[Yijing Prescription regulates the PI3K/Akt/mTOR signaling pathway and autophagy and inhibits the apoptosis of Leydig cells: An experimental study in vitro].

OBJECTIVE: To explore the mechanism of Yijing Prescription (YJP) improving sperm quality in oligozoospermia patients. METHODS: Mouse Leydig (TM3) cells were divided into five groups: normal control, acrolein-induced oxidative stress (ACR) model control, and low-, medium- and high-dose YJP. The ACR model was established in the latter four groups with 100 µmol/L acrolein, and the TM3 cells in the latter three groups were treated with the serum containing 5%, 10% and 20% YJP, respectively. After modeling, the viability of the cells and the contents of MDA, T-AOC and SOD were determined by CCK-8, and the relative expressions of PI3K/Akt/mTOR, Beclin-1, Bcl-2 and LC3-II detected by real-time PCR and Western blot. The results obtained were analyzed and compared among different groups. RESULTS: Compared with the normal control cells, the TM3 cells in the ACR model control group showed a dramatically inhibited survival rate (54%), increased content of MDA, decreased levels of T-AOC and SOD (P < 0.01), down-regulated expressions of p-PI3K/p-Akt protein (P < 0.01), and Bcl-2 protein (P < 0.05) and Bcl-2 mRNA (P < 0.01), and up-regulated mRNA and protein expressions of Beclin-1 and LC3II (P < 0.01). After administration of YJP, all the above-mentioned parameters were reversed in different degrees and improved in a dose-dependent manner. CONCLUSIONS: Yijing Prescription acts against oxidative stress, mediates the regulation of the PI3K/Akt/mTOR signaling pathway and autophagy and inhibition of the apoptosis of Leydig cells, and thus improves the sperm quality of oligozoospermia patients.

[Huang'e Capsules for BPH of the qi-deficiency blood-stasis and damp-heat stagnation type: An open-label single-arm multicenter phase-â £ clinical study].

OBJECTIVE: To evaluate the efficacy of Huang'e Capsules in the treatment of BPH of the qi-deficiency blood-stasis and damp-heat stagnation type under conditions of extensive use. METHODS: Totally, 605 male patients with BPH of the qi-deficiency blood-stasis and damp-heat stagnation type received oral Huang'e Capsules, tid, 4 capsules per time, for 42 days. We recorded the IPSS, maximum urinary flow rate (Qmax), mean urinary flow rate (Qave), quality of life (QOL) score, and prostate volume of the patients before and after medication. RESULTS: A total of 503 patients completed the whole trial. Compared with the baseline, the patients showed significant decreases after treatment in the IPSS (20.1 ± 5.5 vs 12.6 ± 5.0, P < 0.05), QOL score (4.19 ± 0.90 vs 2.50 ± 0.89, P < 0.05) and prostate volume (ï¼»36.6 ± 15.8ï¼½ vs ï¼»34.0 ± 17.6ï¼½ ml, P < 0.05), but remarkable increases in Qmax (ï¼»12.2 ± 5.8ï¼½ vs ï¼»14.2 ± 6.5ï¼½ ml/s, P < 0.05) and Qave (ï¼»5.91 ± 3.12ï¼½ vs ï¼»6.95 ± 3.45ï¼½ ml/s, P < 0.05). CONCLUSIONS: Huang'e Capsules had a good therapeutic effect on BPH of the qi-deficiency blood-stasis and damp-heat stagnation type.

[Efficacy of Huang'e Capsules on benign prostatic hyperplasia with Qi-deficiency, blood stasis and damp heat block: A stratified analysis].

OBJECTIVE: To evaluate the efficacy and safety of Huang'e Capsules in the treatment of BPH with Qi-deficiency, blood stasis and damp heat block. METHODS: This study included 1 456 cases of BPH with Qi-deficiency, blood stasis and damp heat block from 40 hospitals of Zhejiang and Anhui Provinces between June 2014 and July 2017. The patients were aged 40－85 years and treated with Huang'e Capsules at a dose of 4 capsules, tid, for a course of 6 weeks. The IPSSs of the patients were obtained before and after 2, 4 and 6 weeks of medication, and a stratified analysis was made on the factors influencing the therapeutic effects, such as age, the stage of BPH, and concomitant medication of urogenital and reproductive hormone drugs. RESULTS: After 6 weeks of medication, the IPSS of the patients was decreased by 8.4 ± 5.4 (ï¼»42.9 ± 22.7ï¼½ %) as compared with the baseline (19.2 ± 6.8) (P < 0.05), with a total effectiveness rate of 71.9% and an excellence rate of 23.1%. After 6 weeks of medication, the IPSSs of the patients with stage-Ⅰ, -Ⅱ and -Ⅲ BPH were decreased by 7.3 ± 6.8, 6.6 ± 4.3 and 11.0 ± 5.5, with total effective rates of 69.5%, 70.1% and 74.7%, respectively, with statistically significant differences among the three stages (P < 0.05), and so were those in the patients aged ≤50 years (by 7.4 ± 5.8), 51－60 years (by 7.9 ± 5.3), 61－70 years (by 8.7 ± 5.6) and >70 years (by 8.6 ± 5.1), but with no statistically significant differences among different age groups (P > 0.05). At 6 weeks, the IPSS was reduced by 7.1 ± 5.9 by concomitant medication of urogenital and reproductive hormone drugs, 8.7 ± 5.4 by concomitant medication of other drugs, and 8.4 ± 5.3 by non-concomitant medication, with no statistically significant differences among the three types of medication (P > 0.05). CONCLUSIONS: Huang'e Capsules can evidently improve the symptoms of BPH, with the best effect on stage-Ⅲ BPH, and the effect does not differ significantly with age or drug concomitance.

[Yimusake Tablet: safe and efficacious for premature ejaculation].

OBJECTIVE: To objectively evaluate the efficacy and safety of Yimusake Tablet in the treatment of premature ejaculation (PE) through a multi-centered large-sample trial. METHODS: We conducted a multi-centered, open, fixed-dose, and self-compared clinical trial among 300 patients with diagnosed PE. The trial lasted 12 weeks, including 4 weeks without any medication and 8 weeks of treatment with Yimusake Tablet, 2 pills (1 g) per night. We observed the intravaginal ejaculation latency time (IELT) before and after treatment, evaluated the safety of medication, and performed a questionnaire investigation on the patients' satisfaction. RESULTS: Of the 300 PE patients, 288 accomplished the clinical trial. The patients ranged in age from 22 to 60 years, averaging at 31.6 years. The mean IELT of the patient was 62.5 seconds at baseline, 168.9 seconds after 4 weeks of treatment with Yimusake Tablet, and 222.2 seconds after 8 weeks of medication. Among the 157 patients with normal erectile function (IIEF >21), the mean IELT was 71.4 seconds before treatment, 147.4 seconds after 4 weeks of medication, and 172.5 seconds after 8 weeks of medication. The patients' satisfaction was significantly increased after treatment. Those complicated by mild to moderate erectile dysfunction achieved different degrees of improvement in the IIEF-5 score, with a mean increase of 3.8. Only a few patients experienced mild adverse events, including constipation, dry mouth, nose bleeding, abdominal pain, and lumbosacral pain, which were all relieved without drug withdrawal. CONCLUSION: Yimusake Tablet is a safe and effective medicine for the treatment of PE.

[Regulatory effect of yijing fang on adenine-induced infertility in rat models: a pharmacodynamic study].

OBJECTIVE: To investigate the regulatory effect of Yijing Fang (YJF) on adenine-induced infertility in rats with kidney deficiency. METHODS: Sixty healthy Wistar male rats, aged 1.5 mo and weighing (180 +/- 10) g, were normally fed for a week, and then divided into five groups of equal number (blank control, infertile model, high-dose YJF, mid-dose YJF, and low-dose YJF) according to the body weight of the rats. The models were made by intragastric administration of 500 mg/ml adenine in gum arabic solution in the ratio of 1:10 at the dose of 1 ml per 100 g body weight per day for 10 days. YJF was given at 3.38 g, 1.69 g and 0.85 g per 100 g body weight per day to the rats in the high-, mid- and low-dose groups, respectively. After 48 days of treatment, we observed kidney deficiency-related changes in sperm concentration and motility, the levels of testosterone (T) and other hormones and the volumes of the testis, epididymis, seminal vesicle and prostate, and compared the indexes among different groups. RESULTS: YJF exhibited a significant regulatory effect on sperm concentration and motility, the T level and the indexes of the gonad and other accessory glands in the model rats (P < 0.05). After 48 days of treatment, sperm concentrations were (87.85 +/- 28.44), (7.11 +/- 2.15), (35.98 +/- 14.04), (32.65 +/- 11.80) and (33.51 +/- 13.26) x 10(6)/ml in the blank control, infertile model, high-dose YJF, mid-dose YJF, and low-dose YJF groups, respectively; sperm motilities were (52.79 +/- 16.43), (31.14 +/- 3.07), (45.88 +/- 16.97), (51.56 +/- 13.35) and (49.53 +/- 10.16)%; the T levels were (194.07 +/- 40.29), (61.27 +/- 13.70), (121.87 +/- 24.35), (127.44 +/- 19.38) and (127.81 +/- 20.28) nmol/L; the luteinizing hormone (LH) levels were (7.017 +/- 0.269), (6.117 +/- 0.894), (7.060 +/- 0.871), (7.156 +/- 0.937) and (6.967 +/- 0.778) IU/L; the testis volumes were (3.775 +/- 0.183), (2.865 +/- 0.258), (3.236 +/- 0.058), (3.457 +/- 0.066) and (3.398 +/- 0.091) g; the epididymis volumes were (1.119 +/- 0.116), (0.833 +/- 0.226), (1.124 +/- 0.104), (1.132 +/- 0.107) and (1.114 +/- 0.106) g; the prostate volumes were (176.75 +/- 427.09), (131.67 +/- 39.45), (178.70 +/- 37.97), (180.11 +/- 37.39) and (179.00 +/- 35.42) mg; and the body weights were (188.50 +/- 7.12), (189.92 +/- 6.67), (187.42 +/- 5.47), (189.17 +/- 6.19) and (188.75 +/- 6.12) g. Testis histopathology showed obvious injuries in the infertile models and different degrees of improvement in the three YJF groups, most evidently in the mid-dose group. CONCLUSION: Yifing Fang had an evident therapeutic effect on kidney deficiency-related infertility in adenine-induced rat models.

[Effects of yijing recipe on sperm apoptosis and mitochondrial membrane potential in patients with idiopathic oligoathenoteratospermia].

OBJECTIVE: To investigate the effects of Yijing Recipe on sperm apoptosis and mitochondrial membrane potential (MMP) in patients with idiopathic oligoathenoteratospermia. METHODS: Using the self-control method, we examined sperm apoptosis and MMP in 30 patients with oligoathenoteratospermia before and after treated with Yijing Recipe. RESULTS: The rates of early sperm apoptosis (AV +/PI -) and MMP loss were significantly reduced after treatment as compared with pre-medication ([2.86 +/- 1.47]% vs [4.26 +/- 2.79]% and [21.77 +/- 13.46]% vs [41.73 +/- 20.30]%, P<0.05). No statistically significant difference was observed in the sperm death rate (PI+) before and after treatment ([34.10 +/- 16.26]% vs [30.21 +/- 13.50]%, P>0.05). CONCLUSION: Yijing Recipe can reduce early sperm apoptosis and improve MMP, which may be one of the mechanisms underlying its efficacy on oligoathenoteratospermia.

The effects and prospects of the integration of traditional Chinese medicine and Western medicine on andrology in China.

Andrology has a long history in traditional Chinese medicine (TCM) discussions concerning andropathies, and documentation of relevant therapeutic methods abound in the ancient literature on TCM. Integrated treatment combining TCM and Western medicine has seen both broad and in-depth development, with formidable status in the field of modern andrology in China. This article attempts to demonstrate the unique advantage of integrated treatment in the therapy of andropathies through a review of the ancient literature on andrology in the field of TCM and on the integrative treatment of prostatic diseases, sexual dysfunction, male infertility and late-onset hypogonadism. There is a need for the advancement of a medical theory that integrates TCM and Western medicine practices to create a new therapeutic system with standardized therapeutic and evaluative protocols for diseases involving male sexual health.

[P70S6K is involved in the inhibition of testosterone production in TM3 mouse Leydig cells overexpressing Cox7a2].

OBJECTIVE: To investigate the effects of Cox7a2 on the LH-induced testosterone production and the involved autophagy regulating signals in TM3 mouse Leydig cells. METHODS: The Cox7a2-pEYFP-N1 fluorescent protein vector was constructed and transfected into TM3 mouse Leydig cells. The level of testosterone was determined by ELISA, and the effects of Cox7a2 on the expression of the steroidogenic acute regulatory protein (StAR) and the phosphorylation of the autophagy regulatory factor P70S6K were detected by Western blot. RESULTS: LH stimulation increased the StAR protein expression and testosterone production, while Cox7a2 decreased P70S6K phosphorylation, reduced StAR expression and consequently inhibited LH-induced testosterone biosynthesis in the TM3 Leydig cells. CONCLUSION: Cox7a2 inhibits testosterone production by decreasing the StAR protein expression, which might be at least in part related with the activation of autophagy in TM3 mouse Leydig cells.

[Yijingfang increases the expression of CatSper1 in mice].

OBJECTIVE: To observe the effects of Yijingfang on CatSper1 in the mouse model of cyclophosphamide-induced oligoasthenospermia. METHODS: Forty Kunming male mice were randomly divided into a control group (CG), a model group (MG), a small-dose Yijingfang group (SG), and a large-dose Yijingfang group (LG). The mice of CG were intraperitoneally injected with normal saline at 60 mg/kg once a day, while those of MG, SG and LG with cyclophosphamide, all for 5 days. During the next 34 days, the mice of SG and LG received intragastric administration of Yijingfang once a day, the former at a dose 2 times and the latter 5 times that of human routine usage, those of MG given the same volume of normal saline, and CG normally fed. At 35 days, we measured the sperm count, percentages of grades a + b and a + b + c sperm, and the expression of CatSper1 in the epididymal sperm of the mice. RESULTS: The sperm counts of CG, MG, SG and LG were (5.20 +/- 1.34), (1.73 +/- 0.03), (2.08 +/- 0.01) and (3.31 +/- 0.56) x 10(6)/ml, respectively, significantly lower in MG than in CG (P < 0.05), but higher in LG than in MG (P < 0.05). The grade a + b sperm constituted (14.49 +/- 0.30), (6.64 +/- 1.88), (11.99 +/- 1.01) and (19.40 +/- 3.13)% in CG, MG, SG and LG, respectively, remarkably lower in MG than in CG (P < 0.05) but higher in LG than in MG (P < 0.05); the grade a + b + c sperm accounted for (68.39 +/- 15.13), (39.96 +/- 4.89), (62.28 +/- 4.43) and (73.61 +/- 5.05)%, respectively, obviously lower in MG than in CG (P < 0.05) but higher in LG than in MG (P < 0.05); the CatSper1 expressions were 0.76 +/- 0.05, 0.73 +/- 0.03, 0.75 +/- 0.12 and 0.85 +/- 0.04, respectively, markedly higher in LG than in MG (P < 0.05). CONCLUSION: Intraperitoneal injection of cyclophosphamide decreases the sperm count, percentages of grades a + b and a + b + c sperm, and the expression of CatSper1 in mice, while large-dose Yijingfang can increase the above parameters, and hence contributes to the treatment of oligoasthenospermia.

[Acting mechanism of longbixliao capsule on human prostatic stromal cells cultured in vitro].

OBJECTIVE: To explore the mechanism of action of Longbixiao Capsule (LBXC, a Chinese herbal preparation) on human prostatic stromal cell cultured in vitro. METHODS: Nine Japan rabbits were assigned to 3 groups. The high, low dose group was given LBXC [2.0 g/(kg x d), 1.0 g/(kg x d)] by gastro gavage respectively, while equal volume of normal saline was given by gastrog avage 60 rats in the control group, all twice a day with an infeval of 12 h, for 3 successive days. The serum collected at 3 h after the last gastro gavage was added into cell culture fluid. Rabbit's serum containing LBXC was incubated with the cultured stromal cells, and the levels of cell proliferation and apoptosis were determined using relative techniques as TUNEL, ELISA, and immunocytochemistry. Besides, Real-time RT-PCR was applied to detect the mRNA expressions of TGF-beta1, and Smad7 in the stromal cells. RESULTS: The cell proliferation showed culture time dependence in all groups. The proliferation in the drug-serum treated groups was lower than that in the control group, and it was lower in the high dose treated group than in the low dose treated group (all P < 0.01). The unfavorable growth did not occur morphologically after being cultured for 48 h and showed insignificant difference between various groups. Cell apoptosis was not found excepting for a few appeared in the high dose treated group (with a little amount of apoptotic cells occurring). After treatment, the expressions of TGF-beta, and Smad7 were lower in the low dose treated group and high dose treated group than in the control group (P < 0.01). There was not statistical difference between the low dose treated group and high dose treated group (P > 0.05). CONCLUSION: LBXC could reduce the expressions of TGF-beta1, and smad7 mRNA in stromal cells and inhibit the stromal cell proliferation, but its effect on promoting cell apoptosis is unobvious.

[Construction of the male rat model of adenine-induced infertility with kidney-yang deficiency].

OBJECTIVE: To investigate the time- and dose-related reproductive toxicity of adenine in male Wistar rats. METHODS: Adenine was dissolved with Arabian sol at the proportion of 1:10 and different adenine solutions were prepared at the concentration of 0, 50, 100, 150 and 200 mg/ml. Seventy-five male Wistar rats were equally assigned to 5 dose groups and received intragastric administration of the adenine solution at 1 ml/(100 g x d). Five from each group were sacrificed every 10, 20 and 30 days, their sperm quality and body and genital weight measured, pathological examinations conducted, sex hormone changes detected by radioimmunoassay, and analyses made on the time- and dose-related reproductive toxicity of adenine. RESULTS: With the increase in the time and dose of adenine administration, signs of kidney-yang deficiency gradually appeared in all the dose groups on the third day; and statistically significant changes were observed in sperm concentration and motility, and serum testosterone and luteinizing hormone levels in the 100 mg/(100 g x d) group (P < 0.05 or P < 0.01) by the 10th day. The same changes were observed in 50 mg/(100 g x d) group by the 20th day. Different degrees of pathological changes were noted in a time and dose-dependent manner in all the dose groups, suggestive of a progressive reduction of the reproductive function with the increase of time and dose of adenine administration. CONCLUSION: For the construction of the male rat model of adenine-induced infertility with kidney-yang deficiency, the best dose is 50-100 mg/(100 g x d) and the best administration time is 10-20 consecutive days intragastrically.

[Longbixiao capsule reduces expressions of TGF-beta1 and Smoothelin in human prostatic stromal cells cultured in vitro].

OBJECTIVE: To investigate the effects of the Chinese herbal medicine of Longbixiao (LBX) Capsule on the expressions of TGF-beta1 and Smoothelin in human prostatic stromal cells cultured in vitro. METHODS: Blood serum medicated with LBX was incubated with the stromal cells isolated from men with benign prostatic hyperplasia (BPH) and cultured in vitro. The mRNA expression levels of TGF-beta1 and Smoothelin were detected by real-time RT-PCR and other relevant techniques. RESULTS: In the high and low concentration groups, the gene relative expressions of TGF-beta1 were (0.158 +/- 0.020) and (0.169 +/- 0.020) , while those of Smoothelin were (0.035 +/- 0.007) and (0.036 +/- 0.007) respectively, both significantly decreased in comparison with the control group(P < 0.01). CONCLUSION: LBX reduces the mRNA expressions of TGF-beta1 and Smoothelin in human prostatic stromal cells and can be used in the treatment of BPH.

[Discussion on thoughts and methods for the treatment of chronic prostatitis by combination of TCM with Western medicine].

Chronic prostatitis is a common disease in male. So far the etiology and pathogenesis of chronic prostatitis, particularly chronic pelvic pain syndrome (CPPS), remain to be elucidated and there is no unified recognition in the treatment of this disease. This article discusses the thoughts and methods for the diagnosis and treatment of chronic prostatitis by combination of TCM and Western medicine systematically.

[The observation of chronic prostatis patients using the National Institutes of Health Chronic Prostatitis Symptom Index].

OBJECTIVES: The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) was used to determine the chronic prostatitis syndrome in young men (from 20 to 48 years old) of clinical validity. METHODS: 227 patients with chronic prostatitis syndrome (CPS)/chronic pelvic pain syndrome and 32 patients with BPH were randomized to study using NIH-CPSI. RESULTS: 1. The main manifestations of CPS patients were pain or uncomfort. Those were more common in CPS than BPH. 2. 79.30% CPS patients had a sensation of not emptying bladder completely after finished urinating, 44.93% patients had to urinate again less than two hours after finished urinating. 3. 51.51% patients with CPS have more effect on work, 90.31% patients on free life, and 68.72% patients on quality of life than BPH. CONCLUSIONS: According NIH-CPSI, the main manifestations of CPS are pain or uncomfort. CPS patients have more effect on work and quality of life.

[Experimental study on effect of xiaolong tongbi on nitric oxide synthase and epithelial cell apoptosis in prostate of rats].

OBJECTIVE: To explore the effect of Xiaolong Tongbi (XLTB), a Chinese herbal preparation, on nitric oxide synthase (NOS) containing nerve and epithelial cell apoptosis. METHODS: NOS containing nerve level of various groups prostate was determined by NADPH histochemical staining and morphological quantitative analysis, and the cell apoptosis rate in rats prostatic epithelium was tested immunohistochemically with TUNEL method. RESULTS: After 3 weeks treatment with high dose XLTB, the length density of NOS contained nerves in prostate tissue of rats was 0.113 +/- 0.023, which was significantly different to that in the other 3 groups (low dose XLTB, Finasteride and testosterone) respectively (P < 0.01). Cell apoptosis reached its peak at the day 7 of experiment in XLTB treated groups (9.27%), and Finasteride treated group (5.65%), which lowered slightly at day 14 and got some recovery at day 21. Castration induced cell apoptosis began at day 7 and reached its peak at day 14, which was significantly different from that in the other groups. CONCLUSION: XLTB could increase the NOS contained nerve level and accelerate the apoptosis of epithelial cell in prostate tissue of simulating benign prostatic hyperplasia rats.