFA),FOS,MYC and early growth response gene-1(EGR-1),activating transcription factor-3(ATF-3),playing critical role in the process of OA were identified by protein-protein interaction.Some potential small molecular drugs for the treatment of OA have also been screened,such as lycorine and anisomycin.Conclusion: The selected key genes may be targets for the diagnosis of OA or potential targets for the treatment of OA,and the selected small molecular drugs can be developed as the key drugs for the treatment of OA.

Analysis and Identification of Chemical Components in Trichosanthis Fructus by UPLC-LTQ-Orbitrap-MS / 中国实验方剂学杂志

Objective: To analysis and identify the chemical components in Trichosanthis Fructus by UPLC-LTQ-Orbitrap-MS. Method: Samples of Trichosanthis Fructus were extracted by ultrasonic with 70% methanol after smashing and sifting by 40 mesh sieve. Thermo ScientificTM DionexTM UltiMateTM 3000 Rapid Separation LC system performed UPLC separations with Waters HSS T3-C18(2.1 mm×100 mm,1.8 μm) column. The mobile phase was 0.1% formic acid water(A)-methanol(B) with a gradient elution. The volume flow was 0.3 mL ·min-1. A Thermo ScientificTM LTQ-Orbitrap mass spectrometer equipped with a ESI probe was employed. The samples were respectively scanned in MS1 and MS2 mode of positive and negative ions. According to the chromatographic peak separation,mass signal intensity,and the number of molecular ions in MS1 model,the extraction condition,chromatogram and mass spectrum parameters were optimized. The chemical compounds were identified by the accurate mass measurement of molecular ions and fragment ion and comparation with reference substance. Result: 91 chemical compositions in Trichosanthis Fructus were totally identified,including 14 amino acids,5 monoterpenoids,5 tetracyclic triterpenoids,1 pentacyclic triterpene,14 flavonoids, 17 organic acids,3 polysaccharides,7 nucleotides,7 alkaloids and nitrogen compounds,2 volatile components,1 phytosterol,5 other compositions. Conclusion: The established UPLC-LTQ-Orbitrap-MS method can be used to quickly analyze and identify the main chemical constituents of Trichosanthis Fructus. The chemical information concerning the constituents in Trichosanthis Fructus could be helpful to the quality control and further studies of Trichosanthis Fructus.

Analysis of intratesticular condition in micro-dissection testicular sperm extraction era / 北京大学学报(医学版)

OBJECTIVE@#To summarizes the intratesticular condition of azoospermia patients, to understand azoospermia more intuitively, and improve the ability of clinical doctors to predict the success rate of microsperm extraction in azoospermia patients.@*METHODS@#Azoospermia patients (excluding Klinefelter's syndrome) who underwent a micro-TESE during January 2014 and January 2018 in a single center were enrolled. The types of seminiferous tubules were summarized, and the clinical characteristics of different types of seminiferous tubules compared with the success rates of sperm extraction. In this study, 472 cases of non-obstructive azoospermia (excluding Klinefelter's syndrome) were analyzed by SPSS 21.0 software package. Relevant data were expressed by median(minimum,maximum).t-test was used to compare the difference of success rate of sperm extraction between each group and the group with the lowest rate (a type).@*RESULTS@#The 472 patients with non-obstructive azoospermia underwent micro-TESE. The mean age of the patients was 31 (23, 46) years, the mean testicular size was 10 (1, 20) mL, the mean FSH was 15.4 (1.21, 68.4) IU/L, the mean T was 8.34 (0.69, 30.2) nmol/L, and totally 202 patients achieved success in micro-TESE (42.7%, 202/472). According to the seminiferous tubules seen during the operation, they were divided into the following six types: Class a, seminiferous tubules developed well and uniformly; Class b, seminiferous tubules developed well, occasionally slightly thick; Class c, seminiferous tubules were generally thin; Class d, seminiferous tubules basically atrophied, occasionally well-developed seminiferous tubules; Class e, all seminiferous tubules atrophied; Class f, seminiferous tubules were infiltrated by yellow substances. The success rate of micro-TESE varied greatly among different types of the patients. A total of 78 patients with type a were 29 (24, 40) years old, FSH 11.1 (1.21, 15.8) IU/L, T 10.2 (3.29, 26.5) nmol/L), and testicular size 12 (12, 20) mL. The successful rate of sperm extraction was 6.41%; 82 patients with type b were 31 (23, 42) years old, FSH 13.8 (3.23, 19.6) IU/L, T 9.44 (3.58, 30.2) nmol/L), and testicular size 12(8,15) mL. The successful rate of sperm extraction was 74.39%; There were 162 patients in group c, aged 31 (25, 40), FSH 19.6 (9.28, 26.6) IU/L, T 8.75 (5.66, 18.6) nmol/L, and testicular size 8 (5, 12) mL. The successful rate of sperm extraction was 45.06%. There were 36 patients in group d, aged 25 (23,38) years and FSH 28.5 (19.3, 45.6) IU/L, T 6.52 (2.12, 9.83) nmol/L, and testicular size 5 (3, 8) mL, and the success rate of sperm extraction was 94.44%. 26 patients with type e were 28(23, 46) years old, FSH 31.3 (18.5, 68.4) IU/L, T 6.72 (0.69, 18.2) nmol/L, and testicular size 5 (1, 8) mL. The success rate of sperm extraction was 45.38%. 88 patients with type f were 29 (24, 38) years old, FSH 18.5 (5.23, 31.6) IU / L, T 8.32 (3.58, 16.5) nmol/L, and testicular size 12 (6, 20) mL. The success rate of sperm extraction was 28.41%.@*CONCLUSION@#The success rate of micro-TESE in different types of seminiferous tubules in testis can be helpful to the judgement of the surgeon during the operation.

Marker genes of geniposide-induced hepatotoxicity based on genomic strategy / 中国中药杂志

The aim of this paper was to screen out relevant genes of geniposide-induced hepatotoxicity based on genomics,in order to provide a scientific basis for the non-clinical evaluation of drugs containing Gardeniae Fructus and geniposide. Fifty-five SD rats were randomly divided into normal control group,24 h group and 72 h group. The changes of appearance,behavior and weight of rats were observed after administration by gavage for 3 days. The activities of ALT and AST were detected. Molecular mechanism of geniposideinduced hepatotoxicity was investigated by Affymetrix miRNA 4. 0 and Affymetrix Rat Gene 2. 0 to examine the gene expression levels in Sprague-Dawley rat livers at 24 h and 72 h after administration of overdose-geniposide( 300 mg·kg-1 daily),and then verified by Realtime quantitative PCR. Compared with the normal control group,the activities of ALT and AST were markedly increased. In addition,experimental results indicated that 324 genes were differentially expressed,among which 259 were up-regulated and 65 down-regulated.Nine candidate genes were verified by qRT-PCR,including Bcl2,Il1 b,Tpm3,MMP2,Col1α1,Ifit1,Aldob,Nr0 b2,Cyp2 c23. And Bcl2,Col1α1,Aldob,Nr0 b2 and Cyp2 c23 were found to be correlated with geniposide-induced hepatotoxicity. This study provides an important clue for mechanism of geniposide-induced hepatotoxicity.

Dysregulation of NCAPG, KNL1, miR-148a-3p, miR-193b-3p, and miR-1179 may contribute to the progression of gastric cancer

BACKGROUND: Emerging evidence indicate that miRNAs play an important role on gastric cancer (GC) progression via regulating several downstream targets, but it is still partially uncovered. This study aimed to explore the molecular mechanisms of GC by comprehensive analysis of mRNAs and miRNA expression profiles. METHODS: The mRNA and miRNA expression profiles of GSE79973 and GSE67354 downloaded from Gene Expression Omnibus were used to analyze the differentially expressed genes (DEGs) and DE-miRNAs among GC tissues and normal tissues. Then, targets genes of DE-miRNAs were predicted and the DE-miRNA-DEG regulatory network was constructed. Next, function enrichment analysis of the overlapped genes between the predicted DE-miRNAs targets and DEGs was performed and a protein-protein interactions network of overlapped genes was constructed. Finally, RT-PCR analysis was performed to detect the expression levels of several key DEGs and DE-miRNAs. RESULTS: A set of 703 upregulated and 600 downregulated DEGs, as well as 8 upregulated DE-miRNAs and 27 downregulated DE-miRNAs were identified in GC tissue. hsa-miR-193b-3p and hsa-miR-148a-3p, which targeted most DEGs, were highlighted in the DE-miRNA-DEG regulatory network, as well as hsa-miR-1179, which targeted KNL1, was newly predicted to be associated with GC. In addition, NCAPG, which is targeted by miR-193b-3p, and KNL1, which is targeted by hsa-miR-1179, had higher degrees in the PPI network. RT-qPCR results showed that hsa-miR-148a-3p, hsa-miR-193b-3p, and hsa-miR-1179 were downregulated, and NCAPG and KNL1 were upregulated in GC tissues; this is consistent with our bioinformatics-predicted results. CONCLUSIONS: The downregulation of miR-193b-3p might contribute to GC cell proliferation by mediating the upregulation of NCAPG; as additionally, the downregulation of miR-193b-3p might contribute to the mitotic nuclear division of GC cells by mediating the upregulation of KNL1.

Mechanism of RNA interference HOXB7 gene expression in colon cancer on pro-liferation and apoptosis of cancer cells / 中国免疫学杂志

Objective:To investigate the effect of inhibiting of HOXB7 gene expression on proliferation and apoptosis of colon cancer cells.Methods:The synthetic negative control siRNA (negative control group) and HOXB7-siRNA (HOXB7 transfection group) were transfected into human colon cancer SW480 cells by LipofectamineTM2000 liposome mediated method,untreated cells as blank group.RT-PCR and Western blot were used to detect the mRNA and protein expression of HOXB7 after transfected 48 h respectively;cell proliferation was detected by CCK8 assay after transfected 24,48,72,96 h;cells apoptosis was detected by flow cytometry after transfected 48 h;the expression of apoptosis related proteins Bcl-2,Bax and Notch1 signaling pathway Notch1 and Hes1 were detected by Western blot.Results:The mRNA and protein expression of HOXB7 in HOXB7 transfected group was significantly lower than that in blank group(P<0.05);OD value was no statistical significance in the three groups after transfected 24 h(P>0.05), while after transfected 48,72,96 h,compared with the control group,OD value in HOXB7 group was significantly decreased(P<0.05);compared with the blank group,the apoptosis rate in HOXB7 transfection group increased significantly,and the expression of Bcl-2, Notch1 and Hes 1 proteins was down regulated,and the expression of Bax protein was up-regulated(P<0.05).Conclusion:RNA inter-ference in the expression of HOXB7 gene in colon cancer can inhibit the proliferation of cancer cells and induce apoptosis by inhibiting of the Notch1 signaling pathway.

Acute Fornix Deep Brain Stimulation Improves Hippocampal Glucose Metabolism in Aged Mice / 中华医学杂志(英文版)

<p><b>Background</b>A beneficial memory effect of acute fornix deep brain stimulation (DBS) has been reported in clinical studies. The aim of this study was to investigate the acute changes in glucose metabolism induced by fornix DBS.</p><p><b>Methods</b>First, the Morris water maze test and novel object recognition memory test were used to confirm declined memory in aged mice (C57BL/6, 20-22 months old). Then, four groups of mice were used as follows: aged mice with stimulation (n = 12), aged mice with sham-stimulation (n = 8), adult mice (3-4 months old) with stimulation (n = 12), and adult mice with sham-stimulation (n = 8). Ipsilateral hippocampal glucose metabolism and glutamate levels were measured in vivo by microdialysis before, during, and after fornix DBS treatment. Histological staining was used to verify the localization of electrodes and mice with inaccurate placement were excluded from subsequent analyses. The effects of fornix DBS on extracellular glucose, lactate, pyruvate, and glutamate levels over time were analyzed by repeated-measures analysis of variance followed by Fisher's least significant difference post hoc test.</p><p><b>Results</b>The aged mice had a higher basal lactate/pyruvate ratio (LPR) and lactate/glucose ratio (LGR) than the adult mice (LPR: 0.34 ± 0.04 vs. 0.13 ± 0.02, t = 4.626, P < 0.0001; LGR: 6.06 ± 0.59 vs. 4.14 ± 0.36, t = 2.823, P < 0.01). Fornix DBS decreased the ipsilateral hippocampal pyruvate and lactate levels (P < 0.05), but the glucose levels were not obviously changed in aged mice. Similarly, the LGR and LPR also decreased in aged mice after fornix DBS treatment (P < 0.05). Glucose metabolism in adult mice was not significantly influenced by fornix DBS. In addition, fornix DBS significantly decreased the ipsilateral hippocampal extracellular levels of glutamate in aged mice (P < 0.05), while significant alterations were not found in the adult mice.</p><p><b>Conclusions</b>The present study provides experimental evidence that fornix DBS could significantly improve hippocampal glucose metabolism in aged mice by promoting cellular aerobic respiration activity.</p>