Lethal pulmonary thromboembolism in mice induced by intravenous human umbilical cord mesenchymal stem cell-derived large extracellular vesicles in a dose- and tissue factor-dependent manner.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have obvious advantages over MSC therapy. But the strong procoagulant properties of MSC-EVs pose a potential risk of thromboembolism, an issue that remains insufficiently explored. In this study, we systematically investigated the procoagulant activity of large EVs derived from human umbilical cord MSCs (UC-EVs) both in vitro and in vivo. UC-EVs were isolated from cell culture supernatants. Mice were injected with UC-EVs (0.125, 0.25, 0.5, 1, 2, 4 µg/g body weight) in 100 µL PBS via the tail vein. Behavior and mortality were monitored for 30 min after injection. We showed that these UC-EVs activated coagulation in a dose- and tissue factor-dependent manner. UC-EVs-induced coagulation in vitro could be inhibited by addition of tissue factor pathway inhibitor. Notably, intravenous administration of high doses of the UC-EVs (1 µg/g body weight or higher) led to rapid mortality due to multiple thrombus formations in lung tissue, platelets, and fibrinogen depletion, and prolonged prothrombin and activated partial thromboplastin times. Importantly, we demonstrated that pulmonary thromboembolism induced by the UC-EVs could be prevented by either reducing the infusion rate or by pre-injection of heparin, a known anticoagulant. In conclusion, this study elucidates the procoagulant characteristics and mechanisms of large UC-EVs, details the associated coagulation risk during intravenous delivery, sets a safe upper limit for intravenous dose, and offers effective strategies to prevent such mortal risks when high doses of large UC-EVs are needed for optimal therapeutic effects, with implications for the development and application of large UC-EV-based as well as other MSC-EV-based therapies.

The transplantation of rapamycin-treated senescent human mesenchymal stem cells with enhanced proangiogenic activity promotes neovascularization and ischemic limb salvage in mice.

Few therapies can reverse the proangiogenic activity of senescent mesenchymal stromal/stem cells (MSCs). In this study, we investigated the effects of rapamycin on the proangiogenic ability of senescent human umbilical cord MSCs (UCMSCs). An in vitro replicative senescent cell model was established in cultured UCMSCs. We found that late passage (P25 or later) UCMSCs (LP-UCMSCs) exhibited impaired proangiogenic abilities. Treatment of P25 UCMSCs with rapamycin (900 nM) reversed the senescent phenotype and notably enhanced the proangiogenic activity of senescent UCMSCs. In a nude mouse model of hindlimb ischemia, intramuscular injection of rapamycin-treated P25 UCMSCs into the ischemic limb significantly promoted neovascularization and ischemic limb salvage. We further analyzed the changes in the expression of angiogenesis-associated genes in rapamycin-primed MSCs and found higher expression of several genes related to angiogenesis, such as VEGFR2 and CTGF/CCN2, in primed cells than in unprimed MSCs. Taken together, our data demonstrate that rapamycin is a potential drug to restore the proangiogenic activity of senescent MSCs, which is of importance in treating ischemic diseases and tissue engineering.

Smoothing process of conformal vibration polishing for mid-spatial frequency errors: characteristics research and guiding prediction.

By combining the conformal polishing method with short stroke vibration, a novel, to the best of our knowledge, conformal vibration polishing (CVP) method is proposed. The CVP method is expected to be an efficient means of optical processing by its high material removal rate and smoothing characteristics of mid-spatial frequency (MSF) errors. A quantitative time-domain smoothing model and a convergence factor (${\rm CF}_C$) are presented based on the research of smoothing characteristics. The motion mechanism, material removal ability, solution, and expansion of the smoothing model are demonstrated theoretically and experimentally. The experimental results exhibited good agreement with the theoretical predictions for the proposed method. The research provides a certain theoretical foundation for parameter selection and process optimization of the CVP method.

BCR-ABL1-positive microvesicles malignantly transform human bone marrow mesenchymal stem cells in vitro.

The intercellular communication between leukemia cells and bone marrow mesenchymal stem cells (BM-MSCs) plays more important role in chronic myeloid leukemia (CML) than we previously understood. Recently, we found that microvesicles released from human leukemia cell line K562 (K562-MVs) containing BCR-ABL1 mRNA malignantly transformed normal hematopoietic transplants. Here, we investigated whether K562-MVs contribute to the transformation of human bone marrow mesenchymal stem cells (BM-MSCs). We showed that K562-MVs could be integrated into co-cultured normal BM-MSCs and dose-dependently enhanced the proliferation of BM-MSCs. Meanwhile, K562-MVs (400 ng/mL) significantly increased the expression of BCR-ABL1 in these BM-MSCs, accompanied by the enhanced secretion of TGF-ß1. These BM-MSCs in turn could trigger the TGF-ß1-dependent proliferation of K562 cells. Moreover, we confirmed the presence of BCR-ABL1 in circulating MVs from 11 CML patients. Compared to the normal BM-MSCs, the BM-MSCs from CML patients more effectively increased the BCR-ABL1 expression and TGF-ß1 secretion in K562 cells as well as the proliferation of K562 cells. Our findings enrich the mechanisms involved in the interaction between leukemia cells and BM-MSCs and provide novel ways to monitor minimal residual disease and worthwhile approaches to treat CML.

The premature ejaculation diagnostic tool (PEDT): linguistic validity of the Chinese version.

INTRODUCTION: The premature ejaculation diagnostic tool (PEDT) was developed to standardize the diagnosis of PE and has been applied in many countries. However, a linguistic validation of the Chinese version of PEDT does not exist. AIMS: This study aims to undertake the Chinese validation of the PEDT and to evaluate its association with self-estimated intravaginal ejaculatory latency time (IELT) and clinical expert diagnosis of PE. METHODS: A Chinese version of PEDT was confirmed by andrologist and bilingual linguist. Participants were recruited among seven different communities of Shanghai from 2011 to 2012, and their information regarding self-reported PE, self-estimated IELT, expert diagnosis of PE, and PEDT scores were collected. MAIN OUTCOME MEASURES: Validity of the PEDT and its association with clinical expert diagnosis of PE and self-estimated IELT were analyzed. RESULTS: A total of 143 patients without PE (mean age 55.11 ± 7.65 years) and 100 men with PE (mean age 53.07 ± 8.08 years) were enrolled for validation. Of the patients in PE group, the number of men reporting self-estimated IELTs of ≤1, 1-2, and >2 minutes were 34 (34.0%), 22 (22.0%), and 44 (44.0%), respectively. The Cronbach's alpha score (α = 0.77) showed adequate internal consistency, and the test-retest correlation coefficients of each item (r ≥ 0.70, P < 0.001) indicated excellent stability over time. The frequency of agreement showed that there was excellent concordance between PEDT diagnosis and clinician diagnosis when the PEDT scores ≥11. An adequate correlation was found between total PEDT score and self-estimated IELT (ρ = -0.396, P < 0.001), and sensitivity and specificity analyses suggested a score of ≤8 indicated no time-defined PE (self-estimated IELT ≤1 minute). CONCLUSIONS: The Chinese version of PEDT is valid in screening the presence of PE among Chinese men. The PEDT showed an adequate negative correlation with self-estimated IELT and an excellent concordance with clinician diagnosis of PE.

Serum deprivation elevates the levels of microvesicles with different size distributions and selectively enriched proteins in human myeloma cells in vitro.

AIM: To investigate the effects of serum deprivation (SD) on microvesicles (MVs) secreted from human myeloma cells and the implications for disease progression. METHODS: RPMI 8226, U266, and KM3 human myeloma cells were incubated in medium containing 10% (non-SD) or 1% fetal bovine serum (SD) and MVs were isolated. The levels and size distribution of MVs were analyzed with flow cytometry. The protein profiles of MVs were studied using 2D SDS-PAGE, MALDI-TOF-MS, and Western blotting. NF-κB activation was analyzed using EMSA. Angiogenesis was examined in Eahy926 endothelial cells. RESULTS: Exposure of RPMI 8226 cells to SD for 24 h did not alter the number of apoptotic cells. However, SD increased the number of MVs from RPMI 8226, U266, and KM3 cells to 2.5-, 4.3-, and 3.8-fold, respectively. The size distribution of SD MVs was also significantly different from that of non-SD MVs. Three proteins ZNF224, SARM, and COBL in SD MVs were found to be up-regulated, which were involved in cell cycle regulation, signal transduction and metabolism, respectively. Co-culture of SD MVs and RPMI 8226 cells increased NF-κB activation in the target RPMI 8226 cells. Furthermore, SD MVs from RPMI 8226 cells significantly increased the microtubule formation capacity of Eahy926 endothelial cells compared with non-SD MVs. CONCLUSION: SD elevates the levels of microvesicles with different size distribution and selectively enriched proteins in human myeloma cells in vitro. The selectively enriched proteins, especially ZNF224, may play key roles in regulation of myeloma cells, allowing better adaptation to SD.

Microvesicles secreted from human multiple myeloma cells promote angiogenesis.

AIM: To investigate whether human multiple myeloma (MM) cells secrete microvesicles (MVs) and whether the MVs secreted from MM cells (MM-MVs) promote angiogenesis. METHODS: RPMI8226 human MM cells and EA.hy926 human umbilical vein cells were used. MVs isolated from RPMI8226 cells were characterized under laser confocal microscopy, electron microscopy and with flow cytometry. The fusion of MM-MVs and EA.hy926 cells was studied under confocal microscopy, and the transfer of CD138 to EA.hy926 cells was demonstrated with flow cytometry. The proliferation, invasion and tube formation of EA.hy926 cells in vitro were evaluated using MTT, transwell migration and tube formation assays, respectively. The vasculization of EA.hy926 cells in vivo was studied using Matrigel plug assay. The expression of IL-6 and VEGF was analyzed with PCR and ELISA. RESULTS: MM-MVs from the RPMI 8226 cells had the characteristic cup-shape with diameter of 100-1000 nm. Most of the MM-MVs expressed phosphatidylserine and the myeloma cell marker CD138, confirming that they were derived from myeloma cells. After added to EA.hy926 cells, the MM-MVs transferred CD138 to the endothelial cells and significantly stimulated the endothelial cells to proliferate, invade, secrete IL-6 and VEGF, two key angiogenic factors of myeloma, and form tubes in vitro and in vivo. CONCLUSION: Our results confirm the presence of MVs in MM cells and support the idea that MM-MVs are newfound mediators for myeloma angiogenesis and may serve as a therapeutic target to treat MM.

Amplification of functional myeloid-derived suppressor cells during stem cell mobilization induced by granulocyte colony-stimulation-factor.

The effects of granulocyte colony-stimulation-factor (G-CSF) on stem cell mobilization and its impact on the amplification of myeloid-derived suppressor cells (MDSCs) of donor mice were examined. A mouse model of stem cell mobilization was established by consecutive subcutaneous injection of 100 µg/kg G-CSF for 5 days. The blood from the donor mice was routinely examined during mobilization. Stem cells and MDSCs were analyzed by flow cytometry. The immunosuppressive molecules derived from MDSCs in serum and spleen, including hydrogen dioxide (H2O2) and nitric oxide (NO), and the activity of nitric oxide synthase (NOS) were determined during the mobilization. Apoptosis of T lymphocytes was assessed by using Annexin-V/PI. During stem cell mobilization, the number of lymphocytes and white blood cells in the peripheral blood was increased, and peaked on the 4th day. The number of stem cells in G-CSF-treated mice was significantly greater than that in controls (P<0.01). The expansions of MSDCs were also observed after G-CSF mobilization, with a more notable rate of growth in the peripheral blood than in the spleen. The activity of NOS and the production of NO were increased in the donor mice, and the serum H2O2 levels were approximately 4-fold greater than the controls. Consequently, apoptosis of T lymphocytes was increased and showed a positive correlation with the elevated percentage of MDSCs. It was concluded that G-CSF could provide sufficient peripheral blood stem cells for transplantation. Exogenous administration of G-CSF caused the accumulation of MDSCs in the peripheral blood and the spleen, which could lead to apoptosis of T lymphocytes and may offer a new strategy for the prevention and treatment of graft versus host disease.

[Treatment of varicocele infertility men patients of different Chinese medical syndrome types by integrative medicine treatment selection: a primary research].

OBJECTIVE: To explore the optimal treatment selection for treating varicocele (VC) male infertility patients accompanied with oligozoospermia or azoospermia of different Chinese medical syndrome types by comparing the efficacies of integrative medicine. METHODS: One hundred and twenty male infertility patients with VC accompanied with oligozoospermia or azoospermia were assigned to Chinese medical treatment group (A) and the surgical group (B), each consisting of three Chinese medical syndrome types, i.e., damp-heat stagnation syndrome (DHSS), Shen-deficiency blood stasis syndrome (SDBSS), and blood stasis stagnation syndrome (BSSS), 20 in each group. Corresponding Chinese medical treatment was administered to those in Group A, C, and E, while microscopic ligation of internal vena spermatic was administered to those in Group B, D, and F. The routine analysis of semen, biochemical analysis of seminal plasma, and serum sex hormones (prolactin, testosterone, follicle stimulating hormone, luteinizing hormone, and estradiol) were performed before treatment and by the end of the 24th week after treatment. RESULTS: Totally 18 patients' spouses were pregnant. Of them, 1 in Group A of DHSS (abbreviated as Group A), 3 in Group B of DHSS (abbreviated as Group B), 4 in Group A of SDB-SS (abbreviated as Group C), 5 in Group A of SDBSS (abbreviated as Group D), 1 in Group A of BSSS (abbreviated as Group E), and 4 in Group B of BSSS (abbreviated as Group F). After 24-week treatment, the sperm concentration, class a sperm percentage, class a + b sperm percentage, the motility rate, the seminal plasma of fructose density, and the seminal plasma neutral alpha-glucosidase were more significantly improved in Group B, C, D and F, when compared with the same group before treatment (P <0. 01, P <0. 05). There was no statistical difference in the aforesaid indices between before and after treatment in Group A and Group E (P >0.05). As for the improvement percentage of seminal routine indices, the difference of the seminal plasma of fructose density, and the difference of seminal plasma neutral alpha-glucosidase between before and after treatment in the same Chinese medical syndrome types, better effects were obtained in Group B than in Group A (P <0.01), and better effects were obtained in Group F than in Group E (P <0.01). There was no statistical difference between Group C and D (P >0.05). There was no statistical difference in the 5 items of sex hormones in each group between before and after treatment (P >0.05). CONCLUSIONS: Surgical treatment could effectively improve the semen quality for male infertility VC patients accompanied with oligozoospermia or azoospermia. Of them, Chinese medical treatment could be recommended to those of SDBSS who would not receive surgical treatment.

Prognostic value of preoperative prealbumin levels in patients with unresectable hepatocellular carcinoma undergoing transcatheter arterial chemoembolisation.

Background: This retrospective study analyzed the prognostic value of preoperative prealbumin (PAB) levels in patients with unresectable hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolisation (TACE). Methods: Four hundred and two patients diagnosed with unresectable HCC were included in this retrospective study. All patients underwent their first TACE procedure. Based on PAB levels before the first TACE, 402 patients were classified as having low PAB levels and high PAB levels. Potential confounding factors between the two groups were eliminated using. Propensity Score Matching (PSM) analysis. The time to progression (TTP) and overall survival (OS) of the two groups were compared using Kaplan-Meier curves before and after PSM. Risk factors for poor prognosis were determined using univariate and multivariate Cox proportional hazards models. Results: Before PSM, the high PAB level group had a significantly longer median TTP and OS than the low PAB level group (all P values < 0.0001). After PSM, the high PAB level group still had a significantly longer median TTP and OS than the low PAB level group (all P values < 0.05). After PSM, low PAB level was found to be an independent predictor of shorter OS (HR = 0.656; 95% CI:0.448-0.961; P = 0.03). The subgroup analysis before PSM showed that low PAB levels increased the risk of poor prognosis in most subgroups. Conclusions: Low preoperative PAB levels are associated with poor prognosis in patients with unresectable HCC after TACE.

[Initial exploration of epididymal sperm nuclear maturity in obstructive azoospermia patients].

OBJECTIVE: To ascertain the epididymal sperm nuclear maturity in obstructive azoospermia (OA) patients. METHODS: A total of 81 infertile males from andriatry clinic of Renji hospital were selected, including 32 OA patients (OA group) and 49 asthenospermia patients (asthenospermia group). Another 32 fertile males were recruited for the control group. All semen samples of the asthenospermia and control groups underwent computer aided semen analysis (CASA). For the OA group, sperm specimens were collected by percutaneous epididymal sperm aspiration (PESA) and semen analyses completed by manual method. Further acridine orange test and aniline blue stain assay were performed. The results were processed with SPSS 15.0. RESULTS: No statistically significant differences existed in semen volume and sperm density between the asthenospermia and control groups (both P > 0.05). The OA group was significantly lower than the control group in sperm density (P < 0.01). The asthenospermia and OA groups were also significantly lower than the control group in sperm motility (both P < 0.01). As to the percentage of grade a + b sperm, the asthenospermia group was also significantly lower than the control group (P < 0.01). Compared with the control group (81% ± 9%, 85% ± 8%), the negative rate of acridine orange test and aniline blue assay of OA (57% ± 20%, 64% ± 20%) and asthenospermia group (62% ± 19%, 67% ± 15%) were statistically lower (all P < 0.05). CONCLUSIONS: The sperm nuclear maturity is lower in the asthenospermia and OA groups than that in the control group. Male fertility should be further improved.

[Sexual function inspection room for special penile insertion disorder].

OBJECTIVE: To determine the role of the sexual function inspection room in the treatment of patients with special penile insertion disorder. METHODS: This study included 6 couples received at the Andrology Clinic of Shanghai Renji Hospital from September, 2010 to February, 2011, who complained of being unable to accomplish sexual intercourse, all due to the husbands' abnormal penile erection. The couples had tried to make love 3 to 6 times after getting married, but never succeeded. Consequently the wives were planning to divorce, unwilling to attempt sexual activity again. We performed examinations and sexual education for the patients in the sexual function inspection room of Shanghai Institute of Andrology. The inspection room consisted of an inner and an outer section separated by a one-way transparent glass, through which what happened in the outer section could be observed from the inner section. The husband was given 20 mg of tadalafil to induce penile erection, followed by Doppler ultrasonographic determination of penile hemodynamics. Meanwhile, the wife was allowed to observe her husband's penile erection through the glass to get sensory stimuli and relieve the mental burden. In the end, the doctor advised the couple to try sexual intercourse. RESULTS: In nature, the 6 wives were all impatient, while their husbands were all introverted. Doppler ultrasonography displayed normal penile hemodynamics. After sensory stimulation, the wives gained confidence in their husbands' erectile function. A one month follow-up visit showed that all the 6 couples could perform sexual intercourse normally. CONCLUSION: This sexual function inspection room can help doctors and wives to observe the status of the patient's penile erection, and meanwhile disburden the mind of the wives by giving them sensory stimuli, which contributes much to successful attempt at sexual intercourse.

A prospective randomized controlled study on scheduled PDE5i and vacuum erectile devices in the treatment of erectile dysfunction after nerve sparing prostatectomy.

Cavernous nerve injury is an important cause of erectile dysfunction (ED). Although protective nerve technology has been widely used in nerve-sparing radical prostatectomy (nsRP), the incidence of ED is still very high after surgery. The purpose of our study was to evaluate erectile function (EF) and penile length in the non-erectile state (PLNES) following scheduled phosphodiesterase 5 inhibitor (PDE5i), vacuum erectile device (VED) treatment, and combination therapy after nsRP. One hundred patients with localized prostate cancer and normal EF were randomized to scheduled PDE5i group, VED treatment group, a combined treatment group, and the control group without any intervention. The International Index of Erectile Function-5 (IIEF-5) scores and PLNES were evaluated after 6 months and 12 months of treatment. Sexual Encounter Profile (SEP-Question 2 and SEP-Question 3) were evaluated after 12 months of treatment. Ninety-one of the 100 randomized patients completed the study. We found that the 5 mg tadalafil once a day (OaD) combined with VED can help improve IIEF-5 scores in nsRP patients after both 6 months and 12 months. VED alone or combined with tadalafil OaD can help patients maintain PLNES. VED combined with tadalafil OaD can improve the rate of successful penetration (SEP-Question 2) after 12 months. There were no significant differences in the return to target EF after 12 months among the groups. No significant correlation was noted between the variables and return to target EF (IIEF ≥ 17), and between the variables and effective shortening of the patient's penis (shortening ≥ 1 cm) after 12 months of intervention.

Oral tadalafil administration plus low dose vasodilator injection: a novel approach to erection induction for penile color duplex ultrasound.

PURPOSE: We prospectively compared clinical response and penile color duplex ultrasound results of oral tadalafil 20 mg plus low dose intracavernous injection of vasoactive agents with those of intracavernous injection and oral tadalafil 20 mg alone. We also observed the best approach to facilitate penile color duplex ultrasound and that most preferred by patients. MATERIALS AND METHODS: All 56 patients with erectile dysfunction underwent penile color duplex ultrasound 3 times at an interval of at least 1 week using different pharmacological induction methods, including tadalafil mode (20 mg tadalafil), intracavernous injection mode (30 to 60 mg papaverine) and mixed mode (15 mg papaverine plus 20 mg tadalafil). Ultrasound parameters included peak systolic and end diastolic velocity, resistance index and acceleration time. Clinical response was assessed by the erection hardness score. Patient preference was determined when all tests were finished. RESULTS: For penile color duplex ultrasound parameters no significant difference was observed between intracavernous injection and mixed modes. However, for tadalafil mode peak systolic velocity of the 2 cavernous arteries measured 15 minutes after induction were significantly lower than for intracavernous injection and mixed modes. Also, acceleration time of the right cavernous artery measured 5 minutes after induction and left cavernous artery measured 15 minutes after induction in tadalafil mode were significantly shorter than those in intracavernous injection and mixed modes. No severe side effect occurred in tadalafil and mixed modes but 2 patients experienced priapism in intracavernous injection mode. Of the patients 55.4% preferred tadalafil mode, an incidence significantly higher than intracavernous injection (16.1%) and mixed (28.5%) modes. CONCLUSIONS: Oral tadalafil plus low dose vasodilator led to a significantly better clinical response than high dose vasodilator. Penile color duplex ultrasound parameters showed no difference between the 2 modes. Thus, this mixed mode emerges as a possible alternative to high dose vasodilator injection.

[Leptin level in azoospermic patients and its clinical value].

OBJECTIVE: To detect the levels of seminal plasma leptin (SPL) and serum leptin (SL) in patients with azoospermia, and to explore the methods of using SPL and SL alone or the combination of SPL, SL and follicle stimulating hormone (FSH) for the differential diagnosis of obstructive azoospermia (OA) and non-obstructive azoospermia (NOA). METHODS: We enrolled in this study 45 patients with diagnosed OA, 41 with unexplained NOA and 30 men with normal semen parameters as controls. The azoospermia patients underwent percutaneous aspiration from the epididymis (PESA) or aspiration/extraction from the testis (TESA/TESE), and all the subjects were detected for the levels of serum FSH, SPL and SL. Individual and multiple indexes were evaluated by Fisher's discriminant analysis combined with ROC curve analysis. RESULTS: There were no significant differences in the body mass index (BMI) among the three groups. Compared with the normal control, the OA patients showed an obviously elevated level of SPL (P = 0.048), and the NOA patients remarkably increased levels of FSH (P = 0.000), SL (P = 0.000) and SPL (P = 0.000). In comparison with the OA group, the levels of FSH (P = 0.000), SL (P = 0.006) and SPL (P = 0.033) were significantly increased in the NOA group. For the differential diagnosis of OA and NOA, the areas under the ROC curve of SPL and SL were 0.658 (P = 0.014) and 0.702 (P = 0.002) , respectively, both significantly greater than 0.5, while that of the combination of SPL, SL and FSH was the greatest (0.953). In addition, with 0.026 x SPL +0.05 x SL +0.106 x FSH -2.197 as the combined indicator value and -0.289 as the cut-off value (> or = cut-off value for NOA), the sensitivity and specificity of the combination were 0.878 and 0.902, respectively, both reached the maximum. CONCLUSION: Both the levels of SPL and SL are valuable for the differential diagnosis of OA and NOA, but the joint consideration of SPL, SL and FSH may provide better indicators.

Imatinib plasma trough concentration and its correlation with characteristics and response in Chinese CML patients.

AIM: To investigate the pharmacokinetics of imatinib in Chinese chronic myelogenous leukemia (CML) patients. METHODS: Fourty-six naïve Chinese CML patients treated with imatinib (400 and 600 mg daily, n=36 and 10, respectively) were recruited. The correlations of imatinib (400 mg) trough plasma concentrations (C(mins)) with the patients' characteristics and responses were analyzed. RESULTS: The overall mean (+/-SD, CV%) steady-state C(mins) for imatinib at 400 mg (n=36) and 600 mg (n=10) daily was 1325.61 ng/mL (+/-583.53 ng/mL; 44%) and 1550.90 ng/mL (+/-462.63 ng/mL; 30%), respectively, and no statistically significant differences were found between them (P=0.267). At 400 mg daily, female patients had significantly higher C(mins) than the male patients (P=0.048), and molecular responses were not correlated with imatinib C(mins), but they were correlated with time elapsed before imatinib therapy. CONCLUSION: The results suggest that Chinese CML patients have higher imatinib C(mins) than their Caucasian counterparts and that the optimal initial imatinib dose for them requires further investigation.

[Standardized diagnosis and treatment of azoospermia: a report of 1027 cases].

OBJECTIVE: To constitute an appropriate procedure for clinical diagnosis and treatment for men with azoospermia in China. METHODS: Following a procedure which combined the recommendations from WHO, European Association of Urology (EAU), American Urological Association (AUA), American Society for Reproductive Medicine (ASRM) with our own experiences, 1 027 patients with azoospermia were divided into different subtypes according to patients' case histories and outcomes of various routine and specialized examinations. Then appropriate treatments were chosen according to the diagnostic subtypes. RESULTS: There were 516 cases of obstructive azoospermia, 315 of non-obstructive azoospermia and 150 of combined (obstructive and non-obstructive) azoospermia and 46 of azoospermia with special aetiology. Of the 96 patients who adopted surgical intervention, 28 underwent transurethral resection of the ejaculatory ducts, 10 vasovasostomy and 58 vasoepididymostomy. Of the 45 patients who adopted drug intervention, 16 with inflammatory obstructive azoospermia were treated with antibiotics and 29 with hypogonadotropic hypogonadism were treated with hormonal therapy. Of all the subjects, 789 patients chose in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and 142 chose artificial insemination of donor (AID) or adoption. CONCLUSION: (1) A standard procedure should be established for the diagnosis, classification and treatment of azoospermia; (2) Special examinations and treatments should be given to cases of azoospermia with special aetiology; (3) According to the diagnosis and the patients' conditions, the most appropriate treatment options should be recommended to them; (4) The hereditary factors in azoospermia should be seriously considered, and a genetic work-up and counseling should be offered in such cases.

[Seedling regeneration and spatial correlation between seedlings and seed trees in Castanopsis hystrix plantation by large diameter wood cultivation in south subtropical China]. / å—äºšçƒ­å¸¦çº¢é”¥å¤§å¾„æåŸ¹è‚²æž—å¹¼è‹—æ›´æ–°åŠå ¶ä¸Žæ¯æ ‘çš„ç©ºé—´å ³è”æ€§.

Using the paired correlation equation g(r) in the spatial point patterns, we investigated the regeneration characteristics and spatial patterns of Castanopsis hystrix seedlings and the spatial correlation with the seed trees in the plantation by large diameter wood cultivation in south subtropical China. The results showed that natural seedling regeneration in C. hystrix plantation was good, which were widely distributed in the whole plantation. The seedling regeneration were mainly contributed by root sprouts, accounting for 73.6% of the total. The number distribution of C. hystrix seedlings in different age classes showed a pyramidal shape, with the contribution of diameter class1, 2 and 3 being 64.3%, 29.3% and 6.4% of the total, respectively. The C. hystrix seedlings mainly presented aggregated distribution in small scale (<15 m). With the increases of size classes and spatial scales, the aggregation strength gradually weakened and finally presented random distribution. The spatial correlation between seedlings and seed trees was not significant with the increases of size classes or spatial scale.

Up-regulation of circular RNA hsa_circ_01844 induces apoptosis and suppresses proliferation and migration of glioblastoma cells.

BACKGROUND: Previous studies have demonstrated that various circular RNAs are involved in the malignant proliferation of cancers, such as liver cancer, lung cancer, breast cancer, and others. The potential role of circular RNAs in glioblastoma, however, is still uncertain. In this study, we aimed to study the potential role of hsa_circ_01844 in glioblastoma. METHODS: Using reverse transcription-polymerase chain reaction (RT-PCR) method, hsa_circ_01844 expression was measured in five glioblastoma samples and five normal brain samples. To evaluate the potential function of hsa_circ_01844 in glioblastoma, hsa_circ_01844 was overexpressed in glioblastoma cell lines (U251 and U87 cells). Using these two cell lines, in vitro experiments including the flow cytometry assay, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, Transwell assay, and cell apoptosis assay were performed to investigate the role of hsa_circ_01844 in glioblastoma. Student t test and one-way analysis of variance were used for statistical analysis. RESULTS: The expression of circular RNA hsa_circ_01844 was lower in glioblastoma tissues when compared with the normal brain tissues by RT-PCR method (0.034 ±â€Š0.036 vs. 1.630 ±â€Š0.891, P < 0.001). Using two glioblastoma cell lines, we found that overexpression of hsa_circ_01844 in glioblastoma cells suppressed their proliferation, colony formation, migration, and increased the apoptotic rate compared with empty vector group and blank control group (all P < 0.05). CONCLUSION: Hsa_circ_01844 shows decreased expression in glioblastoma and its overexpression induces apoptosis and inhibits proliferation, migration, and invasion of glioblastoma cells.

Autologous Bone Marrow Mononuclear Cell Transplantation Therapy Improved Symptoms in Patients with Refractory Diabetic Sensorimotor Polyneuropathy via the Mechanisms of Paracrine and Immunomodulation: A Controlled Study.

TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-TRC-12002570.URL: http://www.chictr.org.cn/showproj.aspx?proj=6981.