Characteristics and Effects of Chinese Herbal Medicine in the Management of Female Infertility: A Hospital-Based Study.

BACKGROUND: In Taiwan, Chinese herbal medicine (CHM) is used to treat female infertility. Evidence indicates that the absence of monotherapy efficacy assessment and comparison with mainstream interventions may lead to the improper use of CHM for female infertility. METHODS: A retrospective cohort study enrolled female patients at a hospital undergoing CHM intervention to treat infertility from 2012 to 2020 in order to determine the outcomes of CHM monotherapy for female infertility. Kaplan-Meier analysis under strict assumptions was used to estimate the cumulative probability of pregnancy and live births after CHM. Cox hazard regression analysis was used to estimate the hazard ratios of prognostic variables, namely, the woman's age and diagnostic category. RESULTS: 694 women met the inclusion criteria and accounted for 2,145 cycles. A total of 190 pregnancies resulted in 125 live births, all of which were singleton births of babies with 16 perinatal complications requiring hospitalization. The real cumulative pregnancy rate and cumulative live birth rate (CLBR) for the total population after 10 cycles were between 27.4% and 35.2% and between 18% and 22.1%, respectively. Compared with the live birth rate corresponding to patients aged under 35 years, that of older patients, particularly those aged 38-39 years, was significantly lower (hazard ratio: 0.19, 95% confidence interval: 0.11-0.33). Women with other diagnoses, namely, uterine problems or endometriosis, had a greater probability of a live birth than did women with tubal pathology (hazard ratio: 6.31, 95% confidence interval: 1.99-20.07). CONCLUSION: To the best of our knowledge, this is the first retrospective study to employ life table analysis to determine the CHM treatment outcomes in terms of female infertility. The study established a basis to compare in vitro fertilization (IVF) with CHM and identified the advantages and disadvantages of CHM for treating female infertility. Although the CLBR of present study is lower than those reported in IVF studies, CHM in treating female infertility can still be beneficial to women aged younger than 38 years or with diagnoses other than tubal pathology and worth recommendation by reproductive specialists according to the promising results gained from the strict criteria. However, in order to determine the optimal timing, possible mechanism, corresponding side effects, and the efficacy of CHM combined with IVF for treating female infertility, rigorous research is required.In Taiwan wird die chinesische Heilpflanzenmedizin (CHM) zur Behandlung weiblicher Infertilität angewendet. Es liegen Hinweise vor, nach denen fehlende Wirksamkeitsbeurteilungen der Monotherapien und Vergleiche mit herkömmlichen Interventionen zu einer unsachgemäßen Anwendung von CHM bei weiblicher Infertilität führen können.Eine retrospektive Kohortenstudie schloss Patientinnen eines Krankenhauses ein, die von 2012 bis 2020 wegen Infertilität mit CHM behandelt wurden, um die Behandlungsergebnisse der CHM-Monotherapie bei weiblicher Infertilität zu ermitteln. Zur Schätzung der kumulativen Wahrscheinlichkeit von Schwangerschaften und Lebendgeburten nach einer CHM-Behandlung wurde die Kaplan-Meier-Analyse unter strengen Annahmen verwendet. Mit Hilfe der Cox-Hazard-Regressionsanalyse wurden die Risikoverhältnisse der prognostischen Variablen Alter der Frau und Diagnosekategorie geschätzt.694 Frauen erfüllten die Einschlusskriterien und die Zahl der Zyklen betrug 2,145. Insgesamt 190 Schwangerschaften führten zu 125 Lebendgeburten, allesamt Einlingsgeburten, mit 16 perinatalen Komplikationen, die eine Hospitalisierung erforderten. Die reale kumulative Schwangerschaftsrate und die kumulative Lebendgeburtenrate (cumulative live birth rate, CLBR) für die Gesamtpopulation nach 10 Zyklen lagen zwischen 27.4% und 35.2% bzw. zwischen 18% und 22.1%. Die Lebendgeburtenrate bei älteren Patientinnen, insbesondere im Alter von 38 bis 39 Jahren, war deutlich niedriger als bei Patientinnen unter 35 Jahren (Hazard Ratio: 0.19, 95%-Konfidenzintervall: 0.11­0.33). Bei Frauen mit anderen Diagnosen wie Gebärmutterproblemen oder Endometriose war die Wahrscheinlichkeit einer Lebendgeburt höher als bei Frauen mit Eileitererkrankungen (Hazard Ratio: 6.31, 95%-Konfidenzintervall: 1.99­20.07).Unseres Wissens ist dies die erste retrospektive Studie, in der die Ergebnisse der CHM-Behandlung bei weiblicher Infertilität mittels Sterbetafelanalyse ermittelt wurden. Die Studie bildet eine Grundlage für den Vergleich von In-vitro-Fertilisation (IVF) mit CHM und zeigt die Vor- und Nachteile der CHM zur Behandlung weiblicher Infertilität auf. Zwar fällt die kumulative Lebendgeburtenrate in der vorliegenden Studie niedriger aus als in IVF-Studien, doch kann die CHM bei der Behandlung weiblicher Infertilität für Frauen unter 38 Jahren oder Frauen, die eine andere Diagnose als eine Eileitererkrankung haben, von Nutzen sein und angesichts der vielversprechenden Ergebnisse, die aus den strengen Kriterien gewonnen wurden, ist sie eine Empfehlung durch Reproduktionsspezialisten wert. Allerdings sind rigorose Forschungsarbeiten erforderlich, um die optimale Zeitplanung, den möglichen Mechanismus, die entsprechenden Nebenwirkungen und die Wirksamkeit der CHM in Kombination mit IVF zur Behandlung der weiblichen Infertilität zu ermitteln.

Acupressure Improves Cognition and Quality of Life Among Older Adults with Cognitive Disorders in Long-Term Care Settings: A Clustered Randomized Controlled Trial.

OBJECTIVE: To examine the effectiveness of acupressure on cognition and quality of life (QoL) among older adults with cognitive disorders residing in long-term care (LTC) settings. DESIGN: A clustered, randomized, assessor-blinded, controlled trial with a repeated measures design. SETTING AND PARTICIPANTS: Participants were recruited from residential care facilities in Taiwan from August 2020 to February 2021. Ninety-two older residents in 18 facilities were randomized to either the intervention arm (9 facilities, n = 46) or the control arm (9 facilities, n = 46). METHODS: Acupressure was performed at Baihui (GV20), Sishencong (EX-HN1), Shenting (GV24), Fengchi (GB20), Shuigou (GV26), Neiguan (PC6), Shenmen (HT7), and Zusanli (ST36). The duration for pressing each acupoint was 3 minutes. The acupressure force was maintained at 3 kg. Acupressure was performed once a day 5 times a week for 12 weeks. The primary outcome measure was the Cognitive Abilities Screening Instrument (CASI). Secondary outcomes included the digit span backward test, the Wisconsin Card Sorting Test (perseverative responses, perseverative errors, and categories completed), semantic fluency tests of categories of animals, fruits, and vegetables, and the Quality of Life-Alzheimer's Disease (QoL-AD). Data were collected at preintervention and postintervention. Three-level mixed effects models were performed. This study complied with the CONSORT checklist. RESULTS: After adjusting for covariates, there was a significant increase in CASI scores, the digit span backward test, perseverative responses, perseverative errors, categories completed, semantic fluency tests of categories, and QoL-AD scores in the intervention versus control arm at 3 months. CONCLUSIONS AND IMPLICATIONS: This study provides support for the use of acupressure to improve cognition and QoL during care among older residents with cognitive disorders in LTC settings. Acupressure can be integrated into aged care practice to improve cognition and QoL of older residents with cognitive disorders in LTC settings.

Longitudinal Effects of a Combined Program of Pelvic Floor Muscle Training and Yoga on Genitourinary Symptoms in Asian Women of Older Age: A Randomized Experimental Study.

This parallel-two-group randomized experimental study including a supervised group and an unsupervised group examined the longitudinal effects of pelvic floor muscle training (PFMT) combined with yoga on genitourinary symptoms and the health-related quality of life (HRQOL), and compared practice adherence rates of the two groups. A sample of women experiencing ≥1 genitourinary symptom(s) were recruited and assigned to a supervised group or an unsupervised group. The supervised group attended supervised group practice sessions and performed at-home practice of PFMT and yoga. The unsupervised group performed at-home practice of PFMT and yoga. Information was collected at five time points (n = 91). Generalized estimating equation procedures were used to examine the intervention effects. An independent t-test was conducted to compare the practice adherence rates. Both groups' genitourinary symptoms and HRQOL significantly improved over time. The supervised group displayed greater improvements in genitourinary symptoms and HRQOL and better adherence than did the unsupervised group.

Effects of Caloric Restriction with Protein Supplementation on Plasma Protein Profiles in Middle-Aged Women with Metabolic Syndrome-A Preliminary Open Study.

BACKGROUND: Clinical studies have demonstrated that higher protein intake based on caloric restriction (CR) alleviates metabolic abnormalities. However, no study has examined the effects of plasma protein profiles on caloric restriction with protein supplementation (CRPS) in metabolic syndrome (MetS). Therefore, using a proteomic perspective, this pilot study investigated whether CRPS ameliorated metabolic abnormalities associated with MetS in middle-aged women. METHODS: Plasma samples of middle-aged women with MetS in CR (n = 7) and CRPS (n = 6) groups for a 12-week intervention were obtained and their protein profiles were analysed. Briefly, blood samples from qualified participants were drawn before and after the dietary treatment. Anthropometric, clinical, and biochemical variables were measured and correlated with plasma proteomics. RESULTS: In results, we found that body mass index, total body fat, and fasting blood glucose decreased significantly after the interventions but were not different between the CR and CRPS groups. After liquid chromatography⁻tandem mass spectrometry analysis, the relative plasma levels of alpha-2-macroglobulin (A2M), C4b-binding protein alpha chain (C4BPA), complement C1r subcomponent-like protein (C1RL), complement component C6 (C6), complement component C8 gamma chain (C8G), and vitamin K-dependent protein S (PROS) were significantly different between the CRPS and CR groups. These proteins are involved in inflammation, the immune system, and coagulation responses. Moreover, blood low-density lipoprotein cholesterol levels were significantly and positively correlated with C6 plasma levels in both groups. CONCLUSIONS: These findings suggest that CRPS improves inflammatory responses in middle-aged women with MetS. Specific plasma protein expression (i.e., A2M, C4BPA, C1RL, C6, C8G, and PROS) associated with the complement system was highly correlated with fasting blood glucose (FBG), blood lipids (BLs), and body fat.

Downregulation of Cancer Stemness by Novel Diterpenoid Ovatodiolide Inhibits Hepatic Cancer Stem Cell-Like Traits by Repressing Wnt/[Formula: see text]-Catenin Signaling.

The hierarchical tumor propagation or cancer stem cells (CSCs) model of carcinogenesis postulates that like physiologic adult stem cell (ASC), the CSCs positioned at the apex of any tumor population form the crux of tumor evolution with a constitutive regenerative capacity and differentiation potential. The propagation and recurrence of the characteristically heterogeneous and therapy-resistant hepatocellular carcinoma (HCC), adds to accumulating evidence to support this CSCs model. Based on the multi-etiologic basis of HCC formation which among others, focuses on the disruption of the canonical Wnt signaling pathway, this study evaluated the role of cembrane-type phytochemical, Ovatodiolide, in the modulation of the Wnt/[Formula: see text]-catenin pathway, and its subsequent effect on liver CSCs' activities. Our fluorescence-activated cell sorting (FACS) and quantitative RT-PCR analyses of side population (SP) indicated that CD133+ cells were [Formula: see text]-catenin-overexpressing, more aggressive, and resistant to the conventional anticancer agents, Cisplatin and Doxorubicin, when compared to [Formula: see text]-catenin-downregulated group. We demonstrated that marked upregulation of [Formula: see text]-catenin and its downstream targets effectively enhanced hepatosphere formation, with an associated induction of CD133, OCT4 and Sox2 expression and also caused an significant enhancement of HCC proliferation. However, treatment with Ovatodiolide induced downregulation of [Formula: see text]-catenin and its downstream effector genes, abolished hepatosphere formation and reversed the [Formula: see text]-catenin-associated enhancement of HCC growth. In summary, we demonstrated for the first time that Ovatodiolide suppressed the canonical Wnt signaling pathway, and inhibited the generation of liver CSCs; Thus, projecting Ovatodiolide as a putatively effective therapeutic agent for anti-HCC target therapy.

Lysosomal acid phosphatase 2 is an unfavorable prognostic factor but is associated with better survival in stage II colorectal cancer patients receiving chemotherapy.

Colorectal cancer (CRC) is one of the leading cancers worldwide. Surgery is the main therapeutic modality for stage II CRC. However, the implementation of adjuvant chemotherapy remains controversial and is not universally applied so far. In this study, we found that the protein expression of lysosomal acid phosphatase 2 (ACP2) was increased in CRC and that stage II CRC patients with high ACP2 expression showed a poorer outcome than those with low ACP2 expression (p = 0.004). To investigate this discrepancy, we analyzed the relation between ACP2 expression and several clinical cofactors.Among patients who received chemotherapy, those with an high expression of ACP2 showed better survival in both stage II and III CRC than those with low ACP2 expression. In stage II CRC patients, univariate analysis showed ACP2 expression and T stage to be cofactors significantly associated with overall survival (ACP2: p = 0.006; T stage: p = 0.034). Multivariate Cox proportion hazard model analysis also revealed ACP2 to be an independent prognostic factor for overall survival (ACP2: p = 0.006; T stage: p = 0.041). Furthermore, ACP2-knockdown CRC cells showed an increase in chemoresistance to 5-FU treatment and increased proliferation marker in the ACP2 knockdown clone.Taken together, our results suggested that ACP2 is an unfavorable prognostic factor for stage II CRC and may serve as a potential chemotherapy-sensitive marker to help identify a subset of stage II and III CRC patients for whom chemotherapy would improve survival.Highlights1. To the best of our knowledge, the study is the first report to show ACP2 overexpression in human colorectal cancer (CRC) and its association with poor outcome in stage II CRC.2. Patients with stage II and III CRCs with high expression of ACP2 were more sensitive to chemotherapy than those with a low expression.3. ACP2 expression may serve as a marker for CRC patients receiving chemotherapy and help identify the subset of CRC patients who would benefit from chemotherapy.

Pu-erh Tea Extract Attenuates Nicotine-Induced Foam Cell Formation in Primary Cultured Monocytes: An in Vitro Mechanistic Study.

In this study, the mechanisms by which pu-erh tea extract (PETE) attenuates nicotine-induced foam cell formation were investigated. Monocytes were purified from healthy individuals using commercial antibodies coated with magnetic beads. We found that the nicotine-induced (1-10 µM) expression of oxidized low-density lipoprotein receptors (ox-LDLRs) and α9-nAchRs in monocytes was significantly attenuated by 24 h of PETE (10 µg/mL; ∗, p < 0.05) cotreatment. Nicotine (1 µM for 24 h) significantly induced the expression of the surface adhesion molecule ICAM-1 and the monocyte integrin adhesion molecule (CD11b) by human umbilical vein endothelial cells (HUVECs) and triggered monocytes to differentiate into macrophages via interactions with the endothelium. After treatment with nicotine (0.1-10 µM for 24 h), the HUVECs released chemotactic factors (IL-8) to attract monocytes into the tunica intima of the artery, and the monocytes then transformed into foam cells. We demonstrated that PETE treatment (>1 µg/mL for 24 h; ∗, p < 0.05) significantly attenuates nicotine-induced (1 µM) monocyte migration toward HUVECs and foam cell formation. This study suggests that tea components effectively attenuate the initial step (foam cell formation) of nicotine-induced atherosclerosis in circulating monocytes.

Expression of the M3 Muscarinic Receptor on Orexin Neurons that Project to the Rostral Ventrolateral Medulla.

Activation of central cholinergic receptors causes a pressor response in rats, and the hypothalamus is important for this response. Projections from hypothalamic orexin neurons to the rostral ventrolateral medulla (RVLM) are involved in sympatho-excitation of the cardiovascular system. A small population of orexin neurons is regulated by cholinergic inputs through M3 muscarinic acetylcholine receptor (M3 R). To elucidate whether the M3 R on orexin neurons is involved in cardiosympathetic regulation through the RVLM, we examined the presence of the M3 R on retrograde-labeled RVLM-projecting orexin neurons. The retrograde tracer was unilaterally injected into the RVLM. Within the hypothalamus, retrograde-labeled neurons were located predominantly ipsilateral to the injection side. In the anterior hypothalamus (-1.5 to -2.3 mm to the bregma), retrograde-labeled neurons were densely distributed in the paraventricular nuclei and scattered in the retrochiasmatic area. At -2.3 to -3.5 mm from the bregma, labeled neurons were located in the regions where orexin neurons were situated, that is, the tuberal lateral hypothalamic area, perifornical area, and dorsomedial nuclei. Very few retrograde-labeled neurons were observed in the hypothalamus at -3.5 to -4.5 mm from the bregma. About 19.5% ± 1.6% of RVLM-projecting neurons in the tuberal hypothalamus were orexinergic. The M3 R was present on 18.7% ± 3.0% of RVLM-projecting orexin neurons. Injection of a muscarinic agonist, oxotremorine, in the perifornical area resulted in a pressor response, which was attenuated by a pretreatment of atropine. We conclude that cholinergic inputs to orexin neurons may be involved in cardiosympathetic regulation through the M3 R on the orexin neurons that directly project to the RVLM.

Improvement of fecal incontinence and quality of life by electrical stimulation and biofeedback for patients with low rectal cancer after intersphincteric resection.

OBJECTIVE: To assess the efficacy and benefits of pelvic rehabilitation programs in terms of functional outcomes and quality of life for patients with fecal incontinence and defecation disorders after rectal cancer surgery. DESIGN: Prospective, observational study. SETTING: University hospital physiotherapy clinics. PARTICIPANTS: Patients (N=32) who experienced fecal incontinence after sphincter-saving surgery with the intersphincteric resection (ISR) technique and could follow and cooperate with the treatment schedule were included in the present study. INTERVENTIONS: Pelvic rehabilitation programs included electrical stimulation (ES) and biofeedback (BF). MAIN OUTCOME MEASURES: Functional results, Wexner score, and anorectal manometry were used to assess the clinical outcomes of rehabilitation treatment. RESULTS: Maximum squeeze pressure improved after rehabilitation training (P=.014). There were no statistical differences in resting pressure, resting muscle electromyography, and maximum squeeze electromyography (P=.061, P=.76, and P=.99, respectively). The mean stool frequency was 18.8 per 24 hours before the pelvic intervention program and 7.8 per 24 hours after ES and BF training (P<.001). Of the 32 patients, 27 required antidiarrheal medications before treatment, and after completion of the training, only 9 patients still needed antidiarrheal medications (P<.001). Significant improvements were observed in the Wexner score (17.74 vs 12.93; P<.001). CONCLUSIONS: Our data show that ES and BF are effective in the treatment of fecal incontinence, leading to improvement of quality of life for patients with low rectal cancer after ISR.

Pterostilbene inhibits triple-negative breast cancer metastasis via inducing microRNA-205 expression and negatively modulates epithelial-to-mesenchymal transition.

Breast cancer is the leading cause of cancer-related deaths among females in economically developing countries. Greater than 95% of breast malignancies are of epithelial origin; the induction of epithelial-to-mesenchymal transition (EMT) has been shown to initiate the metastatic process in breast carcinoma and remains the key target for drug development. Here, we examine the anti-metastatic potential of pterostilbene in modulating EMT process in breast cancer cells both in vitro and in vivo. The differential invasive ability among MCF7, Hs578t and MDA-MB-231 breast cancer cell lines were closely correlated with the expression of EMT markers, determined by Western blots and Matrigel-coated transwells assay. Pterostilbene inhibited the migratory and invasive potential of triple-negative MDA-MB-231 and Hs578t cells, accompanied by the up-regulation of E-cadherin and down-regulation of Snail, Slug, vimentin and ZEB1. Mechanistic investigations revealed a significant up-regulation of miR-205, which resulted in the reduction of Src expression in pterostilbene-treated breast cancer cells. Importantly, pterostilbene suppressed tumor growth and metastasis in MDA-MB-231-bearing NOD/SCID mice by reducing Src/Fak signaling; this observation was consistent with the negative correlations between miR-205 and Src expression in both normal and malignant breast tissues. Our findings provide supports for the usage of pterostilbene as an inhibitor of EMT process and potential candidate for adjuvant therapy.

BlueBerry Isolate, Pterostilbene, Functions as a Potential Anticancer Stem Cell Agent in Suppressing Irradiation-Mediated Enrichment of Hepatoma Stem Cells.

For many malignancies, radiation therapy remains the second option only to surgery in terms of its curative potential. However, radiation-induced tumor cell death is limited by a number of factors, including the adverse response of the tumor microenvironment to the treatment and either intrinsic or acquired mechanisms of evasive resistance, and the existence of cancer stem cells (CSCs). In this study, we demonstrated that using different doses of irradiation led to the enrichment of CD133(+) Mahlavu cells using flow cytometric method. Subsequently, CD133(+) Mahlavu cells enriched by irradiation were characterized for their stemness gene expression, self-renewal, migration/invasion abilities, and radiation resistance. Having established irradiation-enriched CD133(+) Mahlavu cells with CSC properties, we evaluated a phytochemical, pterostilbene (PT), found abundantly in blueberries, against irradiation-enriched CSCs. It was shown that PT treatment dose-dependently reduced the enrichment of CD133(+) Mahlavu cells upon irradiation; PT treatment also prevented tumor sphere formation, reduced stemness gene expression, and suppressed invasion and migration abilities as well as increasing apoptosis of CD133(+) Mahlavu CSCs. Based on our experimental data, pterostilbene could be used to prevent the enrichment of CD133(+) hepatoma CSCs and should be considered for future clinical testing as a combined agent for HCC patients.