What is the association between elevated baseline LH/FSH ratio and reproductive outcomes, especially ovulatory response, among Chinese women with polycystic ovary syndrome (PCOS) after ovulation induction.
To observe the clinical efficacy of acupuncture combined with auricular point sticking for menstrual headache and to discuss its mechanism.Eighty-five patients with menstrual headache were randomly divided into an observation group (43 cases) and a control group (42 cases). The observation group was treated with body acupuncture combined with auricular point sticking and the control group was treated with flunarizine hydrochloride capsules orally. The treatments of 3 menstrual cycles were required. The clinical efficacy was observed in the two groups. The content of serum prostaglandin F2α, (PGF2α) and plasma arginine vasopressin (AVP) in the menstrual periods of some patients randomly selected in the two groups was tested before and after treatment and was compared with that of 20 cases in a normal group. Results The total effective rate was 95.4% (41/43) in the observation group which was obviously superior to 81.0% (34/42) in the control group (P<0.01). Before treatment, the content of serum PGF2α and plasma AVP of patients in the two groups was higher than that in the normal group (all P<0.01). After treatment,the content of serum PGF2α and plasma AVP was lower than that before treatment in the two groups (P<0.01, P<0.05). The content of serum PGF2α in the observation group was decreased significantly compared with that in the control group (P<0.05) and returned to the level of the normal group.Body acupuncture combined with auricular point sticking achieves positive efficacy for menstrual headache and its mechanism could be related to regulating the abnormal levels of serum PGF2α and plasma AVP.
To investigate the influence of electroacupuncture (EA) on lipid metabolism in both sexes of obesity model rats.A total of 30 male and 30 female SD rats were randomized into normal control, model and EA groups respectively, with 10 rats in each group. EA (2 Hz, 1-2 mA) was applied to the ipsilateral "Zusanli" (ST 36)-"Sanyin-jiao"(SP 6) and bilateral "Fenglong" (ST 40) for 30 min, once daily for 28 days. In addition,"Quchi" (LI 11),"Zhongwan" (CV 12) and "Guanyuan" (CV 4) were punctured with filiform needles and stimulated by manipulating the needle for 1 min, separately. Obesity model was duplicated by subcutaneous injection of 15% glutamic sodium (0.2 mL/10 g) once daily for 5 days and by feeding the animal with high fat forage for 36 days. Lee's index was calculated, and plasma triglyeride (TG) concentration detected by glycerol-phosphoric acid oxidase-peroxydase method, total cholesterol (TC) detected by cholesterol oxidase method, and plasma low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) contents were assayed by one-step method, respectively.In both male and female rats, compared to their own normal groups, the Lee's index, plasma TG, TC and LDL-C contents were increased significantly and plasma HDL-C contents decreased obviously in the model groups (P<0.01), while compared to their own model groups, the Lee's index, plasma TG, TC and LDL-C levels in the EA groups were down-regulated considerably and plasma HDL-C contents up-regulated remarkably after the treatment (P<0.01, P<0.05). The efficacies of the EA intervention were obviously better in reducing Lee's index for male rats, and in down-regulating plasma TG and TC contents in female rats (P<0.05). No significant differences were found between male and female rats in EA intervention for plasma LDL-C and HDL-C levels.EA intervention can effectively regulate obesity rats' Lee's index and plasma TG, TC, LDL-C and HDL-C levels. The effects are different in male and female rats.
Gestational diabetes mellitus (GDM) is associated with a heightened level of oxidative stress, which is characterized by the overproduction of reactive oxygen species (ROS) from mitochondria. Previous studies showed that mitochondrial dysfunction is regulated by dynamin-related protein 1 (Drp1) and p66Shc in GDM.The aim was to investigate the expression of Drp1 and p66Shc and their possible mechanisms in the pathogenesis of GDM.A total of 30 pregnant women, 15 with GDM and 15 without GDM, were enrolled. Peripheral blood mononuclear cells and placental tissue were collected. The human JEG3 trophoblast cell line was cultivated in 5.5 mmol/L or 30 mmol/L glucose and transfected with wild-type (wt)-p66Shc and p66Shc siRNA. P66Shc and Drp1 mRNA levels were detected by quantitative real-time polymerase chain reaction. The expression of p66Shc and Drp1 was assayed by immunohistochemistry and western blotting. ROS was assayed by dihydroethidium staining.The p66Shc mRNA level was increased in the serum (P < 0.01) and placentas (P < 0.01) of women with GDM, and the expression of Drp1 mRNA and protein were also increased in placentas (P < 0.05). In JEG3 cells treated with 30 mmol/L glucose, the mRNA and protein expression of p66Shc and Drp1 were increased at 24 h (both P < 0.05), 48 h (both P < 0.01) and 72 h (both P < 0.001). ROS expression was also increased. High levels of Drp1 and ROS expression were detected in JEG3 cells transfected with wt-p66Shc (P < 0.01), and low levels were detected in JEG3 cells transfected with p66Shc siRNA (P < 0.05).The upregulated expression of Drp1 and p66shc may contribute to the occurrence and development of GDM. Regulation of the mitochondrial fusion-fission balance could be a novel strategy for GDM treatment.
Abstract Background Insulin resistance and hyperinsulinemia play a key role in the pathogenesis of polycystic ovary syndrome (PCOS), which is characterized by hyperandrogenism, ovulatory dysfunction, and presence of polycystic ovaries on pelvic scanning. Insulin resistance is significantly associated with the long-term risks of metabolic syndrome and cardiovascular disease. Berberine has effects on insulin resistance but its use in women with PCOS has not been fully investigated. In this paper, we present a research design evaluating the effects of berberine on insulin resistance in women with PCOS. Methods/design This is a multicenter, randomized, placebo-controlled and double-blind trial. A total of 120 patients will be enrolled in this study and will be randomized into two groups. Berberine or placebo will be taken orally for 12 weeks. The primary outcome is the whole body insulin action assessed with the hyperinsulinemic-euglycemic clamp. Discussion We postulate that women with PCOS will have improved insulin resistance following berberine administration. Trial registration This study is registered at ClinicalTrials.gov, NCT01138930 .
The design of research protocol and quality control are the key to ensure the quality of clinical trial. A randomized clinical trial regarding the effects of medication combined with acupuncture on live birth rate in polycystic ovary syndrome (PCOS), which was initially designed as a comparative effectiveness research, then added with an acupuncture control group and finally became a factorial analysis, is taken as an example to explain the protocol design and optimization process, demonstrating the high level of methodology design and international recognization. By a series of measurements, such as unified purchase of acupuncture equipment, multiple trainings and assessments for acupuncturists' knowledge and operation standardization, in-site supervision of local center experts, the standard operation of acupuncture could be ensured and the credibility and scientificity of research results could be improved.
Abstract Despite major advances in the treatment of estrogen receptor positive (ER+) breast cancer (BC), advanced disease continues to be the main cause of death from this disease. The role of the tumor immune microenvironment (TIME) in the progression of ER+ BC and its response to treatment is not completely understood. The aim of this study was to elucidate the role the TIME in the response of ER+ tumors to estrogen deprivation (ED). We collected samples from 215 postmenopausal patients with stage I-III ER+ BC, treated with letrozole for 2-4 weeks, to induce ED. We used AQUA on pre-treatment biopsies and on-treatment surgical biopsies to assess ER, PR, HER2, and Ki67. Then, we categorized the patients’ response to ED based on the Ki67 score in on-treatment samples: ED-sensitive (ED-S) if natural log (ln) of the Ki67 score ≤1.0 or ≤2.7% Ki67+ cells vs. ED-resistant (ED-R) if ln ≥2.0 or ≥7.4% Ki67+ cells. Firstly, we assessed TIME composition by investigating stromal tumor-infiltrating lymphocytes (sTILs) in H&E-stained FFPE of on-treatment tumor sections. ED-R tumors exhibited a significantly higher stromal TILs score (p=0.0001) relative to ED-S tumors. We next prepared tissue microarrays from 227 (on-treatment) surgical sections and subjected them to cyclic immunofluorescence (CycIF) with 38 antibodies to examine their intra-tumoral immune cell infiltration. From each tumor core, we segmented single cells and labeled them as immune, cancer, or stromal cells based on expression of a set of markers. Briefly, cells that stained strongly for CD45 (leukocyte marker), and/or CD4 (T lymphocyte marker), or CD68 (macrophage marker) were labeled immune cells. CD45/CD4/CD68-negative cells were categorized as tumor if E-cadherin and/or cytokeratin-positive, or stromal cells if -negative. Next, we assessed cell specific spatial enrichment by quantifying the expression of immune markers in the area immediately adjacent to each tumor cell. Immune-suppressive T-reg (FOXP3+) cells were enriched in the ED-S tumors (p=0.0004), as well as PD1+ (exhausted) T cells (p=0.0004), and CD68+ cells (p < 0.0001) compared to ED-R tumors. ED-R tumors exhibited higher CD20+ B cells (p < 0.0001), higher CD8+ T cells (p=0.0329), in addition to higher CD45+ cells (p < 0.0001), compared to ED-S tumors. RNA-sequencing of the same surgical samples showed a higher T cells cytolytic score in ED-R relative to ED-S (p=0.0058), suggesting enhanced CD8+ T cells activity, in addition to their higher infiltration. We are currently analyzing letrozole-induced changes in TIME composition using Geomix digital spatial profiler in paired pre- and on-treatment biopsies from ED-R and ED-S tumors and will be presented at the meeting. Consistent with the CycIF findings, GSEA of hallmark gene signatures from bulk RNA-sequencing of treated tumors revealed that immune-related gene sets, such as “IFN α response”, “IFNɣ response”, and “allograft rejection” were upregulated in ED-R vs. ED-S cancers. ED-R tumors showed enrichment of CXCL9, CXCL10, and CXCL11 chemokines and their receptor, CXCR3. Publicly available datasets of patients with ER+ breast cancers showed that higher expression CXCL9 (HR 1.36; p=0.016), CXCL10 (HR 1.71; p< 0.0001), and CXCL11 (HR 1.5; p=0.0016) are predictive of shorter relapse-free survival on antiestrogen therapy. We are currently investigating whether these chemokines play a causal role in resistance to ED, and if this is phenocopied by co-cultures of ER+ BC cells and CD8+ T-cells. Conclusions ED-resistant tumors are enriched with stromal TILs and exhibit higher immune cell intra-tumoral infiltration and CD8+T cells cytolytic activity compared to ER+ tumors sensitive to estrogen suppression. In contrast, ED-S tumors showed a more immunosuppressed milieu. The role of CXCL9, CXCL10 and CXCL11 in inducing resistance to ED warrants further investigation. Citation Format: Fabiana Napolitano, Yunguan Wang, Dhivya Sudhan, Paula Gonzalez-Ericsson, Luigi Formisano, Lei Guo, M Rosario Chica-Parrado, Chang-Ching Lin, Kyung-Min Lee, Hongli Ma, Nathaniel Evans, Alberto Servetto, Saurabh Mendiratta, Spencer Barnes, Yisheng Fang, Lin Xu, Justin Balko, Gordon Mills, Marilyne Labrie, Ariella Hanker, Carlos Arteaga. Tumor immune microenvironment modulates resistance to estrogen suppression in ER+ breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS03-04.
Hepatitis C virus (HCV) genotype (GT) distribution in China shows significant geographical and demographic difference. As a routinely tested virus in Chinese blood bank systems, rare molecular epidemiology research in blood donors is reported. Our purpose is to investigate the HCV GT/subtypes distribution, phylogenetic analysis and population genetics in Chinese blood donors. Anti-HCV screen positive samples and donor demographics were collected. HCV Core and E1 gene fragments were amplified by RT-PCR, followed by sequencing and phylogenetic analysis to determine HCV GTs/subtypes using MEGA 7.0. The population genetics were performed using Arlequin v3.0 and Beast v1.10.4. SPSS Statistics 17.0 software was used to analyze the correlation between HCV GTs/subtypes distribution and demographic characteristics. 419 and 293 samples based on Core and E1 gene respectively were successfully amplified. HCV la, lb, 2a, 3a, 3b, 6a, 6e and 6n were found, and the corresponding proportions were 0.66% (3/455), 58.68% (267/455), 17.80% (81/455) and 5.05% (23/455), 3.52% (16/455), 12.31% (56/455), 0.88% (4/455) and 0.66% (3/455). Samples from Guangxi showed the most abundant genetic diversity with 8 subtypes were found. The number of haplotypes in HCV-1b is higher than 2a and 6a. The negative Tajima's D and Fu's Fs values of HCV-1b, 2a and 6a suggested the population expansion of those HCV subtypes. The distribution of HCV GT showed significant statistical difference by age and ethnicity. Conclusion: An abundance of HCV genetic diversity was found in Chinese blood donors with mainly 1b and then 2a subtype. There were significant geographical and demographic differences in HCV GTs/subtypes among Chinese blood donors. HCV subtype 1b has stronger viability and HCV subtype 6a has experienced significant expansion.
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