Role of epigenetics in the regulation of skin aging and geroprotective intervention: A new sight.

Multiple epigenetic factors play a regulatory role in maintaining the homeostasis of cutaneous components and are implicated in the aging process of the skin. They have been associated with the activation of the senescence program, which is the primary contributor to age-related decline in the skin. Senescent species drive a series of interconnected processes that impact the immediate surroundings, leading to structural changes, diminished functionality, and heightened vulnerability to infections. Geroprotective medicines that may restore the epigenetic balance represent valid therapeutic alliances against skin aging. Most of them are well-known Western medications such as metformin, nicotinamide adenine dinucleotide (NAD+), rapamycin, and histone deacetylase inhibitors, while others belong to Traditional Chinese Medicine (TCM) remedies for which the scientific literature provides limited information. With the help of the Geroprotectors.org database and a comprehensive analysis of the referenced literature, we have compiled data on compounds and formulae that have shown potential in preventing skin aging and have been identified as epigenetic modulators.

Evaluating the Significance of Fasting C-peptide in Conjunction with the Insulin Resistance Index for Assessing Hepatic Fibrosis in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease.

Background: Non-alcoholic fatty liver disease (NAFLD) has reached pandemic proportions globally, particularly affecting individuals with type 2 diabetes mellitus (T2DM). Objective: Our study aims to elucidate the diagnostic value of fasting C-peptide in combination with insulin resistance for assessing hepatic fibrosis in patients with T2DM and comorbid NAFLD. Design: This was a retrospective study. Setting: The study was conducted at the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine. Participants: The research involved 76 type 2 diabetes mellitus patients with nonalcoholic fatty liver disease, diagnosed at our hospital from April 2020 to October 2022. Patients were categorized into the non-progressive hepatic fibrosis group (n = 64) and progressive hepatic fibrosis group (n = 12) based on fibrosis-4 value. Interventions: General data, systolic/diastolic blood pressure, fasting plasma glucose, fasting C-peptide, fasting insulin, glycosylated hemoglobin, uric acid, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, aspartate transaminase, alanine transaminase, and γ-glutamyl transferase were collected. Insulin resistance was calculated using a designated formula. Primary Outcomes Measures: The predictive impact of fasting C-peptide in combination with insulin resistance was evaluated through receiver operating characteristic curves. Results: The age, body mass index, fasting C-peptide, fasting insulin, aspartate transaminase, and insulin resistance showed a significant increase in the progressive hepatic fibrosis group compared to the non-progressive group (P = .006, P = .014, P < .001, P < .001, P = .004, and P = .021). The combination's sensitivity demonstrated an elevation compared to fasting C-peptide or insulin resistance alone (P = .005). Conclusions: Fasting C-peptide in combination with insulin resistance proves to have a substantial predictive impact on hepatic fibrosis in type 2 diabetes mellitus patients with nonalcoholic fatty liver disease, holding valuable clinical diagnostic potential.

Spiritual care needs and their attributes among Chinese inpatients with advanced breast cancer based on the Kano model: a descriptive cross-sectional study.

BACKGROUND: Numerous previous research have established the need for spiritual care among patients with cancer globally. Nevertheless, there was limited research, primarily qualitative, on the spiritual care needs of Chinese inpatients with advanced breast cancer. Furthermore, the need for spiritual care was rarely explored using the Kano model. To better understand the spiritual care needs and attributes characteristics of inpatients with advanced breast cancer, this study examined the Kano model. METHODS: A descriptive cross-sectional design study was conducted in the oncology departments of three tertiary grade-A hospitals in China from October 2022 to May 2023. To guarantee high-quality reporting of the study, the Strengthening the Reporting of Observational Studies in Epidemiology Checklist was used. Data on the demographic characteristics questionnaire, the Nurse Spiritual Therapeutics Scale (NSTS), and the Kano model-based Nurse Spiritual Therapeutics Attributes Scale (K-NSTAs) were collected through convenience sampling. The Kano model, descriptive statistics, two independent samples t-tests, and one-way analysis of variance were used to analyze the data. RESULTS: The overall score for spiritual care needs was 31.16 ± 7.85. The two dimensions with the highest average scores, "create a good atmosphere" (3.16 ± 0.95), and the lowest average scores, "help religious practice" (1.72 ± 0.73). The 12 items were distributed as follows: three attractive attributes were located in Reserving Area IV; five one-dimensional attributes were distributed as follows: three one-dimensional attributes were located in Predominance Area I, and two were found in Improving Area II; two must-be attributes were located in Improving Area II; and two indifference attributes were located in Secondary Improving Area III. CONCLUSION: The Chinese inpatients with advanced breast cancer had a middle level of spiritual care needs, which need to be further improved. Spiritual care needs attributes were defined, sorted, categorized, and optimized accurately and perfectly by the Kano model. And "create a good atmosphere" and "share self-perception" were primarily one-dimensional and must-be attributes. In contrast, the items in the dimensions of "share self-perception" and "help thinking" were principally attractive attributes. Nursing administrators are advised to optimize attractive attributes and transform indifference attributes by consolidating must-be and one-dimensional attributes, which will enable them to take targeted spiritual care measures based on each patient's characteristics and unique personality traits.

An investigation of the mechanism of ZiyinDianji decoction in treating follicular dysplasia based on network pharmacology and molecular docking.

Follicular development disorder is a common gynaecological endocrine disease that can cause infertility, menstrual disorders, abortion, and other complications. ZiyinDianji decoction (ZYDJD) is a commonly used traditional Chinese medicine in clinical practice to promote follicular growth and development, but its pharmacological activity and mechanism of action are not clear. We combined network pharmacology with molecular docking and in vivo animal experiments to investigate the mechanism of ZYDJD in follicular development disorder. Cytoscape software was used for constructing ZYDJD-active component-target and PPI networks. GO biological process and KEGG pathway enrichment analyses were performed. The main components and key targets were selected for molecular docking. Finally, animal experiments were conducted for validation. The network pharmacology results showed that ZYDJD contained 83 active components and 159 core targets. The six most important active components were quercetin, luteolin, kaempferol, baicalein, isorhamnetin, and ß-sitosterol, and the most important disease targets were AKT1, TNF, IL-6, and P53. GO analysis mainly involved 470 cell biological processes, including effect on hormones, vascular morphogenesis, development, and cell proliferation. KEGG analysis involved cancer pathways, lipid metabolism pathways, and PI3K/AKT signalling pathways. Molecular docking showed good results, and animal experiments further verified that ZYDJD prevented cyclophosphamide from causing excessive activation of primordial follicles. ZYDJD maintained ovarian reserve and reproductive function by inhibiting the hyperphosphorylation of key molecules of the PI3K/Akt pathway, reducing FOXO3a, thereby ensuring the development of normal follicles. In conclusion, based on network pharmacology, molecular docking, and animal experiments, ZYDJD may act through the PI3K/Akt/FOXO3a pathway.

Bazi Bushen alleviates skin senescence by orchestrating skin homeostasis in SAMP6 mice.

Bazi Bushen, a Chinese-patented drug with the function of relieving fatigue and delaying ageing, has been proven effective for extenuating skin senescence. To investigate the potential mechanism, senescence-accelerated mouse prone 6 (SAMP6) was intragastrically administered with Bazi Bushen for 9 weeks to induce skin homeostasis. Skin homeostasis is important in mitigating skin senescence, and it is related to many factors such as oxidative stress, SASP, apoptosis, autophagy and stem cell. In our study, skin damage in SAMP6 mice was observed using HE, Masson and SA-ß-gal staining. The content of hydroxyproline and the activities of SOD, MDA, GSH-PX and T-AOC in the skin were measured using commercial assay kits. The level of SASP factors (IL-6, IL-1ß, TNF-α, MMP2 and MMP9) in skin were measured using ELISA kits. The protein expressions of p16, p21, p53, Bax, Bcl-2, Cleaved caspase-3, LC3, p62, Beclin1, OCT4, SOX2 and NANOG were measured by western blotting. The expression of ITGA6 and COL17A1 was measured by immunofluorescence staining and western blotting. Our findings demonstrated that Bazi Bushen alleviated skin senescence by orchestrating skin homeostasis, reducing the level of oxidative stress and the expression of SASP, regulating the balance of apoptosis and autophagy and enhancing the protein expressions of ITGA6 and COL17A1 to improve skin structure in SAMP6 mice. This study indicated that Bazi Bushen could serve as a potential therapy for alleviating skin senescence.

An Analysis of the Clinical Medication Rules of Traditional Chinese Medicine for Polycystic Ovary Syndrome Based on Data Mining.

Objective: The aim of the present study is to investigate the rules and characteristics of the clinical administration of traditional Chinese medicine (TCM) in the treatment of polycystic ovary syndrome (PCOS) using data mining methods. Method: Medical cases of well-known contemporary TCM doctors treating PCOS were collected from the China National Knowledge Infrastructure, Chinese Biomedical Literature Service System, Wanfang, Chinese Scientific Journals Database, and PubMed; the data were then characterized, and a standardized database of medical cases was built. This database was used to (1) count the frequency of syndrome types and the herbs used in medical cases by data mining methods and (2) analyze drug association rules and systematic clustering methods. Results: A total of 330 papers were included, involving 382 patients and a total of 1,427 consultations. The most common syndrome type was kidney deficiency; sputum stasis was the core pathological product and causative factor. A total of 364 herbs were used. Among them, 22 herbs were used >300 times, including Danggui (Angelicae Sinensis Radix), Tusizi (Semen Cuscutae), Fuling (Poria), Xiangfu (Nutgrass Galingale Rhizome), and Baizhu (Atractylodis Macrocephalae Rhizoma). Additionally, 22 binomial associations were obtained from the analysis of association rules; five clustering formulae were obtained via the analysis of high-frequency drug clusters; and 27 core combinations were obtained by k-means clustering of formula. Conclusion: In the treatment of PCOS, TCM is primarily employed as a combination approach involving tonifying the kidneys, strengthening the spleen, eliminating damp and dissolving phlegm, activating blood circulation, and resolving blood stasis. The core prescription is primarily a compound intervention based on the Cangfu Daotan pill, Liuwei Dihuang pill, and Taohong Siwu decoction.

Hyperhubeins A-I, Bioactive Sesquiterpenes with Diverse Skeletons from Hypericum hubeiense.

Nine new sesquiterpenes, hyperhubeins A-I (1-9), and 14 known analogues (10-23) were isolated from the aerial portions of Hypericum hubeiense. Their structures and absolute configurations were determined unambiguously via spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compounds 1-3 possess an unprecedented sesquiterpene carbon skeleton. Further, a plausible biosynthetic pathway from farnesyl diphosphate (FPP) is proposed. The isolated phytochemicals were evaluated for neuroprotective and anti-neuroinflammatory properties in vitro. Compounds 1, 2, 5-8, 14, and 21 displayed notable neuroprotective activity against hydrogen peroxide (H2O2)-induced lesions in PC-12 cells at 10 µM. Additionally, compounds 1, 2, 12, and 13 exhibited inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV-2 microglial cells, with their IC50 values ranging from 4.92 to 6.81 µM. Possible interactions between these bioactive compounds and inducible nitric oxide synthase (iNOS) were predicted via molecular docking. Moreover, Western blotting indicated that compound 12 exerted anti-neuroinflammatory activity by suppressing LPS-stimulated expression of toll-like receptor-4 (TLR-4) and inhibiting consequent activation of nuclear factor-kappa-B (NF-κB) signaling.

The effectiveness and safety of Chinese herbal medicine in infertile women with luteal phase deficiency: a systematic review and meta-analysis.

BACKGROUND: Chinese herbal medicine (CHM) has been reported to treat infertile women with luteal phase deficiency (LPD) in some clinical studies, however, the efficacy and safety of CHM for LPD are still under controversy. Here, we aim to evaluate the efficacy and safety of CHM using meta-analysis, and further compare it with conventional Western therapies (CWT) to elucidate the improvement in progestin and clinical pregnancy rates. METHODS: Eight randomized controlled trials (RCTs) involving 465 women were included in our systematic review; these RCTs compared CHM with CWT in treating LPD in infertile women. The methodological quality of the included RCTs was assessed according to the Cochrane risk-of-bias assessment criteria. The data were analyzed by Review Manager 5.3 software. We estimated the risk ratio (RR) for dichotomous data and calculated the mean difference for continuous data. RESULTS: In contrast to CWT, CHM was superior in improving clinical pregnancy rates (RR 0.19; 95% CI: 0.11-0.27; P<0.001), increasing progesterone levels in the luteal phase [mean difference (MD) 2.28; 95% CI: 1.91-2.64; P<0.001] and luteal phase estrogen (MD 9.88; 95% CI: 4.53-15.24; P=0.0003), reducing traditional Chinese medicine (TCM) syndrome scores (MD -3.06; 95% CI: -3.95 to -2.17; P<0.001), and the incidence of adverse reactions (RR 0.12; 95% CI: 0.02-0.70; P=0.02). CONCLUSIONS: Evidence from eight small studies suggested that CHM has a therapeutic effect on infertile women with luteal insufficiency. We indicated that CHM may improve the level of progesterone and estradiol in the luteal phase, and the clinical pregnancy rate, with few side effects based on the current studies. However, given the relatively small number of included studies, further studies about the higher quality of study designs, larger population and the underlying mechanism are required to elucidate the role of CHM in LPD treatment.

Bu-shen-zhu-yun decoction inhibits granulosa cell apoptosis in rat polycystic ovary syndrome through estrogen receptor α-mediated PI3K/AKT/mTOR pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bu-shen-zhu-yun decoction (BSZYD) is a traditional chinese herbal prescription is widely used in the treatment of infertility. AIM OF THE STUDY: We aimed to elucidate the impact of a traditional herbal prescription BSZYD on polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: The candidate active compounds in BSZYD and their putative targets were investigated by bioinformatics analysis. A deydroepiandrosterone (DHEA)-induced PCOS rat model was then constructed using female Sprague-Dawley (SD) rats. Serum hormone levels were measured by enzyme-linked immunosorbent assay (ELISA). Pathological changes in ovarian tissues were analyzed with hematoxylin and eosin (H&E) staining. The expressions of estrogen receptor α (ER α)-mediated PI3K/AKT/mTOR pathway were measured by immunofluorescence and western blotting. RESULTS: Bioinformatics analysis showed that the putative targets of active compound candidates in BSZYD were enriched in PI3K/AKT and estrogen signaling pathways related to regulating ovarian ovulation. Animal experiments showed that BSZYD significantly alleviated pathological changes in the ovary, altered hormone levels of serum and reduced apoptosis rate of granulosa cells. In addition, BSZYD treatment notably upregulated the expressions of proteins in ER α-mediated PI3K/AKT/mTOR pathway and downregulated apoptosis-related proteins in PCOS rats. CONCLUSION: BSZYD can restore ovary lesions and ameliorate apoptosis through ER α-mediated PI3K/AKT/mTOR pathway, which might partly contribute to the treatment of PCOS.

Bu-Shen-Zhu-Yun decoction induces PRLR deubiquitination and JAK2/STAT5 activation via CSN5 in vitro.

PURPOSE: To determine the effect of Bu-Shen-Zhu-Yun Decoction (BSZY-D) on the kisspeptin through JAK2/STAT5 signaling pathway in hyperprolactinemia (HPRL) infertility. METHOD: SD rats were treated with BSZY-D for cerebrospinal fluid (CSF) extraction. GT1-7 cells were subjected to different treatments. The phosphorylation levels of JAK2 and STAT5, and the expressions of PRLR and kisspeptin of GT1-7 cells in different groups were detected by western blot, RT-qPCR and immunofluorescence. The expressions of CSN5 and GATA1 and other molecular features were checked by western blot, RT-PCR, co-immunoprecipitation and renilla luciferase activity. RESULTS: The phosphorylation levels of JAK2 and STAT5, and the expressions of PRLR and kisspeptin in the HPRL group were significantly decreased, and these changes could be reversed after BSZY-D treatment. In addition, the presence of PRLR deubiquitination was detected in the HPRL group, which could be reversed by shRNA-CSN5, suggesting that BSZY-D played a role through targeting CSN5. The binding level of GATA1 and CSN5 promoter in the HPRL group was significantly decreased, but elevated in the HPRL (BSZY-D/CSF) group (P < 0.05). CONCLUSION: BSZY-D improved the transcription activity of GATA1 and increased the binding of GATA1 and CSN5. BSZY-D was involved in the deubiquitination of PRLR, which contributes to alleviating the symptoms of HPRL infertility.

Network Pharmacology-Based Prediction of Bioactive Compounds and Potential Targets of Wenjing Decoction for Treatment of Endometriosis.

Endometriosis is a chronic estrogen-dependent inflammatory disorder that negatively affects the quality of life in women. The Wenjing decoction (WJD) is a traditional Chinese medicine that has been shown to have a therapeutic effect on endometriosis. Our study systematically explored the mechanism of WJD against endometriosis using a network pharmacology approach. Potentially bioactive compounds of WJD and their possible targets were retrieved from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The protein-protein interaction network and herbs-compounds-genes multinetwork were constructed using Cytoscape for visualization. Subsequently, the signaling pathways of common targets were retrieved from the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and molecular docking was performed using PyRx software. In total, 48 common targets were screened, such as IL6 and ESR1, which were related to inflammation and the endocrine system. The top five bioactive compounds were quercetin, kaempferol, wogonin, beta-sitosterol, and stigmasterol. KEGG enrichment analysis revealed 65 pathways containing inflammatory- and endocrine-related signaling pathways, such as the "TNF signaling pathway" and the "estrogen signaling pathway." Taken together, the results of our network pharmacology analysis predicted that certain active ingredients of WJD might treat endometriosis by regulating inflammation and/or endocrine, which provided references for further understanding and exploration of WJD on endometriosis.

Anti-inflammatory activity of the Tongmai Yangxin pill in the treatment of coronary heart disease is associated with estrogen receptor and NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Tongmai Yangxin Pill (TMYX) is a patented traditional Chinese medicine originating from two classic prescriptions, Zhigancao Decoction and Shenmai Yin, which composed of 11 Chinese medicinal herbs: Rehmannia glutinosa (Gaertn.) DC., Spatholobus suberectus Dunn, Ophiopogon japonicus (Thunb.) Ker Gawl., Glycyrrhiza uralensis Fisch., Polygonum multiflorum Thunb., Equus asinus L., Schisandra chinensis (Turcz.) Baill., Codonopsis pilosula (Franch.) Nannf., Chinemys reevesii (Gray), Ziziphus jujuba Mill. and Cinnamomum cassia (L.) J.Presl (Committee of the Pharmacopoeia of PR China, 2015). TMYX has marketed in China for the treatment of chest pain, palpitation, angina, irregular heartbeat and coronary heart disease (CHD) for several decades. Previous studies have confirmed that TMYX can treat CHD by reducing inflammation, but the underlying pharmacological mechanism remains unclear. AIM OF THE STUDY: This study aimed to declare the underlying pharmacological mechanism of anti-inflammatory activity of TMYX in the treatment of CHD via clinical trial, microarray study, bioinformatics analysis and the vitro assays. MATERIALS AND METHODS: Eight CHD patients' serum biochemical indices including coagulation function, lipid metabolism, endothelial injury, metalloprotease, adhesion molecule, inflammatory mediator and homocysteine were measured to investigate the reduction of CHD risk by TMYX oral administration (40 pills/time, 2 times/day) for eight weeks. The expression profile chips and Ingenuity Pathway Analysis (IPA) were assessed to reveal the global transcriptional response and predict related functions, diseases and canonical pathways. The in vitro anti-inflammatory actions of TMYX were evaluated using oxidized low-density lipoprotein (100 µg/mL) induced murine RAW264.7 macrophage with an ethanol extract from TMYX (EETMYX) (25-100 µg/mL). RESULTS: TMYX treatment showed reduced levels of apolipoprotein B, endothelin 1, nuclear factor κB (NF-κB) and homocysteine in CHD patients. In contrast, the treatment increased the ratio of apolipoprotein A/apolipoprotein B. EETMYX restored cell morphology and suppressed the lipid deposition of the induced foam cells. EETMYX exerted anti-inflammatory effects by raising the mRNA and protein expression of Estrogen receptor 1 (ESR1), blocking the reduction of IκBa level and the phosphorylation of IKKα/ß, IκBα and NF-κB p65, accompanied by inhibiting MCP-1, TNF-α and IL-6 production, which were consistent with bioinformatics predictions. CONCLUSION: TMYX treatment improved the biochemical indices in CHD patients. EETMYX effectively attenuated macrophage foam cell formation and exhibited anti-inflammatory activity is associated with regulating ESR1 and NF-κB signaling pathway activity.

[Modified Dihuang Decoction improves ovarian reserve in mice by regulating Bcl-2-related mitochondrial apoptosis pathway].

The present study investigated the effect of Modified Dihuang Decoction in improving ovarian reserve in mice through the Bcl-2-related mitochondrial apoptosis pathway. Forty-eight adult female BALB/c mice were randomly divided into the following six groups with eight mice in each group: a blank group, a model group, a femoston group(three cycles of treatment with 0.13 mg·kg~(-1) estradiol tablets for 2 days and 1.43 mg·kg~(-1) estradiol and dydrogesterone tablets for 3 days), and high(64.74 g·kg~(-1))-, medium(43.16 g·kg~(-1))-, and low-dose(21.58 g·kg~(-1)) Modified Dihuang Decoction groups. Mice in other groups except the blank group received a single intraperitoneal injection of 12 mg·kg~(-1) cyclophosphamide and 1.2 mg·kg~(-1) busulfan to induce a model of diminished ovarian reserve(DOR), while those in the blank group received an equal volume of normal saline. Mice were treated with corresponding drugs for 15 d from the 36 th day, once per day, and the mice in the blank group and the model group were treated with an equal volume of normal saline. The general condition and oestrous cycle were observed. The serum hormone levels were detected with the enzyme-linked immunosorbent assay(ELISA). The morphological changes of ovaries were observed by HE staining. Western blot was used to detect the protein expression of cysteinyl aspartate specific proteinase-9(caspase-9), cleaved caspase-3, Bcl-2 associated X protein(Bax), Bcl-2, superoxide dismutase-2(SOD-2), and glutathione peroxidase-1(GPx-1). The mRNA expression of Bax and Bcl-2 was detected by real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR). The results showed that compared with the blank group, the model group showed body weight loss, disordered oestrous cycle, elevated serum levels of follicle-stimulating hormone(FSH) and luteinizing hormone(LH), reduced serum levels of estradiol(E_2), anti-mullerian hormone(AMH), and inhibin B(INHB), the declining number of ovarian follicles and granulosa layers, increased number of atretic follicles, up-regulated protein expression of caspase-9, cleaved caspase-3, and Bax and Bax mRNA expression in ovaries, and down-regulated protein expression of Bcl-2, SOD-2 and GPx-1, and Bcl-2 mRNA expression. Compared with the model group, the Modified Dihuang Decoction groups displayed restored body weight and oestrous cycle, decreased serum levels of FSH and LH, elevated serum levels of E_2, AMH, and INHB, increased number of ovarian follicles, thickened granulosa layers, and declining number of atretic follicles. Additionally, the protein expression of caspase-9, cleaved caspase-3, and Bax, and Bax mRNA expression was down-regulated, and the protein expression of Bcl-2, SOD-2, and GPx-1, and Bcl-2 mRNA expression was up-regulated. The results suggest that Modified Dihuang Decoction can regulate endocrine hormone, promote follicle growth and improve ovarian reserve by enhancing ovarian anti-oxidant capacity, inhibiting the Bcl-2-related mitochondrial apoptosis pathway, and further inhibiting cell apoptosis.

The effects of combined bromocriptine and Bu-shen-zhu-yun decoction on serum hormones, anxiety, and pregnancy in hyperprolactinemic infertility patients.

BACKGROUND: Prolactin (PRL) is a protein hormone secreted by the anterior pituitary gland that regulates pituitary hormones. Hyperprolactinemia (HPRL), a pathological phenomenon of excessive PRL, can cause infertility in severe cases and is currently treated mainly with Western drugs, such as bromocriptine, a dopamine agonist (DA). Unfortunately, DAs produce psychological side effects which limit their long-term use. Traditional Chinese medicine (TCM) has minimal side effects and good results spanning many years of research. The combined treatment of TCM and Western medicine may enhance treatment efficacy and improve the long-term prognosis in HPRL. To analyze the effects of Bu-shen-zhu-yun decoction (BSZY-D) combined with bromocriptine on serum hormones, anxiety, and pregnancy in hyperprolactinemic infertile patients. METHODS: One hundred patients diagnosed with HPRL infertility from June 2020 to June 2021 in the gynecology clinic of Jiangsu Provincial Hospital of Traditional Chinese Medicine were selected and grouped by envelope method. After excluding patients who withdrew or missed visits, 37 cases assigned to the control group were treated with bromocriptine, and 40 cases assigned to the observation group were treated with bromocriptine combined with BSZY-D. The patients' PRL and kisspeptin (KP) serum indexes, improvements in infertility, Anxiety Self-Assessment Scale (SAS) scores, and improvements in the Insomnia Severity Index Scale (ISI) scores were compared between the two groups. RESULTS: At 3 and 6 months of treatment, serum PRL, SAS, and ISI scores were significantly lower, and serum KP was significantly higher in the observation group than in the control group (P<0.05). During the study period, the pregnancy rates were 62.50% (25/40) and 37.84% (14/37) in the observation and control groups, respectively. The observation group also had significantly fewer early miscarriages [10.00% (4/40) vs. 32.43% (12/37)] and less adverse reactions [7.50% (3/40) vs. 24.32% (9/37)] than the control group (all P<0.05). CONCLUSIONS: The combination of bromocriptine with BSZY-D was superior to bromocriptine alone in treating HPRL and HPRL-related infertility, which also demonstrated a positive effect on patients' sleep and low mood.

[Meta-analysis of Kuntai Capsules combined with GnRH-a in treatment of endometriosis].

To systemically evaluate the efficacy and safety of Kuntai Capsules combined with GnRH-a in the treatment of endome-triosis. The databases of CNKI, WanFang, VIP, PubMed, EMbase and Cochrane Library were searched from their establishment to May 2019 to collect the randomized controlled trials of Kuntai Capsules combined with GnRH-a in the treatment of endometriosis. The data were searched, screened and extracted by two researchers according to the inclusion and exclusion criteria, and the data were analyzed by using RevMan 5.3 software. A total of 58 articles were collected and 13 studies were included. The total sample size was 1 041 cases, including 523 cases in the experimental group and 518 cases in the control group. The results of Meta-analysis showed that Kuntai Capsules combined with GnRH-a can reduce the level of follicle stimulating hormone(FSH), luteinizing hormone(LH) and estradiol(E_2) in patients with endometriosis as compared with GnRH-a alone. With a low incidence of adverse events of peri-meno-pausal symptoms during treatment(RR=0.46, 95%CI[0.35, 0.60], P<0.000 01), it can reduce the VAS score of dysmenorrhea(MD=-1.85,95%CI[-1.92,-1.78],P<0.000 01). The recurrence rate in the combined treatment group was lower than that in the control group(RR=0.27, 95%CI[0.09,0.77], P=0.01). This study showed that Kuntai Capsules combined with GnRH-a can reduce the level of FSH, LH and E_2 in patients with endometriosis, reduce the VAS score of dysmenorrhea, with lower incidence of adverse events and recurrence rate, but it still needs large-scale, multicenter, randomized, double-blind and high-quality clinical trials for support and evidence.

Esculetin Inhibits Proliferation, Invasion, and Migration of Laryngeal Cancer In Vitro and In Vivo by Inhibiting Janus Kinas (JAK)-Signal Transducer and Activator of Transcription-3 (STAT3) Activation.

BACKGROUND Laryngeal cancer is one of the most common malignant tumors of the head and neck. Natural compounds in traditional Chinese medicine provide many valuable potential compounds for tumor chemotherapy. Esculetin, a coumarin derivative from several herbs, inhibits proliferation of many types of cancer cells, but its anticancer effect in laryngeal cancer is still not clear. MATERIAL AND METHODS We performed in vitro proliferation assay, invasion assay, and migration assay to assess the effect of esculetin against LC, and in vivo nude mouse xenograft animal model was used as well. Flow cytometry was conducted to analyze the effect of esculetin on cell cycle of LC cells, and Western blot analysis was used to assess the effect esculetin on the JAK-STAT signaling pathway. RESULTS Esculetin remarkably inhibits proliferation, migration, and invasion of LC cells, and reduces in vivo xenograft tumor growth and tumor weight in a dose-dependent manner. Our molecular mechanism study demonstrated that esculetin significantly inhibits STAT3 phosphorylation and blocks translocation of STAT3 into the nucleus, and esculetin also blocks the cell cycle in G1/S phase. CONCLUSIONS In a summary, by inhibiting the STAT3 activation, esculetin shows potential anticancer effects against the laryngeal cancer.

Multistep Consolidated Phototherapy Mediated by a NIR-Activated Photosensitizer.

The multifunctional effect of a single molecule for therapeutic functionalities on a single theranostic nanosystem has a great significance to enhance the accuracy of diagnosis and improve the efficacy of therapy. Herein, a biocompatible multistep phototherapeutic system (Ppa-Cy7-PEG-biotin) that contains a photosensitizer pyropheophorbide A (Ppa) with the covalent conjunction of a near-infrared (NIR) cyanine dye (Cy7) was successfully fabricated and functionalized with biotin for flexible specific tumor-targeting phototherapy. These theranostic micelles will disaggregate after NIR irradiation via the photodegradation of cyanine accompanied by the photothermal conversion and the optically controlled release for the restoration of photodynamic function of quenched Ppa. Consecutively, promoted treatments of photosensitive molecules greatly prolonged the tumor retention time and treatment efficiency, having a multistep antitumor effect both in vitro and in vivo. Different from the simple phototherapeutic configurations that only act on the superficial areas of tumors at mild doses, the multistep therapy can be competent for broadly damaging the superficial and deeper regions of tumors at the same dose. Therefore, as opposed to the general combination phototherapeutic approach, this strategy presents a photoactivation-based multistep phototheranostic platform with an enormous potential in enhanced combined phototherapy for cancer.

Metabolomics of the amniotic fluid: Is it a feasible approach to evaluate the safety of Chinese medicine during pregnancy?

The use of Chinese medicines (CMs) during pregnancy has long been a major public health concern. Although CMs have been shown to be effective in treating infertility and preventing miscarriage, their use has been restricted, mainly because of limited knowledge of their potential toxicity. Accurate toxicology data are urgently required to assess whether these CMs are safe for maternal health and fetal development. Amniotic fluid (AF) contains carbohydrates, lipids and phospholipids, urea and proteins, all of which aid in the growth of the fetus and reflect the mother's health status as well. The changes in metabolomic patterns of AF are related to pathophysiological occurrences during the course of pregnancy. In this review, we provide a summary of the research performed in recent years on metabolomic AF samples, and use our previous study as an example to explore the feasibility of metabolomics of AF to evaluate the safety of CMs during pregnancy. We believe that metabolomics of AF play a far more important role than traditional morphology methods in the safety evaluation of CMs for pregnancy, with a higher sensitivity and correlation.

Tong-Xie-Yao-Fang Regulates 5-HT Level in Diarrhea Predominant Irritable Bowel Syndrome Through Gut Microbiota Modulation.

Tong-Xie-Yao-Fang (TXYF) has been widely used for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) in traditional Chinese medicine. However, its mechanism of action in the treatment of IBS-D remains to be fully understood. Recent reports have shown that Clostridium species in the gut can induce 5-HT production in the colon, which then contributes to IBS-D. Due to the wide use of TXYF in the clinical treatment of IBS-D and the close relationship between gut microbiota and IBS-D, we hypothesize that TXYF treats IBS-D by modulating gut microbiota and regulating colonic 5-HT levels. In this study, variation analysis of 16S rRNA was conducted to evaluate changes in the distribution of gut microbiota in IBS-D model rats after TXYF treatment. Moreover, we investigated whether TXYF could affect colonic 5-HT levels in IBS-D model rats. We then performed fecal transplantation experiments to confirm the effects of TXYF on gut microbiota and 5-HT levels. We found that TXYF treatment can ameliorate IBS-D and regulate 5-HT levels in colon tissue homogenates. TXYF treatment also affected the diversity of gut microbiota and altered the relative abundance of Akkermansia and Clostridium sensu stricto 1 in gut flora populations. Finally, we showed that fecal transplantation from TXYF-treated rats could relieve IBS-D and regulate 5-HT levels in colon tissue homogenates. In conclusion, the present study demonstrates that TXYF treatment diminishes colonic 5-HT levels and alleviates the symptoms of IBS-D by favorably affecting microbiota levels in gut flora communities.

Crocetin attenuates DHT-induced polycystic ovary syndrome in mice via revising kisspeptin neurons.

Polycystic ovarian syndrome (PCOS), the most common endocrine disorder of women in reproductive age, is typical with hyperandrogenism and disturbance of the hypothalamus-pituitary-ovary (HPO) axis, i.e. abnormal expression of hypothalamic gonadotropin-releasing hormone (GnRH) followed by the elevated ratio of serum luteinizing hormone (LH) level to follicle-stimulating hormone (FSH) level. This derangement might have a close relationship with hypothalamic kisspeptin expression that is thought to be a key regulator of GnRH. Crocetin, one of the main components of Saffron clinically used as traditional medicine in gynecology diseases, was evaluated for its therapeutic effects on PCOS induced by prenatally exposure to dihydrotestosterone (DHT) in mice. Herein, we found that DHT-treated mice showed a similar phenotype to human PCOS such as heavier ovary, prolonged diestrus, multiple enlarged follicles with fewer corpus luteum, and higher LH and testosterone levels. Kisspeptin expression was lower in anteroventral periventricular nucleus (AVPV) but higher in arcuate nucleus (ARC). Treatment of crocetin prevented the prolongation of diestrus and reduction in corpora luteum, recover the levels of GnRH, FSH, LH, progesterone (P4), estradiol (E2) and testosterone (T), and increase the kisspeptin level in AVPV but reduce that in ARC. The present study provides in vivo evidence that crocetin improved the PCOS in mice via increasing AVPV-kisspeptin and reducing ARC-kisspeptin expression.