Non-peptide gonadotropin-releasing hormone antagonist (GnRH-antagonist) is a highly efficient and selective antagonist of GnRH receptor. The oral preparations (Elagolix, Relugolix and Linzagolix) had been approved for listing abroad. It shows efficacy in reducing the size of uterine fibroid and controlling heavy bleeding. Appropriate combination of‘add-back’therapy could improve the safety in medical application and patient compliance. Compared with other hormonal pharmaceuticals, oral GnRH-antagonists showed promising prospects in the treatment of uterine fibroid.

Defined as a common gynecologic endocrine disease, endometriosis is characterized by the presence of endometrium outside of the uterus cavity, affecting about 10% to 15% of reproductive-aged women worldwide.Moreover, Asian women tend to have a nine-fold increased risk of endometriosis compared with their white counterparts in Europe and the United States. Endometriosis not only causes chronic pelvic pain, dysmenorrhea, painful sex and other pain symptoms, but also leads to infertility, pushing the patients into a state of fatigue, high sensitivity and anxiety, thus reducing their quality of life. As the aging of Chinese population intensifies and the women's childbearing age delays, it is highly urgent to find solutions to those gynecological endocrine diseases such as endometriosis, which hamper women's fertility. In recent years, studies have shown that patients with endometriosis have abnormal serum lipid metabolism and an increased risk of cardiovascular diseases. At the same time, as a type of cholesterol-lowering drug, statins can inhibit the progression of endometriosis at the cellular and animal levels. Also, a few clinical studies have exhibited that statins exert a positive effect on the treatment of endometriosis. Therefore, this article aims to review the researches regarding the relationship between endometriosis and the cardiovascular disease, as well as the research progress of statin therapy on endometriosis based on the level of cells, animals and human beings. 

AIM: To explore the key points of personalized treatment and medication monitoring by clinical pharmacists in the perioperative period of moyamoya disease patients with endometriosis. METHODS: This study showed a moyamoya disease patient with endometriosis who accepting dual antiplatelet therapy and how to adjust medication during the perioperative period. Besides, monitoring the use proton pump inhibitors in the perioperative period and the formulating a plan of DIE postoperative recurrence prevention are also our objectives. RESULTS: Through individualized assessment of the patient, a personalized medication adjustments for dual antiplatelet therapy was determined. Individualized perioperative proton pump inhibitor regimen and postoperative prevention plan for endometriosis recurrence were developed. CONCLUSION: The development of individualized medication regimens and medication monitoring is the breakthrough point for clinical pharmacists to carry out pharmaceutical services.

Endometriosis (Endometriosis, EMs) is a disease caused by abnormal colonization of the endometrial stroma or glands to sites other than the coated mucosa of the uterine cavity. Phospholipid inositol 3 kinase (phosphoinositide 3-kinase, PI3K)/protein kinase B (protein kinase B, Akt) signaling pathway is involved in the process of focal blood vessel formation, cell autophagic apoptosis, migration and invasion, and is one of the classic pathways regulating the pathological characteristics of EMs. The characteristics of multi-component, multi-target and multi-pathway of TCM have significant advantages in the treatment of EMs. Some TCM active components and TCM compounds can interfere with the PI3K/Akt signaling pathway, thus inhibiting the treatment of endometriotic tissues, reducing pain and alleviating fibrotic lesions. By explaining the connection between the key targets of PI3K/Akt signaling pathway and EMs, this paper summarizes and summarizes the research status of EMs by regulating PI3K/Akt signal pathway in home and abroad, aiming to provide a new perspective and idea for the use of traditional Chinese medicine and compound to treat EMs.

AIM: To rapidly evaluate the effectiveness, safety and economy of dienogest in the treatment of endometriosis so as to provide evidence-based reference for clinical drug selection and decision. METHODS: Retrieved from PubMed, Embase, Cochrane Library, CNKI, SinoMed, Wanfang and health technology assessment (HTA) organization websites, HTA report, systematic review/Meta-analysis and pharmacoeconomic study were included during the inception to Sep 2023. Data extraction and quality evaluation were carried out for the literature that met the inclusion and exclusion criteria, and the research results were summarized and analyzed qualitatively. RESULTS: Nine systematic review/Meta-analyses, and 2 pharmacoeconomic studies were included. The quality of Meta-analysis literatures was low, and the quality of economic research was good. In terms of effectiveness, compared with no treatment, dienogest can significantly reduce postoperative recurrence rate, VAS score, and improve pregnancy rate and effective rate; Dienogest has similar therapeutic effects in terms of recurrence rate as GnRHa and COC; With regard to recurrence rate and pregnancy rate, dienogest is superior to danazol, gestrinone, and mifepristone. In terms of safety, compared with placebo, the incidence of vaginal bleeding and headache was significantly increased with dienogest, and there was no difference in bone loss; The incidence of vaginal bleeding caused by dienogest was significantly higher than that of GnRHa, but the incidence of hot flashes and bone loss was lower. In terms of economy, dienogest has a more cost-effective advantage comparing with GnRHa, but does not have economic benefits comparing with COC. CONCLUSION: Dienogest has good effectiveness and safety in the treatment of endometriosis, and economically superior to GnRHa, but inferior to COC.

AIM: To perform a multidimensional analysis of the clinical study characteristics of endometriosis based on the ClinicalTrials.gov, providing comprehensive and objective information for researchers, clinicians, and clinical pharmacists. METHODS: A thorough investigation was conducted on clinical trials related to endometriosis, registered on the ClinicalTrials.gov from its inception to October 20, 2023. Relevant trial data were extracted and statistically analyzed using bibliometrics and comparative research methods. RESULTS: A total of 667 endometriosis clinical studies were registered globally, showing an annual increase. The United States (127 trials), France (70 trials), and Italy (57 trials) had the highest number of registered trials. Interventional studies were predominant (416 trials, 62.4%), followed by observational studies (251 trials, 37.6%). Within interventional studies, drug therapy was the primary intervention (223 trials, 53.6%). Despite endometriosis being a female condition, male subjects were also considered, with 6 trials specifically requiring male participants and 37 trials not restricting gender. Companies/corporations were the main funding sources, while public and governmental organizations provided relatively less funding. CONCLUSION: Clinical trial research on endometriosis is in a phase of growth, with drug therapy being the main treatment approach. However, there is a relative lack of investment and attention from public funds and governmental organizations.

AIM: To evaluate the clinical effectiveness and safety of generic and branded dienogest in the treatment of endometriosis. so as to provide the basis for clinical use of dienogest. MEHTODS: The data of patients admitted to Third Affiliated Hospital of Zhengzhou University from August 2022 to August 2023 who received dienogest (2 mg/d, orally, for 6 months) for treatment of endometriosis were collected. The clinical efficacy and adverse reactions of generic drugs and original drugs in the treatment of endometriosis-related pain were compared through follow-up surveys of the two groups of patients at 3 months and 6 months respectively. RESULTS: There was highly significant reduction in pelvic pain in both groups with mean of similar in generic group (34.0±3.0) mm and branded group (34.5±3.9) mm. The most frequent drug-related adverse effects in generic dienogest was vaginal bleeding (93%) which was no statistical difference with branded dienogest (90%). CONCLUSION: The generic and branded dienogest have the same clinical effectiveness and similar safety.

Endometriosis is a chronic, relapsing disease that requires long-term management. Adolescent endometriosis is a group that can be ignored, and the drug treatment is an important method for long-term management and fertility preservation. There are many kinds of drugs to treat endometriosis, such as NSAIDs, combined oral contraceptives (COC), progesterone, GnRHa. For the drug treatment selection, the characteristics of adolescents should be carefully considered and individualized treatment should be provided. In order to better long-term management, it is necessary to develop new treatments, which can effectively relieve endometriosis without damaging fertility. This review focuses on the drug treatment options and research progress of basic drug treatment for adolescent endometriosis, so as to delay disease progression, reduce adverse reactions, preserve fertility, and improve quality of life.

AIM: To improve the success rate of experimental modeling of non-alcoholic fatty liver (NAFLD) in rats by high-fat diet through comparing three different formulations of high-fat diets in constructing non-alcoholic fatty liver rats model, so as to provide a reliable animal model for the study of non-alcoholic fatty liver disease. METHODS: SPF-grade male SD rats were divided into four groups randomly: control group, high-fat diet group1 (HFD1), high-fat diet group2 (HFD2), high-fat diet group3 (HFD3). Each group was given the corresponding feed for 8 weeks while modeling. The data on general observation, body weight changes, and ingestion of the rats were recorded during the modeling period. After 8 weeks' feeding, liver ultrasound, CT and MRI examination were performed for the rats of each group to check the status. Blood and liver samples were collected. Changes in liver function (ALT, AST), blood lipids (TC, TG, HDL-C, LDL-C), and inflammatory indexes (IL-1β, IL-6, TNF-α) were detected. The morphology of the livers was observed with the naked eyes, and the liver index and Lee's index were calculated at the end of 8 weeks. The effects of different high-fat diets on the establishment of NAFLD model in SD rats were comprehensively evaluated by comparing the difference of above indexes among the groups. RESULTS: Compared with the control group,rats in the HFD1, HFD2 and HFD3 groups showed poor mental deterioration, decreased activity, severe hair loss, decreased food intake, increased body weights, and significantly increased liver index and Lee's index, along with increased liver volume, blunt edge, steatosis and lipid deposition, and the trend was even more pronounced in the HFD3 group. Compared with the control group, the serum levels of ALT, AST, TC, TG, LDL-C, IL-1β, IL-6 and TNF-α were significantly increased, while the contents of HDL-C was significantly decreased in the HFD1, HFD2 and HFD3 group,especially in the HFD3 group. Compared with the control group, the B ultrasonography showed an enlarged liver with enhanced parenchymal echo and pipe unsharpness, CT showed that the liver and spleen CT ratio decreased obviously,and the MRI images showed obvious difference of liver signal intensity between in/out of phase image in the HFD1, HFD2 and HFD3 group, and the most significant imaging changes was observed in the HFD3 group. CONCLUSION: The above three kinds of high-fat diets can establish NAFLD model in SD rats after 8 weeks' feeding, the models induced by HFD3 was better than those induced by the other two groups. NAFLD lesion is relatively serious and expected to last longer in HFD3 group, which are more suitable for investigating the underlying mechanisms of non-alcoholic fatty liver disease and development of lipid-lowering drugs.

AIM: To investigate the regulatory effects and mechanisms of glycyrrhizin on morphine-induced neurotoxicity. METHODS: A neurotoxicity model was established by intracerebroventricular injection of morphine. Glycyrrhizin was administered intraperitoneally for 5 and 10 days. Pathological observation, protein immunoblotting, cell viability, apoptosis, and primary neuron differentiation were assessed. RESULTS: After morphine treatment, neuronal loss, decreased cell viability, increased apoptosis, axonal breakage, and cell shrinkage were observed in cortical tissue. Glycyrrhizin administration significantly improved cell viability, and axonal, dendritic, and cell body structures gradually became intact, with reduced apoptosis. The phosphorylation levels of protein Akt at position 473 and PKA at position 197 decreased, while autophagy-related proteins Beclin and LC3B1/2 remained unchanged. CONCLUSION: Glycyrrhizin significantly inhibits morphine-induced neuronal differentiation suppression and neuronal apoptosis, which may be mediated through the synergistic effects of glycyrrhizin and morphine on the Akt pathway. 

AIM: To evaluate the clinical efficacy and safety of pneumoperitoneum-free single-hole endoscopy combined with ropivacaine local infiltration anesthesia in pregnancy with ovarian tumor. METHODS: Twenty-eight pregnant women with ovarian tumor were randomly divided into two groups: observation group (n=16) and control group (n=12). The first time out of bed, ventilation time, postoperative hospital stay, non-invasive blood pressure, heart rate (HR), respiratory frequency (RR) and blood oxygen saturation (SpO2) were compared between the two groups. Pain score, Ramsay sedation score, SAS anxiety score, postoperative complications, patient satisfaction and recovery quality scale QoR15 were evaluated at 6, 24 and 48 hours after operation. RESULTS: There was no significant difference in postoperative hospital stay, Ramsay score, RR, SpO2 and the incidence of complications between the two groups(P>0.05), but the time of getting out of bed and ventilation time were shortened, the scores of non-invasive blood pressure, HR, pain and anxiety in the observation group were lower than those in the control group, and the scores of patient satisfaction and QoR15 in the observation group were better than those in the control group (P<0.05). CONCLUSION: The application of pneumoperitoneum-free single-hole endoscope combined with ropivacaine local infiltration anesthesia in pregnancy with ovarian tumor can reach satisfactory clinical results, including reducing postoperative pain and anxiety, which is worth popularizing. 

AIM: To investigate the relationship between the dynamic changes of Lymphocyte-to-monocytes ratios (LMR) before PD-1 inhibitor treatment and the efficacy and prognosis of PD-1 inhibitor treatment in patients with advanced non-small cell lung cancer (NSCLC). METHODS: The clinical case data of 83 patients with advanced non-small cell lung cancer admitted to the Cancer Hospital of Wuhu Second People's Hospital from June 2019 to July 2022 were retrospectively analyzed. The routine blood LMR values of all patients before and after treatment were collected, the cut-off value was calculated according to the ROC curve, and the LMR was divided into two groups: high and low before treatment and after treatment. The differences of ORR, DCR, PFS and OS among the patients in each group were analyzed and compared, and the value of LMR value and dynamic changes after treatment on the efficacy and prognosis of patients with PD-1 inhibitors in the treatment of NSCLC patients was analyzed. RESULTS: According to the ROC curve, the critical value of LMR was 1.8, and the LMR was divided into the low LMR group at baseline (LMRB/S<1.8)，the high LMR group at baseline (LMRB/S≥1.8) and the low LMR group after treatment (LMRafter<1.8) and the high LMR group after treatment (LMRafter≥1.8). The ORR and DCR after immunotherapy in the high LMRB/S group were higher than those in the low LMRB/S group (P=0.037; P=0.002 5). Among the patients with low LMRB/S before treatment, the DCR of the LMRafter≥1.8 group was better than that of the LMRafter<1.8 group after treatment (P=0.005). Among the patients with high LMR before treatment, the DCR of the LMRafter≥1.8 group was better than that of the LMRafter<1.8 group (P=0.034). Kaplan-Meier analysis showed that PFS and OS were longer in the high LMRB/S group than in the low LMRB/S group before treatment. In the low LMRB/S group before treatment, PFS and OS were longer in patients with LMRafter≥1.8 than those with LMRafter<1.8 (P=0.047; P=0.007). Multivariate Cox regression model analysis showed that high LMRB/S value before treatment was an independent risk factor for PFS and OS in NSCLC patients (P=0.006; P=0.033). CONCLUSION: High LMR value of patients before immunotherapy may improve the efficacy of PD-1 inhibitors, improve the prognosis of patients, and prolong the survival time. Moreover, the increase of LMR value after treatment may increase the efficacy of patients with low LMR before treatment and improve the prognosis of patients.

In recent years, significant progress has been made in the study of endometrial epithelial organoids in the field of reproduction. Traditional two-dimensional cell culture models and animal experiments fail to accurately replicate the three-dimensional structure and physiological functions of the endometrium, limiting the in-depth exploration of its normal physiological mechanisms and related disease mechanisms. Emerging organoid technologies have provided new avenues for research. These organoids, formed by self-organization of stem cells or progenitor cells in a three-dimensional culture system, faithfully recapitulate the characteristics of endometrial glands in situ. Not only can these organoid models mimic the changes in the endometrium at different stages of the menstrual cycle, but they can also simulate the interaction between the fertilized embryo and the endometrium. Moreover, organoid systems have become essential tools for fundamental research in the field of reproduction and for disease research, including studies related to reproductive biology, drug screening and development, disease mechanism exploration, drug action mechanisms, drug combination therapies, and targeted therapies. These studies have provided novel insights and methods for a deeper understanding of the biological properties of the endometrium, its disease mechanisms, and the development of therapeutic strategies for related disorders.

Pulmonary fibrosis (PF) is a common, persistent, irreversible, fatal chronic lung disease with a median survival of 2-4 years after diagnosis. It is characterized by excessive extracellular matrix deposition and scarring in the lungs, leading to functional failure, severe respiratory problems and even death. Numerous studies have shown that CXC chemokines and their receptors play important roles in PF and other desmoplastic disorders. Several studies have shown that chemokines may become new targets for the treatment of many diseases. Here, we review the role of key CXC chemokines and their receptors in PF to provide a reference for the treatment of PF.

Coronary heart disease is still one of the most common cardiovascular disease and causes of death worldwide (including China). Antiplatelet drugs are fundamental in the treatment of coronary heart disease. In recent years, more and more studies have found that trimethylamine N-oxide (TMAO), a major metabolite of intestinal flora, can promote atherosclerosis through various mechanisms, affecting the prognosis of patients with coronary heart disease and the efficacy of antiplatelet drugs. This article reviews the effect of TMAO on coronary heart disease and the efficacy of antiplatelet drugs.

Guideline of model-informed drug development was published by National Medical Products Administration in 2020, which provided technical guidance for the application of modeling and simulation in the process of new drug development. In July 2022, Center of Drug Evaluation conducted a questionnaire survey on the practical ability of pharmaceutical industry to apply model-informed drug development (MIDD) in the process of new drug development, in order to investigate the practice of MIDD in China. Based on the feedback data collected from enterprises, this paper analyzes the practice of MIDD in domestic pharmaceutical industry, and briefly discusses several problems that still exist at present.