How have changes in accessibility and public funding influenced contraceptive use among Norwegian adolescents? A cohort study.

INTRODUCTION: The Norwegian Government introduced in 2002 a reimbursement scheme for hormonal contraceptives to adolescents at the same time as public health nurses and midwives received authorization to prescribe hormonal contraceptives. This study examines the impact of increased accessibility and public funding on hormonal contraceptive use among adolescents. MATERIAL AND METHODS: The Norwegian Prescription Database, Statistics Norway, and Norwegian Institute of Public Health served as data sources for this cohort study. The study population comprised 174 653 Norwegian women born 1989-1990, 1994-1995, and 1999-2000. We examined use of hormonal contraceptives through dispensed prescriptions from age 12 through age 19 with duration of first continuous use as primary outcome. The statistical analyses were done in SPSS using chi-squared test, survival analysis, and Joinpoint regression analysis with p-values < 0.05. RESULTS: By age 19, ~75% of the cohorts had used at least one hormonal method. The main providers of the first prescription were general practitioners and public health nurses. Starters of progestogen-only pills (POPs) have increased across the cohorts, while starters of combined oral contraceptives (COCs) have decreased. The use of long-acting reversible contraceptives (LARCs) has increased since its inclusion in the reimbursement scheme (2015). Most switchers shifted from COCs or POPs as a start method to implants after LARCs became part of the reimbursement scheme. There has been a significant increase across the cohorts in the number of women who continuously used hormonal contraceptives from start to the end of the calendar year they became 19 years with the same method and after switching methods. We could not correlate changes in decreasing trends for teenage births or induced abortions (Joinpoint analysis) to time for implementation or changes in the reimbursement of hormonal contraceptives from 2002. CONCLUSIONS: Primarily public health nurses and to a lesser extent midwives became soon after they received authorization to prescribe COCs important providers. The expansion of the reimbursement scheme to cover POPs, patches, vaginal ring, and depot medroxyprogesterone acetate in 2006 had minor impact on increasing the proportion of long-term first-time users. However, the inclusion of LARCs in 2015 significantly increased the proportion of long-term first-time hormonal contraceptive users.

An optimization strategy for charged aerosol detection to linearize the detector response in the multicomponent quantitative analysis of Qishen Yiqi dripping pills.

Charged aerosol detection, increasingly recognized for quantifying pharmaceutical compounds with weak ultraviolet absorption, is a universal detection technique for high-performance liquid chromatography (HPLC). Charged aerosol detection shows a non-linear response with increasing analyte concentration over a wide range, limiting its versatility in various analytical applications. In this work, a co-optimization strategy for power function value (PFV) and power laws was proposed and applied to broaden the linear range of the standard curve of saccharides in Qishen Yiqi dripping pills using the HPLC-charged aerosol detection (HPLC-CAD) method. Power function values for all analytes were optimized based on empirical models. Subsequently, the optimum power laws were investigated based on a preferred PFV. Additionally, various regression equations were evaluated to ensure the accuracy and precision of the results. With the optimized PFV and power law, the ordinary least squares model demonstrated a satisfactory fit. The optimal PFVs and power laws expanded the standard curve's linear range by 2.7 times compared to default settings, reducing model uncertainty. This paper presents a vital method for developing a multi-component quantitative HPLC-CAD approach without external data transformation outside the provided software, especially suitable for analytical applications of traditional Chinese medicine with significant quality differences.

Quality grade evaluation of Nvjin Pills based on traditional Chinese medicine reference drug and network pharmacology of target-focused compounds.

To improve the effectiveness of marketed drugs related to active ingredients, it is necessary to designate a more unified quality evaluation standard. Taking Nvjin Pills as an example, this study reported the development of a novel principle of analysis in traditional Chinese medicine. The core of the experiment is to prepare three batches of traditional Chinese medicine reference drugs by high-quality Chinese materia medica. The active ingredients identified in the herbal formula including glycyrrhizic acid, cinnamaldehyde, paeonol, baicalin, hesperidin, paeoniflorin, and ferulic acid were analyzed in traditional Chinese medicine reference drugs by the high-performance liquid chromatography method combined with wavelength switching. The simple prediction results of network pharmacological analysis verified the feasibility and reliability of the established quantitative analysis method for seven target-focused compounds in Nvjin Pills, which were recommended as candidate indicators for quality evaluation ultimately. Using the seven target-focused compounds as the scientific ruler, quality grade specifications of Nvjin Pills were proposed by comprehensive analysis. Accordingly, 16, 47, and 13 batches of samples were primarily graded as first grade, second grade, and unqualified grade, respectively. This study will provide a chemical basis for quality control of Nvjin Pills, which is necessary for the production process of pharmaceutical development.

Comparison of resumption of ovulation after cessation of oral contraceptives and medroxyprogesterone acetate in women with polycystic ovary syndrome.

OBJECTIVE: Both oral contraceptive pills (OCPs) and cyclic medroxyprogesterone acetate (MPA) are widely used to control menstrual abnormalities in women with polycystic ovary syndrome (PCOS). We aimed to evaluate the chance of ovulation resumption after cessation of OCPs and MPA in women with PCOS. METHODS: A retrospective study was conducted of women with PCOS who were treated with OCPs or cyclic MPA from September 2015 to March 2019. After cessation of medication, ovulation was assessed using basal body temperature and/or measurement of serum progesterone. The odds ratio for ovulation resumption was assessed with multivariable logistic regression. Additionally, doubly robust analysis was performed with inverse-probability-weighted analysis and regression adjustment based on the covariate balancing propensity score to adjust for the effect of covariates on the treatment assignment. RESULTS: Among 272 women with PCOS, 136 were prescribed OCPs and 136 were prescribed cyclic MPA. Ovulation resumed in 18.4% of women (n = 25) after cessation of MPA and in 24.3% of women (n = 33) after cessation of OCPs. The odds of ovulation resumption in MPA users were comparable with those in OCP users (adjusted odds ratio (aOR) 1.00, 95% confidence interval (CI) 0.89-1.12). After multiple imputation due to missing values, the results did not change substantially (aOR 0.99, 95% CI 0.89-1.10). CONCLUSIONS: Among women with PCOS, MPA users have a similar chance of ovulation resumption as OCP users after cessation of medication. Cyclic MPA can be a good alternative to OCPs in women for whom OCPs are contraindicated or who decline to take OCPs.

Gap in knowledge of health benefits and risks of combined oral contraceptives among Lebanese women.

BACKGROUND: Oral Contraceptive Pills (OCPs) are among the most commonly used forms of contraception, but they are associated with several health benefits and risks. This study aims to determine the gap in knowledge of the underlying health benefits and risks of OCPs among Lebanese women and to identify the factors that might influence their beliefs. METHODS: A questionnaire was completed by 817 Lebanese women aged 18-64 years old and assessed sociodemographic details, medical information, contraceptive practices, knowledge of underlying health benefits and risks, and information needs related to OCPs. RESULTS: Among the total participants, 41.5% of women reported using OCPs at some point in their lives yet 46.6% denied receiving information about their benefits and 48% denied receiving information about their risks. The mean total OCP knowledge score was 5.70 out of 25, the mean OCP risk knowledge score was 4.09 out of 15, and the mean OCP benefit knowledge score was 0.77 out of 6. Sociodemographic factors associated with greater total knowledge, risk knowledge and benefit knowledge included OCP usage, being a student, confidence in one's knowledge and satisfaction with one's information. Both the total and risk knowledge scores were found to be higher in women who found that receiving information related to OCPs was important. Finally, participants who lived in central governates had greater total knowledge scores, whereas those with higher levels of education and a family history of endometrial cancer demonstrated better benefit knowledge. CONCLUSIONS: This study highlighted the poor knowledge of health benefits and risks associated with OCP use among Lebanese women and the associated sociodemographic factors that might influence their beliefs.

Exploring the therapeutic efficacy and pharmacological mechanism of Guizhi Fuling Pill on ischemic stroke: a meta-analysis and network pharmacology analysis.

The role of Guizhi Fuling Pill (GZFL) in the treatment of ischemic stroke (IS) is still controversial, and its pharmacological mechanism remains unclear. To evaluate the efficacy and potential pharmacological mechanisms of GZFL on IS, a comprehensive method integrating meta-analysis, network pharmacology, and molecular docking was employed. Eight electronic databases were searched from inception to November 2023. Review Manager 5.4.1 software was used for meta-analysis. Active compounds and targets of GZFL were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database, Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine, and Encyclopaedia of Traditional Chinese Medicine. Relevant targets of IS were obtained from the DisGeNet, Genecards, and DrugBank databases. GO biological function analysis and KEGG enrichment analysis were performed in the Metascape database. AutoDock Tools and PyMOL software were employed for Molecular docking. The intervention group significantly increased the total effective rate and decreased the NIHSS score. Administration of GZFL also improved the whole blood viscosity (low and high shear rates) and levels of fibrinogen, TNF-α, and IL-6. The key active compounds included quercetin, kaempferol, catechin, and beta-sitosterol, and the core target proteins included SRC, MAPK1, TP53, JUN, RELA, AKT1, and TNF. GO analysis mainly involved inflammation response, cellular response to lipids, and regulation of ion transport. The core pathways were lipid and atherosclerosis, cAMP, calcium, IL-17, and MAPK signaling pathways. Key active compounds showed good affinity with the core targets. The underlying mechanisms of GZFL in IS treatment are primarily related to its anti-inflammatory, anti-atherosclerosis, and neuroprotective effects.

Factor Analysis of Patients Who Find Tablets or Capsules Difficult to Swallow Due to Their Large Size: Using the Personal Health Record Infrastructure of Electronic Medication Notebooks.

BACKGROUND: Understanding patient preference regarding taking tablet or capsule formulations plays a pivotal role in treatment efficacy and adherence. Therefore, these preferences should be taken into account when designing formulations and prescriptions. OBJECTIVE: This study investigates the factors affecting patient preference in patients who have difficulties swallowing large tablets or capsules and aims to identify appropriate sizes for tablets and capsules. METHODS: A robust data set was developed based on a questionnaire survey conducted from December 1, 2022, to December 7, 2022, using the harmo smartphone app operated by harmo Co, Ltd. The data set included patient input regarding their tablet and capsule preferences, personal health records (including dispensing history), and drug formulation information (available from package inserts). Based on the medication formulation information, 6 indices were set for each of the tablets or capsules that were considered difficult to swallow owing to their large size and concomitant tablets or capsules (used as controls). Receiver operating characteristic (ROC) analysis was used to evaluate the performance of each index. The index demonstrating the highest area under the curve of the ROC was selected as the best index to determine the tablet or capsule size that leads to swallowing difficulties. From the generated ROCs, the point with the highest discriminative performance that maximized the Youden index was identified, and the optimal threshold for each index was calculated. Multivariate logistic regression analysis was performed to identify the risk factors contributing to difficulty in swallowing oversized tablets or capsules. Additionally, decision tree analysis was performed to estimate the combined risk from several factors, using risk factors that were significant in the multivariate logistic regression analysis. RESULTS: This study analyzed 147 large tablets or capsules and 624 control tablets or capsules. The "long diameter + short diameter + thickness" index (with a 21.5 mm threshold) was identified as the best indicator for causing swallowing difficulties in patients. The multivariate logistic regression analysis (including 132 patients with swallowing difficulties and 1283 patients without) results identified the following contributory risk factors: aged <50 years (odds ratio [OR] 1.59, 95% CI 1.03-2.44), female (OR 2.54, 95% CI 1.70-3.78), dysphagia (OR 3.54, 95% CI 2.22-5.65), and taking large tablets or capsules (OR 9.74, 95% CI 5.19-18.29). The decision tree analysis results suggested an elevated risk of swallowing difficulties for patients with taking large tablets or capsules. CONCLUSIONS: This study identified the most appropriate index and threshold for indicating that a given tablet or capsule size will cause swallowing difficulties, as well as the contributory risk factors. Although some sampling biases (eg, only including smartphone users) may exist, our results can guide the design of patient-friendly formulations and prescriptions, promoting better medication adherence.

The Psychological Impacts of Pill Dysphagia: A Mixed Methods Study.

Pill dysphagia is a common problem amongst older adults, with significant health consequences. Previous research has found that dysphagia can negatively affect an individuals mental health and wellbeing. However, this research has not been extended to pill-specific dysphagia, which presents distinct differences from the challenges posed by swallowing food and liquids. These differences extend to causes, demographics, and physical health ramifications. This study aimed to address this gap in the literature by investigating the effects of pill dysphagia on the wellbeing of older adults. A community sample of 132 Australians aged 65-97 years completed a survey about their wellbeing and difficulty swallowing pills. Thirty-one participants who met the criteria for pill dysphagia completed further open-ended questions detailing the effects of pill dysphagia and how they manage it. Analyses of the quantitative data indicated that difficulty swallowing pills was unrelated to negative affect but negatively related to positive affect, life satisfaction, and eudemonic wellbeing. Supplementary analyses controlling for health-related variables found no significant relationships between difficulty swallowing pills and wellbeing. Responses to the open-ended questions revealed a range of physical, psychological, and practical impacts of pill dysphagia, and successful and unsuccessful methods used to assist in swallowing pills. The findings partially support the hypothesised effects of pill dysphagia on wellbeing. However, further research is required to establish if more severe pill dysphagia predicts wellbeing over and above self-rated health. Future interventions should incorporate wellbeing promotion strategies for older adults with pill dysphagia.

Investigation of Rheological Properties of Molten Materials for Dripping Pills Based on Imaging Monitoring.

INTRODUCTION: Rheological properties, as critical material attributes (CMAs) of solid dispersion drugs such as dripping pills, affect the melting, dispersion, and solidification. Therefore, characterization and assessments of rheological properties in the pharmaceutical process are important in enhancing drug stability and bioavailability. OBJECTIVES: The study aimed to develop a method for analyzing the rheology of molten materials, assessing their consistency and how rheological properties affect the dripping process and pills quality. MATERIALS AND METHODS: The rheological behavior of molten materials composed of Ginkgo biloba leaf extract (GBE) and polyethylene glycol (PEG) 4000 was characterized. Batch consistency of molten materials was evaluated. Image monitoring technology was utilized to capture and process images of the droplet formation process. We established the relationship between the rheological properties of molten materials and various attributes. RESULTS: The quality consistency of molten materials was evaluated, with 12 batches showing similarity above 0.8. The MLR models showed strong correlations (R2 > 0.80) between rheological properties and evaluation attributes. The rheological properties, including consistency coefficient, flow index, and viscosity at 80°C, were identified as critical rheological properties of the molten materials. Rheological property differences of molten materials have an impact on the morphology of droplet and quality performance. CONCLUSION: A rheological method was established, enabling quality consistency evaluation of molten materials in dripping pills. This study revealed the influence of rheological properties on droplet formation process and dripping pills quality, providing a reference for researches on material attributes control of other traditional Chinese medicine dripping pills.

Oral intake of solid medications in patients with post-stroke dysphagia. A challenge for nurses?

AIM: To provide a comprehensive overview of how stroke nurses manage solid medication (SM) delivery to patients with post-stroke dysphagia. DESIGN: Cross-sectional study. METHODS: A self-administered online survey was carried out among nurses in German-speaking countries between September and December 2021. RESULTS: Out of a total of 754 responses, analysis was conducted on 195 nurses who reported working on a stroke unit. To identify swallowing difficulties in acute stroke care, 99 nurses indicated routinely administering standardised screenings, while 10 use unvalidated screenings, and 82 are waiting for a specialist evaluation. Regardless of whether screening methods are used or not, most preferred a non-oral route of medication administration for patients with suspected dysphagia. None of the respondents reported administering whole SMs orally to patients. If screening methods indicate dysphagia, approximately half of the respondents would modify SMs. Participants who stated to use the Gugging Swallowing Screen managed the SM intake guided by its severity levels. One-third of the group who awaited assessment by the dysphagia specialist provided modified medication before the consultation. CONCLUSION: Most of the nurses on stroke units use swallowing screens and avoid the administration of whole SMs in post-stroke dysphagia. In addition to the non-oral administration, SMs are modified if dysphagia is suspected. Precise guidance on the administration of SM is needed, based on screening tests and prior to expert consultation. TRIAL AND PROTOCOL REGISTRATION: ClinicalTrials.gov: Registration ID: NCT05173051/ Protocol ID: 11TS003721. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The present paper serves to alert nurses to the issue of patient safety when administering medication for acute stroke-induced dysphagia. IMPACT: SM delivery after acute stroke-induced dysphagia is often neglected. While nurses are aware of the risk associated with dysphagia and would not give whole SMs to patients, the modification of tablets and their administration with semisolids are common. REPORTING METHOD: This study was reported according to the Checklist for Reporting of Survey Studies (CROSS).

Online identification of chemical constituents in Mongolian medicine Zhachong-13 pills by UHPLC-Q-exactive Orbitrap MS.

Zhachong-13 pills (ZC-13), as a traditional prescription of Mongolian medicine, are often used in the clinical practice of Mongolian hospitals for the treatment of stroke and rheumatic arthritis. In this experiment, UHPLC-Q-Exactive Orbitrap MS was used to explore the chemical composition of ZC-13. The results showed that 315 compounds were identified or inferred, including 56 alkaloids, 77 2-(2-phenylethyl)chromones, 61 flavonoids, 31 tannins, 8 coumarins, 16 lignans, 21 terpenoids, 5 amino acids, 19 organic acids, and 21 other components. In addition, the pharmacological activities related to anti-cerebral ischemia of these components were summarized. This result laid a foundation for further study on the pharmacodynamic material basis of ZC-13 and provided a scientific basis for the formulation of ZC-13 quality specifications.

Evaluating Patient-Reported Adherence And Safety for Oral Contraception Treatment in Women via a Direct-To-Consumer Prescription Platform: A Cross-Sectional Study.

Background: The acceptance of telemedicine in the German health care system is growing. This also extends to gynecological applications such as the prescription of contraceptives. This study investigates the contraceptive use and adherence of patients using a direct-to-consumer (DTC) prescription platform for oral contraception. Methods: A retrospective cross-sectional study was conducted using anonymized data obtained from a DTC prescription platform between May 2021 and March 2023. The patient-reported outcome was evaluated after 3 months through a follow-up questionnaire. Results: In total, 8,065 patient records were available and 1,008 patients responded to the follow-up questionnaire. Patients were mostly taking combined oral contraceptives (COCs) and only 6% were taking a progestin-only pill (POP). Even in patient populations at higher risk, such as smokers and obese women, the proportion of POP users was less than 20%. Over 90% of users reported that they took the pill without any intake errors, with the main intake error being forgotten intake. Overall, 23% of patients reported adverse events while taking the pill, with POP users reporting more adverse events than COC users (36.7% vs. 22.2%). Over 70% of patients regularly attended cervical screening. Conclusions: Users of a DTC prescribing platform exhibit strong adherence, with over 90% successfully taking oral contraceptive pills. The platform effectively identifies absolute contraindications but could enhance recommendations for contraceptives in the presence of relative contraindications. For healthy women familiar with pill usage, DTC platforms offer a viable and convenient alternative to traditional doctor's office prescriptions.

The woman is the active agent: General practitioners and the agentive displacement of abortion in Ireland.

After the legalization of abortion in 2018, Ireland needed clinicians to become abortion providers and make this political win a medical reality. Yet Irish doctors had next-to-no training in abortion care, and barriers ranging from stigma to economic pressures in the healthcare system impacted doctors' desire to volunteer. How did hundreds of Irish doctors make the shift from family doctor to abortion provider? Drawing on ethnographic research conducted between 2017 and 2020, this article explores the process by which Irish general practitioners became abortion providers, attending to the material impact of medical technologies on that journey. Drawing from medical anthropologists who have examined similar themes of agency, pharmaceuticals, and medico-legal frameworks within the topic of assisted dying, I build on Anita Hannig's idea of "agentive displacement" to frame the productive impact of abortion pills on this transition.

Comparative Pharmacokinetics Research of 13 Bioactive Components of Jieyu Pills in Control and Attention Deficit Hyperactivity Disorder Model Rats Based on UPLC-Orbitrap Fusion MS.

Jieyu Pills (JYPs), a Chinese medicine consisting of 10 herbal elements, have displayed promising clinical effectiveness and low by-effects in the treatment of depression. Prior investigations mostly focused on elucidating the mechanism and therapeutic efficacy of JYPs. In our earlier study, we provided an analysis of the chemical composition, serum pharmacochemistry, and concentrations of the main bioactive chemicals found in JYPs. However, our precise understanding of the pharmacokinetics and metabolism remained vague. This study involved a comprehensive and meticulous examination of the pharmacokinetics of 13 bioactive compounds in JYPs. Using UPLC-Orbitrap Fusion MS, we analyzed the metabolic characteristics and established the pharmacokinetic parameters in both control rats and model rats with attention deficit hyperactivity disorder (ADHD) following oral administration of the drug. Before analysis, plasma samples that were collected at different time intervals after the administration underwent methanol pre-treatment with Puerarin used as the internal standard (IS) solution. Subsequently, the sample was chromatographed on a C18 column employing gradient elution. The mobile phase consisted of methanol solution containing 0.1% formic acid in water. The electrospray ionization source (ESI) was utilized for ionization, whereas the scanning mode employed was selected ion monitoring (SIM). The UPLC-Orbitrap Fusion MS method was subjected to a comprehensive validation process to assess its performance. The method demonstrated excellent linearity (r ≥ 0.9944), precise measurements (RSD < 8.78%), accurate results (RE: -7.88% to 8.98%), and appropriate extraction recoveries (87.83-102.23%). Additionally, the method exhibited minimal matrix effects (87.58-101.08%) and satisfactory stability (RSD: 1.52-12.42%). These results demonstrated adherence to the criteria for evaluating and determining biological material. The 13 bioactive compounds exhibited unique pharmacokinetic patterns in vivo. In control rats, all bioactive compounds except Ferulic acid exhibited linear pharmacokinetics within the dose ranges. In the ADHD model, the absorption rate and amount of most of the components were both observed to have increased. Essentially, this work is an important reference for examining the metabolism of JYPs and providing guidelines for clinical therapy.

Abortion pill marketing and sourcing on twitter following Dobbs v. Jackson supreme court ruling.

OBJECTIVE: This study examines abortion-related discourse on Twitter (X) pre-and post-Dobbs v. Jackson ruling, which eliminated the constitutional right to abortion. STUDY DESIGN: We used a custom data collection tool to collect tweets directly from Twitter using abortion-related keywords. We used the BERTopic language model and examined the top 30 retweeted and top 30 textually similar tweets from relevant topic clusters using an inductive coding approach. We also conducted statistical testing to assess potential associations between abortion themes. RESULTS: 166,799 unique tweets were collected from December 2020-December 2022. 464 unique tweets were coded for abortion-related themes with 154 identified as relevant. Of these, 66 tweets marketed abortion pills, 17 tweets were identified as offering consultations, and 91 tweets were relevant to self-managed abortion. All marketing and consultation tweets were posted post-Dobbs decision and 7 (7.69%) of self-managed tweets were posted pre-Dobbs versus 84 (92.30%) posted post-Dobbs. A positive association was found between tweets offering a medical consultation with tweets marketing abortion pills and discussing self-managed abortion. CONCLUSION: This study detected online marketing of abortion pills, consultations and discussions about self-managed abortion following the Dobbs v. Jackson ruling. These results provide more context to the type of abortion-related information that is available online.

This study examined tweets occurring both pre and post Dobbs decision and identified relevant discussions about self-managed abortion services, marketing and sale of abortion pills, and offering purported medical consultations. These findings indicate that abortion-related tweets, particularly those marketing abortion medications, increased after the Dobbs v. Jackson ruling. These findings highlight the evolving abortion information environment in the United States on Twitter, which represents a platform where health and politicised issues are commonly discussed.

Efficacy of Danzhixiaoyao tablets combined with methylcobalamin tablets in the treatment of burning mouth syndrome: an open-label, randomized controlled trial.

OBJECTIVES: This randomized controlled trial compared the efficacy and tolerability of danzhixiaoyao pills in the accurate treatment of patients with burning mouth syndrome (BMS). METHOD: Collect a total of 78 patients (75 female patients and 3 male patients) from the oral mucosa department who were considered eligible fromOctober 2020 to October 2022.The patients were randomized and divided into trial group and control group.The trail group received danzhixiaoyao pills and mecobalamine tablets while the control group was given mecobalamine tablets.The Visual Analogue Scale (VAS), Beck Anxiety Inventory(BAI), Beck Depression Inventory (BDI), Oral Health Impact Profile (OHIP-14), Traditional Chinese medicine(TCM) syndrome integral and adverse reactions were performed at baseline and after 2, 4, and 6 weeks of treatment. Descriptive statistics, including the Wilcoxon rank-sum test and the Chi-square test for median comparisons between different times, were used. RESULT: 1.After treatment, the VAS, BDI,OHIP-14, and TCM syndrome integral in the trial group had a significant decrease than the control group(P< 0.05).However, there was no statistical difference in the BAI scores between the two groups (P> 0.05). 2.According to the efficacy determination criteria , the total effective rate of the test group was 73.68% , the control group was 52.94% and the recurrence rate was 0. There was a significant difference between the two groups (Z=-2.688, P < 0.05). The results showed that the curative effect of test group was better than that of control group.3. No adverse effects occurred in patients in either group. CONCLUSION: Danzhixiaoyao pills has demonstrated to have a positive effect in relieving BMS symptoms and in improving a patient's overall quality of life with no AEs compared with the control group. The efficacy evaluation systems that can be verified and complementary in this study provide a perfect, effective and referential evaluation system for the use of Chinese patent medicine in the treatment of oral mucosal diseases. TRIAL REGISTRATION: Registry name: Chinese Clinical trail Registry Registration number: ChiCTR2000038189 Date of Registration: 2020-09-13 Please visit ( https://www.chictr.org.cn/showproj.html?proj=61462 ) to the protocol.

[Establishment and Optimization of Quality Standards for the Traditional Tibetan Medicine Preparation of Liuwei Nengxiao Pills]. / è—è¯å ­å‘³èƒ½æ¶ˆä¸¸è´¨é‡æ ‡å‡†çš„å»ºç«‹ä¸Žä¼˜åŒ–.

Objective: To establish quality standards for Liuwei Nengxiao pills, to optimize the quality control method, and to provide references for the quality control of Liuwei Nengxiao pills. Methods: Chebula, dried ginger, and Tibetan liqueur root in Liuwei Nengxiao pills of different batch numbers were analyzed by thin layer chromatography (TLC). Then, the content of chrysophanol in the preparation was determined by high performance liquid chromatography (HPLC). Furthermore, a series of methodological validation, including the investigation of the linear relationship, precision, stability, and reproducibility and sample recovery test, were performed to verify the reliability of the results. Results: The TLC identification method was easy to perform and demonstrated high specificity, clear spots, and good separation effect. In addition, the negative controls showed no interference. The HPLC method showed high accuracy. The results of methodological validation showed that the peak area of chrysophanol had a good linear relationship (r2=1.0) in the range of 0.06-0.80 µg, presenting good precision (with the relative standard deviation being lower than 2.0%), good stability and reproducibility (with the relative standard deviation being lower than 1.0%), and an average recovery rate of 100.8%. Conclusion: TLC and HPLC are easy to perform, showing high accuracy and reproducibility. The quality standards established are scientific, reasonable, stable, and feasible, providing references for the quality control of Liuwei Nengxiao pills.

[Effect of Shoutai Pills on expression of key glycolytic proteins and apoptosis related factors at maternal fetal interface in mouse model of threatened abortion with syndrome of kidney deficiency].

This study aims to explore the mechanism of Shoutai Pills in treating threatened abortion. According to the random number table method, ICR female mice were randomized into a normal group, a model group, a dydrogesterone group, and a Shoutai Pills group, with 15 mice in each group. Mice were administrated with normal saline(normal and model groups) or the suspension of Shoutai Pills or dydrogesterone by gavage at 9:00 am every day. At 16:00 every day, mice in the normal group were administrated with an equal volume of distilled water, while those in the model, Shoutai Pills, and dydrogesterone groups were administrated with hydrocortisone solution by gavage for 4 consecutive days. ICR female and male mice were caged in a ratio of 2∶1 during the pre-estrous or estrous period. From the first day of pregnancy, drug administration was continued for 5 consecutive days. On day 6, mice were administrated with mifepristone by gavage to establish the model of kidney deficiency-induced abortion. On day 6 of pregnancy, 10 female ICR mice were randomly selected from each group, and the uterus was collected for observation of the pathological changes of trophoblasts at the maternal-fetal interface by hematoxylin-eosin(HE) staining. The protein levels of key enzymes of glycolysis, hexokinase 2(HK2), enolase 1(ENO1), pyruvate kinase M2(PKM2), and lactate dehydrogenase A(LDHA), were determined by Western blot and immunofluorescence. The expression of apoptosis-related proteins including B cell lymphoma-2(Bcl-2), Bcl-2-associated protein X(Bax), and cysteinyl aspartate-specific proteinase-3(caspase-3) was determined by Western blot and real-time PCR. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling was employed to examine apoptosis. The embryo loss rate of the remaining five female mice was calculated by trypan blue staining method on day 14 of pregnancy. On day 14 of pregnancy, the embryo loss rate of the normal group was 5.00%, which was lower than that(27.78%) in the model group(P<0.05). Dydrogesterone and Shoutai Pills groups showed reduced embryo loss rates(10.26% and 7.50%, respectively) compared with the model group. On day 6 of pregnancy, compared with the normal group, the model group showed down-regulated expression of HK2, ENO1, PKM2, LDHA, and Bcl-2 and up-regulated expression of Bax and caspase-3(P<0.05). Compared with the model group, dydrogesterone and Shoutai Pills up-regulated the expression of HK2, ENO1, PKM2, LDHA, and Bcl-2 and down-regulated the expression of Bax and caspase-3(P<0.05). Compared with that in the normal group, the apoptosis rate in the model group increased(P<0.05). Compared with the model group, dydrogesterone and Shoutai Pills reduced the apoptosis rate(P<0.05). In conclusion, Shoutai Pills can reduce the embryo loss rate and protect embryos by promoting aerobic glycolysis at the maternal-fetal interface and inhibiting the apoptosis of trophoblasts in mice.

[Effect and mechanism of Yueju Pills on breast cancer induced by DMBA in rats].

This paper aims to explore the inhibitory effect of Yueju Pills on breast cancer and decipher the underlying mechanism. A total of 92 SPF-grade SD female rats were involved in this study, and 14 of them were randomly selected into control group. The remaining 78 rats were administrated with 7,12-dimethylbenzanthracene(DMBA) by gavage to establish the breast cancer model. The modeled rats were randomized into model, tamoxifen(1.9 mg·kg~(-1)·d~(-1)), and low-and high-dose(17, 34 g·kg~(-1)·d~(-1)) Yueju Pills groups. The mental state, food intake, and activities of the rats were observed daily, and the body weight was measured on alternate days. After 12 weeks of administration, the rats were sacrificed and the tumor weight was measured. The serum estrogen and progeste-rone levels were determined by enzyme-linked immunosorbent assay. The histopathological changes of the breast and tumor were observed by hematoxylin-eosin staining. Western blot was employed to measure the protein levels of glucose transporter 1(GLUT1), lactate dehydrogenase A(LDHA), phosphofructokinase muscle(PFKM), pyruvate kinase isozyme type M2(PKM2), hexokinase 2(HK2), nuclear factor-kappaB(NF-κB), and phosphorylated NF-κB. The intestinal microbiome was examined by 16S rRNA high-throughput sequencing. The results showed that compared with the model group, high and low-dose Yueju Pills showed the tumor inhibition rate of 15.8% and 64.5%, respectively, and the low dose group had stronger inhibitory effect. Compared with the control group, the model group presented elevated the levels of estrogen and progesterone in serum. The administration of Yueju Pills lowered such ele-vation, and the low-dose group showed stronger lowering effect(P<0.05). Compared with the model group, Yueju Pills reduced the glands with increased breast tissue, the degree of breast duct expansion, the number and area of acinar cavity, the secretions, and the layers of mammary epithelial cells. Furthermore, Yueju Pills down-regulated the expression of GLUT1, LDHA, PFKM, PKM2, HK2, and NF-κB(P<0.05) and altered the diversity, composition, structure, and abundance of intestinal flora. The results showed that Yueju Pills could inhibit breast cancer by regulating the secretion of estrogen and progesterone, glycolysis, inflammatory cytokines, and intestinal flora.

[Zuogui Pills improve testicular development of offspring rats exposed to prenatal stress via Cx43].

This study aims to reveal the mechanism of prenatal stress in affecting the testicular development of offspring rats and the intervention effects of Zuogui Pills via connexin 43(Cx43). Forty pregnant SD rats were randomized into a blank control group, a mo-del group, a high-dose(18.9 g·kg~(-1)) Zuogui Pills group, a low-dose(9.45 g·kg~(-1)) Zuogui Pills group, and a vitamin E(1.44 mg·kg~(-1)) group. The other groups except the blank control group was subjected to chronic unpredictable mild stress for the modeling of prenatal stress. The model was evaluated by sucrose preference test, open field test, and enzyme-linked immunosorbent assay(ELISA) of the glucocorticoid level. ELISA was employed to measure the thyroxine 4(T4), testosterone(T), and follicle-stimulating hormone(FSH) levels to assess kidney deficiency. Hematoxylin-eosin(HE) staining was employed to evaluate the status of testicular germ cells. An automatic sperm analyzer was used to measure the sperm quality. Immunofluorescence double staining was employed to detect the expression of Cx43 and follicle-stimulating hormone receptor(FSHR) in the testes of offspring rats. The mRNA and protein levels of Cx43, FSHR, phosphatidylinositol 3-kinase(PI3K), and protein kinase B(Akt) were determined by real-time fluorescence quantitative polymerase chain reaction and Western blot, respectively. Prenatal stress induced testicular development disorders in offspring rats. The HE staining results showed that on the day of birth, the model group had reduced seminiferous tubules in the testes, elevated FSH level in the serum, and lowered Cx43 level in the testicular tissue. Male offspring rats of 60 days old had reduced testicular spermatogenic function, decreased sperm quality, elevated FSH level and lowered T level in the serum, and down-regulated protein and mRNA levels of Cx43, FSHR, PI3K, and Akt in the testicular tissue. Zuogui Pills alleviated the abnormal development and dysfunction of testicles in the offspring rats caused by prenatal stress. In summary, Zuogui Pills may weaken the effects of prenatal stress on testicular development and spermatogenic function of offspring rats by activating the PI3K/Akt pathway to regulate Cx43 expression in the testicular tissue.