A dual-adjuvant neoantigen nanovaccine loaded with imiquimod and magnesium enhances anti-tumor immune responses of melanoma.

Neoantigen-based tumor vaccines have been applied in patient-specific melanoma-derived immunogenic mutated epitopes (neoantigens), with potential antineoplastic and immunomodulating effects. Yet, their use is limited by different physicochemical properties and poor pharmacokinetics. Herein, we constructed a human serum albumin-based dual adjuvant neoantigen nanovaccine loaded with imiquimod and magnesium. Magnesium, in coordination with imiquimod, could greatly activate dendritic and T cells. After subcutaneous injection, the nanovaccine effectively targeted tumor-draining lymph nodes (LNs) and promoted the presentation of neoantigens, thus generating a large number of effector T cells. In the B16F10 mouse melanoma prevention model, the nanovaccine effectively inhibited tumor growth and prolonged the survival time of tumor-bearing mice. To sum up, this new neoantigen nanovaccine could be used as a new method for targeting melanoma and may be potentially applied in clinical work.

Zuogui Wan improves spermatogenesis of GC1-spg cells through modulating AR-related pathways.

Zuogui Wan (ZGW) is a common prescription medication used in traditional Chinese medicine (TCM) to significantly improve the sperm quality and treat male infertility. This study evaluated the repair effect of ZGW and Levocarnitine (LEV) on GC1-spg cell injury induced by Glucosides of Tripterygium WilforDII Hook (GTW). The results showed that the ultrastructure and apoptosis rate of GC1- spg cells in LEV and ZGW group were considerably better than GTW. The transcriptional and translational level of CYP1A1, CYP17A1, androgen receptor (AR), SRD5A2 and proliferating cell nuclear antigen (PCNA) in GC-1spg cells of the LEV group were considerably elevated than GTW group (p < 0.05 or 0.01). Furthermore, the transcriptional and translational levels of CYP19A1, CYP17A1, AR, SRD5A2 and PCNA in GC-1spg cells in ZGW group were found to be considerably elevated than the LEV group (p < 0.05 or 0.01). The findings indicate that ZGW and LEV could increase the expression of PCNA, CYP17A1, CYP19A1, SRD5A2 and AR at transcriptional and translational levels, inhibit GC-1spg cell apoptosis and promoting cell proliferation, and the effect of ZGW was found to be significantly better than that of LEV.

Mechanism by which Huoxue Tongluo Qiwei Decoction improves the erectile function of rats with diabetic erectile dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Huoxue Tongluo Qiwei Decoction is a classical herbal formula, which can improve the symptoms of erectile dysfunction (ED) patients and has a good therapeutic effect on patients with diabetic erectile dysfunction (DIED). The main function of Huoxue Tongluo Qiwei Decoction is to stimulate the blood circulation and dredge collaterals, remove blood stasis, and calm wind. RATIONALE: To further explore the mechanism of Huoxue Tongluo Qiwei Decoction in the treatment of DIED, related animal experiments were designed. MATERIALS AND METHODS: The chemical constituents of Huoxue Tongluo Qiwei Decoction were identified with the help of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A rat model was induced by streptozotocin (STZ) and screened by apomorphine (APO). Serum sE-selectin, lysyl oxidase-1 (LOX-1), malondialdehyde (MDA) and other markers of vascular endothelial injury and related indicators of oxidative stress were studied through enzyme-linked immunosorbent assay (ELISA). The endothelial cells and ultrastructure of the corpus cavernosum were examined by electron microscopy and HE staining. The expression of protein and mRNA was detected by western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The results of the study revealed that the sE-selectin, LOX-1, intercellular adhesion molecule-1 (sICAM-1), endothelial microparticles (EMPs), P-selectin (CD62P), and MDA levels in the serum of group M rats were considerably higher than rats of group K, while the superoxide dismutase (SOD) level showed a significant decrease. In addition, the PKC pathway was activated, and the expression of related proteins and mRNA was increased. After 8 weeks of intervention with Huoxue Tongluo Qiwei Decoction and LY333531, serum level of sE-selectin, LOX-1, sICAM-1, EMPs, CD62P and MDA in L, D and G groups were remarkably lower than group M while SOD level increased significantly, protein kinase C (PKC) pathway was inhibited with the improved erectile function of rats. CONCLUSION: Huoxue Tongluo Qiwei Decoction can inhibit the expression of protein and mRNA of the PKCß signaling pathway related molecules in DIED rats to cure the injury of vascular endothelial, enhance antioxidant capacity, and prevent the activation of platelet, thus improving erectile function in rats with DIED.

Network Pharmacology Analysis of the Effects of Achyranthis Bidentatae Radix Plus Semen Vaccariae on Migraine-induced Erectile Dysfunction.

BACKGROUND AND AIM: Achyranthis Bidentatae Radix plus Semen Vaccariae are traditional Chinese medicines, which have been widely applied in the treatment of migraine and Erectile Dysfunction (ED) for many years. This study verified the effect of Achyranthis Bidentatae Radix plus Semen Vaccariae in improving migraine-induced ED and explored its potential mechanism. METHODS: Key targets and signaling pathways of Achyranthis Bidentatae Radix plus Semen Vaccariae in migraine-induced erectile dysfunction treatment were predicted by network pharmacology. A rat model of migraine was established by nitroglycerin injection. Apomorphine was injected into rats to screen the migraine-induced erectile dysfunction model, Achyranthis Bidentatae Radix-Semen Vaccariae granule suspension administered, and erectile function evaluated. Hematoxylin and eosin staining was used to compare the histological structure of the penile tissue, while RT-qPCR and Western blotting were used to determine mRNA and protein levels, respectively. RESULTS: Screening allowed us to identify common targets for migraine and ED; the signaling pathway exhibiting the greatest change was the Myosin light chain kinase- Calcium (MLCK-CaM) signal pathway. From Western blotting and RT-qPCR, we found that the levels of MLCK mRNA and protein in rats from Group B rats were significantly higher (P <0.05) than those in Groups A and C. Furthermore, the mRNA and protein levels of CaM were significantly higher in Group B (P <0.05) than in Groups A and C. CONCLUSION: Data indicate that the regulatory effects of Achyranthis Bidentatae Radix plus Semen Vaccariae on migraine-induced ED in a rat model are mediated by the MLCK-CaM signaling pathway.

Effectiveness of Yiqi Fumai lyophilized injection for acute heart failure: Rationale and design of the AUGUST-AHF cohort study.

Introduction: The effect of Yiqi Fumai lyophilized injection (YQFM) on acute heart failure (AHF) patients has been evaluated in a large sample, randomized, controlled trial (AUGUST-AHF RCT study). However, restrictive eligibility criteria from a randomized clinical trial may raise concerns about the generalizability of the results to under-represented groups or complex patients with multimorbidity. Therefore, we intend to conduct the AUGUST-AHF cohort study which aims to assess the effectiveness of YQFM in patients with AHF in a real-world setting and compare the results with AUGUST-AHF RCT study. Methods and analysis: This prospective, multicenter cohort study will be conducted at 50 secondary and tertiary hospitals in China and comprise 1,200 patients with AHF. The participants will be followed for up to at least 180 days. The primary outcome is a composite of 90-day all-cause mortality or readmission for heart failure. The secondary outcomes include length of hospital stay, cardiac-specific death, MACE, NYHA cardiac function classification. Cox proportional-hazards regression models will be used to estimate the association between YQFM use and the primary outcome. The primary analysis will use propensity-score matching methods to balance the differences in baseline variables between treatment cohorts. Ethics and dissemination: Approval for the study has been obtained from the Ethical Committee of Dongzhimen Hospital (approval No. 2022DZMEC-327-02) and registered at ClinicalTrials.gov (NCT05586048). The study results will be published in peer-reviewed journals and presented at scientific conferences.

Potential mechanism of Achyranthis bidentatae radix plus semen vaccariae granules in the treatment of diabetes mellitus-induced erectile dysfunction in rats utilizing combined experimental model and network pharmacology.

CONTEXT: Achyranthes bidentata Blume (Amaranthaceae) (ABR) and semen vaccariae (SV) are used commonly in the clinical treatment of erectile dysfunction in males with diabetes mellitus (DMED) to strengthen the kidney and promote blood circulation, and often achieve good curative effects. OBJECTIVE: Explore mechanistic details of ABR + SV treatment against DMED. MATERIALS AND METHODS: Prediction of key targets by network pharmacology. A rat model of DM was established by streptozotocin injection (55 mg/kg). Apomorphine (100 µg/kg) was injected into rats to screen the DMED model. Group C (n = 6) and group M (n = 6) were gavaged with deionized water; group T (n = 6) was given Achyranthis bidentatae radix-semen vaccariae granule suspension (2.5 g/kg). It lasted 8 weeks. Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were used to measure the expression of tissue-related proteins and mRNA. RESULTS: The predicted key targets are albumin (ALB), caspase-3 (CASP3), vascular endothelial growth factor A (VEGFA), angiotensin-converting enzyme (ACE), and endothelial nitric oxide synthase (eNOS). Compared with the M group (0.52 ± 0.04; 0.50 ± 0.03; 0.49 ± 0.02; 0.23 ± 0.03), CASP3, VEGFA, and ACE protein expression reduced in the T group (0.39 ± 0.06; 0.34 ± 0.03; 0.39 ± 0.03), and eNOS protein expression increased (0.34 ± 0.03). CONCLUSION: ABR + SV can improve erectile function in DMED rats. This study provides a potential mechanism for the treatment of DMED with ABR + SV and can benefit from more patients.

To study the mechanism of Cuscuta chinensis Lam. And Lycium barbarum L. in the treatment of asthenospermia based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Cuscuta chinensis Lam. and Lycium barbarum L. (SC-FL) is a commonly used kidney tonic Chinese medicine combination that is widely used in the clinical treatment of oligoasthenospermia.However, its specific mechanism remains unclear and requires in-depth study. AIM OF THE STUDY: To explore the potential targets of SC-FL in the treatment of oligoasthenospermia using network pharmacology, and to verify the results with in vivo and in vitro experiments. MATERIALS AND METHODS: A herb-compound-target-disease network and PPI network were constructed with Cytoscape software. The targets of SC-FL for the treatment of male sterility were introduced into a bioinformatics annotation database, and the GO and KEGG databases were used for pathway enrichment analysis. Subsequently, Tripterygium wilfordii Hook. f. (GTW) polyglycoside was used to induce a spermatogenic dysfunction model in GC-1 spg cells and SD male rats in in vitro and in vivo experiments, respectively. The SC-FL and PI3K pathway inhibitor LY294002 was used to intervene in the spermatogenic dysfunction model to detect the expression of proteins and mRNA related to the PI3K pathway and to detect the indicators related to proliferation and apoptosis. RESULTS: In in vitro experiments, the percentage of spermatogenic cells and the proportion of GC-1 spg cells at G0/G1 and G2/M stages in the model group (GTW group) and the inhibitor group (LY group) were significantly decreased (P < 0.01) compared with the blank control group (NC group). The apoptosis rate of the GTW group was significantly increased (P < 0.01). The ultrastructures of GC-1 spg cells in the GTW group and LY group were obviously destroyed. Compared with the GTW group, the SC-FL group had a significantly reduced apoptosis rate of GC-1 spg cells, reduced percentage of cells in S phase, and a significantly improved mitochondrial membrane potential. SC-FL can repair the ultrastructure of GC-1 spg cells damaged by GTW. The above effects of SC-FL are closely related to up-regulation of GFRa1, RET, PI3K, p-AKT, and Bcl-2 and down-regulation of BAD and BAX proteins and mRNA expression. In vivo, compared with the GTW group, the body mass, testicular mass, and epididymal weight of the GTW + SC-FL group were significantly increased (P < 0.01). Sperm concentrations and the PR + NP of GTW + SC-FL were significantly higher than in the GTW group (P < 0.01 or P < 0.05). FSH, LH, and T levels in the GTW + SC-FL and LY + SC-FL groups were significantly higher than those in the GTW and LY group (P < 0.01 or P < 0.05). HE staining results showed that the morphology of testicular tissue in the GTW + SC-FL and LY + SC-FL groups was superior to that in the GTW and LY group. The above effects of SC-FL are closely related to the up-regulation of proteins and mRNA expression of PI3K, p-AKT, and Bcl-2. CONCLUSION: Through the PI3K/Akt signaling pathway, SC-FL up-regulates GFRa1, RET, PI3K, p-AKT, and Bcl-2, and down-regulates the expression of BAD and BAX proteins and mRNA, thus reducing the percentage of GC-1 spg cells in S-phase, significantly increasing the mitochondrial membrane potential, significantly reducing cell apoptosis, and improving sperm counts and viability.

A Network Pharmacology Approach to Reveal the Underlying Mechanisms of Zuogui Yin in the Treatment of Male Infertility.

BACKGROUND AND AIM: Traditional Chinese medicine (TCM), as a complementary and alternative therapy, has played increasingly important roles in clinical treatment and disease prevention. Zuogui Yin (ZGY) is one of the well-known TCM prescriptions used for the treatment of male infertility. To fully reveal the potential mechanisms underlying the therapeutic effects of ZGY on male infertility, a network pharmacology approach was conducted at the molecular level. METHODS: Network pharmacology approach was used in this study, which mainly included active compound screening, target prediction, gene enrichment analysis, and network analysis. RESULTS: The network analysis successfully identified 148 potential active ingredients of ZGY and 155 predicted targets that were associated with male infertility. ZGY might play a role in the treatment of male infertility by regulating ten hub targets (VEGFA, CASP3, TNF, AKT1, EGF, EGFR, IL-6, MAPK1, TP53, and PTGS2) and six pathways (TNF signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, Toll-like receptor signaling pathway, VEGF signaling pathway, and MAPK signaling pathway). CONCLUSION: This study explored the pharmacological activity and molecular mechanisms of ZGY against male infertility from a holistic perspective. The underlying molecular mechanisms were closely related to the intervention of oxidative stress and apoptosis with CASP3, TP53, AKT1, and MAPK1 being possible targets.

Effect of leech-centipede medicine on improving erectile function in DIED rats via PKC signalling pathway-related molecules.

ETHNOPHARMACOLOGICAL RELEVANCE: Leeches (pinyin name Shui Zhi; Latin scientific name Hirudo; Hirudinea; Hirudinidae) and centipedes (pinyin name Wu Gong; Latin scientific name Scolopendridae; Chilopoda; Scolopendridae) are traditional Chinese medicines, and they belong to the family entomology. A combination of leech and centipede is used as an effective medicine to promote blood circulation and remove blood stasis in traditional Chinese medicine, and "leech-centipede" medicine has been used in many prescriptions to treat diabetic vascular disease, including diabetic erectile dysfunction (DIED). However, its specific mechanism remains unclear and requires in-depth study. AIM OF THE STUDY: This study aimed to investigate the mechanism of "leech-centipede" medicine to improve erectile dysfunction-associated diabetes by detecting PKC pathway-related molecules. MATERIALS AND METHODS: The active ingredients of "leech-centipede" medicine were identified using high performance liquid chromatography (HPLC). Fifty male SPF rats were injected with streptozotocin to induce the DM model. Eight weeks later, the DMED model was validated with apomorphine. The DIED rats were divided into five groups-T,P,DD,DZ, and DG-and were separately treated with tadalafil, pathway inhibitor LY333531 and low-, medium-, and high-dose "leech-centipede" medicine for 8 weeks. After treatment, the blood glucose level was measured, erectile function with apomorphine was assessed, the LOX-1, sE-selectin, sICAM-1, SOD, and MDA in serum was evaluated by enzyme-linked immunosorbent assay, and flow cytometry was performed. After the collection of penile tissue, the related protein and mRNA expression was assessed by Western blotting and PCR, and the tissue and ultrastructure were analysed by HE staining, immunohistochemistry and scanning electron microscopy. RESULTS: After treatment, the erectile function of rats was significantly improved in the T,P,DD,DZ, and DG groups compared with that in the model group. Thus, "leech-centipede" medicine can significantly reduce the levels of LOX-1, sE-selectin, sICAM-1, EMPs and CD62P to protect vascular endothelial function and anti-platelet activation, improving DIED rat erectile function. Additionally, "leech-centipede" medicine can increase SOD expression and decrease MDA expression, reducing the possibility of oxidative stress injury in DIED rats and improving the antioxidant capacity. Moreover, "leech-centipede" therapy can dramatically reduce the protein and mRNA expression of DAG, PKCß, NF-κB, and ICAM-1, improve vascular endothelial injury in DIED rats and inhibit abnormal platelet activation. CONCLUSION: "leech-centipede" medicine can improve erectile dysfunction by inhibiting the expression of PKC pathway-related molecules in DIED rats and protects endothelial function and anti-platelet activation.

Effectiveness comparison of a Chinese dicitraditionalmene formula Wuzi Yanzong Pill and its analogous prescriptions for the treatment of oligoasthenozoospermia: A systematic review and meta-analysis protocol.

BACKGROUND: Among male sterility factors, oligoasthenozoospermia is the most common. As people's lifestyle changes and the population ages, the incidence of oligoasthenozoospermia continues to increase. The studies have shown that about 15% of married couples in the world are affected by infertility, among which infertility caused by male factors alone accounts for about 50%. Many clinical trials have proven that Wuzi Yanzong Pill has a significant effect in the treatment of oligoasthenozoospermia. In this systematic review, we aim to evaluate the effectiveness and safety of Wuzi Yanzong Pill for oligoasthenozoospermia. METHODS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online, and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to April 2019. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of oligoasthenozoospermia. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of Wuzi Yanzong Pill for treating oligoasthenozoospermia. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process Trial. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019119170.

Effectiveness comparisons of acupuncture for premature ejaculation: Protocol for a network meta-analysis.

BACKGROUND: As one of the common male sexual dysfunction diseases, the treatment effect of premature ejaculation is often difficult to guarantee. In China, there are many randomized clinical trials that confirm that acupuncture has a good therapeutic effect on premature ejaculation. The aim of this study was to compare the efficacy and safety of acupuncture for premature ejaculation from intravaginal ejaculation latency (IELT), premature ejaculation diagnostic tool (PEDT), Arab premature ejaculation index (AIPE), and premature ejaculation index (IPE). METHODS: We will use PubMed, EMBASE, Nursing and Related Health Literature Cumulative Index, Joint and Supplemental Drug Database, Cochrane Center Controlled Trials Registry (CENTRAL), China Biomedical Literature Database (CBM) and China Knowledge Infrastructure (CNKI), The Chinese Science and Technology Periodical Database (VIP), and Wanfang Database conduct systematic searches until October 31, 2018. At the same time, manually search for gray documents, including unpublished meeting articles. The primary outcome included intravaginal ejaculation latency (IELT). Secondary outcomes were premature ejaculation diagnostic tools (PEDT), Arab premature ejaculation index (AIPE), and premature ejaculation index (IPE). The quality and evidence that the risk of inclusion of the BiB tool will be assessed will be assessed on a scale. RESULTS: This study will generate a comprehensive review of current evidence of acupuncture for premature ejaculation. CONCLUSION: The study will provide updated evidence to evaluate the efficacy and safety of acupuncture for premature ejaculation. ETHICS AND COMMUNICATION: Because this research is based on a meta-analysis of published research, ethical recognition and patient consent are unnecessary. AGREEMENT REGISTRATION NUMBER: PROSPERO CRD42018111661.

Acupuncture for pain caused by prostate cancer: Protocol for a systematic review.

BACKGROUND: Prostate cancer is a male malignant tumor disease with high prevalence in recent years. Patients with advanced prostate cancer are more likely to have bone metastasis and strong bone pain, and even lead to pathological fracture, which has a serious impact on the quality of life of patients. Acupuncture has good clinical efficacy in treating pain caused by prostate cancer. This review hopes to adopt meta-analysis to evaluate the efficacy and safety of acupuncture in the treatment of pain caused by prostate cancer and provides evidence for its application in clinical practice. METHODS AND ANALYSIS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet, Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to November 2018. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata 13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of epididymitis. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of acupuncture for pain caused by prostate cancer. Owing to the fact that all of the data used in this systematic review and meta-analysis have been published, this review does not require ethical approval. Furthermore, all data will be anonymously analyzed during the review process trial. TRIAL REGISTRATION NUMBER: PROSPERO CRD42018111550.

The safety and efficacy of acupuncture for erectile dysfunction: A network meta-analysis.

BACKGROUND: Erectile dysfunction is a common male disease, the constant pace of life, increasing pressure on life, and changes in diet, living environment, lifestyle, etc., lead to an increase in the number of patients with erectile dysfunction (ED). Acupuncture has been widely used in clinical trials of ED in recent years. There are many clinical trials that confirm that acupuncture can improve male erectile function. This study used a network meta-analysis (NMA) to compare the effectiveness and safety of different forms of acupuncture on ED. METHODS: We will search for PubMed, Cochrane Library, AMED, EMBASE, WorldSciNet; Nature, Science online and China Journal Full-text Database (China National Knowledge Infrastructure), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials (RCTs) included in the China Resources Database. The time is limited from the construction of the library to December 2018. The quality of the included RCTs will be evaluated with the risk of bias tool and evidence will be evaluated by Grading of Recommendations Assessment, Development and Evaluation. STATA 13.0 and WinBUGS 1.4.3 through the GeMTC package will be used to perform an NMA to synthesize direct and indirect evidence.

The safety and efficacy of acupuncture for epididymitis protocol for a systematic review.

BACKGROUND: Epididymitis is a common disease in non-specific infections of the male reproductive system. According to the clinical incidence of acute epididymitis and chronic epididymitis, which is more common in chronic epididymitis. There are many clinical trials confirmed that acupuncture treatment can relieve pain and improve symptoms of epididymitis to some extent. In this systematic review, we aim to evaluate the effectiveness and safety of acupuncture for epididymitis. METHODS AND ANALYSIS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to November 2018. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of epididymitis. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of acupuncture for epididymitis. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process trial. REGISTRATION NUMBER: PROSPERO CRD42018111348.

Acupuncture for premature ejaculation: Protocol for a systematic review.

BACKGROUND: Premature ejaculation is a common sexual dysfunction disease in adult males. It can be divided into primary and secondary premature ejaculation. Acupuncture is widely used in the treatment of premature ejaculation in China. There are many clinical trials confirmed that acupuncture can prolong the ejaculation latency in the vagina. We aim to use a meta-analysis to evaluate the efficacy and safety of acupuncture for premature ejaculation. METHOD: We will systematically search all randomized controlled trials (RCTs) by electronic and manual search, until June 31, 2018. Electronic retrieval of the database includes Medline, EMBASE, the Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, the Cochrane Library, the Chinese BioMedical Literature Database, the China National Knowledge Infrastructure (CNKI), the China Science and Technology Journal database (VIP), and the Wanfang database. Manual search will retrieve gray literature, including unpublished conference articles. The primary outcomes include the Intravaginal Ejaculatory Latency Time (IELT). At the same time, Premature Ejaculation Diagnostic Tool (PEDT), Arabic index of Premature Ejaculation (AIPE), Index of Premature Ejaculation (IPE) will be the secondary outcomes. Two reviewers will independently read the articles, extract the data information, and give the assessment of risk of bias. Data analysis will be used the special software like RevMan (version 5.3) and EndNote X7. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of acupuncture for premature ejaculation. This review does not require ethical approval and will be reported in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42018092783.