Acupoint Thread Embedding Combined With Wenshen Bugu Decoction for the Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptom Among Postmenopausal Breast Cancer Patients: Study Protocol of a Randomized Controlled Trial.

BACKGROUND: Aromatase inhibitors (AIs) are recommended as the preferred therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As a result, aromatase inhibitor-associated musculoskeletal symptom (AIMSS) have become a major problem leading to therapy discontinuation and decreased quality of life in patients receiving adjuvant AIs treatment. Multiple therapies have been attempted, but have yielded limited clinical results. This study will be performed to determine whether acupoint thread embedding (ATE) combined with Wenshen Bugu Decoction can effectively treat AIMSS, so as to improve the AIs medication compliance of postmenopausal breast cancer patients. METHODS: This study will utilize a randomized, 2 parallel groups controlled trial design. A total of 128 eligible postmenopausal breast cancer women with AIMSS will be randomized to receive a 12-week treatment with Wenshen Bugu Decoction alone (control group) or in combination with ATE (treatment group) in a 1:1 ratio. The primary outcome will be the 12 week Brief Pain Inventory Worst Pain (BPI-WP) score. The secondary outcome measures will include response rate, Brief Pain Inventory-Short Form (BFI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES), Functional Assessment of Cancer Therapy-Breast (FACT-B), bone marrow density (BMD), blood markers of bone metabolite, Morisky medication adherence scale-8 (MMAS-8), credibility and expectancy, and survival outcomes. DISCUSSION: This trial may provide clinical evidence that ATE combined with Wenshen Bugu Decoction can be beneficial for treating AIMSS among postmenopausal breast cancer survivors. Our findings will be helpful to enhance the quality of life and reduce the occurrence of AIs withdrawal.

Phylogeography of the desert scorpion illuminates a route out of Central Asia.

A comprehensive understanding of phylogeography requires the integration of knowledge across different organisms, ecosystems, and geographic regions. However, a critical knowledge gap exists in the arid biota of the vast Asian drylands. To narrow this gap, here we test an "out-of-Central Asia" hypothesis for the desert scorpion Mesobuthus mongolicus by combining Bayesian phylogeographic reconstruction and ecological niche modeling. Phylogenetic analyses of one mitochondrial and three nuclear loci and molecular dating revealed that M. mongolicus represents a coherent lineage that diverged from its most closely related lineage in Central Asia about 1.36 Ma and underwent radiation ever since. Bayesian phylogeographic reconstruction indicated that the ancestral population dispersed from Central Asia gradually eastward to the Gobi region via the Junggar Basin, suggesting that the Junggar Basin has severed as a corridor for Quaternary faunal exchange between Central Asia and East Asia. Two major dispersal events occurred probably during interglacial periods (around 0.8 and 0.4 Ma, respectively) when climatic conditions were analogous to present-day status, under which the scorpion achieved its maximum distributional range. M. mongolicus underwent demographic expansion during the Last Glacial Maximum, although the predicted distributional areas were smaller than those at present and during the Last Interglacial. Development of desert ecosystems in northwest China incurred by intensified aridification might have opened up empty habitats that sustained population expansion. Our results extend the spatiotemporal dimensions of trans-Eurasia faunal exchange and suggest that species' adaptation is an important determinant of their phylogeographic and demographic responses to climate changes.

Down-regulation of DJ-1 Augments Neuroinflammation via Nrf2/Trx1/NLRP3 Axis in MPTP-induced Parkinson's Disease Mouse Model.

Microglia-mediated neuroinflammation plays a significant role in the pathogenesis of Parkinson's disease (PD). Down-regulation of DJ-1, a PD-associated protein, has been recently found to increase microglial sensitivity to lipopolysaccharides (LPS). However, the role of DJ-1 in microglia-mediated neuroinflammation in PD remains unclear. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish a PD model with mice and tyrosine hydroxylase (TH) staining was performed to validate the model. Adenovirus strategy and shRNA was employed to knockdown the expression of DJ-1 in mice and BV2 microglia, respectively. Western Blot and quantitative PCR were carried out to determine the expression of cytokines, DJ-1, Nrf2, Trx1 and NRLP3. Immunoprecipitation was used to examine the potential interaction between DJ-1 and Nrf2 or Trx1. Flow cytometry-based Annexin V/7-AAD assay were performed to evaluate cell apoptosis. We found that down-regulation of DJ-1 exacerbated neuroinflammation in PD mice. DJ-1 and Nrf2 knockdown promoted inflammation and cell apoptosis in BV2 microglia, while NLRP3 knockdown had opposite effects. Furthermore, DJ-1 regulated the expression of NLRP3 by upregulating Nrf2/Trx1 axis. Taken together, these data suggested that down-regulation of DJ-1 accelerated microglia-mediated neuroinflammation and cell apoptosis via Nrf2/Trx1/NLRP3 axis. Thus, our results demonstrated the important role of DJ-1 in PD pathogenesis and warranted further investigation of DJ-1 as a therapeutic target for PD.

Typical ulcerative colitis treated by herbs-partitioned moxibustion: A case report.

BACKGROUND: Ulcerative colitis (UC), also known as chronic nonspecific UC, is an inflammatory bowel disease characterized by diffuse colonic mucosal inflammation. The incidence and prevalence of UC have risen markedly, and the disease seriously affects the quality of life of patients, and poses a great burden on the world health care infrastructure and economy. CASE SUMMARY: We present a 60-year-old man who had ulcerative colitis for more than 10 years, with recurrent abdominal pain, bloody diarrhea with mucopurulent stool. The treatments with sulfasalazine, mesalazine, and traditional Chinese medicine were not effective, and herbs-partitioned moxibustion (HPM) was then applied at "Zhongwan" (RN12), "Tianshu"(ST25), and "Qihai" (RN6) once a day for about 30 min, 3 times per week, for 6 mo.His main clinical symptoms of abdominal pain, bloody diarrhea with mucopurulent stool gradually improved, and the mucosa had nearly healed, as observed under endoscopy by the 6th mo. The patient's condition was alleviated without relapsing during the subsequent 3-mo follow-up period. HPM showed a significant effect in the treatment of ulcerative colitis in this case, and the effect would help the patient to maintain remission for at least 3 mo. CONCLUSION: A series of symptoms of this UC patient significantly improved with the treatment of HPM.

Switching to anastrozole plus goserelin vs continued tamoxifen for adjuvant therapy of premenopausal early-stage breast cancer: preliminary results from a randomized trial.

PURPOSE: To assess the efficacy, safety, and quality-of-life impact of switching adjuvant treatment in hormone receptor-positive primary breast cancer patients who are still premenopausal after 2-3 years of tamoxifen therapy to anastrozole plus goserelin as compared with continuing tamoxifen over a total period of 5 years. PATIENTS AND METHODS: Hormone receptor-positive, premenopausal, lymph node-positive, or tumor size ≥4 cm breast cancer patients who had received tamoxifen for 2-3 years were randomly assigned to continue tamoxifen treatment (TAM group) or switch to adjuvant anastrozole plus goserelin (ADD group) and continue treatment for another 2-3 years (total treatment duration 5 years). Endpoints evaluated were adverse events (AEs), changes in bone mineral density, quality of life, and disease-free survival-related events. RESULTS: A total of 62 patients (33 in the ADD group and 29 in the TAM group) were evaluated. Grade 3-4 drug-related AEs occurred in five patients (15.2%) in the ADD group vs none in the TAM group. In the ADD group, arthralgias were the most common AEs (5/33 patients; 15.2%), and three patients in this group were discontinued because of AEs. Treatment was temporarily suspended due to AEs in three patients (9.1%) in the ADD group and one patient (3.4%) in the TAM group. Compared with continuing TAM therapy, switching to anastrozole plus goserelin did not result in any worsening of bone mineral density or quality of life. During a median follow-up of 34 months, five patients (15.2%) in the ADD group had disease-free survival events vs four patients (13.8%) in the TAM group. CONCLUSION: For early-stage breast cancer patients who remain premenopausal following 2-3 years of adjuvant tamoxifen therapy, switching to anastrozole plus goserelin therapy was safe with tolerable adverse effects. However, it did not show superior efficacy compared to remaining on tamoxifen treatment. TRIAL REGISTRATION: ClinicalTrials.gov (identifier NCT01352091).

Polymorphisms in the MTHFR gene are associated with breast cancer risk and prognosis in a Chinese population.

Breast cancer is the most common cancer affecting women in China and the world. Folate supplementation is proven to be effective in reducing the risk of breast cancer or improving its prognosis. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism and DNA synthesis. This study aims to examine whether single nucleotide polymorphisms (SNP) in the MTHFR gene are associated with risk and survival of breast cancer and serum folate levels in healthy controls. We genotyped nine tagging SNPs in the MTHFR gene in a case-control study, including 560 breast cancer cases and 560 healthy controls in China. We found that TT genotype of rs1801133 had significant increased risk of breast cancer [adjusted odds ratio (OR) = 1.60, 95 % confidence interval (CI) 1.12-2.28] compared with CC genotype, and CC genotype of rs9651118 conferred significant reduced risk of breast cancer (adjusted OR = 0.65, 95 % CI 0.45-0.95) compared to TT genotype. Haplotype analysis also showed that MTHFR CACCAA and AGTCAC haplotypes (rs12121543-rs13306553-rs9651118-rs1801133-rs4846048-rs1801131) had significant reduced risk of breast cancer (adjusted OR = 0.70, 95 % CI 0.58-0.86; adjusted OR = 0.57, 95 % CI 0.40-0.80) compared with CATTAA haplotype. Besides, MTHFR rs9651118 CC genotype was significantly associated with survival in breast cancer cases (adjusted hazard ratio (HR) = 0.63, 95 % CI 0.40-0.99). But none of the SNPs in the MTHFR gene was associated with serum folate level in healthy controls. These findings suggest that variants in the MTHFR gene may influence the risk and prognosis of breast cancer.

Performance of breast cancer screening methods and modality among Chinese women: a report from a society-based breast screening program (SBSP) in Shanghai.

To evaluate the screening performance of individual and combined use of clinical breast examination, ultrasonography and mammography in Chinese women, we conducted a biennial breast cancer screening program among 14,464 women aged 35 to 74 years old who lived in Qibao County, Minhang district of Shanghai, China, between May 2008 and Sept 2012. All participants were submitted to clinical breast examination, and then women with positive results and all women at age of 45-69 years old were preformed breast ultrasonography and mammography. The examination results were compared against pathological findings as the gold standard of reference. A total of 66 women were diagnosed with breast cancer in the two rounds of the screening, yielding an incident rate of 194 per 100,000 person-years. The sensitivity of clinical breast examination, ultrasonography and mammography alone were 61.4%, 53.7% and 67.3%, respectively. While mammography performed better in elder age groups and hormone receptor positive disease groups, ultrasonography had a higher sensitivity in younger age group and did not differ in sensitivity by estrogen receptor or progesterone receptor status. Combined use of the two imaging examinations increased the sensitivity in almost all age groups, but had a higher sensitivity in hormone receptor positive cancers than in those negative. Our results suggest that the Qibao modality is an effective strategy for breast cancer screening among Chinese women, especially for early detection of elder and hormone receptor positive breast cancer.

Impact of climate changes from Middle Miocene onwards on evolutionary diversification in Eurasia: insights from the mesobuthid scorpions.

The aridification from Middle Miocene onwards has transformed the Asian interior into an arid environment, and the Pleistocene glacial-interglacial oscillations exerted further ecological impact. Therefore, both aridification and glaciation would have considerably influenced the evolution of many mid-latitude species in temperate Asia. Here, we tested this perspective by a phylogeographic study of the mesobuthid scorpions across temperate Asia using one mitochondrial and three nuclear genes. Concordant mitochondrial and nuclear gene trees were obtained, which are consistent with species tree inferred using a Bayesian approach. The age of the most recent common ancestor (MRCA) of all the studied scorpions was estimated to be 12.49 Ma (late Middle Miocene); Mesobuthus eupeus diverged from the clade composing Mesobuthus caucasicus and Mesobuthus martensii in early Late Miocene (10.21 Ma); M. martensii diverged from M. caucasicus at 5.53 Ma in Late Miocene. The estimated MRCA ages of M. martensii and the Chinese lineage of M. eupeus were 2.37 and 0.68 Ma, respectively. Central Asia was identified as the ancestral area for the lineage leading to M. martensii and M. caucasicus and the Chinese lineage of M. eupeus. The ancestral habitat of the genus Mesobuthus is likely to have been characterized by an arid environment; a shift towards more humid habitat occurred in the MRCA of M. martensii and a lineage of M. caucasicus, finally leading to the adaptation of M. martensii to humid environment. Our data strongly support the idea that the stepwise intensified aridifications from Mid-Miocene onwards drove the diversification of mesobuthid scorpions, and suggest that M. martensii and M. eupeus observed today in China originated from an ancestral lineage distributed in Central Asia. Both the colonization and the ensuing evolution of these species in East Asia appear to have been further moulded by Quaternary glaciations.

Unexpected relationships of substructured populations in Chinese Locusta migratoria.

BACKGROUND: Highly migratory species are usually expected to have minimal population substructure because strong gene flow has the effect of homogenizing genetic variation over geographical populations, counteracting random drift, selection and mutation. The migratory locust Locusta migratoria belongs to a monotypic genus, and is an infamous pest insect with exceptional migratory ability - with dispersal documented over a thousand kilometers. Its distributional area is greater than that of any other locust or grasshopper, occurring in practically all the temperate and tropical regions of the eastern hemisphere. Consequently, minimal population substructuring is expected. However, in marked contrast to its high dispersal ability, three geographical subspecies have been distinguished in China, with more than nine being biologically and morphologically identified in the world. Such subspecies status has been under considerable debate. RESULTS: By multilocus microsatellite genotyping analysis, we provide ample genetic evidence for strong population substructure in this highly migratory insect that conforms to geography. More importantly, our genetic data identified an unexpected cryptic subdivision and demonstrated a strong affiliation of the East China locusts to those in Northwest/Northern China. The migratory locusts in China formed three distinct groups, viz. (1) the Tibetan group, comprising locusts from Tibet and nearby West China high mountain regions; this is congruent with the previously recognized Tibetan subspecies, L. m. tibetensis; (2) the South China group, containing locusts from the Hainan islands; this corresponds to the Southeast Asia oriental tropical subspecies L. m. manilensis; (3) the North China group, including locusts from the Northwest and Northern China (the Asiatic subspecies L. m. migratoria), Central China and Eastern China regions. Therefore, the traditional concept on Locusta subspecies status established from Uvarov in 1930s needs to be revised. The three groups of locusts probably have separate evolutionary histories that were most likely linked to Quaternary glaciations events, and derived from different ancestral refugial populations following postglacial expansions. CONCLUSION: The migratory locust populations in China have differentiated into three genetically distinct groups despite high dispersal capability. While this clarified long-standing suspicions on the subspecific diversification of this species in China, it also revealed that the locusts in the vast area of East China are not the oriental subspecies but the Asiatic subspecies, an unexpected substructuring pattern. The distribution pattern of the three locust groups in China may be primarily defined by adaptive differentiation coupled to Quaternary glaciations events. Our results are of general significance both for locust research and for phylogeographical study of flora and fauna in China, illustrating the potential importance of phylogeographical history in shaping the divergence and distribution patterns of widespread species with strong dispersal ability.

Haplotype reconstruction for scnp DNA: a consensus vote approach with extensive sequence data from populations of the migratory locust (Locusta migratoria).

Single copy nuclear polymorphic (scnp) DNA is potentially a powerful molecular marker for evolutionary studies of populations. However, a practical obstacle to its employment is the general problem of haplotype determination due to the common occurrence of heterozygosity in diploid organisms. We explore here a 'consensus vote' (CV) approach to this question, combining statistical haplotype reconstruction and experimental verification using as an example an indel-free scnp DNA marker from the flanking region of a microsatellite locus of the migratory locust. The raw data comprise 251-bp sequences from 526 locust individuals (1052 chromosomes), with 71 (28.3%) polymorphic nucleotide sites (including seven triallelic sites) and 141 distinct genotypes (with frequencies ranging from 0.2 to 25.5%). Six representative statistical haplotype reconstruction algorithms are employed in our CV approach, including one parsimony method, two expectation-maximization (EM) methods and three Bayesian methods. The phases of 116 ambiguous individuals inferred by this approach are verified by molecular cloning experiments. We demonstrate the effectiveness of the CV approach compared to inferences based on individual statistical algorithms. First, it has the unique power to partition the inferrals into a reliable group and an uncertain group, thereby allowing the identification of the inferrals with greater uncertainty (12.7% of the total sample in this case). This considerably reduces subsequent efforts of experimental verification. Second, this approach is capable of handling genotype data pooled from many geographical populations, thus tolerating heterogeneity of genetic diversity among populations. Third, the performance of the CV approach is not influenced by the number of heterozygous sites in the ambiguous genotypes. Therefore, the CV approach is potentially a reliable strategy for effective haplotype determination of nuclear DNA markers. Our results also show that rare variations and rare inferrals tend to be more vulnerable to inference error, and hence deserve extra surveillance.

Eight polymorphic microsatellite markers developed in the Chinese scorpion, Mesobuthus martensii (Scorpiones: Buthidae).

Eight polymorphic di- and trinucleotide microsatellite loci were developed in the Chinese scorpion, Mesobuthus martensii. The expected heterozygosity at these loci ranges from 0.019 to 0.860, with the observed allele numbers varying from two to 25. Overall, there were no deviations from Hardy-Weinberg equilibrium and no observed linkage disequilibrium after Bonferroni correction. Cross-species amplification of these loci in Mesobuthus eupeus revealed that five loci can amplify successfully in this species. The polymorphic microsatellite DNA markers reported here should provide helpful means to address questions concerning phylogeographical patterns and evolutionary history of M. martensii and closely related species.