Chinese Medicine Syndrome Differentiation for Early Breast Cancer: A Multicenter Prospective Clinical Study.

Background: Chinese medicine (CM) syndrome differentiation is one of the fundamental principles that guide the practice of Chinese herbal medicine (CHM). CHM has been widely used among breast cancer patients. Contemporary literature varies in syndrome diagnosis, and there is a need to standardize syndrome differentiation according to the different stages of breast cancer treatment. This multicenter clinical study aims to identify the CM syndromes and the clinical signs and symptoms in women with early breast cancer. Methods: Participants who met the inclusion and exclusion criteria were interviewed during the five treatment stages: preoperative, postoperative, chemotherapy, radiation therapy, and endocrine therapy. Patient demographic data and CM syndrome (as recorded by the treating CM clinicians in medical records) were gathered. Signs and symptoms were analyzed using descriptive statistics to derive the standardized CM syndromes using hierarchical cluster analysis. Results: The analysis included 964 interviews with 620 participants enrolled between April 29, 2020 and May 30, 2021 from eight participating hospitals in China. The two most frequent syndromes recorded in medical records were dual deficiency of qi and blood, and dual deficiency of qi and yin during all but the preoperative stage. The symptoms of lassitude, lack of strength, and insomnia were common in all but the preoperative stage. Cluster analysis identified two clusters in the preoperative stage that most closely resembled the syndrome diagnoses of liver stagnation with congealing phlegm, and dual deficiency of the liver and kidney. Two clusters-dual deficiency of qi and blood, and dual deficiency of qi and yin-were common to multiple treatment stages. The syndrome cluster of spleen and stomach disharmony existed in both the postoperative and chemotherapy stages. Cluster analysis of the radiation therapy stage identified the unique syndrome of yin deficiency with fire toxin, while the endocrine therapy included the syndromes of liver depression and kidney deficiency. Conclusions: This multicenter clinical study showed consistency between results from cluster analysis and the most common syndromes recorded in the medical records. Findings from this clinical study will be further validated in a Delphi study to standardize CM syndromes for various stages of breast cancer treatment. Clinical Trial Registration: www.chictr.org.cn/index.aspx, identifier ChiCTR2000032497.

Development of a high-performance liquid chromatography with tandem mass spectrometry method for identifying common adulterant content in saffron (Crocus sativus L.).

OBJECTIVES: This study aimed to develop an efficient and reliable method for estimating common adulterants in saffron by detecting their characteristic components to warrant its efficacy and regular use as a highly valuable medicinal herb. METHODS: A selective and sensitive high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method was developed to estimate the common adulterants in saffron from corn stigma, chrysanthemum and safflower through the simultaneous determination of specific constituents including allantoin, chlorogenic acid (ChA) and hydroxysafflor yellow A (HSYA). Peak identification of each target compound was confirmed from product ions obtained using multiple reaction monitoring triggered enhanced product ions mass chromatogram. Method validation in terms of linearity, sensitivity, reproducibility, accuracy and stability was systematically performed according to official guidelines. KEY FINDINGS: Satisfactory separation of the three components was achieved on a C18 column (4.6 × 250 mm, 5 µm) with methanol-acetonitrile-ammonium acetate (3.0 mm) as the mobile phase at gradient elution. The identification of these specific constituents was accomplished using the multiple reaction monitoring mode in combination with enhanced product ion supplementary confirmation. The established method was validated in terms of linearity, sensitivity, reproducibility, accuracy and recovery, which were found satisfactory for sensitive detection of the three target compounds. CONCLUSIONS: By detecting the specific constituents allantoin, ChA and HSYA in one run, the adulterants of corn stigma, chrysanthemum and safflower can be effectively identified and estimated in saffron. This is the first report on developing a simple, sensitive and operational method for the identification and estimation of common adulterants of saffron, that was forwarded for broaden application.

Effects of Folic Acid and Vitamin B12, Alone and in Combination on Cognitive Function and Inflammatory Factors in the Elderly with Mild Cognitive Impairment: A Single-blind Experimental Design.

BACKGROUND: Folate and vitamin B12 are well-known as essential nutrients that play key roles in the normal functions of the brain. Inflammatory processes play at least some role in the pathology of AD. Effective nutritional intervention approaches for improving cognitive deficits that reduce the peripheral inflammatory cytokine levels have garnered special attention. OBJECTIVE: The present study aimed to determine whether supplementation with folic acid and vitamin B12, alone and in combination improves cognitive performance via reducing levels of peripheral inflammatory cytokines. METHODS: 240 participants with MCI were randomly assigned in equal proportion to four treatment groups: folic acid alone, vitamin B12 alone, folic acid plus vitamin B12 or control without treatment daily for 6 months. Cognition was measured with WAIS-RC. The levels of inflammatory cytokines were measured using ELISA. Changes in cognitive function or blood biomarkers were analyzed by repeatedmeasure analysis of variance or mixed-effects models. This trial has been registered with trial number ChiCTR-ROC-16008305. RESULTS: Compared with control group, the folic acid plus vitamin B12 group had significantly greater improvements in serum folate, homocysteine, vitamin B12 and IL-6, TNF-α, MCP-1. The folic acid plus vitamin B12 supplementation significantly changed the Full Scale IQ (effect size d = 0.169; P = 0.024), verbal IQ (effect size d = 0.146; P = 0.033), Information (d = 0.172; P = 0.019) and Digit Span (d = 0.187; P = 0.009) scores. Post hoc Turkey tests found that folic acid and vitamin B12 supplementation was significantly more effective than folic acid alone for all endpoints. CONCLUSIONS: The combination of oral folic acid plus vitamin B12 in MCI elderly for six months can significantly improve cognitive performance and reduce the levels of inflammatory cytokines in human peripheral blood. The combination of folic acid and vitamin B12 was significantly superior to either folic acid or vitamin B12 alone.

Yanghe Huayan decoction inhibits the capability of trans-endothelium and angiogenesis of HER2+ breast cancer via pAkt signaling.

Background: Yanghe Huayan Decoction (YHD), a traditional Chinese medicine, is one of the most common complementary medicine currently used in the treatment of breast cancer (BC). It has been recently linked to suppress precancerous lesion and tumor development. The current study sought to explore the role of YHD on trans-endothelium and angiogenesis of BC. Methods: HER2+ BC cells were treated with YHD, Trastuzumab, or the combination in vitro and in vivo to compare the effects of them on trans-endothelium and angiogenesis features. The present study also investigated the potential molecular mechanism of YHD in inhibiting angiogenesis of BC. Results: YHD significantly suppressed the invasion and angiogenesis of BC cells via elevated pAkt signaling. Administration of YHD in vivo also strikingly repressed angiogenesis in tumor grafts. Conclusion: YHD could partially inhibit and reverse tumorigenesis of BC. It also could inhibit Akt activation and angiogenesis in vitro and in vivo Its effect was superior to trastuzumab. Thus it was suitable for prevention and treatment of BC.

Effects of folic acid supplementation on cognitive function and Aß-related biomarkers in mild cognitive impairment: a randomized controlled trial.

PURPOSE: Observational studies have frequently reported that low blood folate concentrations are associated with poor cognitive performance. Our previous studies have shown the potential beneficial effect on the metabolite levels of methionine cycle and peripheral blood inflammatory cytokines from 6- and 12-month folic acid supplementation on cognitive function in mild cognitive impairment (MCI). This study aims to continue exploring the effect of 24-month folic acid supplementation on cognitive function and pathological mechanism in MCI. METHODS: 180 individuals with MCI were identified and randomly divided into intervention (folic acid 400 µg/day, n = 90) and convention (n = 90) groups. Cognitive function (WAIS-RC) and blood Aß-related biomarkers were measured at baseline and at 6, 12, 18, and 24 months. Data were analyzed using generalized estimating equation. This trial has been registered with Trial Number: ChiCTR-TRC-13003227. RESULTS: During the follow-up, scores of full scale IQ, verbal IQ, and subdomains of Information and Digit Span were significantly higher in the intervention group than those in the convention group (P < 0.05). In the intervention group, blood homocysteine, S-adenosylhomocysteine (SAH), Aß-42, and the expression of APP-mRNA were decreased (P < 0.05), while S-adenosylmethionine (SAM), SAM/SAH ratio, and the expression of DNA methyltransferase mRNA were increased (P < 0.05). CONCLUSION: Folic acid supplementation appears to improve cognitive function and reduce blood levels of Aß-related biomarkers in MCI. Larger-scale double-blind placebo-controlled randomized trials of longer duration are needed.

Folic acid supplementation improves cognitive function by reducing the levels of peripheral inflammatory cytokines in elderly Chinese subjects with MCI.

This study aimed to evaluate whether folic acid supplementation would improve cognitive performance by reducing serum inflammatory cytokine concentrations. This RCT was performed in Tianjin, China. Participants with mild cognitive impairment (MCI) were randomly assigned to the folic acid (400 µg/day) or conventional treatment groups. Neuropsychological tests were administered, and folate, homocysteine, vitamin B12, IL-6, TNF-α, Aß-42, and Aß-40 were measured at baseline and at 6- and 12-month time points.152 participants (folic acid: 77, conventional: 75) completed the trial. Significant improvements in folate (ηp2 = 0.703, P = 0.011), homocysteine (ηp2 = 0.644, P = 0.009), Aß-42 (ηp2 = 0.687, P = 0.013), peripheral IL-6 (ηp2 = 0.477, P = 0.025), TNF-α (ηp2 = 0.709, P = 0.009) levels were observed in folic acid group compared with conventional group. Folic acid supplementation improved the Full Scale Intelligence Quotient (P = 0.028; effect size d = 0.153), Information (P = 0.031; d = 0.157) and Digit Span (P = 0.009; d = 0.172) scores at 12 months compared with conventional treatment. Based on these findings, daily oral administration of a 400-µg folic acid supplement to MCI subjects for 12 months can significantly improve cognitive performance and reduce peripheral inflammatory cytokine levels.

[Progress of diagnosis and treatment of precancerous pathological lesions of mammary cancer].

Prevention and treatment of mammary cancer has been taken into great account recently. "Mutistage developing mode" provides the basis for interrupting and reversing precancerous changes. Traditional Chinese medicine (TCM) has shown effects on precancerous changes through inhibiting angiogenesis, promoting apoptosis, modulating endocrine system and restraining oncogene expression. It was stressed in this review that TCM should study the precancerous change of mammary cancer from the aspects of recognizing the essence of precancerous changes of mammary cancer, formulating the standard of TCM diagnosis and treatment, widening the aim of treatment, and focusing on the mechanism of Chinese herbal medicine in intervening it.

[Clinical research on relationship between angiogensis and TCM syndrome type of cyclomastopathy].

OBJECTIVE: To study the relationship between angiogensis and TCM Syndrome type of cyclomastopathy (CMP) to investigate the objective standardization of TCM Syndrome diagnosis of the disease. METHODS: One hundred and forty patients with CMP were divided into three groups according to TCM syndrome typing. The pathological type, grade and expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and microvascular density (MVD) in mammary biopsy were observed. RESULTS: The expressions of VEGF, bFGF and MVD was different in CMP patients of different TCM types and pathological grades (P < 0.05). The proportion of atypical proliferation, the count of MVD and the expression of VEGF and bFGF were higher in patients of phlegm and stasis type than those in Gan stagnation caused Qistagnation type and Chong and Ren meridians disorder type. CONCLUSION: TCM Syndrome type of CMP patients is related with vascular activity and grade of angiogensis. The pathological characteristics of mammary tissue and expression of VEGF, bFGF and MVD can be regarded as the objective indexes of TCM typing and clinical efficacy evaluation for CMP.