The CuSCN layer between BiVO4 and NiFeOx for facilitating photogenerated carrier transfer and water oxidation kinetics.

Modification of oxygen evolution co-catalyst (OEC) on the surface of bismuth vanadate (BiVO4) can effectively improve the kinetics of water oxidation, but it is still limited by the small hole extraction driving force at the BiVO4/OEC interface. Modulating the BiVO4/OEC interface with a hole transfer layer (HTL) is expected to facilitate hole transport from BiVO4 to the OEC surface. Herein, a copper(I) thiocyanate (CuSCN) HTL is inserted between BiVO4 and NiFeOx OEC to create BiVO4/CuSCN/NiFeOx photoanode, resulting in a significant enhancement of photoelectrochemical (PEC) water splitting performance. From electrochemical analyses and density functional theory (DFT) simulations, the markedly enhanced PEC performance is attributed to the insertion of CuSCN as an HTL, which promotes the extraction of holes from BiVO4 surface and boosts the water oxidation kinetics. The optimal photoanode achieves a photocurrent density of 5.6 mA cm-2 at 1.23 V versus the reversible hydrogen electrode (vs. RHE) and an impressive charge separation efficiency of 96.2 %. This work offers valuable insights into the development of advanced photoanodes for solar energy conversion and emphasizes the importance of selecting an appropriate HTL to mitigate recombination at the BiVO4/OEC interface.

Surgical management of nervus intermedius neuralgia: A report of 4 cases and literature review.

BACKGROUND: Nervus intermedius neuralgia (NIN) is characterized by paroxysmal episodes of sharp, lancinating pain in the deep ear. Unfortunately, only a few studies exist in the literature on this pain syndrome, its pathology and postoperative outcomes. METHOD: We conducted a retrospective review of four cases diagnosed with NIN who underwent a neurosurgical intervention at our center from January 2015 to January 2023. Detailed information on their MRI examinations, intraoperative findings and other clinical presentations were obtained, and the glossopharyngeal and vagus nerves were isolated for immunohistochemistry examination. RESULTS: A total of 4 NIN patients who underwent a microsurgical intervention at our institution were included in this report. The NI was sectioned in all patients and 3 of them underwent a microvascular decompression. Of these 4 patients, 1 had a concomitant trigeminal neuralgia (TN), and 1 a concomitant glossopharyngeal neuralgia (GPN). Three patients underwent treatment for TN and 2 for GPN. Follow-up assessments ranged from 8 to 99 months. Three patients reported complete pain relief immediately after the surgery until last follow-up, while in the remaining patient the preoperative pain gradually resolved over the 3 month period. Immunohistochemistry revealed that a greater amount of CD4+ and CD8+ T cells had infiltrated the glossopharyngeal versus vagus nerve. CONCLUSIONS: NIN is an extremely rare condition showing a high degree of overlap with TN/GPN. An in depth neurosurgical intervention is effective to completely relieve NIN pain, without any serious complications. It appears that T cells may play regulatory role in the pathophysiology of CN neuralgia.

Identification of hypoxia- and immune-related biomarkers in patients with ischemic stroke.

Background: The immune microenvironment and hypoxia play crucial roles in the pathophysiology of ischemic stroke (IS). Hence, in this study, we aimed to identify hypoxia- and immune-related biomarkers in IS. Methods: The IS microarray dataset GSE16561 was examined to determine differentially expressed genes (DEGs) utilizing bioinformatics-based analysis. The intersection of hypoxia-related genes and DEGs was conducted to identify differentially expressed hypoxia-related genes (DEHRGs). Then, using weighted correlation network analysis (WGCNA), all of the genes in GSE16561 dataset were examined to create a co-expression network, and module-clinical trait correlations were examined for the purpose of examining the genes linked to immune cells. The immune-related DEHRGs were submitted to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A protein-protein interaction (PPI) network was constructed by Cytoscape plugin MCODE, in order to extract hub genes. The miRNet was used to predict hub gene-related transcription factors (TFs) and miRNAs. Finally, a diagnostic model was developed by least absolute shrinkage and selection operator (LASSO) logistic regression. Results: Between the control and IS samples, 4171 DEGs were found. Thereafter, the intersection of hypoxia-related genes and DEGs was conducted to obtain 45 DEHRGs. Ten significantly differentially infiltrated immune cells were found-namely, CD56dim natural killer cells, activated CD8 T cells, activated dendritic cells, activated B cells, central memory CD8 T cells, effector memory CD8 T cells, natural killer cells, gamma delta T cells, plasmacytoid dendritic cells, and neutrophils-between IS and control samples. Subsequently, we identified 27 immune-related DEHRGs through the intersection of DEHRGs and genes in important modules of WGCNA. The immune-related DEHRGs were primarily enriched in response to hypoxia, cellular polysaccharide metabolic process, response to decreased oxygen levels, polysaccharide metabolic process, lipid and atherosclerosis, and HIF-1 signaling pathway H. Using MCODE, FOS, DDIT3, DUSP1, and NFIL3 were found to be hub genes. In the validation cohort and training set, the AUC values of the diagnostic model were 0.9188034 and 0.9395085, respectively. Conclusion: In brief, we identified and validated four hub genes-FOS, DDIT3, DUSP1, and NFIL3-which might be involved in the pathological development of IS, potentially providing novel perspectives for the diagnosis and treatment of IS.

Lemur tyrosine kinase 2 has a tumor-inhibition function in human glioblastoma by regulating the RUNX3/Notch pathway.

Deregulation of lemur tyrosine kinase 2 (LMTK2) is a vital determinant for the onset and progression of malignancies, yet the relationship between LMTK2 and glioblastoma (GBM) is undetermined. This study was carried out to determine the relevance of LMTK2 in GBM. Initiating investigation by assessing The Cancer Genome Atlas (TCGA) data showed LMTK2 mRNA levels were decreased in GBM tissue. Later examination of clinical specimens confirmed low levels of LMTK2 mRNA and protein in GBM tissue. The downregulated level of LMTK2 in patients with GBM was related to poor overall survival. A suppressive function of LMTK2 on the proliferative capability and metastatic potential of GBM cells was demonstrated by overexpressing LMTK2 in GBM cell lines. Moreover, the restoration of LMTK2 augmented the sensitivity of GBM cells to the chemotherapy drug temozolomide. The mechanistic investigation uncovered LMTK2 as a regulator of the runt-related transcription factor 3 (RUNX3)/Notch signaling pathway. The overexpression of LMTK2 increased the expression of RUNX3 while inhibiting the activation of Notch signaling. The silencing of RUNX3 diminished the regulatory role of LMTK2 on Notch signaling. The inhibition of Notch signaling reversed the LMTK2-silencing-elicited protumor effects. Importantly, LMTK2-overexpressed GBM cells displayed weakened tumorigenicity in xenograft models. Our findings illustrate that LMTK2 has a tumor-inhibition function in GBM by constraining Notch signaling via RUNX3. This work indicates the deregulation of the LMTK2-mediated RUNX3/Notch signaling pathway may be a novel molecular mechanism for the malignant transformation of GBMs. This work highlights the interest in LMTK2-related approaches for treating GBM.

Macrophage/Microglia Sirt3 Contributes to the Anti-inflammatory Effects of Resveratrol Against Experimental Intracerebral Hemorrhage in Mice.

Intracerebral hemorrhage (ICH) is a devastating stroke type with high mortality and disability. Inflammatory response induced by macrophages/microglia (M/Ms) activation is one of the leading causes of brain damage after ICH. The anti-inflammatory effects of resveratrol (RSV) have already been evaluated in several models of central nervous system disease. Therefore, we designed the current study to assess the role of RSV in ICH and explore its downstream mechanism related to Sirt3. The autologous artery blood injection was administrated to create an ICH mouse model. M/Ms-specific Sirt3 knockout Sirt3f/f; CX3CR1-Cre (Sirt3 cKO) mouse was used to evaluate the role of Sirt3 on RSV treatment. Neuronal function and hematoma volume were assessed to indicate brain damage. The pro-inflammatory marker (CD16) and cytokine (TNF) were measured to evaluate the inflammatory effects. Our results showed that RSV treatment alleviates neurological deficits, reduces cell death, and increases hematoma clearance on day 7 after ICH. In addition, RSV effectively suppressed CD16+ M/Ms activation and decreased TNF release. In Sirt3 cKO mice, the protective effects of RSV were abolished, indicating the potential mechanism of RSV was partially due to Sirt3 signaling activation. Therefore, RSV could be a promising candidate and therapeutic agent for ICH and Sirt3 could be a potential target to inhibit inflammation.

Identification of a Fibroblast-Related Prognostic Model in Glioma Based on Bioinformatics Methods.

BACKGROUND: Glioma is the most common primary tumor of the central nervous system with a high lethality rate. This study aims to mine fibroblast-related genes with prognostic value and construct a corresponding prognostic model. METHODS: A glioma-related TCGA (The Cancer Genome Atlas) cohort and a CGGA (Chinese Glioma Genome Atlas) cohort were incorporated into this study. Variance expression profiling was executed via the "limma" R package. The "clusterProfiler" R package was applied to perform a GO (Gene Ontology) analysis. The Kaplan-Meier (K-M) curve, LASSO regression analysis, and Cox analyses were implemented to determine the prognostic genes. A fibroblast-related risk model was created and affirmed by independent cohorts. We derived enriched pathways between the fibroblast-related high- and low-risk subgroups using gene set variation analysis (GSEA). The immune infiltration cell and the stromal cell were calculated using the microenvironment cell populations-counter (MCP-counter) method, and the immunotherapy response was assessed with the SubMap algorithm. The chemotherapy sensitivity was estimated using the "pRRophetic" R package. RESULTS: A total of 93 differentially expressed fibroblast-related genes (DEFRGs) were uncovered in glioma. Seven prognostic genes were filtered out to create a fibroblast-related gene signature in the TCGA-glioma cohort training set. We then affirmed the fibroblast-related risk model via TCGA-glioma cohort and CGGA-glioma cohort testing sets. The Cox regression analysis proved that the fibroblast-related risk score was an independent prognostic predictor in prediction of the overall survival of glioma patients. The fibroblast-related gene signature revealed by the GSEA was applicable to the immune-relevant pathways. The MCP-counter algorithm results pointed to significant distinctions in the tumor microenvironment between fibroblast-related high- and low-risk subgroups. The SubMap analysis proved that the fibroblast-related risk score could predict the clinical sensitivity of immunotherapy. The chemotherapy sensitivity analysis indicated that low-risk patients were more sensitive to multiple chemotherapeutic drugs. CONCLUSION: Our study identified prognostic fibroblast-related genes and generated a novel risk signature that could evaluate the prognosis of glioma and offer a theoretical basis for clinical glioma therapy.

A systematic review and meta-analysis of surgeries performed for cerebral cavernous malformation-related epilepsy in pediatric patients.

Background: The clinical benefit of surgery for the treatment of cerebral cavernous malformation (CCM)-related epilepsy in pediatric patients is still controversial. Although surgical treatment of CCM-related epilepsy in children is widely recognized, the clinical benefits of controlling the seizure rate must be balanced against the risk of leading to perioperative morbidity. Methods: We conducted a comprehensive search to identify relevant studies via Ovid Medline, Web of Science and PubMed (January 1995-June 2020). The following search terms were used: "hemangioma, cavernous, central nervous system," "brain cavernous hemangioma," "cerebral cavernous hemangioma," "CCM," "epilepsy," and "seizures." The seizure control rate and the risk of postoperative adverse outcomes along with their 95% confidence intervals (CIs) were calculated. Results: A total of 216 patients across 10 studies were included in meta-analysis. The results showed that the control rate of epilepsy was 88% (95% CI: 76-95%). Four percent (95% CI: 2-10%) of the patients experienced temporary symptomatic adverse effects following surgical resection, and 3% (95% CI: 0-26%) of the patients developed permanent symptomatic adverse effects in the long-term follow-up after surgical excision of the CCMs. None of the patients died as a result of the CCMs or surgical treatment. Conclusion: Surgery is an effective and safe treatment for CCM -related epilepsy in pediatric patients with a low risk of postoperative complications and death.

Lung cancer combined with diffuse peritoneal and mesenteric amyloidosis detected on 18F-FDG PET/CT: A case report.

RATIONALE: Amyloidosis is a heterogeneous group of diseases characterized by extracellular deposition of amyloid fibrils. Lung carcinoma is rarely reported to be associated with AA amyloidosis. With regard to the manifestation of amyloidosis infiltrating organs, most of the cases focus on the heart, liver, kidneys, and peripheral nervous system. Amyloidosis with diffuse abdominal involvement in combination with pulmonary squamous cell carcinoma carcinoma is an exceptionally rare occurrence. PATIENT CONCERNS: A 70-year-old man was admitted to hospital for a 2-month history of repeated cough, low grade fever, hemoptysis and left back shoulder pain, which was not relieved by nonsteroid anti-inflammatory drugs. Meanwhile, he complained of intermittent diffuse abdominal discomfort and chronic persistent constipation. DIAGNOSES: The patient was diagnosed with poorly differentiated lung squamous cell carcinoma and diffuse peritoneal and mesenteric amyloidosis based on the pathological biopsy. INTERVENTIONS: The patient received surgery and chemotherapy for lung tumor. He did not receive any treatment against amyloidosis. OUTCOMES: The patient died of a severe respiratory infection. LESSONS: This case indicates that lung carcinoma is suspected to play a causative role in the development of amyloidosis. In addition, amyloidosis should be considered in the differential diagnosis in cases in which diffuse greater omentum, peritoneal, and mesenteric calcifications on 18F-2-fluoro-2-deoxy-D-glucose(18F-FDG) photon emission computed tomography (PET/CT).

Microsurgery vs. Gamma Knife Radiosurgery for the Treatment of Brainstem Cavernous Malformations: A Systematic Review and Meta-Analysis.

Background: Brainstem cavernous malformations (BSCMs) are a subset of cerebral cavernous malformations with precarious locations and potentially devastating clinical courses. The effects and outcomes of treating BSCMs by microsurgery or gamma knife radiosurgery (GKRS) vary across studies. Methods: We searched the Medline, Web of Science, The Cochrane Library, PubMed, and China Biology Medicine disc databases for original articles published in peer-reviewed journals of cohort studies reporting on 20 or more patients of any age with BSCMs with at least 80% completeness of follow-up. Results: We included 43 cohorts involving 2,492 patients. Both microsurgery (RR = 0.04, 95% CI 0.01-0.16, P < 0.01) and GKRS (RR = 0.11, 95% CI 0.08-0.16, P < 0.01) demonstrated great efficacy in reducing the rehemorrhage rate after treatment for BSCMs. The incidence rates of composite outcomes were 19.8 (95% CI 16.8-22.8) and 15.7 (95% CI 11.7-19.6) after neurosurgery and radiosurgery, respectively. In addition, we found statistically significant differences in the median numbers of patients between neurosurgical and radiosurgical cohorts in terms of symptomatic intracranial hemorrhage (ICH; neurosurgical cohorts: median 0, range 0-33; radiosurgical cohorts: median 4, range 1-14; P < 0.05) and persistent focal neurological deficit (FND; neurosurgical cohorts: median 5, range 0-140; radiosurgical cohorts: median 1, range 0-3; P < 0.05). Conclusions: The reported effects of treating BSCMs by microsurgery or GKRS are favorable for reducing recurrent hemorrhage from BSCMs. Patients in the neurosurgery cohort had a lower incidence of symptomatic ICH, while patients in the radiosurgical cohort had a lower incidence of persistent FND.

Treatment of Cerebral Cavernous Malformations Presenting With Seizures: A Systematic Review and Meta-Analysis.

Background: Cerebral cavernous malformations (CCMs) presenting with seizures can be treated with neurosurgery or radiosurgery, but the ideal treatment remains unclear. Currently, there is no adequate randomized controlled trial comparing surgical treatment and radiotherapy for epileptogenic CCMs. Therefore, we conducted a systematic review and meta-analysis of available data from published literature to compare the efficacy and safety of neurosurgery and radiosurgery for epileptogenic CCMs. Methods: We performed a comprehensive search of the Ovid MEDLINE, Web of Science, PubMed, China Biological Medicine and China National Knowledge Infrastructure databases for studies published between January 1994 and October 2019. The search terms were as follows: "epilepsy," "seizures," "brain cavernous hemangioma," "cerebral cavernous malformation," "cerebral cavernous hemangioma," "hemangioma, cavernous, central nervous system." Two researchers independently extracted the data and reviewed all the articles. We compared the advantages and disadvantages of the two treatments. Results: A total of 45 studies were included in our analysis. Overall, the seizure control rate was 79% (95% CI: 75-83%) for neurosurgery and 49% (95% CI: 38-59%) for radiosurgery. In the neurosurgery studies, 4.4% of patients experienced permanent morbidity, while no patients in the radiotherapy studies had permanent morbidity. In addition, the results of subgroup analysis showed that ethnicity, CCMs location and average lesion number are likely significant factors influencing the seizure outcome following treatment. Conclusions: The epilepsy control rate after neurosurgery was higher than that after radiosurgery, but neurosurgery also had a relatively higher rate of permanent morbidity.

Operation for locally advanced cervical cancer after concurrent chemoradiotherapy.

OBJECTIVE: This paper aimed to discuss the scope of operation and clinical effects for locally advanced cervical cancer (LACC) after concurrent chemoradiotherapy (CCRT). METHODS: We retrospectively reviewed the records of 444 patients with stages IB2-IIB cervical cancer who were divided into two groups whether or not they received CCRT before radical operation in our institute from January 2013 to December 2016. Patients' characteristics, treatments, and outcomes were analyzed. RESULTS: The total efficiency (CR + PR) of the CCRT + operation group was 96.2%. Specifically, the CR rate was 9.1%, and the PR rate was 87.1%. The positive rates of cervical deep interstitial infiltration, lymphatic metastasis, and lymphangial infiltration of the operation group were significantly higher than those of the CCRT + operation group (P < 0.05). A total of 24 and 162 patients in the CCRT + operation group and the operation group, respectively, received adjuvant therapy (P < 0.05). The incidence rate of edema of the lower extremity, radiation enteritis, and radiocystitis after postoperative adjuvant radiotherapy in the operation group was significantly higher than that of the CCRT + operation group (P < 0.05). The 5-year survival rates and 5-year progression-free survival (PFS) rates of the CCRT + operation and operation groups were 79.3% versus 64.0% and 68.9% versus 45.2%, respectively (P < 0.05). CONCLUSIONS: Comprehensive treatment that combines CCRT and radical operation to LACC achieves satisfying clinical effects without increasing the occurrence rate of intraoperative and postoperative complications. Moreover, such treatment can improve the 5-year PFS rate and OS rate.

MicroRNA-34a induces apoptosis in the human glioma cell line, A172, through enhanced ROS production and NOX2 expression.

BACKGROUND: MicroRNA is a type of non-coding small RNA involved in regulating genes and signaling pathways through incomplete complementation with target genes. Recent research supports key roles of miRNA in the formation and development of human glioma. METHODS: The relative quantity of miR-34a was initially determined in human glioma A172 cells and glioma tissues. Next, we analyzed the impact of miR-34a on A172 cell viability with the MTT assay. The effects of miR-34a overexpression on apoptosis were confirmed with flow cytometry and Hoechst staining experiments. We further defined the target genes of miR-34a using immunofluorescence and Western blot. RESULTS: MiR-34a expression was significantly reduced in human glioma A172 cells and glioma tissue, compared with normal glial cells and tissue samples. Our MTT data suggest that up-regulation of miR-34a inhibits cell viability while suppression of miR-34a enhances cell viability. Flow cytometry and Hoechst staining results revealed increased rates of apoptosis in A172 human glioma cells overexpressing miR-34a. Using immunofluorescence and Western blot analyses, we identified NOX2 as a target of miR-34a in A172 cells. CONCLUSION: MiR-34a serves as a tumor suppressor in human glioma mainly by decreasing NOX2 expression.

The interleukin-6-572G/C gene polymorphism and the risk of intracranial aneurysms in a Chinese population.

Interleukin-6 (IL-6) is an important proinflammatory cytokine that plays an important role in the pathogenesis of intracranial aneurysms (IAs). The aim of this study was to investigate the association between the IL-6-572G/C polymorphism and the risk of IAs in a Chinese population. The IL-6-572G/C gene polymorphisms in 220 IA cases and 220 controls were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. The IL-6-572GG (odds ratio [OR]=3.35, 95% confidence intervals [CIs]=1.65, 6.82; p=0.001) and G allele frequencies (OR=1.48, 95% CIs=1.09, 2.00; p=0.01) in the IA group were higher than those in the control group. The C allele frequencies (OR=0.68, 95% CIs=0.50, 0.92; p=0.01) were significantly lower in patients than in controls. When stratified by the site, shape, size, and the Fisher Grade of IAs, no statistically significant result was observed. This study suggested that the IL-6-572GG genotype was associated with a higher risk of IA in a Chinese population.

Transsphenoidal pseudocapsule-based extracapsular resection for pituitary adenomas.

BACKGROUND: In the past several years, increasing attention has been paid to the utility of a pseudocapsule in transphenoidal surgery for pituitary adenomas. However, prior studies focused more on the histological structure of the pseudocapsule and surgical technique. The objective of this study was to evaluate the overall therapeutic effectiveness of transsphenoidal pseudocapsule-based extracapsular resection for pituitary adenomas. METHODS: Between January 2004 and October 2007, 78 patients with pituitary adenomas underwent transsphenoidal pseudocapsule-based extracapsular removal surgery (extracapsular resection group, ER group). During the same period, 64 patients underwent transsphenoidal intracapsular resection operations (intracapsular resection group, IR group). RESULTS: Complete resection rates were achieved in 90.6%, 84.6% and 65.5%, 52.6% of modified Hardy types II and III in the ER and IR groups, showing a significant difference (both P < 0.05). Statistical significance in the remission rates was also found between the two groups with modified Hardy types II and III, respectively (both P < 0.05). Complications occurred in 29.5% of the ER group and 26.6% of the IR group, with no difference between groups (P > 0.05). The recurrence rate of the ER group (2.56%) was lower than that of the IR group (14.06%). CONCLUSION: The transsphenoidal pseudocapsule-based extracapsular resection approach provides a more effective and safe alternative compared to the traditional intracapsular one because of its higher tumor removal and remission rates, and lower recurrence rate.

[The comparison of the indoor environmental factors associated with asthma and related allergies among school-child between urban and suburban areas in Beijing].

OBJECTIVE: To study the indoor environmental factors associated with the prevalence of asthma and related allergies among school children. METHODS: A cluster sampling method was used and the ISAAC questionnaire was conducted. A total of 4612 elementary students under Grade Five of 7 schools were enrolled in the survey for the impact of indoor environmental factors on the prevalence of asthma and related allergies in several urban and suburban schools of Beijing. RESULTS: A total of 4060 sample were finally analyzed including 1992 urban and 2068 suburban. The prevalence of wheeze, allergic rhinoconjunctivitis and atopic eczema in the past 12 months was 3.1% (61/1992), 5.3% (106/1992), 1.1% (22/1992) among urban children while 1.3% (27/2068), 3.1% (65/2068), 1.0% (22/2068) among suburban children respectively. The prevalence of wheeze and allergic rhinoconjunctivitis of the past 12 months in urban were both significantly higher than that in suburban (χ(2) = 14.77, 11.93, P < 0.01). The incidences of having asthma and eczema ever among urban children (5.3% (105/1992), 29.4% (586/1992)) were significantly (χ(2) = 39.03, 147.22, P < 0.01) higher than that among suburban (1.7% (35/2068), 13.8% (285/2068)). Although the distributions of indoor environmental factors were similar in both areas, passive smoking and interior decoration had different influence on the prevalence of asthma and related allergies among school children in the two areas. The significant impact of passive smoking on having asthma ever among suburban children was observed (OR = 2.70, 95%CI = 1.17 - 6.23) while no significant result in urban (OR = 1.06, 95%CI = 0.71 - 1.58); the percentage of interior decoration was 84.0% (1673/1992) among urban children and 80.0% (1655/2068) among suburban children, there was significant impact of interior decoration on the prevalence of having eczema ever among urban children (OR = 1.57, 95%CI = 1.17 - 2.10) but no significant results were found in suburban sample (OR = 1.06, 95%CI = 0.76 - 1.48). CONCLUSION: The prevalence of asthma and related allergies among school children is much higher in urban areas than that in suburban areas and the indoor environmental factors such as passive smoking and interior decoration may differently explain the prevalence of asthma and related allergies in the two areas.

D-Limonene: safety and clinical applications.

D-limonene is one of the most common terpenes in nature. It is a major constituent in several citrus oils (orange, lemon, mandarin, lime, and grapefruit). D-limonene is listed in the Code of Federal Regulations as generally recognized as safe (GRAS) for a flavoring agent and can be found in common food items such as fruit juices, soft drinks, baked goods, ice cream, and pudding. D-limonene is considered to have fairly low toxicity. It has been tested for carcinogenicity in mice and rats. Although initial results showed d-limonene increased the incidence of renal tubular tumors in male rats, female rats and mice in both genders showed no evidence of any tumor. Subsequent studies have determined how these tumors occur and established that d-limonene does not pose a mutagenic, carcinogenic, or nephrotoxic risk to humans. In humans, d-limonene has demonstrated low toxicity after single and repeated dosing for up to one year. Being a solvent of cholesterol, d-limonene has been used clinically to dissolve cholesterol-containing gallstones. Because of its gastric acid neutralizing effect and its support of normal peristalsis, it has also been used for relief of heartburn and gastroesophageal reflux (GERD). D-limonene has well-established chemopreventive activity against many types of cancer. Evidence from a phase I clinical trial demonstrated a partial response in a patient with breast cancer and stable disease for more than six months in three patients with colorectal cancer.

Morning/evening menopausal formula relieves menopausal symptoms: a pilot study.

OBJECTIVE: The purpose of the study was to determine the efficacy of a morning/evening menopause formula (morning capsule contains panax ginseng, black cohosh, soy, and green tea extracts; evening capsule contains black cohosh, soy, kava, hops, and valerian extracts) for relieving menopausal symptoms such as hot flashes and sleep disturbance. METHODS: Healthy postmenopausal women, between 45 and 65 years of age, were asked to take the menopause formula orally, one capsule of the morning formula every morning and one capsule of the evening formula every evening for 2 months. The Greene Climacteric Scale (GCS) and the Pittsburgh Sleep Quality Index (PSQI) were used to determine the efficacy. RESULTS: Morning/evening menopause formula significantly reduced the number of hot flashes. The reduction in the number of hot flashes was observed as early as at the end of the second week. At the end of the second week, the number of hot flashes was reduced by 47%. The morning/evening menopause formula also significantly reduced the GCS total and subscale scores. At the end of the eighth week, the vasomotor, anxiety, and depression scores of GCS were reduced by 50%, 56%, and 32%, respectively. Furthermore, the morning/evening menopause formula significantly reduced global PSQI score and scores in five components (sleep quality, sleep latency, sleep duration, sleep disturbance, and daytime dysfunction) by 18%-46%. CONCLUSIONS: This study suggests that the morning/evening menopausal formula is safe and effective for relieving menopausal symptoms including hot flashes and sleep disturbance.