The effect of BMI and age on the outcomes of microsurgical vasoepididymostomy: a retrospective analysis of 181 patients operated by a single surgeon / 亚洲男科学杂志(英文版)

To design a treatment plan for patients with epididymal obstruction, we explored the potential impact of factors such as body mass index (BMI) and age on the surgical outcomes of vasoepididymostomy (VE). In this retrospective study, 181 patients diagnosed with obstructive azoospermia (OA) due to epididymal obstruction between September 2014 and September 2017 were reviewed. All patients underwent single-armed microsurgical intussusception VEs with longitudinal two-suture placement performed by a single surgeon (KH) in a single hospital (Peking University Third Hospital, Beijing, China). Six factors that could possibly influence the patency rates were analyzed, including BMI, age, mode of anastomosis, site of anastomosis, and sperm motility and quantity in the intraoperative epididymal fluid. Single-factor outcome analysis was performed via Chi-square test and multivariable analysis was performed using logistic regression. A total of 159 (87.8%, 159/181) patients were followed up. The follow-up time (mean ± standard deviation [s.d.]) was 27.7 ± 9.3 months, ranging from 12 months to 48 months. The overall patency rate was 73.0% (116/159). The multivariable analysis revealed that BMI and age significantly influenced the patency rate (P = 0.008 and 0.028, respectively). Younger age (≤28 years; odds ratio [OR] = 3.531, 95% confidence interval [95% CI]: 1.397-8.924) and lower BMI score (<26.0 kg m-2; OR = 2.352, 95% CI: 1.095-5.054) appeared to be associated with a higher patency rate. BMI and age were independent factors affecting the outcomes of microsurgical VEs depending on surgical expertise and the use of advanced technology.

Low Grip Strength and Increased Mortality Hazard among Middle-Aged and Older Chinese Adults with Chronic Diseases / 生物医学与环境科学（英文）

OBJECTIVE@#This study aims to evaluate the association between lower grip strength and mortality hazard.@*METHODS@#We selected 10,280 adults aged 45 to 96 years old from the China Health and Retirement Longitudinal Study and used multivariate Cox proportional hazard models to assess the association of grip strength with mortality hazard. In addition, we explored the possibility of a nonlinear relationship using a 4-knot restricted spline regression.@*RESULTS@#We found that elevated grip strength was associated with lower mortality up to a certain threshold. The baseline quartile values of grip strength were 30, 37, and 44 kg for males and 25, 30, and 35 kg for females. After adjusting for confounders, with category 1 as the reference group, the adjusted HRs were 0.58 (0.42-0.79) in males and 0.70 (0.48-0.99) in females (category 4). We also found a linear association between grip strength values and all-cause death risk (males, P = 0.274; females, P = 0.883) using restricted spline regression. For males with a grip strength < 37 kg and females with a grip strength < 30 kg, grip strength and death were negatively associated.@*CONCLUSION@#Grip strength below a sex-specific threshold is inversely associated with mortality hazard among middle-aged and older Chinese adults with chronic diseases.

Relationship between serum reproductive hormones and sperm parameters and surgical outcomes in Micro-TESE / 现代泌尿外科杂志

【Objective】 To investigate the relationship between serum reproductive hormones and sperm parameters and outcomes of micro-testicular sperm extraction (Micro-TESE). 【Methods】 Clinical data of 1 091 patients treated in our hospital during Jan. and Dec.2021 were retrospectively analyzed. According to the sperm concentration,the patients were divided into non-obstructive azoospermia (NOA) group (group A,n=418),normal sperm concentration group (group B,n=615),mild to moderate oligospermia group (group C,n=18),severe oligospermia group (group D,n=18),and obstructive azoospermia group (group E,n=22). In group A,244 cases treated with Micro-TESE were grouped into the sperm-acquired group (Micro-TESE positive group,n=82) and non-sperm-acquired group (Micro-TESE negative group,n=162),and according to the pathological types of testicular tissue,the patients were divided into normal testicular tissue with hypospermatogenesis group (HYPO group,n=129),maturation arrest group (MA group,n=10),and support-only cell syndrome group (SCO group,n=122). Differences in semen parameters and reproductive hormone levels were compared,and relationship between reproductive hormones and sperm parameters and Micro-TESE outcomes was determined with Pearson correlation analysis. 【Results】 In the sperm concentration subgroup,the testicular volume of group A was lower than that of group B and group E (P<0.05); the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in group A were the highest (P<0.05),but the level of testosterone (T) was the lowest (P<0.05); the levels of anti-mullerian hormone (AMH) and serum inhibin B (INHB) in group A were lower than those in group B and group E (P<0.05),the normal sperm morphology rate in group B was higher than that in group A and group E (P<0.05); the percentage of forward moving sperm in group B was the highest (P<0.05). Pearson correlation analysis revealed that sperm concentration,normal sperm morphology rate,and percentage of forward moving sperm were negatively correlated with age,FSH,LH (P<0.05),and positively correlated with testicular volume,T,AMH,and INHB (P<0.05). NOA patients were grouped according to testicular histology and pathology. The INHB in the SCO group was the smallest of the three groups (P<0.05); the FSH and LH levels in the SCO group were higher than those in the MA group (P<0.05),while the 17β-estradiol (E2) levels in the HYPO group were higher than those in the SCO group (P<0.05). NOA patients were grouped according to the results of Micro-TESE surgical treatment. There was a statistically significant difference in AMH and INHB levels between the Micro-TESE positive and negative groups (P<0.05). The binary logistic regression analysis of factors affecting the Micro-TESE outcomes of NOA patients showed AMH was negatively correlated with the Micro-TESE outcome (OR=0.904,95%CI:0.91-1.08,P<0.05). 【Conclusion】 Age,FSH,LH,AMH,and INHB are correlated with sperm concentration,normal sperm morphology rate,and percentage of forward moving sperm. The INHB level was the lowest in the SCO group. The results of Micro-TESE in patients with NOA can be predicted by serum AMH level.

Clinical analysis of testicular rhabdomyosarcoma / 北京大学学报(医学版)

Testicular rhabdomyosarcoma is relatively rare in testicular tumors, but the age of patient is relatively young and the degree of malignancy is high. Therefore, this article introduces 4 cases of testicular rhabdomyosarcoma who were admitted to Peking University Third Hospital from May 1994 to February 2019, and reviews the literature to improve the diagnosis and treatment of this disease. The average age of the 4 patients was 17.5 years (14-21 years), the average hospital stay was 22.0 d (17-31 d), and the average body mass index was 19.6 kg/m2 (14.7-25.8 kg/m2). All the patients underwent routine preoperative blood and urine routine, biochemical tests, as well as serum tumor markers. Preoperative examinations also included chest radiograph, electrocardiogram, ultrasound of the scrotum and groin, and abdominal enhanced CT. Lung CT or other examinations were performed if necessary. The median serum human chorionic gonadotropin (HCG) of the 4 patients was 0.20 IU/L (0.06-0.86 IU/L) (all normal), and the median serum alpha-fetoprotein (AFP) was 1.03 g/L (0.65-1.66 g/L) (all normal). The average maximum diameter of the tumor was 10.0 cm (4.5-15.0 cm). Testicular rhabdomyosarcoma was mainly diagnosed by pathology. The main treatment was radical orchiectomy combined with retroperitoneal lymph node dissection, with or without postoperative adjuvant chemotherapy. The clinical manifestations of the patients with testicular rhabdomyosarcoma had no specific characteristics, but most patients were young at onset with mainly painless masses in the testicles, which were already large when they were found. Patients with testicular rhabdomyosarcoma have a poor prognosis, most of whom recur within two years. Because of the small number of cases of testicular rhabdomyosarcoma, there is no standard treatment currently. It is recommended that patients with testicular rhabdomyosarcoma undergo radical testicular resection combined with retroperitoneal lymph node dissection. Retroperitoneal lymph node metastasis is an important prognostic factor, and patients with postoperative adjuvant chemotherapy can still survive for a longer time. If local recurrence or limited metastasis is found after operation, local resection and salvage radiotherapy are feasible.

Genetic analysis of three cases of acephalic spermatozoa syndrome caused by SUN5 mutation and the outcome of assisted reproductive technology / 北京大学学报(医学版)

To explore the genetic causes of 3 male infertility patients with acephalospermia and the outcome of assisted reproductive technology. Clinical diagnosis, sperm morphology examination, sperm transmission electron microscopy examination were performed on 3 patients, and the whole exome sequencing technology was used for screening, Sanger sequencing verification, mutation pathogenicity analysis, and protein sequence homology comparison. Assisted reproductive technology was implemented to assist pregnancy treatment. The 3 patients were all sporadic infertile men, aged 25, 42 and 26 years, and there was no obvious abnormality in the general physical examination. Male external genitalia developed normally, bilateral testicles were normal in volume, and bilateral epididymis and spermatic vein were palpated without nodules, cysts, and tenderness. Repeated semen analysis showed that a large number of immature sperm could be seen, and they had the ability to move. The SUN5 gene of the 3 male infertile patients was a case of homozygous missense mutation c.7C>T (p.Arg3Trp), a case of compound heterozygous missense mutation c.1067G>A (p.Arg356His) and nonsense mutation c.216G>A (p.Trp72*) and a case of homozygous missense mutation c.1043A>T (p.Asn348Ile), of which c.7C>T (p.Arg3Trp) and c.1067G>A (p.Arg356His) were new variants that had not been reported. SIFT, Mutation Taster and PolyPhen-2 software function prediction results were all harmful, the nonsense mutation c.216G>A (p.Trp72*) led to the premature termination of peptide chain synthesis which might have a greater impact on protein function. The homology regions in the protein sequence homology alignment were all highly conserved.The 3 male patients and their spouses obtained 4 biological offspring through intracytoplasmic sperm injection, all of which were boys, and one of them was a twin.Three male infertile patients might be caused by SUN5 gene mutations. Such patients could obtain their biological offspring through assisted reproductive technology. It was still necessary to pay attention to the genetic risk of ASS, it was recommended that both men and women conduct genetic counseling and screening at the same time. In clinical diagnosis, whole exome sequencing technology could be used to perform auxiliary examinations to determine the treatment plan and assisted reproductive methods as soon as possible to reduce the burden on the family and society. The newly discovered mutation sites of SUN5 gene provided clues and directions for elucidating the pathogenic mechanism, and at the same time expanded the pathogenic mutation spectrum of ASS.

Comparison of two methods for detection of Chlamydia trachomatis and Ureaplasma urealyticum in male reproductive tract / 北京大学学报(医学版)

OBJECTIVE@#To investigate the value of clinical application of simultaneous amplification and testing of RNA (SAT-RNA) for detecting Chlamydia trachomatis (CT) and Ureaplasma urealyticum (UU) by comparing with the polymerase chain reaction testing of DNA (PCR-DNA) method.@*METHODS@#Specimens from both urethra swab and the first avoid urine which should be at least one hour after the previous urination were collected from 163 men who were scheduled for in vitro fertilization and embryo transfer (IVF-ET) treatment due to female factors at Center for Reproductive Medicine, Shengjing Hospital of China Medical University during the period of April 2016 to April 2017. Among the 163 men, 109 simultaneously provided semen that was collected after 3-7 days of sexual abstinence for the testing. Urine and semen specimens were detected for CT and UU with SAT-RNA, while urethra swab specimens were detected for CT and UU with standard PCR-DNA. Detection results of the SAT-RNA were compared with those of the PCR-DNA method.@*RESULTS@#The positive rate of UU in the urethra swab detected with PCR-DNA and that of UU in the urine with SAT-RNA were 47.24% and 47.85%, respectively, and the coincidence rate was 93.25%. In addition, the positive and negative coincidence rates were 93.51% and 93.02%, respectively, and the concordance between the two methods was very good (Kappa=0.865). On the other hand, the positive rate of CT in the swab specimen tested with PCR-DNA was 3.07% and that of CT in urine with SAT-RNA was 4.29%, and the coincidence rate was 97.55%. Moreover, the positive and negative coincidence rates were 80.00% and 98.10%, respectively, and the concordance between the two methods was good (Kappa=0.654). Regarding SAT-RNA detection of UU in the urine and semen specimen of the 109 patients, the positive rates of UU in the urine and semen specimens were 50.46% and 44.95%, respectively; and the coincidence rate between the two specimens was 88.99%. In addition, the positive coincidence rate and the negative coincidence rate was 93.88% and 85.00%, respectively, and the concordance between the two specimens was good (Kappa=0.780). Similarly, SAT-RNA detection of CT in the urine and semen specimens showed the positive rate was 5.50% and 3.67%, respectively; and the two specimens showed 98.17% coincidence rate. The positive and negative coincidence rates were 100.00% and 98.10%, respectively, and the concordance was also good (Kappa=0.791).@*CONCLUSION@#SAT-RNA detection of CT and UU in the urine specimen showed good concordance with the PCR-DNA detection of CT and UU in the urethra swab specimen. In addition, the concordance was also good between the urine and semen specimens detected with SAT-RNA. These results indicate that, as a less invasive and equally accurate procedure, SAT-RNA may be more suitable for clinical application.

Use of real-time transrectal ultrasound guidance in seminal vesiculoscopy / 中华泌尿外科杂志

Objective:To explore the application of real-time transrectal ultrasound (TRUS) during seminal vesiculoscopy in infertile men with azoospermia or oligoasthenospermia.Methods:We retrospectively analyzed the clinical data of 25 cases of azoospermia or oligoasthenospermia due to ejaculate ducts obstruction who were treated with real-time transrectal ultrasound-guided seminal vesiculoscopy between September 2011 and December 2015. Patients’ age was(29.4±4.5) years. All patients accepted semen analysis, serum sex hormone, MRI, TRUS and then diagnosed as obstructive azoospermia, and 13 cases had intractable obstructive azoospermia or oligoasthenospermia after the failure of simple seminal vesiculoscopy(the path to the ejaculatory duct and seminal vesicle couldn’t be found). All patients were treated with seminal vesiculoscopy under real-time guidance with TRUS. We assessed the success rate of surgery, surgical time and complications.Results:The scope was successfully inserted into the seminal vesicle in 21 of the 25 cases (success rate, 84%). The median operative time was 75(31, 148) min. None of the patients developed severe complications. Among 4 failure cases (4/25, 16%), 1 was due to abnormal congenital development. In 2 cases, a clear outlet of the dual ejaculatory duct could not be found after it was inserted into the prostatic utricle. One case was considered as a Müllerian tubular cyst, and the seminal vesicle scope was used to assess the cystic side wall. The 21 patients were followed up for 3 to 6 months, semen volume 2.0(0-5.2)ml, total sperm 28(0-832) ×10 6/ejaculate, sperm density 5.6(0-110.3)×10 6/ml, mobility rate of sperm 5.4%(0-63.6%), and the differences were significant as compared to that before the surgery [semen volume 0.4(0-2.8)ml, total sperm 0(0-342)×10 6/ejaculate, sperm density 0(0-90.7)×10 6/ml, mobility rate of sperm 0(0-24.1%), all P<0.05]. Among the 17 patients who underwent follow-up of 5 to 9 years, 3 patients was conceived naturally and 9 patients’ postoperative sperm quality has improved and pregnancy in vitro fertilization by extracting sperm from semen. Conclusions:Intraoperative real-time transrectal ultrasound guidance can improved the success rate of seminal vesiculoscopy and promoted operative safety.

Associations of exposure to secondhand smoke with hypertension risk and blood pressure values in adults

BACKGROUND@#The effects of environmental chemical exposure on blood pressure (BP) have been confirmed, but the association between exposure to secondhand smoke (SHS) and hypertension risk and BP in the general population remains unknown.@*METHODS@#Cross-sectional associations between SHS exposure and hypertension risk and BP values were evaluated using data for subjects who participated in the National Health and Nutrition Examination Survey (NHANES), 1999-2016. Logistic regression and linear regression were performed after adjusting for age, sex, race, alcohol consumption, poverty-to-income ratio (PIR), body mass index (BMI), estimated glomerular filtration rate, physical activity, diabetes, cardiovascular disease, and NHANES cycle. Restricted cubic spline models were created to display the potential nonlinear association between SHS and BP levels.@*RESULTS@#Higher risk of hypertension was found at the highest SHS concentrations (OR = 1.13, 95% CI 1.04, 1.24, P for trend = 0.007). Additionally, SHS exposure had a strong positive association with systolic blood pressure (SBP) but was negatively associated with diastolic blood pressure (DBP). Furthermore, the nonlinear model result showed a significant association between SHS and SBP (P = 0.017); however, the nonlinear model result was not significant for SHS or DBP.@*CONCLUSIONS@#Our results suggest a potential association between high SHS exposure and the risk of hypertension. Further research is needed to elucidate the underlying mechanisms.

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.

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.

SDF-1α/CXCR4 axis promotes migration and invasion of pancreatic cancer cells through inducing epithelial-mesenchymal transition / 中国病理生理杂志

AIM:To investigate the role of SDF-1α/CXCR4 axis in pancreatic cancer cell migration and invasion.METHODS:The mRNA expression of CXCR4 in 4 pancreatic cancer cell lines was detected by RT-qPCR.The migration and invasion abilities of PANC-1 cells with the axis activated by exogenous SDF-1αor inhibited by CXCR4 inhibitor AMD3100 were detected by Transwell assays.The cell viability was measured by MTS assay.The protein expression of the epithelial-mesenchymal transition (EMT) -related molecules in the cells treated with exogenous SDF-1αor AMD3100 was determined by Western blot.RESULTS:All of the 4 pancreatic cancer cell lines expressed CXCR4 mRNA, while the PANC-1 cell line expressed the most.Exogenous SDF-1αpromoted the migration and invasion abilities of PANC-1 cells, which was inhibited by AMD3100.The PANC-1 cells treated with exogenous SDF-1αfor 72 h grew faster, while SDF-1αcombined with AMD3100 made little significance to the viability of PANC-1 cells.Exogenous SDF-1αinduced EMT of PANC-1 cells by up-regulating the expression of SNAIL and TWIST, and AMD3100 reversed this effect.CONCLUSION:SDF-1α/CXCR4 axis enhances the migration and invasion abilities of pancreatic cancer cells through inducing EMT.

Effects of 2-12alkyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione(DMDD)on diffuse large B lymphoma and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects and molecular mechanisms of 2-12alkyl-6-methoxycyclohexa-2,5-diene-1,4-dione(DMDD) on diffuse large B lymphoma (DLBCL).@*METHODS@#In animal experiments, 4-week-aged BALB/C mice were divided into 5 groups, 20 mice in each group. Mice were inguinal injected with DLBCL cell line OCI-LY19 cells 0.1 ml at the concention of 1 × 10 /ml. Two days later, mice were treated with DMDD at the doses of 0, 1, 5, 25 and 125 mg/kg by intragastric administration respectively, once /2 days. Ten mice of each group were killed on the 18th day of administration, and the tumor tissues were weighed. The survival time of the remaining mice were recorded. In cell experiments, OCI-LY19 cells were added to 96-well culture plates, 100 μl 1×10 cells/ml per well, then 100 μl DMDD was added to the well and the final concentrations were 0, 1, 5, 25 and 125 μmol/L respectively. The cells were treated with DMDD for 0, 24, 48 and 72 h, three wells in each group. The cell proliferation activity was detected by MTS assay. According to the results of cell proliferation experiments, OCI-LY19 cells were treated with DMDD at the concentrations of 0 μmol/L, 5 μmol/L and 25 μmol/L for 24 h. The apoptosis rate was analyzed by flow cytometry, the nuclear type was observed by hoechst staining, the mitochondrial membrane potential was observed by JC-1 staining, cytotoxicity of drugs was evaluated by LDH release experiment, gene expression and transcription were analyzed by qPCR and Western blot.@*RESULTS@#Compared with 0 mg/kg drug group, DMDD at the dose of 1～125 mg/kg could inhibit the growth of tumor tissue in mice and prolong their survival time (P＜0.01). Cell experiments showed: in DMDD group, the proliferation activity of OCI-LY19 cells was decreased significantly and the level of apoptosis was increased significantly (P＜0.01), nuclear fragmentation, agglutination, apoptotic bodies occurred and mitochondrial membrane potential was decreased, the LDH release rate was increased significantly (P＜0.01), the expressions of caspase-3 and bax genes and the phosphorylation level of Ikappa B alpha in cells were up-regulated significantly, the protein expression levels of bcl-2, bcl-xL, jak2 and stat3 were inhibited significantly (P＜0.01).@*CONCLUSION@#DMDD can inhibit the expressions of JAK2, STAT3 and p-Ikappa B alpha in JAK2/STAT3 and NF-kappa B signal pathways, down-regulate BCL-2/BAX and activate Caspase-3, finally, activate the endogenous pathway of mitochondrial apoptosis in OCI-LY19 cells and promote the apoptosis of DLBCL cells, inhibit proliferation of OCI-LY19 cells. It has inhibitive effects on DLBCL.

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.

Construction of prognostic model and identification of prognostic biomarkers based on the expression of long non-coding RNA in bladder cancer via bioinformatics / 北京大学学报(医学版)

OBJECTIVE@#To construct the prognostic model and identify the prognostic biomarkers based on long non-coding RNA (lncRNA) in bladder cancer.@*METHODS@#The lncRNA expression data and corresponding clinical data of bladder cancer were collected from The Cancer Genome Atlas (TCGA) database. The software Perl and R, and R packages were used for data integration, extraction, analysis and visualization. Detailly, R package "edgeR" was utilized to screen differentially expressed lncRNA in bladder cancer tissues compared with the normal bladder samples. The univariate Cox regression and the least absolute shrinkage and selection operator (Lasso) regression were performed to identify key lncRNA that were utilized to construct the prognostic model by the multivariate Cox regression. According to the median value of the risk score, all patients were divided into the high-risk group and low-risk group to perform the Kaplan-Meier (K-M) survival curves, receiver operating characteristic (ROC) curve and C-index, estimating the prognostic power of the prognostic model. In addition, the hazard ratio (HR) and 95% confidence interval (CI) of each key lncRNA were also calculated by the multivariate Cox regression. Moreover, we performed the K-M survival analysis for each significant key lncRNA from the result of the multivariate Cox regression.@*RESULTS@#A total of 691 lncRNA were identified as differentially expressed lncRNA, and 35 lncRNA signatures were initially considered associated with the prognosis of bladder cancer, where in 23 lncRNA were identified as key lncRNA associated with the prognosis. The overall survival time in years of the low-risk group was obviously longer than that of the high-risk group [(2.85±2.72) years vs. (1.58±1.51) years, P<0.001]. The area under the ROC curve (AUC) was 0.813 (3-year survival) and 0.778 (5-year survival) respectively, and the C-index was 0.73. In addition, HR and 95%CI of each key lncRNA were calculated by the multivariate Cox regression and 11 lncRNA were significant. Furthermore, K-M survival analysis revealed the independent prognostic value of 3 lncRNA, including AL589765.1 (P=0.004), AC023824.1 (P=0.022)and PKN2-AS1 (P=0.016).@*CONCLUSION@#The present study successfully constructed the prognostic model based on the expression level of 23 lncRNA and finally identified one protective prognostic biomarker AL589765.1, and two adverse prognostic biomarkers including AC023824.1 and PKN2-AS1 in bladder cancer.

Organ-sparing partial orchietectomy for testicular adenomatoid tumor / 北京大学学报(医学版)

OBJECTIVE@#The incidence of testicular tumors is relatively low which are mainly malignant, so the main way to treat testicular tumors is radical testicular resection. Testicular adenomatoid tumor is a rare testicular benign tumor, but is easily misdiagnosed as malignant tumors with removal of organs. This article aims to explore the clinical features of testicular adenomatoid tumor and its treatment.@*METHODS@#There were 133 cases of testicular tumor in the Peking University Third Hospital from May 1994 to November 2016. We conducted a retrospective analysis of three patients who underwent the treatment of partial orchiectomy with preservation of the organ and were pathologically diagnosed with testicular adenomatoid tumor after surgery. The follow-up was done by outpatient clinics and telephone inquiry after surgery. The related literature was also reviewed for further discussion.@*RESULTS@#Of all the 133 patients, 116 had radical resection of the testis and 17 had partial testicular resection due to specific reasons (5 cases of epidermoid cyst, 4 cases of teratoma, 3 cases of seminoma, 3 cases of adenomatoid tumor, and 2 cases of Sertoli cell tumor). The mean age of the 3 patients was (42.67±10.97) years (30-49 years), the mean hospital stay was (9.00±5.20) d (6-15 d), the mean body mass index was (26.20±1.42) kg/m2 (25.00-27.76 kg/m2), the mean serum human choionic gonadotophin (HCG) was (1.15±0.11) IU/L (1.07-1.23 IU/L) (all normal) and the mean serum alpha-fetoprotein (AFP) was (2.12±0.66) μg/L (1.65-2.58 μg/L) (both were normal). Ultrasound features revealed a clear or unclear border, solid, moderate echo nodule tumor in the testis. The mean maximal diameter of the tumor was (1.00±0.44) cm (0.50-1.30 cm), and the mean duration of intraoperative warm ischemia time was (19.67±17.10) min (0-31 min) (only the last two cases). No recurrence or malignant transformation was observed during the follow-up.@*CONCLUSION@#Testicular adenomatoid tumor is mainly based on the characteristics of ultrasound to determine preoperatively, but easy to be misdiagnosed with testicular radical resection. The recommended surgery for adenomatoid tumor is partial resection of the testis via the inguinal approach according to the frozen section pathology to determine whether to retain the organ.

Multifactor analysis of postoperative patency of microsurgical vasoepididymostomy / 中华泌尿外科杂志

Objective To analyze the factors which may affect postoperative patency of microsurgical vasoepididymostomy (VE).Methods Ninety-four patients underwent VEs from September 2014 to June 2016 in the Department of Urology,Peking University Third Hospital,with average age of (30.7 ± 4.8) years,and body mass index (BMI) of (25.1 ± 3.0) kg/m2.Semen analyses were performed 1 month,3 months and 5 to 6 months after the operation.The following semen analyses were performed every 3-6 months thereafter.Patency was defined by finding sperms in twice or more analyses during the followup until August 2017.Patients were followed up by face-to-face or telephone interview.Seven factors (age,BMI,bilateral or unilateral anastomosis,anastomosis sites,the adjustment of anastomosis sites,motility and quantity of sperms found in epididymal fluid) were analyzed by Chi-square analysis and multifactor logistic regression analysis.Results Eighty-two patients were followed up (87.2％,82/94) while 12 patients were lost of follow-up.The mean follow-up time was 19 months.Sperms were found in the ejaculate in 59 patients postoperatively.The overall patency rate was 72.0％ (59/82),and natural paternity rate was 32.8％ (19/58).Patients ≤28 years old and those ＞28 years old had patency rates of 89.3％ (25/28) and 63.0％ (34/54,P =0.012),respectively.Patients with BMI ＜26.0 kg/m2 and BMI≥26.0 kg/m2 had patency rates of 80.4％ (41/51) and 58.1％ (18/31,P =0.029),respectively.Patency rate of bilateral surgery was 72.1％ (44/61) and of unilateral surgery was 71.4％ (44/62,P =0.727).Patency rate of caput anastomosis achieved 75.0％ (15/20) and of corpus/caudal anastomosis was 71.0％ (44/62,P =0.727).Patency rates of patients with and without adjustment of anastomosis sites were 77.8％ (7/9) and 71.2％ (52/73,P =0.680),respectively.Patency rates of a lot,a few,motile and seldom-motile sperms in epididymal fluid were 74.3％ (55/74) vs.50.0％ (4/8,P =0.146) and 70.0％ (28/40) vs.73.8％ (31/42,P =0.701),respectively.Multifactor logistic regression analysis showed that age was well associated with patency rate (OR=4.705,95％CI 1.181-18.742,P=0.028).Conclusions Age ≤28 years is an independent factor leading to higher patency rates.Patients with lower BMIs and younger could have higher patency rates.Factors of anastomosis sides,anastomosis sites,the adjustment of anastomosis sites,motility and quantity of sperms found in epididymal fluid showed no statistical difference in patency rates.

Preparation and characterization of laser microporous acellular osteochondral scaffolds / 中国组织工程研究

BACKGROUND: Preparing a scaffold with cartilage derived components and good initial mechanical strength is the direction of tissue engineering cartilage research. OBJECTIVE: To prepare porous acellular osteochondral scaffolds, and to explore their mechanical properties and cell compatibility. METHODS: Osteochondral bone from the porcine knee joint was taken, and then porous osteochondral scaffolds were made by laser microporation technology. Subsequently, the scaffolds were decellularized chemical methods. Scaffold structure was observed by scanning electron microscopy, and the compression modulus of the scaffolds was determined. Bone marrow mesenchymal stem cells were cultured in L-DMEM containing 10% fetal bovine serum (control group) and cultured in the medium extract of porous acellular osteochondral scaffolds (experimental group), respectively. Cell proliferation was detected by cell counting kit-8 method within 5 days of culture. Bone marrow mesenchymal stem cells were seeded on the porous acellular osteochondral scaffolds, and within 28 days of co-culture, cell growth was observed by hematoxylin-eosin staining and toluidine blue staining. RESULTS AND CONCLUSION: (1) Observation under scanning electron microscopy: The porous acellular osteochondral scaffolds had the smooth surface with evenly distributed pores. The pores of the scaffold extended longitudinally into the subchondral bone. (2) Mechanical properties: The average compressive modulus of porous acellular osteochondral scaffolds was 0.77 MPa, which was close to the compression modulus of the normal cartilage (1.15 MPa). (3) Cell counting kit-8 test: There were no differences in cell proliferation between the control and experimental groups at 1, 2, 3, 4 and 5 days of culture. (4) Cell-scaffold co-culture: A large amount of bone marrow mesenchymal stem cells were observed to be adherent to the scaffold after 1 day of culture through hematoxylin-eosin and toluidine blue staining. However, as time went on, a few cells adhered to the pore wall or grew into the pores at 7 and 21 days of culture. There were also some adherent cells but a large amount of cell masses formed in the pores at 28 days of culture. To conclude, the porous acellular osteochondral scaffold has good mechanical properties and cell compatibility.

Intra-articular migration of transplanted bone marrow mesenchymal stem cells in rats with articular cartilage injury / 中国组织工程研究

BACKGROUND: The application of mesenchymal stem cells (MSCs) in the treatment of cartilage damage has become a hot spot of research. Further studies on the distribution of MSCs in the body after injection and on the underlying mechanism of action are needed. OBJECTIVE: To observe the migration of bone marrow mesenchymal stem cells (BMSCs) after injection into the region of osteochondral defect. METHODS: Thirty Sprague-Dawley rats were randomized into two groups (n=15 per group). In the control group, the femoral tochlear was exposed but an osteochondral defect was not made; and after the suture, PKH26-labeled BMSCs were directly injected into the articular cavity of rats. In the experimental group, a cartilage defect of 1 mm in diameter and 1 mm in depth was made in the rat femoral trochlea, and 5×106PKH26-labeled BMSCs were injected into the defect after operation. At 1, 3 and 7 days after injection, the femoral condyle was taken to make frozen sections followed by DAPI staining. The distribution of BMSCs was observed under laser scanning confocal microscope. RESULTS AND CONCLUSION: In the control group, PKH26-labeled BMSCs were not transferred to the subchondral bone. In the experimental group, BMSCs were detected in the subchondral bone area at 1, 3 days after injection of PKH26-BMSCs in the bone cartilage defect area, and the BMSCs were also found in the bone marrow cavity at 7 days after injection. In conclusion, BMSCs in the articular cavity cannot migrate into the subchondral bone and bone marrow cavity unless the cartilage of the femoral condyle is damaged.

Effect of testicular puncture biopsy on the success rate of microdissection testicular sperm extraction for idiopathic non-obstructive azoospermia / 北京大学学报(医学版)

OBJECTIVE@#To explore the predictive effect of testicular puncture biopsy and the biopsy results on the success rate of microdissection testicular sperm extraction (micro-TESE) in patients with idiopathic non-obstructive azoospermia.@*METHODS@#We retrospectively evaluated the micro-TESE performance in patients with idiopathic non-obstructive azoospermia (NOA) referred to the Reproductive Medicine Center of Peking University Third Hospital between January 2012 and August 2017. We discussed whether to take the testicular biopsy and testicular biopsy results, including the intraoperative microscopic examination and postoperative pathology findings, could predict the success rate of the late micro-TESE.@*RESULTS@#There were 237 patients who were diagnosed as idiopathic NOA and received micro-TESE involved in the study and the total sperm retrieve rate was 25.7%. In 103 patients without testicular biopsy and 134 patients with preoperative testicular biopsy, the sperm retrieve rate was 26.2% and 25.4%, respectively. And there was no significant difference between the two groups. The testicular volume and serum follicle stimulating hormone levels of the two groups were (4.3±1.4) mL vs.(8.5±2.4) mL and (36.1±5.2) IU/L vs.(26.1±3.5) IU/L, respectively. Compared to the patients with preoperative testicular biopsy, the group of patients without testicular biopsy had a much smaller test volume and higher serum follicle stimulating hormone and the difference between the two groups was statistically significant. For the patients who were found with a small amount of sperm in both intraoperative microscopic examination and postoperative pathological examination, the sperm retrieve rate was 100% (7/7). And for the patients who were only found with sperm in intraoperative microscopic examination or postoperative pathology examination, the sperm retrieve rate (SRR) was 47.2% (17/36). For the patients who could be not found with sperm in both intraoperative microscopic examination and postoperative pathological examination, the SRR was only 11% (10/91). The difference between the groups was statistically significant.@*CONCLUSION@#Idiopathic non-obstructive azoospermia patients with smaller testicular volume still have a chance to be found with sperm by micro-TESE. The testicular biopsy results, including intraoperative microscopic examination and postoperative pathological findings, have predictive effect on the SRR for late micro-TESE. The patient who could not be found with sperm in both intraoperative microscopic examination and postoperative pathological examination have a small chance of success in micro-TESE.