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Ding Tang,1 Xufen Zhang,1 Yani Xu,1 Linglin Dai,1 Jianlan Sun,1 Hantong Hu,2 Huangwei Jiang,3 Ping Jin,3 Lifang Chen,2 Jianqiao Fang4 1The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Acupuncture, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Radiological, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4The Third Clinical Medical College of Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Lifang ChenDepartment of Acupuncture, The Third Affiliated Hospital of Zhejiang Chinese Medical University, No. 219 Moganshan Road, XiHu District, Hangzhou, Zhejiang, 310005, People’s Republic of ChinaEmail clfang@163.comJianqiao FangZhejiang Chinese Medical University, NO. 548 Binwen Road, Binjiang District, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaEmail fangjianqiao7532@163.comObjective: To verify the efficacy of electroacupuncture (EA) on classical trigeminal neuralgia (CTN), and to observe the brain functional status of patients with CTN and the intervention effects of EA on brain function by resting-state functional magnetic resonance imaging (rs-fMRI).Methods and Analysis: Thirty CTN patients will be randomly divided into EA combined with carbamazepine group and carbamazepine group in 2:1 ratio by using a random number table. Patients in EA combined with carbamazepine will receive EA treatment and carbamazepine for four weeks. The carbamazepine group will only receive carbamazepine treatment. VAS (visual analogue scale), HAMA (Hamilton Anxiety Scale), HAMD (Hamilton Depression Scale) and SF-36 (short form 36 health survey) will be performed before, after four-week treatments and at three-month follow-up in CTN patients. Six CTN patients will be randomly selected from EA combined with carbamazepine group and carbamazepine group, respectively, before treatment, and twelve paired healthy participants will be recruited at the same time. The twelve CTN patients will be scanned by rs-fMRI before and after treatment, and the healthy participants will be scanned by rs-fMRI only at baseline. Regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) analysis will be carried out to compare the dysfunctional brain regions between CTN patients and healthy participants, as well as the differences between two groups of patients with CTN after treatment.Trial Registration: ChiCTR-1900027873.Keywords: electroacupuncture, trigeminal neuralgia, pre-experimental, fMRI, randomized controlled trial, protocol

Introduction“Subclinical stage” of premature ovarian insufficiency (POI) refers to menstrual disorders with FSH levels in the range of 15-25 U/L in women under 40 years old caused by diminished ovarian function. Early intervention of subclinical POI may be able to protect ovarian function more effectively and prevent further development to POI. Currently, no standard-of-care exists for subclinical POI. Previous studies have shown effectiveness of electroacupuncture (EA) on POI and transcutaneous electrical acupoint stimulation (TEAS) on diminished ovarian reserve, but no published studies focus on the treatment of subclinical POI. This study aims to assess whether EA or TEAS will be effective in improving ovarian function at the subclinical stage of POI and preventing the progression.Methods114 subclinical POI patients between 25 and 40 years will be randomly assigned to three groups (an EA group, a TEAS group and a waiting for treatment group) in this randomized, controlled, assessor-blinded trial. The treatment will last for three months and the follow-up will last for twelve months. The primary outcomes will be anti-Mullerian hormone (AMH) and follicle-stimulating hormone (FSH). Secondary outcomes will include serum estradiol (E2), luteinizing hormone (LH), FSH/LH ratio, the menstrual status assessment, and modified Kupperman Menopausal Index. We will also investigate the incidence of adverse events.Trial registrationTrial was registered in the Chinese Clinical Trail Registry (ChiCTR-2100045598); Pre-results.

Benign prostatic hyperplasia (BPH) is characterized by symptoms such as frequent urination and difficulty in urination. Currently, treatment is mainly carried out using medications and surgery, but all of these methods can lead to certain adverse effects. In this case, a ninety-year-old male elderly patient came to our acupuncture clinic for treatment of urinary tract occlusion due to BPH. According to the patient's condition, we adopted the eletroacupuncture treatment protocol of Prof. Zhanglian Wang, a famous experienced Chinese medicine doctor. After six weeks of acupuncture treatment, the patient's urinary status improved significantly. This case suggests that acupuncture may be an effective complementary alternative therapy for BPH.

We previously reported that Plasmodium infection promotes antitumor immunity in a murine Lewis lung cancer. In this study, we investigated the effects of Plasmodium infection on the tumor inhibition and antitumor CD8+ T cell responses in a murine triple negative breast cancer (TNBCA) model. The results showed that Plasmodium infection significantly inhibited tumor growth, and increased the survival rate of the tumor-bearing mice. Both effector and memory CD8+ T cells were increased in peripheral blood and tumor-draining lymph node (DLN) in the infected mice. The co-stimulatory (CD40L, GITR and OX-40) and co-inhibitory (PD-1, CTLA-4, TIM-3, LAG3) immune checkpoints were up-regulated on CD8+ T cells in infected mice. Importantly, Py induced remarkable effects on the infiltration of CD8+ T cells in the tumor and granzym B+ CD8+ T cells in tumor-bearing mice while not in tumor-free mice. In summary, the results suggested that the effects of Plasmodium infection on murine 4T1 breast cancer might be related to the induction of CD8+ T cell-mediated antitumor immune responses. This finding may provide a novel strategy for the treatment of triple negative breast cancer.

We previously reported that Plasmodium infection promotes antitumor immunity in a murine Lewis lung cancer. In this study, we investigated the effects of Plasmodium infection on the tumor inhibition and antitumor CD8

Background A major challenge in the development of effective cancer immunotherapy is the ability of tumors and their microenvironment to suppress immune cells through immunosuppressive cells such as myeloid -derived suppressor cells and regulatory T cells. We previously demonstrated that Plasmodium infection promotes innate and adaptive immunity against cancer in a murine Lewis lung cancer model but its effects on immunosuppressive cells in the tumor microenvironment are unknown. Methods Whole Tumors and tumor-derived sorted cells from tumor-bearing mice treated with or without plasmodium infected red blood cells were harvested 17 days post tumor implantation and analyzed using QPCR, western blotting, flow cytometry, and functional assays. Differences between groups were analyzed for statistical significance using Student’s t-test. Results Here we found that Plasmodium infection significantly reduced the proportions of MDSCs and Tregs in the lung tumor tissues of the treated mice by downregulating their recruiting molecules and blocking cellular activation pathways. Importantly, CD8+ T cells isolated from the tumors of Plasmodium-treated mice exhibited significantly higher levels of granzyme B and perforin and remarkably lower levels of PD-1. Conclusion We reveal for the first time, the effects of Plasmodium infection on the expansion and activation of MDSCs and Tregs with a consequent elevation of CD8+T cell-mediated cytotoxicity within the tumor microenvironment and hold great promise for the development of effective immunotherapeutic strategies. Electronic supplementary material The online version of this article (10.1186/s12964-019-0342-6) contains supplementary material, which is available to authorized users.

Identification of novel chemotypes with antimalarial efficacy is imperative to combat the rise of Plasmodium species resistant to current antimalarial drugs. We have used a hybrid target-phenotype approach to identify and evaluate novel chemotypes for malaria. In our search for drug-like aspartic protease inhibitors in publicly available phenotypic antimalarial databases, we identified GNF-Pf-4691, a 4-aryl-N-benzylpyrrolidine-3-carboxamide, as having a structure reminiscent of known inhibitors of aspartic proteases. Extensive profiling of the two terminal aryl rings revealed a structure-activity relationship in which relatively few substituents are tolerated at the benzylic position, but the 3-aryl position tolerates a range of hydrophobic groups and some heterocycles. Out of this effort, we identified (+)−54b (CWHM-1008) as a lead compound. 54b has EC(50) values of 46 nM and 21 nM against drug sensitive Plasmodium falciparum 3D7 and drug resistant Dd2 strains, respectively. Furthermore, 54b has a long half-life in mice (4.4 h) and is orally efficacious in a mouse model of malaria (q.d.; ED(99) ~ 30 mg/kg/day). Thus, the 4-aryl-N-benzylpyrrolidine-3-carboxamide chemotype is a promising novel chemotype for malaria drug discovery.

Table S2. List of antibodies used for western blotting and the companies from which they were obtained. (DOCX 12 kb)

Table S1. List of primers used for qRT-PCR. (DOCX 161 kb)