Effect of type of carrier material on the in vitro properties of solid dispersions of progesterone / 药学学报

This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.

Research advance in progesterone therapy for endometrial cancer / 中国临床药理学与治疗学

Endometrial cancer originates from the endometrium and is one of the common gynecologic malignancies, with its incidence and mortality rate increasing year by year. Although endometrial cancer is more prevalent in the peri- and postmenopausal female population, it has been an evident trend in recent years towards younger patients. For young patients who have not yet given birth but intend to do so, the application of progestins in endometrial cancer treatment has made significant progress in clinical practice. Considering the existence of large individual differences and unclear mechanisms of action in the clinical application of progestins, this paper aims to provide an overview of the current clinical application status, efficacy, hormone resistance, and its mechanisms in the context of hormone therapy.

Role of sex hormones in keratoconus and potential therapeutic targets / 国际眼科杂志(Guoji Yanke Zazhi)

Keratoconus is a blinding corneal disease characterized by central or paracentral corneal thinning and conical ectasia, and usually happens in adolescence. Currently, the etiology of keratoconus is unclear. Multiple studies have identified an association between genetics, eye rubbing, allergic diseases, ultraviolet exposure and keratoconus. Recently, several studies identified that sex hormones also played important roles in the pathogenesis of keratoconus. The disturbance of sex hormones may increase the risk of occurrence and progress of keratoconus. This review aims to summarize the pathophysiological effects of sex hormones on the cornea, clarify the effects of sex hormones on keratoconus and its related inflammatory or immune mechanisms, and explore the role of sex hormones in the early diagnosis and treatment of keratoconus, providing reference and help for clinical work.

Contraindicated use of modern contraceptives among mothers from a Pelotas Birth Cohort

ABSTRACT OBJECTIVE To describe the prevalence of contraindicated use of combined hormonal contraceptives, progesterone-only contraceptives, and intrauterine devices in mothers participating in the 2015 Pelotas Birth Cohort according to the WHO medical eligibility criteria. METHODS The biological mothers of children belonging to the 2015 Pelotas birth cohort who attended the 48-month follow-up were studied. The 48-month follow-up data were collected from January 1, 2019, to December 31, 2019. Contraindicated use of modern contraceptives was considered to occur when these women presented at least one of the contraindications for the use of modern contraceptives and were using these methods. The prevalence of contraindicated use was calculated according to each independent variable and their respective 95% confidence intervals (95%CI). RESULTS The analyzed sample consisted of 3,053 women who used any modern contraceptive method. The prevalence of contraindicated use of modern contraceptives totaled 25.9% (95%CI: 24.4-27.5). Combined hormonal contraceptives showed the highest prevalence of contraindicated use (52.1%; 95%CI: 49.3-54.8). The prevalence of contraindicated use of modern contraceptives methods was greater in women with family income between one and three minimum wages, a 25-30 kg/m2 body mass index, indication by a gynecologist for the used method, and purchasing the contraceptive method at a pharmacy. The higher the women's education, the lower the prevalence of inappropriate use of modern contraceptives. CONCLUSION In total, one in four women used modern contraceptives despite showing at least one contraindication. Policies regarding women's reproductive health should be strengthened.

Comparing the effects of serum GPER-1 and oxidant/antioxidant levels on retinopathy in patients with diabetes and healthy individuals: a pilot study / Comparando o impacto do soro GPER-1 e dos níveis de oxidante/antioxidante na retinopatia em pacientes diabéticos e em indivíduos saudáveis: um estudo piloto

ABSTRACT Purpose: This study aimed to determine the effect of serum G receptor-mediated protein-1 levels on the development of retinopathy in patients with diabetes in comparison with healthy individuals. Methods: The study enrolled patients with diabetic retinopathy (Group 1), patients without diabetic retinopathy (Group 2), and healthy individuals (Group 3). Levels of serum progesterone, serum G receptor-mediated protein-1, estradiol, oxidant/antioxidants, and thyroid-releasing hormones were analyzed and compared among the groups. Post-hoc analysis was performed to compare the subgroups in which significant differences were found. Results: Groups 1, 2, and 3 each included 40 patients. A significant difference was found among all groups in terms of serum G receptor-mediated protein-1, oxidant/antioxidant, and estradiol levels (p<0.01), but no significant difference was found in terms of thyroid-releasing hormone or progesterone (p=0.496, p=0.220, respectively). In the post-hoc analysis of the groups with significant differences, another significant difference was found among all groups for serum G receptor-mediated protein-1 and oxidant/antioxidant levels (p<0.05). Serum G receptor-mediated protein-1 and oxidant levels were positively correlated, whereas serum G receptor-mediated protein-1 and antioxidant levels were negatively correlated (r=0.622/p<0.01, r=0.453/p<0.01, r=0.460/p<0.01, respectively). The multiple regression analysis showed that increased levels of serum G receptor-mediated protein-1 may help prevent diabetic retinopathy. Conclusions: Serum G receptor-mediated protein-1 levels, which were the highest in the diabetic retinopathy Group, increased as the oxidant/antioxidant balance changed in favor of oxidative stress. This appears to be a defense mechanism for preventing neuronal damage.

RESUMO Objetivo: Esta pesquisa buscou determinar o im­pacto dos níveis de proteína G sérica no desenvolvimento da retinopatia em pacientes diabéticos, comparando-os a indivíduos saudáveis. Métodos: Foram incluídos, no estudo, 40 pacientes com retinopatia diabética (Grupo 1), 40 pacientes sem retinopatia diabética (Grupo 2) e 40 indivíduos saudáveis (Grupo 3). Os níveis hormonais de progesterona sérica, de proteína G sérica, estradiol, oxidante/antioxidante e hormônio liberado pela tireoide foram analisados e comparados. A análise post hoc foi realizada para comparar os subgrupos nos quais diferenças estatisticamente significativas foram encontradas. Resultados: Uma diferença significativa foi encontrada entre todos os grupos em termos de proteína G sérica, oxidante/antioxidante e níveis de estradiol (p<0.01), mas nenhuma diferença significativa foi encontrada em termos de hormônio liberado pela tireoide ou progesterona (p=0,496, p=0,220, respectivamente). Na análise post hoc dos grupos com diferenças estatisticamente significativas, outra diferença significativa foi encontrada entre todos os grupos para proteína G sérica e níveis oxidantes/antioxidantes (p<0,05). Os níveis de proteína G sérica e os níveis de oxidante foram positivamente correlacionados, enquanto os níveis de proteína G sérica e os níveis de antioxidantes foram negativamente correlacio­nados (r=0,622/p<0,01, r=0,453/p<0,01, r=0,460/p<0,01, respectivamente). A análise de regressão múltipla mos­trou que o aumento da proteína G sérica pode ajudar a prevenir a retinopatia diabética. Conclusões: Os níveis de proteína G sérica que eram mais altos no grupo de retinopatia diabética, aumentaram à medida que o equilíbrio oxidante/antioxidante mudou em favor do estresse oxidativo. Este parece ser um mecanismo de defesa para prevenir danos neuronais.

Expression and clinical significance of miR-141-5p as a biomarker in the serum of patients with early spontaneous abortion

Abstract Aim miR-141-5p expression in patients with Early Spontaneous Abortion (ESA) and its correlation with hormone levels during pregnancy were investigated. Methods A total of 70 pregnant women with ESA were selected as the research group, and 70 normal pregnant women who chose abortion for non-medical reasons were selected as the Con group. Serum β-HCG, Progesterone (P), and Estrogen (E2) were detected by enzyme-linked immunosorbent assay. Differentially expressed miRNAs were screened by miRNA microarray analysis. miR-141-5p expression was detected by RT-qPCR, and its correlation with serum β-HCG, P, and E2 levels was analyzed. The diagnostic value of miR-141-5p for ESA was evaluated by the ROC curve. Results Serum β-HCG, P, and E2 were decreased and serum miR-141-5p was increased in patients with ESA. Pearson correlation analysis showed that serum β-HCG, P, and E2 levels were negatively correlated with miR-141-5p expression levels. ROC curve showed that miR-141-5p had a diagnostic value for ESA. Conclusions miR-141-5p is related to hormone levels during pregnancy and is expected to become a new candidate diagnostic marker for ESA.

Postnatal Exposure to Exogenous progesterone Exacerbates the Prenatally-Induced Abnormal Sperms Production and Function in Rats / La exposición Posnatal a la Progesterona Exógena Exacerba la Producción y Función Anormales de Espermatozoides Inducidas Prenatalmente en Ratas

SUMMARY: This study aimed at clarifying the impact of long-term prenatal and postnatal exposure to exogenous progesterone on sperm production and function, relative sex organs weights, and the levels of the relevant hormones in rats. Sixty male Wistar rats were included and classified into three groups (n=20 in each). A test I group had mature rats born to dams treated with progesterone prenatally. A test II group included rats exposed to progesterone during prenatal as well as postnatal periods, and a control group had rats treated with a placebo (olive oil). The test groups revealed a significant reduction in sperm count, motility, and viability with higher abnormal forms than the control group (P< 0.05). Similarly, the test groups revealed significantly lower serum testosterone and higher FSH and LH levels (P< 0.001). Interestingly, the test II group showed pronounced sperm abnormalities, an alarming decrease in sperm viability and motility, and a significant accretion in the relative testicular weight compared to the test I group (p <0.001). Long-term (prenatal and early postnatal) treatment with synthetic progesterone hurts sperm quantity and quality, adversely affecting future male fertility.

Este estudio tuvo como objetivo aclarar el impacto de la exposición prenatal y posnatal a largo plazo a la progesterona exógena en la producción y función de los espermatozoides, el peso relativo de los órganos sexuales y los niveles de las hormonas relevantes en ratas. Sesenta ratas macho Wistar fueron incluidas y clasificadas en tres grupos (n=20 en cada uno). Un grupo de prueba I tenía ratas maduras nacidas de madres tratadas con progesterona prenatalmente. Un grupo de prueba II incluyó ratas expuestas a progesterona durante los períodos prenatal y posnatal, y un grupo de control tenía ratas tratadas con un placebo (aceite de oliva). Los grupos de prueba revelaron una reducción significativa en el recuento, la motilidad y la viabilidad de los espermatozoides con formas anormales más altas que el grupo de control (P < 0,05). De manera similar, los grupos de prueba revelaron niveles significativamente más bajos de testosterona sérica y niveles más altos de FSH y LH (P < 0.001). Curiosamente, el grupo de prueba II mostró anormalidades espermáticas pronunciadas, una disminución alarmante en la viabilidad y motilidad de los espermatozoides y una acumulación significativa en el peso testicular relativo en comparación con el grupo de prueba I (p <0.001). El tratamiento a largo plazo (prenatal y posnatal temprano) con progesterona sintética daña la cantidad y la calidad del esperma, lo que afecta negativamente la futura fertilidad masculina.

Evaluation the Effect of Ginseng Plant Root Extract on Complications of Azathioprine on Ovarian Follicles and TSH, LH and Progesterone Hormones in Rats

Background: The search for herbal remedies has gained significant attention due to chemical drugs’ potentially harmful side effects. Finding plants that can mitigate these adverse effects is crucial for enhancing the well-being of individuals undergoing chemical drug treatments. Aim: Numerous studies have demonstrated the potent antioxidant properties of ginseng. Azathioprine, a widely used drug, has been shown to induce detrimental side effects on various body tissues. Thus, this study aimed to assess the efficacy of ginseng in reducing the harmful effects of azathioprine on ovarian tissue. Materials and Methods: In this study, mice were divided into groups and injected with ginseng root extract and azathioprine. Ovarian weight and histological analysis were conducted to evaluate the number of ovarian follicles and corpus luteum. Furthermore, the levels of FSH, LH, and progesterone in the blood of the study groups were assessed using ELISA. Results: In treatment group 4 (ginseng extract and azathioprine), compared to treatment group 2 (azathioprine only), a significant increase in the weight of both left and right ovaries was observed. Treatment group 4 also exhibited a notable increase (P<0.05) in the number of primordial, primary, and atretic follicles. The concentration of progesterone significantly increased in treatment group 4 compared to treatment group 2 (p<0.01). Conclusion: The findings of this study indicate that azathioprine can have destructive effects on ovarian tissues, while ginseng extract demonstrates the potential to reduce these detrimental side effects. Furthermore, ginseng extract appears to positively regulate FSH and progesterone hormones.

Immunofluorescence Analysis of Estrogen and Progesterone Receptors and Ki-67 Nuclear Protein in Canine Uteri Treated with Medroxyprogesterone Acetate During Anestrus / Análisis de Inmunofluorescencia de Receptores de Estrógeno y Progesterona y Proteína Nuclear Ki-67 en Úteros Caninos Tratados con Acetato de Medroxiprogesterona Durante el Anestr

SUMMARY: Estradiol and progesterone receptors play an essential role in the changes occurring in the uterus during the estrus cycle in dogs (Canis lupus familiaris). In order to investigate the potential effect of progestational agent medroxyprogesterone acetate (MPA) when is used during anestrus on the expression of estradiol receptors [ER], progesterone receptors [PR] and nuclear protein Ki67, we evaluated uterine tissue immunohistochemically. Uteri were grouped as nulliparous (control, n=11), multiparous (n=11) and treated with MPA (n=11; nulliparous with two treatments; 5mg/kg; i.m.). The amount and location of PR, ER and Ki67 were studied on the epithelial surface, apical and basal regions of the endometrium and myometrium using immunohistochemical techniques with a spectral confocal microscope and analyzed by ANOVA. Differences in ER were observed between the multiparous and MPA-treated groups in the apical region of the endometrium (p=0.0022). Differences in cell proliferation were detected between the nulliparous and multiparous groups (p=0.0037) and nulliparous and MPA-treated groups (p=0.0003) in the basal region of the endometrium. In conclusion, two doses of MPA (5mg/kg; i.m.) do not have a significant effect on the expression of ER and PR; however, they inhibit cell proliferation in the basal region of the endometrium, which includes the stroma, subepithelial cell layer, compact layer, and spongy layer. The clinical and long-term effect of this treatment should be evaluated in subsequent studies.

Los receptores de estradiol y progesterona juegan un rol fundamental en los cambios que se producen en el útero durante el ciclo estral de las perras (Canis lupus familiaris). El objetivo de este estudio fue evaluar las expresiones de ER-a y PR en el útero y la proliferación de células endometriales detectando la expresión nuclear de la proteína Ki67 en perras expuestas a la progestina sintética MPA y compararlas con perras nulíparas y multíparas expuestas a progesterona luteal. Úteros fueron agrupados como nulíparas (control, n=11), multíparas (n=11) y tratadas con MPA (n=11; nulíparas con dos tratamientos; 5 mg/kg; i.m.). La expresión de PR, ER-a y Ki67 fue evaluada en la regiones apicales y basales del endometrio y miometrio con un microscopio confocal espectral. Se observó diferencias en ER-a entre los grupos multíparas y tratados con MPA en la región apical del endometrio (p=0,0022). Se detectaron diferencias en la proliferación celular entre los grupos de nulíparas y multíparas (p=0,0037) y los grupos de nulíparas y tratados con MPA (p=0,0003) en la región basal del endometrio. En conclusión, dos dosis de MPA (5mg/kg; i.m.) no tienen un efecto significativo sobre la expresión de ER y PR; sin embargo, inhiben la proliferación celular en la región basal del endometrio, el cual incluye a estroma, capa de células subepiteliales, estratos compacto y esponjoso. El efecto clínico a largo plazo de este tratamiento debe ser evaluado en estudios posteriores.

A logarithmic model for hormone receptor-positive and breast cancer patients treated with neoadjuvant chemotherapy

SUMMARY OBJECTIVE: The aim of this study was to investigate the predictive importance of the previously validated log(ER)*log(PgR)/Ki-67 predictive model in a larger patient population. METHODS: Patients with hormone receptor positive/HER-2 negative and clinical node positive before chemotherapy were included. Log(ER)*log(PgR)/Ki-67 values of the patients were determined, and the ideal cutoff value was calculated using a receiver operating characteristic curve analysis. It was analyzed with a logistic regression model along with other clinical and pathological characteristics. RESULTS: A total of 181 patients were included in the study. The ideal cutoff value for pathological response was 0.12 (area under the curve=0.585, p=0.032). In the univariate analysis, no statistical correlation was observed between luminal subtype (p=0.294), histological type (p=0.238), clinical t-stage (p=0.927), progesterone receptor level (p=0.261), Ki-67 cutoff value (p=0.425), and pathological complete response. There was a positive relationship between numerical increase in age and residual disease. As the grade of the patients increased, the probability of residual disease decreased. Patients with log(ER)*log(PgR)/Ki-67 above 0.12 had an approximately threefold increased risk of residual disease when compared to patients with 0.12 and below (odds ratio: 3.17, 95% confidence interval: 1.48-6.75, p=0.003). When age, grade, and logarithmic formula were assessed together, the logarithmic formula maintained its statistical significance (odds ratio: 2.47, 95% confidence interval: 1.07-5.69, p=0.034). CONCLUSION: In hormone receptor-positive breast cancer patients receiving neoadjuvant chemotherapy, the logarithmic model has been shown in a larger patient population to be an inexpensive, easy, and rapidly applicable predictive marker that can be used to predict response.

Papel de las hormonas progesterona, estradiol y oxitocina en la función del miometrio durante el embarazo y el trabajo de parto / Role of progesterone, estradiol and oxytocin hormones in myometrial function during pregnancy and labor

Resumen El trabajo de parto es la transición de un estado de inactividad y relajación muscular a un estado de excitación, en el cual la capa muscular del útero (miometrio) realiza crecientes contracciones coordinadas para llevar a cabo la expulsión del feto y la placenta. Durante el inicio del trabajo de parto, el miometrio experimenta una serie de cambios fisiológicos, bioquímicos y moleculares, pasando de un estado de quiescencia a un fenotipo contráctil que inducirá el parto. En parte, esto es provocado por la acción de las hormonas progesterona, estradiol y oxitocina. En general, la progesterona mantiene la quiescencia del miometrio durante el embarazo al inhibir la expresión de moléculas proinflamatorias y proteínas asociadas a la contracción, mientras que al término del embarazo, el estradiol induce la expresión de dichas moléculas. Por su parte, la oxitocina induce un aumento en la concentración de calcio intracelular para llevar a cabo las contracciones de los miocitos uterinos. El objetivo del presente trabajo es presentar un resumen acerca de los mecanismos moleculares involucrados en la regulación de la actividad de las células miometriales por medio de las hormonas progesterona, estradiol y oxitocina, así como discutir las perspectivas de esta interesante área de investigación.

Abstract Labor is the transition from a state of inactivity and muscle relaxation to a state of muscle excitation, in which the muscular layer of the uterus (myometrium) performs increasingly coordinated contractions to deliver the fetus and expel the placenta. During the onset of labor, the myometrium undergoes a series of physiological, biochemical, and molecular changes, allowing the tissue to transition from a quiescent state to a contractile phenotype that will support labor. This is partly caused by the action of the hormones progesterone, estradiol, and oxytocin. In general, progesterone maintains the quiescence of the myometrium during pregnancy by decreasing the expression of proinflammatory molecules and contraction-associated proteins. In contrast, at the end of pregnancy, estradiol induces the expression of these molecules. For its part, oxytocin induces an increase in intracellular calcium concentration to carry out the contractions of uterine myocytes. The objective of this review is to present a summary of the molecular mechanisms involved in regulating myometrial cell activity through the hormones progesterone, estradiol and oxytocin, as well as to discuss the perspectives of this exciting area of research.

Expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2/neu in gallbladder carcinoma in North Indian population

Background: Gallbladder carcinoma (GBC) although rare is most frequent malignant neoplasm of biliary tract system and sixth most common malignancy of digestive tract. GBC is more common in females and there are studies which show expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 neu (HER2/neu) in GBC suggesting possible molecules for targeted therapy, but results are inconsistent. Aims and Objectives: The aim of this study was to find out expression of ER, PR, and HER2/neu in GBC in North Indian population and their possible association with clinicopathological features. Materials and Methods: A total 59 resected cases of GBC diagnosed by histopathological examination were included in the study. Expression of ER, PR, and HER2/neu was accessed by immunohistochemistry method and correlated with various clinicopathological features. Results: ER expression was absent in all GBC cases. PR expression was present in only one case. Positive expression of HER2/neu was present in 13 (22%) cases, in which 12 cases were of conventional adenocarcinoma and one case was of papillary adenocarcinoma. Well and moderately differentiated tumor had significantly higher HER2/neu expression as compared to poorly differentiated tumors (P = 0.001). Pre-obese patients had significantly higher HER2/neu expression as compared to non-obese patients (P = 0.008). Conclusion: In our study, there was no expression of estrogen and PR in GBC in North Indian population. Although small in number, there is a subset of patients who overexpress HER2/neu receptor that may benefit from targeted therapy.

Perda gestacional de repetição e o papel dos progestagênios: evidências atuais / Recurrent pregnancy loss and the role of progestagens: current evidence

Objetivo: Discutir o uso dos progestagênios em mulheres com perda gestacional de repetição (PGR) sem causa aparente, abordando tipos de progestagênios e resultados de ensaios clínicos, revisões sistemáticas e metanálises. Métodos: Trata-se de uma revisão não sistemática de artigos publicados nas bases eletrônicas PubMed, Cochrane e SciELO nos últimos cinco anos, utilizando-se os seguintes descritores: "progesterone", "dydrogesterone", "recurrent pregnancy loss" e "recurrent abortion". Resultados: Duas grandes metanálises encontraram uma redução da taxa de abortamento e aumento da taxa de nascidos vivos com o uso do progestágeno sintético em pacientes com PGR inexplicada, porém essa conclusão foi contestada em uma metanálise mais recente. Entretanto, a progesterona vaginal micronizada poderia aumentar a taxa de nascidos vivos em mulheres com ameaça de aborto e com história de um ou mais abortos anteriores (risco relativo [RR]: 1,08, intervalo de confiança [IC] de 95%: 1,02-1,15). O benefício foi maior no subgrupo de mulheres com três ou mais perdas anteriores. Conclusão: Ainda restam dúvidas sobre o uso de "progesterona" nas pacientes com PGR inexplicada. Sua administração deve ser discutida individualmente com cada mulher, levando-se em conta especialmente a idade materna, o número de abortos prévios e a história de sangramento na gestação em curso, evitando-se tratamentos que trazem custos e não são isentos de efeitos colaterais.(AU)

Objective: To discuss the use of progestins in women with recurrent pregnancy loss (RPL) with no apparent cause, addressing types of progestins, and results of clinical trials, systematic reviews, and meta-analyses. Methods: This is a non-systematic review of articles published in the PubMed, Cochrane, SciELO electronic databases in the last five years, using the following descriptors: "progesterone", "dydrogesterone", "recurrent pregnancy loss", and "recurrent abortion". Results: Two large meta-analyses found a reduction in the rate of miscarriage, and an increase in the rate of live births with the use of synthetic progestin in patients with unexplained RPL, but this conclusion was challenged in a more recent meta-analysis. However, micronized vaginal progesterone could increase the rate of live births in women with a threatened miscarriage and a history of one or more previous miscarriages (RR: 1.08, 95% CI: 1.02-1.15). The benefit was greatest in the subgroup of women with three or more previous losses. Conclusion: There are still doubts about the use of "progesterone" in patients with unexplained RPL. Its administration should be discussed individually with each woman, taking into account especially the maternal age, number of previous abor tions, and history of bleeding during pregnancy, avoiding treatments that bring costs and are not free from side effects.(AU)

Effectiveness of Zhenqi Buxue Oral Liquid Combined with Progesterone for Treatment of Oligomenorrhea and Hypomenorrhea with Qi-Blood and Kidney (Shen) Essence Deficiency: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the effectiveness and safety of Zhenqi Buxue Oral Liquid (ZQ), progesterone capsules, and their combination in treating oligomenorrhea and hypomenorrhea with qi-blood and Kidney (Shen) essence deficiency.@*METHODS@#This was a prospective, randomized, multi-center controlled trial between June 2022 to December 2022. Ninety-six oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency were randomly assigned to receive ZQ (ZQ group, 29 cases), progesterone capsules (PG group, 32 cases), or the combined Chinese and Western medicine (COM group, 31 cases) at a ratio of 1:1:1. Patients in the ZQ or PG group took daily 10 mL twice a day of ZQ or 200 mg once a day of progesterone capsules for 10 consecutive days on day 15 of the menstrual cycle respectively, and patients in the COM group received the same ZQ combined with progesterone capsules. The treatment course lasted for 3 months and follow-up was performed at 1 and 3 months after the end of treatment. Primary endpoint was the menstrual Traditional Chinese Medicine Syndrome Scale (TCMSS) scores. Secondary endpoints included pictorial blood loss assessment chart (PBAC) scores, clinical efficacy rate, 36-item Short Form Health Survey (SF-36) scores, sex hormones and thickness of endometrium. Adverse events (AEs) were recorded.@*RESULTS@#TCMSS scores after 1- and 3-month treatment in all groups were significantly lower than those at baseline (P<0.05). Only TCMSS scores after 3-month treatment in the ZQ and COM groups continuously decreased compared with those after 1-month treatment in the same group (P<0.01). TCMSS scores after 3-month treatment in the ZQ and COM groups were significantly lower than those in the PG group (P<0.05, P<0.01). Compared with baseline, PBAC scores in the ZQ and COM groups after 3 months of treatment were also significantly higher (both P<0.01). The total effective rates of TCM syndrome of 3-month treatment were significantly improved in all groups compared with that after 1 month of treatment (P<0.05). The total effective rate of the COM group was the highest in the 3rd month of treatment and significantly higher than that of PG group alone (P<0.05). Compared with baseline, only the SF-36 scores of COM group were significantly improved after 3 months of treatment (P<0.05). No serious adverse reactions were observed after treatment.@*CONCLUSIONS@#The combination of ZQ and PG, or ZQ only had better effects on reducing TCMSS scores compared with PG, and COM showed the higher total effective rate compared with monotherapy. Besides, COM could effectively improve menstrual blood loss and quality of life. ZQ combined with PG may be an effective and safe option for oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency.

Efficacy of Chinese medicine Kuntai capsule combined with sequential estrogen progesterone therapy in treatment of early-onset ovarian dysfunction / 中华全科医师杂志

Clinical data of 102 patients with premature ovarian failure admitted to Zhang Zhongjing Hospital from December 2018 to December 2021 were retrospectively analyzed. Fifty-one patients received (control group), and another 51 patients received Chinse medicine Kuntai capsule in addition to sequential estrogen progesterone therapy(study group); both groups were treated for 3 menstrual cycles. After treatment, the total effective rate of the study group was higher than that of the control group (94.1% (48/51) vs. 72.6% (37/51), χ2=4.07, P=0.044). After treatment, the proportion of patients with mild Kupperman score and serum estradiol level in both groups were increased, and the proportion in study group was higher than that in the control group. The proportion of patients with moderate and severe Kupperman score and the total score decreased after treatment in both groups, and the proportion of patients with moderate Kupperman score in the study group was lower than that in the control group. Serum luteinizing hormone and folliclestimulating hormone levels were significantly decreased, and the levels in study group were lower than those in the control group. The levels of resistance index and PI were significantly decreased after treatment in both group and the study group decrease more markedly (all P<0.05). The peak systolic flow velocity level was increased after treatment in both groups and the study group increased more markedly (all P<0.05). It is suggested that the application of Chinese medicine Kuntai capsule combined with sequential estrogen progesterone therapy can effectively improve the clinical therapeutic effect, stabilize sex hormones, uterine microcirculation and effectively alleviate the condition of patients with premature ovarian failure.

Effects of Qingruxiao granules combined with tamoxifen on mammary hyperplasia and its effects on serum hypoxia inducible factor-1α, angiopoietin-2 and prolactin levels / 中国基层医药

Objective:To investigate the efficacy of Qingruxiao granules combined with tamoxifen in the treatment of breast hyperplasia and its effect on serum hypoxia-inducible factor-alpha (HIF-α), angiopoietin-2 (Ang-2) and prolactin (PRL) levels. Methods:Ninety-eight patients with breast hyperplasia admitted to Xi'an No.3 Hospital from June 2020 to January 2022 were retrospectively included in this study. They were divided into control and observation groups ( n = 49/group) according to different treatments. The control group was treated with tamoxifen alone. The observation group was treated with Qingruxiao granules combined with tamoxifen. Clinical efficacy, symptom score, ultrasound parameters (glandular layer thickness, longest diameter of mass, maximum diameter of hypoechoic area, inner diameter of lactating tube), endocrine hormone levels (estradiol, progesterone, and prolactin), HIF-α, and Ang-2 pre- and post-treatment, as well as the incidence of adverse reactions were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [93.88% (4/49) vs. 77.55%, χ2 = 5.33, P < 0.05). After treatment, breast mass score, breast pain, systemic accompanying symptom, and nipple discharge in the observation group were (1.34 ± 0.29) points, (1.02 ± 0.36) points, (0.68 ± 0.17) points, (0.97 ± 0.15) points, respectively, which were significantly lower than (1.57 ± 0.23) points, (1.45 ± 0.41) points, (0.95 ± 0.26) points, and (1.28 ± 0.26) points, respectively, in the control group ( t = 4.35, 5.52, 6.08, 7.23, all P < 0.001). The glandular layer thickness, the longest diameter of mass, the maximum diameter of hypoechoic area, and the inner diameter of lactating duct in the observation group were (9.45 ± 1.67) mm, (11.46 ± 3.68) mm, (14.37 ± 4.22) mm, and (1.23 ± 0.39) mm, respectively, which were significantly lower than (11.26 ± 2.51) mm, (16.33 ± 4.01) mm, (19.87 ± 5.01) mm, (1.54 ± 0.48) mm in the control group ( t = 4.20, 2.26, 5.88, 3.51, all P < 0.001). Serum estradiol and prolactin levels in the observation group were (122.35 ± 29.76) ng/L and (205.64 ± 36.42) IU/L, respectively, which were significantly lower than (139.76 ± 30.48) ng/L and (251.49 ± 41.87) IU/L in the control group ( t = 2.86, 5.78, both P < 0.05). Serum progesterone level in the observation group was (9.22 ± 1.57) μg/L, which was significantly higher than (7.18 ± 1.21) μg/L in the control group ( t = -7.20, P < 0.05). Serum HIF-α and Ang-2 levels in the observation group were (0.15 ± 0.05) ng/L and (0.98 ± 0.11) ng/L, respectively, which were significantly lower than (0.24 ± 0.07) ng/L and (1.49 ± 0.22) ng/L in the control group ( t = 7.32, 14.51, both P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Qingruxiao granules combined with tamoxifen can effectively improve clinical symptoms, reduce tumor size, regulate endocrine hormone levels, decrease the expression of angiogenic factors in patients with breast hyperplasia, and is highly safe.

Safety and effectiveness of superselective embolization of the uterine arteries in the treatment of uterine fibroids / 中国基层医药

Objective:To analyze the safety and effectiveness of superselective embolization of the uterine arteries in the treatment of uterine fibroids.Methods:The clinical data of 60 patients with uterine fibroids who were admitted to Zhejiang Veteran Hospital from February 2020 to February 2022 were retrospectively analyzed. These patients were divided into a control group and an observation group ( n = 30/group) according to different surgical methods. The control group underwent conventional surgery. The observation group underwent superselective embolization of the uterine arteries. Uterine size, uterine fibroid size, postoperative hormone level, and complications were compared between the two groups. Results:There was no significant difference in total response rate between the observation and control groups [93.33 (28/30) vs. 83.33 (25/30), χ2 = 1.46, P > 0.05]. After surgery, serum estradiol, luteinizing hormone, follicle-stimulating hormone, and progesterone levels in the observation group were (164.14 ± 19.97) ng/L, (2.43 ± 1.47) IU/L, (2.51 ± 1.14) IU/L, and (5.05 ± 0.43) μg/L, respectively, which were significantly lower than (190.23 ± 21.62) ng/L, (3.78 ± 1.63) IU/L, (3.94 ± 1.23) IU/L, (8.22 ± 1.35) μg/L in the control group ( t = 4.86, 3.37, 4.67, 12.25, all P < 0.05). The incidence of postoperative complications in the observation group was significantly lower than that in the control group [3.33% (1/30) vs. 20.00% (6/30), χ2 = 4.04, P < 0.05). Conclusion:Compared with conventional surgery, superselective embolization of the uterine arteries is more effective on uterine fibroids, better keep postoperative hormone level stable, and reduce or avoid short- and long-term complications. Therefore, superselective embolization of the uterine arteries for the treatment of uterine fibroids deserves the clinical promotion.

Correlation between progesterone receptor G1978T polymorphism and endometrial cancer / 中国临床药理学与治疗学

To explore the relationship between progesterone receptor (PGR) gene G1978T polymorphism and endometrial carcinoma. METHODS: After searching PubMed, EMBASE, Wan-fang and CNKI databases for literatures on PGR G1978T genotyping of endometrial cancer patients, the data were extracted and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using STATA15. The whole blood samples of endometrial carcinoma cases (EC group) and normal women (control group) were collected. Allelic-specific primers matching G1978T wild type G allele and mutant type T allele were designed with 3' terminal phosphorothioate modification, and the two-directional primer extension was performed using Exo + polymerase to genotype PGR gene G1978T polymorphism and Sanger sequencing was used to verify the genotype. RESULTS: PGR gene G1978T mutation was marginally associated with endometrial carcinoma risk (ORper allele =1.10, 95%CI=0.98-1.24, P= 0.072). At the same time, only 1 normal blood samples were found with PGR gene G1978T mutation, and the differences in genotypes and allele frequency between the case group and the control group were not statistically significantP>0.05. CONCLUSION: The G1978T polymorphism of the PGR gene maybe not be associated with the risk of endometrial carcinoma.

Expression of PGRMC1 in patients with polycystic ovary syndrome and its molecular mechanism for regulating ovarian granulosa cell apoptosis and glucolipid metabolism / 中南大学学报(医学版)

OBJECTIVES@#Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases in women with reproductive age, which is associated with hyperandrogenism, insulin resistance, and ovulatory dysfunction. Progesterone receptor membrane component 1 (PGRMC1) can mediate progesterone to inhibit the apoptosis of ovarian granulosa cells and the growth of follicles, and to induce glucolipid metabolism disorder in ovarian granulosa cells, which is closely related to the occurrence and development of PCOS. This study aims to determine the expression of PGRMC1 in serum, ovarian tissue, ovarian granulosa cells, and follicular fluid in PCOS patients and non-PCOS patients, analyze the value of PGRMC1 in diagnosis and prognosis evaluation of PCOS, and investigate its molecular mechanism on ovarian granulosa cell apoptosis and glucolipid metabolism.@*METHODS@#A total of 123 patients were collected from the Department of Obstetrics and Gynecology in Guangdong Women and Children Hospital (hereinafter referred to as "our hospital") from August 2021 to March 2022 and divided into 3 groups: a PCOS pre-treatment group (n=42), a PCOS treatment group (n=36), and a control group (n=45). The level of PGRMC1 in serum was detected by enzyme linked immunosorbent assay (ELISA). The diagnostic and prognostic value of PGRMC1 was evaluated in patients with PCOS by receiver operating characteristic (ROC) curve. Sixty patients who underwent a laparoscopic surgery from the Department of Obstetrics and Gynecology in our hospital from January 2014 to December 2016 were collected and divided into a PCOS group and a control group (n=30). The expression and distribution of PGRMC1 protein in ovarian tissues were detected by immunohistochemical staining. Twenty-two patients were collected from Reproductive Medicine Center in our hospital from December 2020 to March 2021, and they divided into a PCOS group and a control group (n=11). ELISA was used to detect the level of PGRMC1 in follicular fluid; real-time RT-PCR was used to detect the expression level of PGRMC1 mRNA in ovarian granulosa cells. Human ovarian granular cell line KGN cells were divided into a scrambled group which was transfected with small interfering RNA (siRNA) without interference and a siPGRMC1 group which was transfected with specific siRNA targeting PGRMC1. The apoptotic rate of KGN cells was detected by flow cytometry. The mRNA expression levels of PGRMC1, insulin receptor (INSR), glucose transporter 4 (GLUT4), very low density lipoprotein receptor (VLDLR), and low density lipoprotein receptor (LDLR) were determined by real-time RT-PCR.@*RESULTS@#The serum level of PGRMC1 in the PCOS pre-treatment group was significantly higher than that in the control group (P<0.001), and the serum level of PGRMC1 in the PCOS treatment group was significantly lower than that in the PCOS pre-treatment group (P<0.001). The areas under curve (AUC) of PGRMC1 for the diagnosing and prognosis evaluation of PCOS were 0.923 and 0.893, respectively, and the cut-off values were 620.32 and 814.70 pg/mL, respectively. The positive staining was observed on both ovarian granulosa cells and ovarian stroma, which the staining was deepest in the ovarian granulosa cells. The average optical density of PGRMC1 in the PCOS group was significantly increased in ovarian tissue and ovarian granulosa cells than that in the control group (both P<0.05). Compared with the control group, the PGRMC1 expression levels in ovarian granulosa cells and follicular fluid in the PCOS group were significantly up-regulated (P<0.001 and P<0.01, respectively). Compared with the scrambled group, the apoptotic rate of ovarian granulosa cells was significantly increased in the siPGRMC1 group (P<0.01), the mRNA expression levels of PGRMC1 and INSR in the siPGRMC1 group were significantly down-regulated (P<0.001 and P<0.05, respectively), and the mRNA expression levels of GLUT4, VLDLR and LDLR were significantly up-regulated (all P<0.05).@*CONCLUSIONS@#Serum level of PGRMC1 is increased in PCOS patients, and decreased after standard treatment. PGRMC1 could be used as molecular marker for diagnosis and prognosis evaluation of PCOS. PGRMC1 mainly localizes in ovarian granulosa cells and might play a key role in regulating ovarian granulosa cell apoptosis and glycolipid metabolism.

Adaptation of the electron transport chain improves the biocatalytic efficiency of progesterone 17α hydroxylation / 生物工程学报

17α hydroxylase is a key enzyme for the conversion of progesterone to prepare various progestational drug intermediates. To improve the specific hydroxylation capability of this enzyme in steroid biocatalysis, the CYP260A1 derived from cellulose-mucilaginous bacteria Sorangium cellulosum Soce56 and the Fpr and bovine adrenal-derived Adx4-108 derived from Escherichia coli str. K-12 were used to construct a new electron transfer system for the conversion of progesterone. Selective mutation of CYP260A1 resulted in a mutant S276I with significantly enhanced 17α hydroxylase activity, and the yield of 17α-OH progesterone reached 58% after optimization of the catalytic system in vitro. In addition, the effect of phosphorylation of the ferredoxin Adx4-108 on 17α hydroxyl activity was evaluated using a targeted mutation technique, and the results showed that the mutation Adx4-108T69E transferred electrons to S276I more efficiently, which further enhanced the catalytic specificity in the C17 position of progesterone, and the yield of 17α-OH progesterone was eventually increased to 74%. This study provides a new option for the production of 17α-OH progesterone by specific transformation of bacterial-derived 17α hydroxylase, and lays a theoretical foundation for the industrial production of progesterone analogs using biotransformation method.