[Exploring the mechanisms of Jujing pill on varicocele-associated male infertility via network pharmacology and molecular docking technology].

OBJECTIVE: To investigate the potential mechanism of treating varicocele-associated male infertility with Jujing pill using network pharmacology and molecular docking technology. METHODS: The TCMSP and BATMAN databases were used to search for the Chinese medicine components of the Jujing pill and obtain the corresponding targets. The databases GeneCards, DISGENET, OMIM, and HPO were searched for 'varicocele' and 'male infertility' to identify the potential targets of varicocele-associated male infertility. Wayne diagrams were drawn using the jvenn tool to determine the intersection targets of the Chinese medicine targets and disease targets. The intersecting targets were further analyzed to identify the components and Chinese medicine corresponding to them. A Chinese medicine-active ingredient-target network map was constructed in Cytoscape 3.8.2. The protein-protein interaction (PPI) network of the intersecting targets was constructed using the STRING platform. The intersecting targets were imported into the DAVID database for GO enrichment analysis and KEGG-based pathway enrichment analysis. The KEGG database was used to select the most relevant pathway to the topic, and a KEGG pathway map was constructed using the mapper tool. The top 15 pathways with FDR values and their related targets and components were used to draw a core ingredient-target-pathway map. Finally, molecular docking was performed to verify the protein receptors and small molecule ligands of the core genes, and the results were visualized using AutoDock and PyMol software. RESULTS: A total of 207 ingredients and 1103 predicted targets of Jujing pill were screened. Additionally, 285 targets of varicocele were also identified. By using a Venn diagram, 86 common targets were obtained. The analysis of Gene Ontology (GO) results revealed significant enrichment in various biological processes (BP) such as positive regulation of gene expression, positive regulation of transcription, positive and negative regulation of apoptotic processes, response to hypoxia, response to estradiol, and positive regulation of nitric oxide biosynthesis processes. Furthermore, significant enrichment in cellular components (CC) was observed in macromolecules, cytoplasm, nucleus, and phosphatidylinositol 3-kinase complex. In terms of molecular function (MF), enrichment was found in enzyme binding, identical protein binding, transcriptional co-activator binding, and others. KEGG analysis demonstrated enrichment in pathways related to cancer, AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, FoxO signaling pathway, and more. Molecular docking results indicated that the core ingredients exhibited a strong binding capacity with the key targets. Conclusion： The effective active ingredients of Jujing pill exert their therapeutic effects on varicocele-associated male infertility through multiple targets and pathways. These findings provide a theoretical basis for future cell and animal experiments to verify the mechanism of action of Jujing pill in treating varicocele-associated male infertility.

[Efficacy of Jujing Decoction combined with lipoic acid in the treatment of asthenospermia and teratospermia].

OBJECTIVE: To observe the clinical efficacy of Jujing Decoction combined with lipoic acid in the treatment of asthenospermia and teratospermia. METHODS: Fifty patients with asthenospermia and teratospermia meeting the inclusion criteria were randomly divided into a blank control (n = 10) and a medication group (n = 40), the former provided with fertility guidance and the latter treated with Jujing Decoction combined with lipoic acid. After 12 weeks of treatment, the clinical therapeutic effects were evaluated by comparing the semen volume, sperm concentration, percentages of progressively motile sperm (PMS) and morphologically abnormal sperm (MAS), rate of acrosome integrity, sperm DNA fragment index (DFI) and pregnancy rate between the two groups. RESULTS: Compared with the control group, the medication group achieved a significantly higher overall effectiveness rate (10% ï¼»1/10ï¼½ vs 88.89% ï¼»32/36ï¼½, P < 0.05) and pregnancy rate (0% ï¼»0/10ï¼½ vs 8.33% ï¼»3/36ï¼½, P < 0.05) after treatment. The medication group also showed remarkably increased PMS from (21.04 ± 6.49)% to (32.66 ± 7.05)%, decreased MAS from (98.31 ± 1.28)% to (96.52 ± 1.11)%, elevated acrosome integrity from (42.18 ± 16.67)% to (60.42 ± 11.61)%, and reduced sperm DFI from (21.92 ± 6.96)% to (12.37 ± 3.79)%, all with statistically significant differences compared with the blank control group. CONCLUSION: Jujing Decoction combined with lipoic acid can significantly improve sperm motility, reduce MAS and DFI and increase the pregnancy rate through antioxidant stress, and has a high clinical safety.

[Clinical efficacy of Jujing Decoction on teratospermia: An investigation based on the theory of "yin forming"].

OBJECTIVE: To study the clinical efficacy of Jujing Decoction (JJD) based on the theory of "yin forming" in the treatment of teratospermia and its effects on semen parameters, sperm morphology, sperm DNA fragmentation index (DFI) and the ultrastructure of sperm mitochondria. METHODS: We randomly divided 40 patients with teratospermia into a blank control group (n = 16) and a JJD group (n = 24), the former treated by reproductive health guidance and the latter with JJD, respectively. After 12 weeks of intervention, we observed the clinical effects and changes in the semen volume, sperm concentration, percentages of progressively motile sperm (PMS) and morphologically abnormal sperm (MAS), sperm DFI and the ultrastructure of sperm mitochondria, and analyzed the data obtained based on the "yin forming" theory. RESULTS: The total effectiveness rate was significantly higher in the JJD than in the blank control group (87.50% vs 6.66%, P < 0.05). Compared with the baseline, the patients after treated with JJD showed significant improvement in semen volume (ï¼»3.27 ± 1.14ï¼½ vs ï¼»4.16 ± 1.84ï¼½ ml, P < 0.05), sperm concentration (ï¼»38.85 ± 15.88ï¼½ vs ï¼»39.35 ± 14.58ï¼½ × 106/ml, P < 0.05), PMS (ï¼»37.47 ± 2.74ï¼½% vs ï¼»42.55 ± 7.07ï¼½%, P < 0.05), MAS (ï¼»97.43 ± 1.01ï¼½% vs ï¼»95.52 ± 0.85ï¼½%, P < 0.05), acrosomal integrity (ï¼»45.27 ± 5.14ï¼½% vs ï¼»51.88 ± 4.48ï¼½%, P < 0.05), and DFI (ï¼»25.53 ± 6.89ï¼½% vs ï¼»17.68 ± 2.38ï¼½%, P < 0.05), while the blank controls exhibited only slightly increased semen volume (ï¼»3.67 ± 1.77ï¼½ vs ï¼»4.40 ± 1.78ï¼½ ml) and sperm concentration (ï¼»37.24 ± 9.31ï¼½ vs ï¼»38.32 ± 10.54ï¼½ ×106/ml), but no significant improvement in the other parameters (P> 0.05). Before treatment, folded and discontinuous sperm acrosomal membrane was observed under the transmission electron microscope in the sperm mitochondria of the two groups of patients, the mitochondria stacked and differently sized in the neck and disorderly arranged and some obviously swollen around the tail microtubule. After treated with JJD, the ultrastructure of sperm mitochondria was significantly improved, with relative continuity and integrity of the acrosomal membrane and well-arranged and relatively intact and uniform-sized mitochondria in the neck and tail. CONCLUSION: Jujing Decoction can increase the semen volume, sperm concentration and percentage of progressively motile sperm, reduce the percentage of morphologically abnormal sperm and sperm DFI, improve sperm acrosomal integrity, maintain the stability of sperm ultrastructure and protect the structure of sperm mitochondria.

[Distribution of TCM syndrome types and their correlation semen parameters in infertility patients with varicocele].

OBJECTIVE: To explore the distribution of Traditional Chinese Medicine (TCM) syndrome types and their relationship with semen parameters in infertility male patients with varicocele (VC). METHODS: Using Questionnaire on Clinical Symptoms of Varicocele-Caused Male Infertility, we made an investigation among 147 infertility male patients with VC, determined the types of their TCM syndromes, obtained their semen parameters, and analyzed the distribution of the TCM syndrome types and their correlation with semen parameters. RESULTS: Of the TCM syndrome types identified, kidney deficiency and stagnated heat constituted the largest proportion (34.7%), and the mixed type accounted for a significantly higher percentage than the simple type (P < 0.05). The patients with kidney deficiency and stagnated heat, compared with those with other syndrome types, had a dramatically lower sperm concentration (ï¼»21.62 ± 9.25ï¼½ vs ï¼»28.88 ± 12.92ï¼½ ×106/ml, P < 0.01), but a higher percentage of morphologically abnormal sperm (ï¼»98.33 ± 0.15ï¼½% vs ï¼»96.27 ± 0.18ï¼½%, P < 0.05) and DNA fragmentation index (ï¼»19.72 ± 3.17ï¼½% vs ï¼»10.96 ± 3.82ï¼½%, P < 0.01). No statistically significant differences were observed in the percentage of progressively motile sperm among different TCM syndrome types. CONCLUSIONS: Kidney deficiency and stagnated heat is a main TCM syndrome type in infertility male patients with varicocele and correlated with sperm concentration, the percentage of morphologically abnormal sperm and DNA fragmentation index.

[A clinical analysis of 15 children with systemic lupus erythematosus accompanied by pulmonary hypertension].

OBJECTIVE: To evaluate the clinical features, laboratory findings, diagnosis and treatment, and prognosis of children with systemic lupus erythematosus (SLE) accompanied by pulmonary hypertension (PH). METHODS: The clinical symptoms, laboratory findings, echocardiographic features, SLE disease activity index, and treatment outcome of 15 hospitalized children with SLE accompanied by PH were retrospectively analyzed. RESULTS: Among the 15 patients, the median interval from diagnosis of SLE to diagnosis of PH was 0.1 year (range: 0-6.5 years). Aside from PH-related symptoms, Raynaud's phenomenon was observed in 6 (40%) of the 15 patients. There was no significant difference in SLE disease activity (evaluated by complements 3 and 4 levels, erythrocyte sedimentation rate, and positive rate of anti-double-stranded DNA) between patients with mild-to-moderate PH and those with severe PH (P<0.05). As for treatment, 13 patients received immunosuppressive therapy with glucocorticoids, and among them 2 patients received PH-targeted therapy. During a median follow-up of 8.0 years (range: 0.5-18.1 years) since the diagnosis of PH, 2 deaths were noted with class III or IV cardiac function (World Health Organization), while the other patients were in a stable condition. CONCLUSIONS: Raynaud's phenomenon is a common clinical manifestation in children with SLE accompanied by pulmonary hypertension (PH). PH severity is not significantly associated with SLE disease activity, and thus greater focus should be placed upon early screening of pulmonary arterial pressure in SLE patients. Early diagnosis and early treatment can improve the prognosis of children with SLE.

[Modified Jujing No.2 Decoction for varicocele-induced male infertility].

Objective: To investigate the clinical effect of Jujing No.2 Decoction on male infertility induced by varicocele. METHODS: We equally randomized 70 male patients with varicocele-induced infertility into a treatment group and a control group, the former treated with modified Jujing No.2 Decoction (1 dose a day, bid) and the latter given Danshen Tablets (4 tablets once, tid) plus Liu Wei Di Huang Wan (8 pills once, tid), both for 3 months. We examined the spermatic veins of the patients by ultrasonography and performed seminal analysis before and after medication. RESULTS: Compared with the controls, the patients in the treatment group showed significant improvement after medication in sperm concentration (ï¼»12.35±2.12ï¼½ vs ï¼»18.56±4.16ï¼½ ×106/ml, P<0.05), progressively motile sperm (ï¼»16.18±6.34ï¼½ vs ï¼»24.63±8.51ï¼½ %, P<0.05), and morphologically normal sperm (ï¼»11.59±5.31ï¼½ vs ï¼»14.17±6.02ï¼½ %, P<0.05). In the control group, sperm concentration was increased from (12.29±2.07) ×106/ml at the baseline to (13.13±3.13) ×106/ml after medication, progressively motile sperm from (16.13±6.45) % to (20.55±7.30) % (P<0.05), and morphologically normal sperm from (11.62±5.35) % to (12.69±5.77) %. The total effectiveness rate was significantly higher in the treatment than in the control group (71.88% vs 46.67%, P<0.05). The inner diameter of the left spermatic vein was decreased from (0.32±0.05) mm at the baseline to ï¼»0.26±0.05ï¼½ mm after medication in the treatment group (P<0.05) and from (0.32±0.03) mm to (0.29±0.04) mm in the control (P<0.05), with statistically significant difference between the two groups after medication (P<0.05). CONCLUSIONS: Jujing No.2 Decoction is effective in the treatment of varicocele-induced male infertility.

[Clinical and genetic analysis of Dent disease in 4 Chinese children].

OBJECTIVE: To study the clinical features and gene mutations of 4 Chinese children with Dent disease. METHODS: The clinical and laboratory data of 4 children with Dent disease were analyzed retrospectively. Genetic testing of the 4 cases was carried out. RESULTS: All of 4 cases were boys. The first impression of Cases 1-3 was Fanconi syndrome. Proteinuria was presented as the first impression in Case 4. All 4 boys presented with low-molecular weight proteinuria (LMWP) and hypercalciuria, including 3 cases with hematuria, 1 case with kidney stones, 2 cases with nephrocalcinosis, 3 cases with hypophosphatemia, and 3 cases with rickets. Mutations of the CLCN5 gene were revealed in three patients (Cases 1, 2 and 4), including exon 6-7del, c.785_787de l(p.263del Leu) and c.1039 C>T (p.Arg347Term). The first two gene mutations had never reported before. CONCLUSIONS: Urine protein electrophoresis should be carried out for patients with proteinuria. Dent disease should be taken into consideration when patients with Fanconi syndrome have hypercalciuria, nephrocalcinosis or kindey stones. Genetic analyses are needed for a definite diagnosis.

[Therapeutic efficacy of Bushengzhuyang Fang (Yangjing Capsule) on phytoestrogen-induced erectile dysfunction: an experimental study].

OBJECTIVE: To investigate the effect of Bushengzhuyang Fang (Yangjing Capsule, YJC) on penile erectile function and its action mechanisms in rats. METHODS: Fifty-six male SD rats were randomly divided into seven groups of equal number: blank control, daidzein, daidzein + testosterone, daidzein + sildenafil, daidzein + low-dose YJC, daidzein + medium-dose YJC, and daidzein + high-dose YJC. The rats in the blank control group were treated intragastrically with normal saline and those in the other groups with daidzein at the dose of 100 mg per kg per day for 30 days. Then the last five groups received additionally testosterone (4 mg per kg per day), sildenafil (2.5 mg per kg per day), low-dose YJC, (0.315 mg per kg per day), medium-dose YJC (0.63 mg per kg per day), and high-dose YJC (1. 26 mg per kg per day), respectively. At 0, 30 and 60 days of treatment, we observed the apomorphine-induced spontaneous erectile response and pathological changes in the corpus cavernosum of the rats, recorded the number of penile erection and erectile incubation period, and determined the serum levels of testosterone (T) and luteinizing hormone (LH). RESULTS: At 30 days of treatment, the number of apomorphine-induced erections was decreased, the erectile incubation period prolonged, and the serum levels of T and LH reduced remarkably in all groups of rats (P < 0.05). Compared with the findings at 30 days, the number of penile erections was significantly decreased at 60 days in the daidzein group (1.39 ± 0.42 vs 2.67 ± 0.33, P < 0.05) and daidzein + low-dose YJC group (1.33 ± 0.49 vs 2.83 ± 0.61, P < 0.05); the erectile incubation period was markedly ex- tended ([16.33 ± 3.11] vs [8.50 ± 0.93] min and [15.50 ± 3.21] vs [8.63 ± 1.54] min, P < 0.05); and the serum levels of T ([5.34 ± 0.89] vs [1.24 ± 0.30] ng/ml and [5.28 ± 1.12] vs [2.07 ± 0.76] ng/ml, P < 0.05) and LH ([3.62 ± 0.37] vs [2.09 ± 0.12] ng/ml and [3.79 ± 0.28] vs [2.17 ± 0.33] ng/ml, P < 0.05) were significantly reduced in the daidzein and daidzein + low-dose YJC groups, respectively. Pathological examination revealed slightly decreased cavernous sinuses and blood vessels in the corpus cavernosum of the rats in the daidzein + testosterone, daidzein + sildenafil, daidzein + medium-dose YJC, and daidzein + high-dose YJC groups as compared with those in the blank control group. CONCLUSION: High-dose Yangjing Capsule is efficacious for the recovery of erectile function in rats, especially for phytoestrogen-induced erectile dysfunction.

[A preliminary study of serum free testosterone and testosterone secreting index in men with erectile dysfunction].

OBJECTIVE: To observe the changes of serum free testosterone (FT) and testosterone secreting index (TSI) in ED patients, and to assess the contribution of these two indexes to the diagnosis of ED caused by endocrine factors. METHODS: We studied 120 ED patients and 30 healthy men undergoing pre-marital medical check-up in Jiangsu Province Hospital of TCM by analyzing the scores on erectile function and desire domain in IIEF, testing the serum total testosterone, luteinizing hormone by chemiluminescent enzyme immunoassay (CLIA), measuring free testosterone by radioimmunoassay( RIA), and calculating TSI. RESULTS: Of the 120 ED patients, 5% and 1538% were below the reference norm of TT and FT values respectively. TT, FT and TSI decreased with age, with statistical with FT and TSI, but not with TT. FT and TSI statistically declined with lower IIEF score on ED domain, but this was not the case with TT. There were no significant differences in TI, FT and TSI among different sexual desire groups the ED patients. CONCLUSION: FT is much more valuable than TF in the diagnosis of ED with hypogonadism. Both FT and TSI are important parameters in assessing the severity of ED.

[Experimental study on the effects of jujingwan on oligospermia].

OBJECTIVE: To investigate the effects of Jujingwan on the spermatozoal ultrastructure and apoptosis of germ cells in oligospermia patients. METHODS: We treated 50 oligospermia patients with Jujingwan and observed the spermatozoal ultrastructure, the apoptosis of germ cells and the changes in the DNA ploidy proportion of spermatogenic cells by electron microscopy and FCM before the treatment and 3, 6, 9 and 12 months after it. RESULTS: Jujingwan increased sperm acrosome base density 6 months after the treatment and remarkably improved the integrity of acrosome membrane 12 months after it, with no obvious pathological changes in the nuclei and tails. Three months after the treatment, cell debris and apoptotic cells decreased significantly as compared with pre-treatment (P < 0. 05) , and very significantly 12 months after the treatment (P <0. 01). The proportion of haploid spermatozoa increased very significantly (P <0.01) , and the lost primary spermatocytes decreased significantly (P <0. 05) compared with pre-treatment. CONCLUSION: Jujingwan can increase the density of sperm acrosome base and improve the pathological changes of acrosome membrane in oligospermia patients; it can improve the activity of acrosome enzyme and the integrity of acrosome membrane, decrease the apoptosis rate of germ cells and sperm and increase the percentage of haploid spermatozoa; it can also reduce the percentage of apoptotic bodies and diploid sperm cells. It is indicated that Jujingwan can inhibit the apoptosis of germ cells and sperm and improve spermatogenesis in oligospermia patients.