The Clinical Effect of Pretreatment with Heat-sensitive Moxibustion on Primary Dysmenorrhea and Its Influence on Uterine Artery Blood Flow： A Randomized， Blinded Controlled Trial / 中医杂志

ObjectiveTo compare the clinical effect of heat-sensitive moxibustion before menstruation and since the first day of menstruation on primary dysmenorrhoea （PD）， thereby optimizing the clinical treatment plan. MethodsSixty patients with PD were randomly divided into pretreatment group （treated before menstruation） and conventional treatment group （treated since the first day of menstruation） of 30 cases each. For all patients， the area surrounded by bilateral Zigong （EX-CA1） and bilateral Guilai （ST 29） in the supine position， and that formed by bilateral Shenshu （BL 23） and Ciliao （BL 32） in the prone position were selected for circling moxibustion （2 min）， sparrow-pecking moxibustion （1 min）， and then moxibustion along the channels to stimulate the moxibustion sensation and obtain two heat-sensitive points with the best sensation for treatment. In the pretreatment group， moxibustion was applied 3-7 days before the onset of menstruation， and in the conventional treatment group， moxibustion was applied on the day of menstruation. Both groups were treated once daily for 7 days per menstrual cycle for 3 consecutive cycles. The clinical outcomes of the two groups were measured before and after treatment in terms of the COX menstrual pain symptom scale （CMSS） scores， visual analogue scale for pain （VAS） scores， and uterine artery hemodynamic indicators including blood pulsation index （PI） and resistance index （RI）， and the clinical effect was compared. ResultsAfter treatment， the CMSS scores， VAS scores， PI and RI in the two groups decreased， and lower scores were found in the pretreatment group （P＜0.05 or P＜0.01）. The total effective rate after treatment was 93.3% （28/30） in the pretreatment group， which was better than 73.3% （22/30） in the conventional treatment group （P＜0.05）. ConclusionThe clinical effect of heat-sensitive moxibustion before the menstruation for PD was better than that implemented since the first day of menstruation， by significantly improving the patients' dysmenorrhoea symptoms and uterine artery blood flow index.

Material basis and mechanism of Curcuma longa tuberous roots with and without vinegar processing in treating primary dysmenorrhea / 中国中药杂志

Liquid chromatography-mass spectrometry was employed to analyze the chemical components in Curcuma longa tuberous roots(HSYJ), C. longa tuberous roots processed with vinegar(CHSYJ), and rat serum after the administration. The active components of HSYJ and CHSYJ absorbed in serum were identified based on the secondary spectrum of database and literature. The targets of primary dysmenorrhea was screened out from database. The protein-protein interaction network analysis, gene ontology(GO) functional annotation, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the common targets shared by the drug active components in serum and primary dysmenorrhea, and the component-target-pathway network was constructed. AutoDock was used to conduct molecular docking between the core components and targets. A total of 44 chemical components were identified from HSYJ and CHSYJ, including 18 absorbed in serum. On the basis of network pharmacology, we identified 8 core components(including procurcumenol, isobutyl p-hydroxybenzoate, ferulic acid, and zedoarondiol) and 10 core targets \[including interleukin-6(IL-6), estrogen receptor 1(ESR1), and prostaglandin-endoperoxide synthase 2(PTGS2)\]. The core targets were mainly distributed in the heart, liver, uterus, and smooth muscle. The molecular docking results showed that the core components were well bound to the core targets, indicating that HSYJ and CHSYJ may exert therapeutic effect on primary dysmenorrhea via estrogen, ovarian steroidogenesis, tumor necrosis factor(TNF), hypoxia-inducible factor-1(HIF-1), IL-17 and other signaling pathways. This study clarifies the HSYJ and CHSYJ components absorbed in serum, as well as the corresponding mechanism, providing a reference for further elucidating the therapeutic material basis and clinical application of HSYJ and CHSYJ.

Effects of electroacupuncture on NLRP3 inflammasome and pyroptosis protein GSDMD in uterine tissue in rats with primary dysmenorrhea / 中国针灸

OBJECTIVE@#To observe the effects of electroacupuncture (EA) on NLRP3 inflammasome and its downstream protein gastermin D (GSDMD) in rats with primary dysmenorrhea (PDM), and to explore the potential mechanism of EA on the treatment of PDM.@*METHODS@#Forty healthy female SD rats without pregnancy were randomly divided into a control group, a model group, an EA group and an ibuprofen group, 10 rats in each group. PDM model was prepared by injection of estradiol benzoate and oxytocin. Except the control group, the rats in each group were subcutaneously injected with estradiol benzoate for 10 days, and oxytocin was injected on the 11th day. The rats in the EA group were intervened with EA (dense wave, frequency of 50 Hz) at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) at the same time of modeling, once a day, 20 min each time, for 10 consecutive days. The rats in the ibuprofen group were treated with 0.8 mL of ibuprofen by gavage (concentration of ibuprofen solution was 1.25 mg/mL) for 10 consecutive days. After modeling, the writhing reaction was observed. After intervention, the HE staining method was used to observe the histological morphology of uterus and evaluate the pathological damage score of uterus; ELISA method was used to detect the serum levels of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α); Western blot method was used to detect the protein expression of NLRP3, apoptosis related spot like protein (ASC), caspase-1, GSDMD, GSDMD-N and inflammatory factors (interleukin [IL]-1β, IL-18) in uterine tissue.@*RESULTS@#In the model group, a large number of vacuolar degeneration and death of endometrial epithelial cells, spiral arterioles congestion in lamina propria and neutrophil infiltration were observed. In the EA group, there was a small amount of vacuolar degeneration and death of endometrial epithelial cells, a small amount of spiral arterioles congestion in the lamina propria, and a small amount of neutrophils infiltration. In the ibuprofen group, there was very small number of degeneration and death of endometrial epithelial cells, and no obvious arterial congestion was found in lamina propria, and neutrophil infiltration was occasionally seen. Compared with the control group, in the model group the number of writhing was increased (P<0.01), the writhing reaction score and serum level of PGF2α and PGF2α/PGE2 value were increased (P<0.01), the level of PGE2 was decreased (P<0.01). Compared with the model group, in the EA group and the ibuprofen group the number of writhing were decreased (P<0.05), the latency of writhing was prolonged (P<0.01), the writhing reaction scores and serum levels of PGF2α and PGF2α/PGE2 values were decreased (P<0.05, P<0.01), the levels of PGE2 were increased (P<0.01). Compared with the control group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18 in the uterine tissues of rats was increased in the model group (P<0.01). Compared with the model group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1β and IL-18 in the uterine tissues of rats was decreased in the EA group and the ibuprofen group (P<0.01, P<0.05). There was no significant difference between the EA group and the ibuprofen group in the above indexes (P>0.05).@*CONCLUSION@#EA could alleviate pain and uterine tissue injury in rats with PDM. The mechanism may be related to the inhibition of the activation of NLRP3 inflammasome in rat uterine tissues, thereby inhibiting pyroptosis and its inflammatory factors release.

Effectiveness and Safety of Chinese Medicine at Shenque (CV 8) for Primary Dysmenorrhea: A Systematic Review and Meta-Analysis of Randomized Controlled Trials / 中国结合医学杂志

BACKGROUND@#Primary dysmenorrhea (PD) is the most common complaint associated with menstruation and affects up to three-quarters of women at some stage of their reproductive life. In Chinese medicine, navel therapy, treatment provided at Shenque (CV 8), is used as a treatment option for PD.@*OBJECTIVE@#To evaluate the effect of navel therapy on pain relief and quality of life in women with PD, compared with Western medicine (WM).@*METHODS@#China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), SinoMed and Wanfang Database, MEDLINE, the Cochrane Library, Embase, Web of Science, and the International Clinical Trial Registry of the U.S. National Institutes of Health were searched from their inceptions to April 1, 2021. Randomized controlled trials (RCTs) assessing therapeutic effects of navel therapy on PD were eligible for inclusion. RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool.@*RESULTS@#Totally 24 RCTs involving 2,614 participants were identified. Interventions applied to acupuncture point CV 8 included: herbal patching, moxibustion or combined navel therapy (using at least 2 types of stimulation). Compared to placebo, there was a significant effect in favor of navel therapy on reducing overall menstrual symptom scores at the end of treatment [mean difference: -0.82, 95% confidence interval (CI): -1.00 to -0.64, n=90; 1 RCT]. As compared with Western medicine, navel therapy had a superior effect on pain intensity as assessed by Visual Analogue Scale at the end of treatment [standardized mean difference (SMD): -0.64, 95% CI: -1.22 to -0.06, I2=80%, n=262; 3 RCTs]; on symptom resolution rate at 3-month follow-up (risk ratio: 1.94, 95% CI: 1.47 to 2.56, n=1527, I2=38%; 13 RCTs); and on global menstrual symptoms score at the end of treatment (SMD: -0.67, 95% CI: -0.90 to -0.45, I2=63%, n=990; 12 RCTs). Subgroup analyses showed either a better or an equivalent effect comparing navel therapy with Western medicine. No major adverse events were reported. The methodological quality of included trials was poor overall.@*CONCLUSIONS@#Navel therapy appears to be more effective than Western medicine in decreasing menstrual pain and improving overall symptoms of PD. However, these findings need to be confirmed by well-designed clinical trials with adequate sample size (Systematic review registration at PROSPERO, No. CRD42021240350).

A cross-sectional study depicting prevalence of primary dysmenorrhea in adolescent females of Hyderabad: A major urban center of South India

Background: Primary dysmenorrhea (PD) affects adolescent girls within 2 years of menarche and roughly 16–91% suffer from it, heavily incapacitating their educational and social life. Elevated prostaglandins (PG’s), especially PGF2? is alleged to be the culprit behind PD but the prevalence continues to remain variable across various geographical domains. Aim and Objectives: The aim of the study was to ascertain the prevalence of PD and to determine the association between PD and body mass index (BMI). Materials and Methods: A cross-sectional study 250 randomly selected adolescent girls was conducted across different government and private schools of Hyderabad. The participants were asked to fill a self-administered questionnaire which included sociodemographic details, anthropometric measurements, and complete menstrual history including the prevalence and severity of PD. Participants were segregated into four groups according to the Revised IAP BMI charts and the intensity of pain was scored by Numerical Pain Rating Scale. Results: The prevalence of PD was estimated to be 70% with 34.7% complaining of severe PD. About 42.4% participants reported to suffer from PD, a day before menstrual flow and the most commonly associated symptoms were nausea and fatigue. About 52.68% participants suffered from PD every month. While assessing the impact of BMI on PD, the prevalence and severity of PD were found higher in overweight and obese participants and the difference was statistically significant. Lower age of menarche, longer cycles, and heavier flow were associated with increased risk of PD. Conclusion: PD is physically and emotionally challenging and as rising adolescent obesity is a correctible predisposing factor, there is an urgent need to acknowledge the issue.

Ayurvedic Management of Primary Dysmenorrhea with Abhayatrivrudadi Kashayam- Case Report

Dysmenorrhea, one of the most prevalent gynaecological problems in young women, particularly among teenagers, characterized by painful menstruation severe enough to prevent a person from doing day-to-day activities. It is the main factor behind young women's missed job and school days of teenagers. Primary dysmenorrhea is widely prevalent in more than 70% of teenagers and 30 -50% of menstruating women. Among Yonirogas, Udavarta yonivyapat is a condition characterized by painful menstruation and the relief of discomfort following blood discharge, which is typical of primary dysmenorrhea. In modern medical science, various forms of treatments are available for the relief of Primary dysmenorrhea which includes antispasmodic, analgesics, prostaglandin synthesis inhibitors, hormonal therapy etc. Reluctance of young girls and ladies to adopt the hormone therapies bring them to Ayurvedic treatment or any other alternative treatment of their choice. Ayurvedic management aims at vatanulomana through Snehana, Swedana, Vasti along with Samana oushadha which can alleviate Vata. Abhayatrivrudadi kashaya mentioned in the context of Udavarta chikitsa from Chikitsa manjari consists of Abhaya, Trivrut, Kulatha, Pippali and Eranda taila. Properties of this yoga include Vatanulomana, Sulaghna and Udavartahara. An 18 year old girl complained with severe pain during menstruation, low back ache, nausea and vomiting came to the OPD of Prasutitantra & Streeroga, Government Ayurveda College, Tripunithura is taken for this study. It is evident from the case study that Abhayatrivrudadi kashaya is effective in the management of primary dysmenorrhea.

NLRP3 Inflammasome in the Pathogenesis of Dysmenorrhea and Role of Mefenamic Acid as its Inhibitor

While the role of prostaglandin as a trigger in dysmenorrhea is well known, not many are aware that inflammation and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome are also implicated in primary dysmenorrhea (PD). Inhibition of NLRP3 inflammasome and inflammation pathways is an important approach to treating dysmenorrhea and also the symptoms of premenstrual syndrome. Mefenamic acid is an effective and selective inhibitor of the NLRP3 inflammasome, which can be considered the most important option for PD treatment owing to its action via various pathways. In this article, the authors have reviewed the role of inflammation and NLRP3 inflammasome in causing PD, how inhibitors of NLRP3 inflammasome can treat dysmenorrhea and the mechanism of action of mefenamic acid as NLRP3 inflammasome inhibitor and its role in PD.

Role of Prostaglandins in Pathogenesis of Dysmenorrhea and Place of Mefenamic Acid and Dicyclomine in its Management

Despite being one of the most common gynecological issues faced by women of reproductive age, dysmenorrhea largely remains an ignored, underdiagnosed and untreated condition. It continues to be a public health issue and has a significant impact on the quality of life of the affected women in terms of inability to lead routine activities, absenteeism from academic activities or work and reduced social activities. Currently, existing evidence correlates and implicates the excessive synthesis of prostaglandins with the menstrual pain. Hence, treatment approaches that can inhibit prostaglandins' production or already formed prostaglandins can provide relief in dysmenorrhea. In this review, the impact of dysmenorrhea on the quality of life of women, the role of prostaglandins in the pathogenesis of dysmenorrhea, and how nonsteroidal anti-inflammatory drugs (NSAIDs) like mefenamic acid can be safe and effective in managing dysmenorrhea are discussed.

Research Progress on Dysemenorrhea of Essential Oils of Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Dysmenorrhea is a common gynecological disease in clinic， with primary dysmenorrhea and secondary dysmenorrhea. Primary dysmenorrhea is usually not accompanied by organic lesions in genital organs， which is mainly related to the increase of prostaglandin content in endometrium during menstruation. Secondary dysmenorrhea is accompanied by organic lesions of reproductive organs， often associated with local lesions of reproductive organs， but also with patients' mental factors and neuroendocrine factors.The incidence of dysmenorrhea is as high as 73.8%， and there is no radical cure method， which has a great impact on the life， work and learning of patients. Chinese medicine essential oil widely exists in aromatic Chinese medicine， with antibacterial， antioxidant and anticancer activities. It can regulate neuroendocrine function， anti-inflammatory and analgesic effects， and improve mood by regulating the levels of prostaglandins， oxytocin and other hormones in the body and regulating the emotions of patients， there by alleviating dysmenorrhea to a certain extent. In recent years， many scholars have made more in-depth research on Chinese medicine essential oil in alleviating dysmenorrhea， but there is a lack of comprehensive collation of such studies. In this regard， the author has systematically sorted out the generation and classification of dysmenorrhea， the mechanism of action of essential oil of traditional Chinese medicine to alleviate dysmenorrhea and the application of essential oil of traditional Chinese medicine in the field of dysmenorrhea by consulting relevant literature in Chinese and foreign languages in recent years， so as to provide reference for the treatment of dysmenorrhea.

Effectiveness and Safety of Moxibustion Robots on Primary Dysmenorrhea: A Randomized Controlled Pilot Trial / 中国结合医学杂志

OBJECTIVE@#To conduct a pilot trial to explore the effectiveness and safety of moxibustion robots in treating primary dysmenorrhea (PD) and evaluate its feasibility in clinic.@*METHODS@#A total of 70 participants with PD were allocated to either moxibustion robot (MR) group (35 cases) or manual moxibustion (MM) group (35 cases) using computer-generated randomization. One acupoint Guanyuan (CV 4) was selected to receive moxa heat stimulation. Two groups of participants were given 3 menstrual cycles of MM and MR treatment respectively (once a day, 5 days a session) and received another 3 menstrual cycles follow-up. The degree of pain was evaluated by short-form McGill pain questionnaire (SF-MPQ) and the symptoms of dysmenorrhea were evaluated by Cox Menstrual Symptom Scale (CMSS). The safety was measured by the occurrence rate of adverse events (AEs), including burns (blisters, red and swollen), itching, bowel changes, menstrual cycle disorder, menorrhagia and fatigue, etc. RESULTS: A total of 62 patients completed the trial, 32 in MR group and 30 in MM group. Compared with baseline, scores of SF-MPQ and CMSS significantly decreased in both groups (P0.05). The total occurrence rate of AEs in MR group was 2.1%, which was significantly lower than MM group (7.2%, P<0.05).@*CONCLUSIONS@#MR has the same effect as MM at SF-MPQ and CMSS in patients with PD. However, MR is safer than MM (Trial registration No. ChiCTR1800018236).

Mechanism of Danggui Sini Decoction in treatment of primary dysmenorrhea based on network pharmacology and molecular docking / 中国中药杂志

Network pharmacology, molecular docking and in vivo experiments were used to explore the pharmacodynamic basis and potential mechanism of Danggui Sini Decoction in the treatment of primary dysmenorrhea(PD). The chemical constituents of Danggui(Angelicae Sinensis Radix), Guizhi(Cinnamomi Ramulus), Tongcao(Tetrapanacis Medulla), Baishao(Paeoniae Radix Alba), Xixin(Asari Radix et Rhizoma), Gancao(Glycyrrhizae Radix et Rhizoma), and Dazao(Jujubae Fructus) from Danggui Sini Decoction were retrieved through TCMSP(Traditional Chinese Medicine Systems Pharmacology Database), and the action targets of Danggui Sini Decoction were collected through DrugBank. "Primary dysmenorrhea" and "dysmenorrhea" were used as the key words to search the corresponding targets in the GeneCards, OMIM and TTD databases, and then the intersection targets of Danggui Sini Decoction and the primary dysmenorrhea targets were taken for reverse screening to obtain the corresponding active ingredients. Cytoscape 3.6.1 software was used to construct a traditional Chinese medicine-compound-target-disease network; STRING database was used to build a protein-protein interaction(PPI) network; Gene ontology(GO) function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were conducted by using DAVID database. The action mechanism of the intersection targets were then predicted, and a histogram chart and bubble chart were drawn for visualization. Then the top five targets in the PPI network were used for docking with the most compounds. In animal experiments, Sprague Dawley(SD) female rats were used to establish a primary dysmenorrhea model by intraperitoneal injection of diethylstilbestrol once a day. A total of 60 SD female rats were randomly divided into 6 groups, namely control group, model group, Danggui Sini Decoction low(1.5 g·kg~(-1)), medium(3.0 g·kg~(-1)), high(6.0 g·kg~(-1)) dose groups, and ibuprofen(20 mg·kg~(-1)) positive control group, with 10 rats in each group. From day 4, except for the control group, rats in the other groups were given intragastric administration of corresponding drugs, and the control group received intragastric administration of normal saline for 7 consecutive days. The number of writhing before and after the administration, the ute-rine contraction inhibition rate and the uterine index after administration were observed, and ELISA assay was used to detect the levels of prostaglandin-endoperoxide synthase 2(PTGS2) and vascular endothelial growth factor A(VEGFA) in the tissues of each group as well as the levels of serum inflammatory factors interleukin 1(IL-1), interleukin 6(IL-6), and tumor necrosis factor-alpha(TNF-α). According to network analysis, 7 Chinese medicines contained 114 active ingredients, 149 targets, and 30 common target genes with PD were obtained. The key targets included VEGFA, IL6, PTGS2, TNF, etc.; GO function enrichment analysis showed a total of 399 terms(P<0.05) were obtained, 353 of which were biological process(BP) terms, 21 were cell composition(CC) terms, and 25 were molecular function(MF) terms. In KEGG pathway enrichment analysis, 14 signaling pathways were obtained, 3 of which were related to inflammation, namely arachidonic acid metabolism, MAPK signaling pathway and NOD-like receptor signaling pathway. The compounds in Danggui Sini Decoction can play a therapeutic role in the treatment of PD by acting on VEGFA, IL-6, PTGS2, TNF and other targets to regulate arachidonic acid and inflammatory signaling pathways.

Analgesic Effect and Action Mechanisms of Wenjing Zhitong Prescription on Primary Dysmenorrhea / 中国实验方剂学杂志

Objective:To evaluate the analgesic effects of Wenjing Zhitong prescription （WZP） and explore its possible analgesic mechanisms so as to provide experimental basis for research and development of new Chinese medicine. Method:Analgesic effects of WZP were evaluated by observing the writhing latency and number in the writhing models which were induced by oxytocin in rats as well as those induced by acetic acid and prostaglandin E₁ （PGE₁）， respectively in mice. Effect of WZP on uterine contraction frequency， amplitude and activity were evaluated by observing the oxytocin-induced contraction of uterine smooth muscle in rats and rabbits <italic>in vivo</italic>. In the oxytocin-induced rat writhing models， the content of prostaglandin F₂<italic>_α</italic>（PGF₂<italic>_α</italic>） and prostaglandin E₂（PGE₂） in rat uterine tissues and the content of beta-endorphins （<italic>β</italic>-EP） in rat serum were detected by enzyme-linked immunosorbent assay （ELISA）. Expression of estrogen receptor （ER） and oxytocin receptor （OTR） in rat uterine were tested by Real-time polymerase chain reaction（Real-time PCR） method to investigate the possible molecular mechanism of WZP for its analgesic effect. Result:Results of analgesic effect showed that in oxytocin-induced rat writhing experiment， the number of writhing responses in both the WZP （1.5，3.0 g·kg^-1） group was lower than than in the model group （<italic>P</italic><0.05）. In acetic acid-induced mice writhing experiment， the latency of writhing response in WZP （6.0 g·kg^-1） group was significantly prolonged as compared with that in model group <italic>（P</italic><0.01）， and the number of writhing response was significantly reduced （<italic>P</italic><0.05）. In PGE₁-induced mice writhing model， the writhing number in WZP （1.5，3.0，6.0 g·kg^-1） groups was significantly lower than that in the model group （<italic>P</italic><0.05，<italic>P</italic><0.01）. Results of effect on uterine smooth muscle demonstrated that WZP （0.38，0.75，1.50 g·kg^-1） could significantly reduce the frequency of uterine smooth muscle contraction in rabbits （<italic>P</italic><0.05，<italic>P</italic><0.01）， WZP （0.75，1.50，3.00 g·kg^-1） could significantly reduce the contractile amplitude and activity of smooth muscle in the uterus of rats （<italic>P</italic><0.05）. Results of molecular mechanisms of analgesic effects showed that the WZP （0.75，1.50，3.00 g·kg^-1） significantly reduced the content of PGF₂<italic>_α</italic> and the ratio of PGF₂<italic>_α</italic> to PGE₂ in the uterine tissue of rats （<italic>P</italic><0.01）. In the WZP （3.00 g·kg^-1） group， the levels of <italic>β</italic>-EP in the serum of rats were significantly increased （<italic>P</italic><0.01）， and the levels of OTR in uterus of rats in the WZP （1.50，3.00 g·kg^-1） group were significantly decreased （<italic>P</italic><0.05）. Conclusion:Pharmacological studies demonstrated potent analgesic effect of WZP， and such analgesic effect were mediated by significantly inhibiting contraction of uterine smooth muscle， decreasing the contents of PGF₂<italic>_α </italic>and ratio of PGF₂<italic>_α</italic>/PGE₂， reducing OTR expression in uterine as well as increasing the amount of <italic>β</italic>-EP in serum.

Mechanisms of Wenjing Huayu Zhitong Therapy for Primary Dysmenorrhea with Cold Coagulation and Blood Stasis Syndrome Based on MAPK/ERK Signaling Pathway / 中国实验方剂学杂志

Objective:To study the effect of Wenjing Huayu Zhitong therapy （Xiangyan Zhitong prescription， XZP） on the mitogen activated protein kinase （MAPK）/extracelluar regulated protein kinase （ERK） signaling pathway of primary dysmenorrhea （PD） rats， and explore the pathogenesis of PD and the mechanism of action of Wenjing Huayu Zhitong therapy. Method:Forty-eight female SPF-grade Wistar rats were randomly divided into blank group，model group， western medicine group， low-dose XZP group， medium-dose XZP group， and high-dose XZP group， with 8 rats in each group. In addition to the blank group， dysmenorrhea rat model with cold coagulation and blood stasis syndrome was established by cold stimulation combined with estradiol benzoate and oxytocin. The rats in the blank group，model group，western medicine group， low-dose XZP group， medium-dose XZP group， and high-dose XZP group were given distilled water， distilled water，0.06 g·kg^-1 ibuprofen， 6.55 g·kg^-1 XZP， 13.09 g·kg^-1 XZP， and 26.18 g·kg^-1 XZP， respectively， by gavage for 6 days. The writhing latency and writhing frequency of rats were recorded within 30 min after oxytocin injection.Western blot was used to detect the protein expression of B-Raf， mitogen activates extracellular regulated kinases1/2 （MEK1/2）， extracellular regulated kinases1/2 （ERK1/2）， p-MEK1/2， p-ERK1/2， c-Jun， and cyclooxygenase-2 （COX-2） in rat uterus. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to detect the mRNA expression of B-Raf， MEK1， MEK2， ERK1， ERK2， c-Jun， and cyclooxygenase-2 （COX-2） in rat uterus. Result:Compared with the model group，the treatment groups showed insignificantly prolonged writhing latency and significantly reduced writhing frequency （<italic>P</italic><0.01）. On the 6^th day of modeling， there was no significant difference in the quantitative scores of symptoms and signs among the treatment groups. On the 12^th day of modeling， the scores changed little in the western medicine group and the low-dose XZP group and decreased significantly in the medium- and high-dose XZP groups （<italic>P</italic><0.01） compared with those in the model group. Compared with those in the blank group， the protein and mRNA levels of p-MEK1/2， p-ERK， B-Raf， c-Jun， and COX-2 in the model group were significantly up-regulated （<italic>P</italic><0.01）. Compared with those in the model group， the protein and mRNA levels of p-MEK1/2， p-ERK1/2， B-Raf， c-Jun， and COX-2 in the western medicine group， medium-dose XZP group， and high-dose XZP group were significantly down-regulated （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:The mechanism of Wenjing Huayu Zhitong therapy in treating PD with cold coagulation and blood stasis syndrome may be related to the down-regulation of MAPK/ERK signaling pathway.

Role of Puerariae Lobatae Radix in Gegen Decoction for treatment of primary dysmenorrhea / 中国中药杂志

This study aimed to explore the characteristic role of Puerariae Lobatae Radix(PLR) in Gegen Decoction for the treatment of primary dysmenorrhea(PD). Estrogen(E_2) was combined with oxytocin to establish a mouse model of PD. The mice were randomly divided into a normal group, a model group, a Gegen Decoction group, a PLR-free Gegen Decoction group, a PLR group, and a positive drug group(ibuprofen). Writhing response times and writhing incubation of mice in each group were tested by behavio-ral assessment, and the serum levels of prostaglandin F_(2α)(PGF_(2α)), prostaglandin E_2(PGE_2), E_2, and progesterone(PROG) were detected by ELISA kits. Western blot method was adopted to detect cyclooxygenase-2(COX-2) and estrogen receptor alpha(ER_α) expression levels in uterine tissues. Doppler ultrasound was employed to detect changes in uterine artery blood flow in mice, including peak systolic blood flow velocity(maximum velocity), end-diastolic velocity(minimum velocity), peak systolic blood flow velocity/end-diastolic velocity(S/D), pulsatility index(PI), and resistive index(RI). Histopathological changes in the uterus were detected by HE staining. Based on the oxytocin-induced isolated uterine contraction model, the effects of Gegen Decoction, PLR-free Gegen Decoction, and PLR on the amplitude, frequency, and activity of isolated uterine contraction were compared to investigate the role of PLR in Gegen Decoction for the treatment of PD. The results showed that compared with the Gegen Decoction group, the PLR-free Gegen Decoction improved the indicators of PD except for E_2 content, ER_α expression, and uterine artery blood flow. PLR could significantly down-regulate the serum content of E_2 and the protein expression of uterine ER_α, and improve the uterine artery blood flow. The data suggested that PLR, as the sovereign drug of Gegen Decoction, might function in Gegen Decoction for the treatment of PD by mediating E_(2 )and improving the uterine artery blood flow.

Different stimulation methods on auricular points for primary dysmenorrhea: a randomized controlled trial / 中国针灸

OBJECTIVE@#To prove the therapeutic effect of auricular intradermal needling and auricular point sticking on primary dysmenorrhea (PD), and to explore its mechanism.@*METHODS@#A total of 90 patients with PD were randomized into an auricular intradermal needling group, an auricular point sticking group and a placebo group, 30 cases in each one. Neishengzhiqi (TF@*RESULTS@#Compared before treatment, the scores of CMSS, VAS and SAS were decreased at each time point of treatment in the auricular intradermal needling group, 2, 3 courses into treatment and at follow-up in the auricular point sticking group and 3 courses into treatment in the placebo group (@*CONCLUSION@#Auricular intradermal needling and auricular point sticking can both improve the clinical symptom of primary dysmenorrhea, relieve the pain and anxiety, their mechanism may be related to regulating the serum levels of PGF

Dexketoprofen más pamabrom versus acetaminofen en dismenorrea primaria: estudio controlado, randomizado, doble ciego, multicéntrico / Dexketoprofen plus pamabrom versus acetaminophen in primary dysmenorrhea: a controlled, randomized, double-blind, multicenter study

RESUMEN Introducción: se sabe que las concentraciones plasmáticas de hormona antidiurética o vasopresina son más altas en las mujeres con dismenorrea primaria (DiPr) y podría ser causa de retención de agua con signos y síntomas concomitantes que agravan su cuadro clínico. La monoterapia con AINEs en ocasiones alcanza solo un alivio parcial porque no incide sobre la vasopresina. Objetivo: evaluar la eficacia y tolerabilidad del dexketoprofeno + pamabrom en la DiPr tomando como referencia el acetaminofén. Materiales y métodos: estudio doble ciego, controlado, randomizado, en pacientes con DiPr asignados al azar. Fueron aleatorizadas 172 pacientes, 86 en cada grupo 1) Grupo casos (DP): dexketoprofeno + pamabrom o 2) Grupo control (AC): acetaminofén. Se evaluó la evolución de la intensidad del dolor, el alivio del dolor, la gravedad de otros síntomas presentes y la satisfacción global del médico y paciente. Se registró las reacciones adversas. Resultados: la disminución de la intensidad del dolor, de los síntomas acompañantes y el alivio del dolor evaluados por la EVA, la PID, la SPID, el PAR y el TOTPAR respectivamente es mayor y más rápida de modo significativo en todos los tiempos para la combinación DP. Las reacciones adversas fueron mínimas. La satisfacción global de pacientes y médicos respecto al tratamiento es significativa a favor de la combinación DP. Conclusiones: dexketoprofeno + pamabrom es significativamente más eficaz y rápido en el control del dolor y otros síntomas presentes en la dismenorrea primaria que acetaminofén demostrando la validez de añadir un diurético suave a un AINE para incrementar su eficacia. El tratamiento DP es bien tolerado (AU).

ABSTRACT Background: It is known that plasma concentrations of antidiuretic hormone or vasopressin are higher in women with primary dysmenorrhea (DiPr) and could cause water retention with concomitant signs and symptoms that aggravate the illness. Monotherapy with NSAIDs sometimes achieves only partial relief because it does not affect vasopressin. Objective: The aim was to evaluate the efficacy and tolerability of dexketoprofen + pamabrom in DiPr taking as reference acetaminophen. Materials and methods: Double-blind, controlled, randomized study in patients with DiPr random to 1) Case group (PD): dexketoprofen + pamabrom or 2) Control group (CA): acetaminophen. The evolution of pain intensity, pain relief, severity of other present symptoms and overall satisfaction of the doctor and patient were evaluated. Adverse reactions were recorded. Results: 172 patients were randomized, 86 in each group. The decrease in pain intensity, accompanying symptoms and pain relief evaluated by VAS, PID, SPID, PAR and TOTPAR respectively is significantly greater and faster at all times for the combination DP. Adverse reactions were minimal. The overall satisfaction of patients and doctors regarding treatment is significant in favor of the DP combination. Conclusions: Dexketoprofen + pamabrom is significantly more effective and faster in the control of pain and other symptoms present in primary dysmenorrhea than acetaminophen demonstrating the validity of adding a mild diuretic to an NSAID to increase its effectiveness. DP treatment is well tolerated (AU).

The relationship between serum ischemia-modified albumin levels and uterine artery doppler parameters in patients with primary dysmenorrhea

Abstract Objective Primary dysmenorrhea occurs due to abnormal levels of prostanoids, uterine contractions, and uterine blood flow. However, the reasons for pain in primary dysmenorrhea have not yet been clarified. We examined the blood flow alterations in patients with primary dysmenorrhea and determined the relationship between ischemia-modified albumin (IMA) levels, as an ischemia indicator, and primary dysmenorrhea. Methods In the present study, 37 patients who had primary dysmenorrhea and were in their luteal and menstrual phase of their menstrual cycles were included. Thirty individuals who had similar demographic characteristics, who were between 18 and 30 years old and did not have gynecologic disease were included as control individuals. Their uterine artery Doppler indices and serum IMA levels were measured. Results Menstrual phase plasma IMA levels were significantly higher than luteal phase IMA levels, both in the patient and in the control groups (p < 0.001). Although the menstrual phase IMA levels of patients were significantly higher than those of controls, luteal phase IMA levels were not significantly different between the two groups. Menstrual uterine artery pulsatility index (PI) and resistance index (RI) of primary dysmenorrhea patients were significantly different when compared with luteal uterine artery PI and RI levels. There was a positive correlation between menstrual phase IMA and uterine artery PI and RI in the primary dysmenorrhea. Conclusion Ischemia plays an important role in the etiology of the pain, which is frequently observed in patients with primary dysmenorrhea. Ischemia-modified albumin levels are considered as an efficient marker to determine the severity of pain and to indicate ischemia in primary dysmenorrhea.

Características sociodemográficas e avaliação da dor através do questionário de McGill em mulheres com dismenorreia primária submetidas à auriculoterapia / Sociodemographic characteristics and pain assessment through the McGill questionnaire in women with primary dysmenorrhoea submitted to auriculotherapy

A dismenorreia caracteriza-se como uma dor intensa durante a menstruação ou algumas horas antes, localizada na região de baixo ventre ou região inferior do abdômen, é uma patologia de origem primária ou secundária, em que 40 a 45% dos casos de dor pélvica crônica, se manifestam como dismenorreia. OBJETIVO: Investigar as características sociodemográficas de mulheres que possuem dismenorreia primaria, e avaliar as influências da auriculoterapia para a dor menstrual, mensurada antes e após o método por meio do questionário de McGill. MÉTODOS: Trata-se de estudo clínico, randomizado, controlado e duplo cego, de delineamento longitudinal, com abordagem quali-quantitativa, realizado por meio de uma população de 118 estudantes. O tamanho da amostra foi calculado usando uma única fórmula média onde n é o tamanho da amostra necessário; d é erro marginal de 5% ( d = 0,05); z é o grau de precisão requerido a 95% de nível de confiança. Inicialmente, as voluntárias foram submetidas a responderem o questionário sociodemografico, e após, ao questionário de McGill, que avalia vários aspectos da dor, e receberam aplicações durante 2 meses e 3 semanas, 2 vezes por semanas, por 20 minutos. RESULTADOS: A média de idade das participantes desta pesquisa é de 19,8 anos, com predominância na etnia parda e com ciclo menstrual regular, e 55% apresenta dor dois dias antes da menstruação. Depois das aplicações de auriculoterapia os dados dos questionários de McGill após intervenção apresentaram valores estatísticos significantes nos domínio de aspectos sensitivos, afetivos, domínios avaliativos e aspectos miscelâneos. CONCLUSÃO: O presente estudo obteve o delineamento nos aspectos sociodemograficos da população que possui dismenorreia primária. E em relação às influências da auriculoterapia sobre as características da dor, o método apresentou se estatisticamente significativo.

Dysmenorrhea is characterized as severepain during menstruation or a few hours before, located in the lower abdomen or lower abdomen, it is pathology of primary or secondary origin, in which 40 to 45% of pain cases chronic pelvic, manifests as dysmenorrhea. OBJECTIVE: To investigate the sociodemographic characteristics of women who have primary dysmenorrhea, and to evaluate the influence of auriculotherapy for menstruation, measured before and after the McGill questionnaire method. METHODS: This is a clinical, randomized, controlled and double-blind study, with a longitudinal design, with a qualitative and quantitative approach, carried out with a population of 118 students. The sample size was calculated using a single average formula, where the sample size is required; marginal error of 5% (d = 0.05); z is the degree of precision required at 95% of the confidence level. Initially, as volunteers, they were submitted to a sociodemographic questionnaire, and then to McGill's questionnaire, which evaluated various aspects of pain, and applied it for 2 months and 3 weeks, twice a week, for 20 minutes. RESULTS: The average age of the participants in this research is 19.8 years, with a predominance of mixed race and with regular menstrual cycle, and 55% present pain two days before menstruation. After auriculotherapy applications and data from McGill's questionnaires, after the intervention of significant statistical values in the domain of sensitive, affective, assessed domains and diverse aspects. CONCLUSION: The present study used or the design in the sociodemographic aspects of the population that has primary desmenorrhea. And in relation to the influences of auriculotherapy on the characteristics of pain, the method presented is statistically significant.

Active components and mechanism of Taohong Siwu Decoction in treatment of primary dysmenorrhea based on network pharmacology and molecular docking technology / 中国中药杂志

This paper aimed to investigate the active components and mechanism of Taohong Siwu Decoction in the treatment of primary dysmenorrhea(PD) based on network pharmacology and molecular docking technology. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) was used to search the chemical compositions and targets of six herbs in Taohong Siwu Decoction. The targets for PD treatment were selected through the databases of DrugBank, OMIM, TTD and CTD, and gene annotation of the targets was conducted with UniProt database. Cytoscape 3.7.2 was then used to construct the drug-compound-target network. The protein-protein interaction(PPI) network was constructed based on STRING, and the core targets of Taohong Siwu Decoction in the treatment of PD were selected according to the topological parameters. David database was used for GO enrichment analysis and KOBAS 3.0 was used for KEGG enrichment analysis. The molecular docking technology was used to connect the components with higher medium values in the network with core targets. The results showed that the network contained 36 compounds such as quercetin, kaempferol, luteolin, myricanone and ferulic acid, and 99 targets such as PTGS2, PTGS2, PGR and PPARG. Totally 102 GO terms were obtained by GO functional enrichment analysis(P<0.01), and 228 signal pathways were obtained by KEGG pathway enrichment(P<0.05), mainly involving inflammatory factors, hormone regulation, central analgesia, amino acid metabolism and spasmolysis. The results of molecular docking showed that the main active components can spontaneously bind to the targets. This study preliminarily revealed the mechanism of Taohong Siwu Decoction for treatment of primary dysmenorrheal through multi-components, multi-targets and multi-pathways, providing theoretical references for further researches on mechanism of Taohong Siwu Decoction.

Prescription compatibility connotation and action mechanism of Siwu Decoction in treating primary dysmenorrhea / 中国中药杂志

The aim of this paper was to study the prescription compatibility connotation in the treatment of primary dysmenorrhea(PD) and verify the mechanism as predicted by network pharmacology of Siwu Decoction(SWD). Mice PD model was constructed by using estradiol benzoate-oxytocin. PD mice were randomly divided into 8 groups, namely normal group, model group, positive group, complete formula group, Rehmanniae Radix Praeparata-free group, Paeoniae Radix Alba-free group, volatile oil-free group, Chuan-xiong Rhizoma and Angelicae Sinensis Radix-free group. Latent time, writhing times, inhibition rate, prostaglandin F_2_α(PGF_2_α) and prostaglandin E_2(PGE_2) levels in serum, endothelin-1, Ca~(2+), expression levels of prostaglandin synthase 2 G/H(PTGS2), estrogen receptor(ESR1), glucocorticoid receptor gene(NR3 C1) mRNA and protein expression levels in the uterus homogenate and pathological changes of uterine tissue were index to explore the prescription compatibility connotation and verify the mechanism of SWD in the treatment of PD. Compared with the extraction liquid of the whole recipe, the effect of Rehmanniae Radix Praeparata-free group and Paeoniae Radix Alba-free group with volatile oil were slightly lower, the effect of essential oil-free group was significantly lower, and the effect of Chuanxiong Rhizoma and Angelicae Sinensis Radix-free group was worse than that of the whole recipe. The relative expression levels of PTGS2 protein and mRNA were significantly reduced by the SWD. The relative expressions of protein and mRNA of ESR1, NR3 C1 were significantly increased. SWD treats PD by regulating the expression of key proteins PTGS2, ESR1 and NR3 C1.Its main medicinal herbs were Angelicae Sinensis Radix and Chuanxiong Rhizoma. Active components were mainly in volatile oil, but Paeo-niae Radix Alba and Rehmanniae Radix Praeparata also had some contributions.