Efficacy and safety of Xiaofeng powder in the treatment of chronic urticaria: A systematic review and meta-analysis.

BACKGROUND: Chronic urticaria is a group of skin diseases characterized by pruritus and/or vascular oedema and belongs to the category of "addictive rash" in Traditional Chinese Medicine, and its aetiology is closely related to wind evil. Antihistamines are often used in treatment. Although they have certain effects, they also easily cause disease recurrence. Xiaofeng powder treats this disease has a significant effect in improving the disease state and reducing the recurrence rate. However, there is a lack of evidencebased research. This study to systematically evaluate the clinical efficacy of modified Xiaofeng powder in the treatment of chronic urticaria (CU). METHODS: Computer searches of Chinese databases such as China National Knowledge Infrastructure, China Scientific Journal Database, China Biomedical Literature Database, and WanFang Date and foreign databases such as PubMed and the Web of Science were performed. We retrieved published clinical randomized controlled trials of Xiaofeng powder in the treatment of CU from the establishment of the databases to November 2023. The data were extracted from clinical trials that met the inclusion criteria of this study, and the quality was evaluated through the Cochrane Handbook of Systematic Reviews 5.1.0. Finally, a meta-analysis was performed using RevMan 5.3 statistical software. RESULTS: A total of 11 randomized controlled trials involving 1076 patients were included. The cure rate odds ratio (OR) and 95% confidence interval (CI; shown in brackets) were 2.11 [1.45, 3.07]; the total effective rate OR and CI were 2.42 [1.60, 3.68]; the recurrence rate OR and CI were 0.22 [0.15, 0.34]; the adverse reaction rate OR and CI were 0.23 [0.12, 0.45]; and the mean weighted mean difference (MD) and 95% CI (shown in brackets) of itching degree, wind mass size, wind mass number and wind mass duration in symptom and sign integrals were -0.70 [-0.73, 0.67], -0.64 [-0.96, 0.31], , -0.72 [-1.23, 0.22], and -0.68 [-1.13, 0.23], , respectively. CONCLUSION: The clinical efficacy of modified Xiaofeng powder in the treatment of CU is better than that of antihistamine drugs, with lower adverse reaction and recurrence rates and higher safety. However, the quality of clinical research included is relatively low, and findings need to be confirmed by high-quality research.

Evaluation of the Clinical Value of KL-6 and Tumor Markers in Primary Sjögren's Syndrome Complicated with Interstitial Lung Disease.

OBJECTIVE: primary Sjögren's syndrome (pSS) is an autoimmune disease, of which the most common complication is interstitial lung disease (ILD). This study aimed to analyze the clinical value of Krebs von den Lungen-6 (KL-6), carcinoembryonic antigen (CEA), and carbohydrate antigen 153(CA153) in patients with pSS complicated with ILD (pSS-ILD), given that only few studies have evaluated this. METHODS: This is a cross-sectional study. Serum KL-6 levels (U/mL) were measured using chemiluminescence immunoassay, and concentrations of serum tumor markers were determined using the immunofluorescence method in 64 cases of pSS-ILD (pSS-ILD group), 23 cases without ILD (non-ILD group), and 45 healthy controls. The correlation between KL-6 and tumor markers as well as lung function was analyzed, and the factors that were associated with pSS-ILD were screened. RESULTS: The serum KL-6 was more abnormally increased in patients with pSS-ILD, and the serum KL-6, CEA, carbohydrate antigen 125 (CA125), and CA153 levels were significantly higher in the pSS-ILD group than in the non-ILD and healthy control groups (p < 0.05). KL-6, CEA, and CA153 were negatively correlated with forced vital capacity (FVC%), forced expiratory volume in 1 s (FEV1%), total lung capacity (TLC%), and diffusing capacity for carbon monoxide (DLCO%) (all p < 0.05). Multivariate logistic analysis showed that KL-6 was an independent factor associated with pSS-ILD. CONCLUSIONS: In conclusion, we evaluated the association between clinical values of KL-6, tumor markers, and pSS-ILD, and found that KL-6 and tumor markers such as CEA, CA153, and CA125 in patients with pSS-ILD were higher than in patients with non-ILD, and KL-6 was more abnormally increased and significantly associated with ILD development in patients with pSS.

Resident intruder paradigm-induced PMDD rat model of premenstrual irritability: behavioral phenotypes, drug intervention, and biomarkers.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is high in women of childbearing age with obvious premenstrual irritability. However, reliable animal models are still lacking. MATERIALS AND METHODS: PMDD rat model of premenstrual irritability was induced by the resident-intruder paradigm (RIP). Behavioral characteristics were determined by the aggressive behavior test, elevated plus maze, open-field test, and breast width measurement. The estrous cycle in rats was artificially manipulated by bilateral ovariectomy and exogenous hormone injection to verify the model phenotype's dependence on the estrous cycle. Fluoxetine and Baixiangdan capsules were administered by gavage to determine the symptom improvement effect of PMDD irritability. Biomarkers in serum and brain were detected using ELISA, and GABRA4 was detected in the brain by RT-PCR and Western blot. RESULTS: Rat models demonstrated similar clinical characteristics as PMDD, such as premenstrual irritability and anxiety, and the above symptoms were estrous cycle-dependent. In addition, the levels of progesterone (P) and ALLO hormones decreased in the serum, hippocampus, amygdala, and frontal lobe in the NR phase. The contents of 5-HT in the brain were significantly increased, while NE and GABA contents were considerably reduced. Moreover, mRNA and protein expression of GABRA4 levels in model rats' amygdala, hippocampus, and frontal lobe were significantly increased, while drug intervention downregulated its expression in these tissues. CONCLUSION: Premenstrual irritability rat model of PMDD demonstrates a behavioral phenotype consistent with the clinical symptoms of PMDD and micro index. The increased levels of 5-HT, NE, and expression of GABRA4, as well as the decrease of GABA, P, and ALLO levels, may be critical biomarkers of the abnormal changes that occur during the pathogenesis of PMDD.

Gabrb2 knock-out mice exhibit double-directed PMDD-like symptoms: GABAAR subunits, neurotransmitter metabolism disruption, and allopregnanolone binding.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a severe mood disorder with pathological changes rooted in GABRB2 copy number variation. Here, we aimed to elucidate the gene dose effect and allopregnanolone binding mechanism of Gabrb2 on possible PMDD-like and comorbid phenotypes in knockout mice. METHODS: PMDD-like behaviors of Gabrb2-knockout mice were measured through various tests. Western Blot and ELISA were used to detect changes in the GABAAR subunits and related neurotransmitter changes in mice respectively for the internal mechanism. The response of mice to allopregnanolone (ALLO) was examined through an exogenous ALLO injection, then validated by the patch-clamp technique to elaborate the potential mechanism of ALLO-mediated GABAAR. RESULTS: Gabrb2-knockout mice displayed changes in anxiety-like and depression-like emotions opposite to PMDD symptoms, changes in social, learning, and memory capacities similar to PMDD symptoms, and pain threshold changes opposite to PMDD symptoms. GABAAR δ subunit expression in the brains of the Gabrb2-knockout mice was significantly higher than that of Wild-type mice (P<0.05). Gabrb2-knockout mice demonstrated neurotransmitter metabolism disturbance of GABA, Glu, acetylcholine, DA, norepinephrine, and epinephrine. Moreover, Gabrb2-knockout mice did not display the expected phenotypic effect after ALLO injection. Relative to WT mice, the knockout of the ß2 subunit gene enhanced the agonistic effect of ALLO on GABAA receptors in cortical neuronal cells. CONCLUSIONS: GABAAR ß 2 regulates PMDD-like behaviors. The ALLO binding site may not be located on ß two subunits, abnormal δ and ε subunit expression in the mouse brain and the disturbance of neurotransmitters may result in ALLO sensitivity.

Global hotspots and prospects of perimenopausal depression: A bibliometric analysis via CiteSpace.

Background: Perimenopausal depression (PMD) is characterized by affective symptoms as well as menopause-specific somatic complaints and has attracted increasing attention over the past few decades. Using a bibliometric tool, this study aims to evaluate the origin, current hotspots, and research trends on PMD. Methods: Articles with research on PMD were retrieved from Web of Science Core Collection (WoSCC). We used the bibliometric method to analyze publication years, journals, countries, institutions, authors, research hotspots, and trends. We plotted the reference co-citation network and used keywords to analyze the research hotspots and trends. Results: A total of 209 publications related to PMD were identified from WoSCC on May 8, 2022. The number of publications concerning PMD every year shows an upward trend. Further analysis indicated that 209 articles were contributed by 45 countries, 288 institutions, and 501 authors. The United States contributed the most significant number of publications, followed by China. Harvard University is the core institution of PMD research, and Cohen's work has had an important impact on another research. The occurrence and pathological mechanisms of depression during the menopausal transition from the knowledge base of PMD. All of them belong to the category of gynecology and psychosis, which reflects the focus of the research topics. Major depression, postmenopausal women, symptoms like hot flashes, and prevalence and risk factors are research hotspots in the PMD field. The frontiers in PMD field that will impact future research are anxiety, meta-analysis, association, and Beck Depression Inventory-II (BDI-II). Conclusion: These findings provide us with the core countries, institutions, and authors in PMD research and point out the direction of attention in this field. The current research focuses on depression, postmenopausal women, hot flashes, and other symptoms, as well as the prevalence and risk factors. The frontiers will be anxiety, meta-analysis, related factors, and depression assessment in future research.

Night-shift work, breast cancer incidence, and all-cause mortality: an updated meta-analysis of prospective cohort studies.

OBJECTIVES: Night-shift work exposure is proposed to link to a wide range of health issues, especially cancer incidence, cancer-specific death, and all-cause death. However, the epidemiological associations among night-shift work exposure, breast cancer, breast cancer-specific death, and all-cause mortality remain inconclusive. METHODS: We performed an updated systematic review and meta-analysis to confirm potential associations among night-shift work exposure, breast cancer, and all-cause mortality. RESULTS: A total of 31 prospective cohort studies, involving 9.3 million participants, 31,244 incident breast cancer cases, 12,728 cancer-related deaths, 7882 cardiovascular deaths, and 30,807 all-cause mortalities were included. Overall, the summary RR of incident breast cancer in females for an increase of night-shift work was 1.029 (95% CI 1.003-1.055). Compared with standard day workers, night-shift workers had a statistically significantly increased RR (1.086, 95% CI 1.032-1.142) for breast cancer incidence in the subgroup of > 10 years exposure. Furthermore, a positive association was revealed in subgroup studies of rotating night-shift work (RR = 1.053, 95% CI 1.018-1.090). A significant increased risk of cardiovascular mortality was demonstrated in the night-shift work group (RR = 1.031; 95% CI 1.006-1.057). CONCLUSION: Our systematic review and meta-analysis provided convincing evidence supporting positive associations among night-shift work exposure, breast cancer incidence, and cardiovascular mortality. Taken together, night-shift work exposure significantly increased the risk of breast cancer morbidity by 2.9% for total, 8.6% for the subgroup of more than 10 years night-shift work, and 5.3% for rotating night-shift work. In addition, night-shift work increased the risk of cardiovascular mortality by 3.1%.

Brain reactivity to emotional stimuli in women with premenstrual dysphoric disorder and related personality characteristics.

AIMS: Premenstrual dysphoric disorder (PMDD) is a psychiatric condition that is associated with the menstrual cycle. Elucidation of the neural regulation mechanisms of brain reactivity to emotional stimuli among women with PMDD may inform PMDD treatment. METHODS: Eighty-six women (42 PMDD, 44 healthy controls) were allocated into two groups (anger-induced group: 23 PMDD vs. 23 controls; depression-induced group: 19 PMDD vs. 21 controls). During the luteal phases of the menstrual cycle, all the women were subjected to functional magnetic resonance imaging (fMRI). fMRI resting-state scans were performed before and after the study participants had performed an emotional stimuli task. After the emotional stimuli task, emotional status of the participants were evaluated by Self-Rating Depression Scales (SDS) and Trait Anger Expression Inventory-II (STAXI-II). In addition, all the participants were requested to complete the Eysenck Personality Questionnaire (EPQ) and the Twenty-Item Toronto Alexithymia Scale (TAS-20). RESULTS: Compared to healthy controls, all women with PMDD exhibited significantly high scores in Tas-20 (p<0.001), higher neuroticism and psychoticism scores as well as significantly low extraversion and social desirability scores (p<0.05). Compared to the controls, f-MRI revealed that PMDD women had elevated ReHo in the middle frontal gyrus (BA10), temporal lobe (BA42), left cerebellum (BA37), as well as decreased activation in the precuneus (BA7), superior frontal gyrus (BA8), lobulus paracentralis (BA6), and right cerebellum (BA48) (p<0.05). Moreover, depression stimuli showed that women with PMDD had elevated ReHo levels in the middle frontal gyrus (BA11), the middle gyrus (BA47) and in the cingulate gyrus (BA23) vs. healthy controls (p<0.05). CONCLUSIONS: Women with more neuroticism and psychoticism, less extraversion and social desirability tend to report PMDD symptoms. Women with this condition experience difficulties in regulating emotions during the luteal phase of the menstrual cycle. Abnormal ReHo levels in the precuneus, superior frontal gyrus, lobulus paracentralis, and right cerebellum may contribute to anger dysregulation. Hypoactivation in the middle frontal gyrus, the middle gyrus and the cingulate gyrus may be generally associated with depression dysregulation in PMDD.

Technique Success, Technique Efficacy and Complications of HIFU Ablation for Palliation of Pain in Patients With Bone Lesions: A Meta-Analysis of 28 Feasibility Studies.

Several feasibility studies have reported that high-intensity focused ultrasound (HIFU) ablation can be applied to ease patients' bone pain. However, the effect of HIFU ablation to palliate bone pain remains unclear. To evaluate the technique's success, efficacy, minor complication and major complication on patients suffering from bone pain, we searched the PubMed, MEDLINE, EMBASE and Cochrane Library databases from January 1998 to March 2019. Clinical studies that have assessed the association between bone pain and HIFU ablation were involved. We filtered out 28 feasibility studies, which reported the association between HIFU ablation and bone pain, including a total of 717 patients and 736 bone lesions. Overall, our results indicate that the rate of technique success of HIFU ablation was 93% (95% confidence interval [CI] 89%-96%) for patients with bone lesions. The technique efficacy rate of HIFU ablation for palliation of pain from bone lesions was 80% (95% CI 74%-87%) in all the patients, 96% (91%-100%) in the subgroup of retrospective studies and 77% (69%-85%) in the subgroup of prospective studies. In regard to HIFU ablation treatment safety, the hazard ratio for minor complication was 12% (95% CI 7%-17%), and the hazard ratio for major complication was 2% (95% CI 1%-3%). In conclusion, the summary rates for various considerations of using HIFU ablation for the palliation of bone pain are as follows: technique success is 93%, technique efficacy is 77%, minor complication is 12% and major complication is 2%. Our results suggest that extracorporeal HIFU ablation is a promising method for palliation of pain in bone lesions, with high technique success and efficacy, but low adverse events.

TV-circRGPD6 Nanoparticle Suppresses Breast Cancer Stem Cell-Mediated Metastasis via the miR-26b/YAF2 Axis.

Metastatic tumor is a major contributor to death caused by breast cancer. However, effective and targeted therapy for metastatic breast cancer remains to be developed. Initially, we exploited a feasible biological rationale of the association between metastatic status and tumor-initiating properties in metastatic breast cancer stem cells (BCSCs). Further, we explored that circular RNA RANBP2-like and GRIP domain-containing protein 6 (circRGPD6) regulates the maintenance of stem cell-like characteristics of BCSCs. Targeted expression of circRGPD6 via human telomerase reverse transcriptase (hTERT) promoter-driven VP16-GAL4-woodchuck hepatitis virus post-transcriptional regulatory element (WPRE)-integrated systemic amplifier delivery composite vector (TV-circRGPD6) significantly inhibited expression of stem-cell marker CD44 and increased expression of the DNA damage marker p-H2AX. Furthermore, we determined TV-circRGPD6, alone or synergized with docetaxel, displays significant therapeutic responses on metastatic BCSCs. Mechanistic analyses exploited that TV-circRGPD6 suppresses BCSC-mediated metastasis via the microRNA (miR)-26b/YAF2 axis. Clinically, for the first time, we observed that expressions of circRGPD6 and YAF2 predict a favorable prognosis in patients with breast cancer, whereas expression of miR-26b is an unfavorable prognostic factor. Overall, we have developed a TV-circRGPD6 nanoparticle that selectively expresses circRGPD6 in metastatic BCSCs to eradicate breast cancer metastasis, therefore providing a novel avenue to treat breast cancers.

Raw and wine processed Schisandra chinensis attenuate anxiety like behavior via modulating gut microbiota and lipid metabolism pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, the fruit of Schisandra chinensis (Turcz.) Baill (SC) is used to treat various nervous system diseases, such as dysphoria, anxiety, insomnia and many dreams. It is worthy to be noted that wine processed Schisandra chinensis (WSC) has been applied in clinic for thousands of years. AIM OF STUDY: This study aimed to investigate the possible mechanism and related metabolism of SC and WSC ameliorating anxiety behavior through modulating gut microbiota. MATERIALS AND METHODS: The ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used for the quality control of chemical components in SC and WSC. Chronic unpredictable stress procedure (CUSP)-induced anxiety rats were administrated with SC and WSC via gavage for five weeks. An untargeted UPLC/LTQ-Orbitrap MS metabolomic analysis of plasma was conducted to understand the effects of long-term intake of WSC and SC extracts on anxious rats. 16S rRNA microbial sequencing technology was applied to investigate gut microbiota structure. Expression of GPR81, TNF-α, S1PR2 as well as molecules in cAMP pathway was assayed by immunohistochemistry staining, RT-qPCR, or Western blot, respectively. RESULTS: 12 compounds were identified using UPLC-QTOF-MS technology, all of which are lignans. Results demonstrate that the amounts of 6-O-Benzoylgomisin O, Schisandrin, Gomisin D, Schizandrin A, Gomisin T, Schizandrin B, Schisandrin C were higher in wine-processed samples than in raw samples. Furthermore, both SC and WSC significantly ameliorated anxiety- and depression-like behavior and lipid metabolism dysfunction and attenuated hippocampal neuritis in anxiety rats. After WSC treatment, the structure and composition of gut microbiota in anxiety rats changed significantly, and gut microbiota derivatives lactate level was significantly lower in the plasma and feces. WSC treatment help restore gut microbial ecosystem dysbiosis and reverse the changes in Lachnospiraceae, Lactobacillus, Alloprevotella, and Bacteroidales in anxiety rat. In addition, the expression of liver GPR81 was decreased, and the molecules in cAMP pathway were increased in SC and WSC-treated anxiety rat. CONCLUSION: Raw and wine processed Schisandra chinensis treatment improved anxiety- and depression-like behavior through modulating gut microbiota derivatives in association with GPR81 receptor-mediated lipid metabolism pathway. And WSC has more exhibition than SC.

Efficacy of Active Charcoal and Mannitol in Patients with Haff Disease Caused by the Consumption of Crayfish (Procambarus clarkii): A Retrospective Cohort Study.

This study evaluates the clinical efficacy of activated charcoal combined with mannitol (ACM) for the treatment of Haff disease. This is a retrospective cohort study conducted at the Emergency Department of Affiliated Hospital of Integrated Traditional Chinese and Western Medicine. Consecutive patients who were hospitalized during a two-year time frame (from June 2016 to August 2017) and diagnosed with Haff disease were reviewed. Clinical symptoms, laboratory findings, pain/anxiety scores, and treatment-related adverse events were collected. Sixty-eight Haff disease patients after boiled crayfish consumption were enrolled in this study. Besides standard treatments for Haff disease, 22 patients had an oral administration of activated charcoal and mannitol within 12 hours of hospital admission (ACM group), while the other 46 patients did not receive such treatment (non-ACM group). Baseline characteristics including clinical symptoms, serum enzyme levels, and pain/anxiety scores were comparable between the two groups. Activated charcoal and mannitol treatment led to lower CK-MB and AST levels from 12 hours to 60 hours, lower ALT and LDH levels from 12 hours to 72 hours, and lower CK levels from 24 hours to 72 hours after hospitalization. Patients in the ACM group had significantly shortened duration of hospital stays (7.5 [6.0-8.0] days vs 8.0 [6.8-10.0] days, p = 0.032) and lower anxiety scores 24 hours after hospital admission (40.7 ± 4.9 vs 44.1 ± 6.3, p = 0.032) than in the non-ACM group. No patient experienced treatment-related adverse events. The overall prognosis of both groups is good. Among patients with Haff disease caused by boiled crayfish, activated charcoal combined with mannitol treatment resulted in shorter hospital stays, lower serum CK, CK-MB, AST, ALT, and LDH levels, and lower anxiety scores.

A clinical rule for the difficulty prediction on scalp intravenous access in infants (SIAI) from emergency room.

Infant intravenous access poses a significant challenge to the operator. Scalp vein is the ideal location for emergency medical staff to perform intravenous access for administration of fluids or medications. To tackle this challenge, we developed a clinical rule for the difficulty prediction on scalp intravenous access in infants (SIAI) conducting a prospective cohort study in a pediatric emergency room. A total of 658 infant patients who underwent SVI from January 2017 to September 2018 were recruited in this study. The failure rate of SIAI on the first attempt was 20.2%. Five variables, including dehydration condition, obesity, vein invisibility, vein impalpability and hyperactive status of infant, were independently and statistically associated with failure rate of SIAI. Furthermore, we indicated that any one alone of the above five variables did not significantly lead to greater than 50% failure rate of indwelling needle SIAI (p > 0.05). However, summary effects of more than one of these five variables were statistically significant associated with greater than 50% failure rate of SIAI (p < 0.05). When employing the five-variable model, validation cohort subjects displayed dehydration, obesity, vein invisibility, vein impalpability and hyperactive status had a 67.5% likelihood of failed first attempt on SIAI (C = 0.675; 95% CI: 0.622-0.727; p < 0.001). For the first time, we developed the difficult model for SIAI. We found that dehydration, obesity, vein invisibility, vein impalpability and hyperactive status of the infant patients are the independent and significant predictors associated with SIAI failure. Our predicted model indicates that infant patients with combination of more than one of the five variables contribute to greater than 50% failure rate of indwelling needle in SIAI.

Inappropriate admissions of the cardiology and orthopedics departments of a tertiary hospital in Shanghai, China.

OBJECTIVES: Admission rates have increased in China, despite the fact that accessibility to primary care is improving. Hospital care could be cost-inefficient, and little is currently known about the appropriateness of admissions to tertiary hospitals in China. This study aims to measure the extent of inappropriate admissions in the cardiology and orthopedics departments of a tertiary hospital in Shanghai, to explore the factors associated with inappropriateness for each department, and to identify the causes of inappropriate admissions. METHODS: The records of inpatients discharged on randomly sampled two days each week during March 2013 to February 2014 from the two departments were extracted. Two reviewers were recruited to assess the records according to the Chinese version of the Appropriateness Evaluation Protocol (C-AEP). Demographic, socio-economic, and other admissions-related variables were collected. Logistic regression analysis was adopted to determine the associated factors of inappropriateness. RESULTS: 35.0% (N = 120) of the 343 admissions and 38.7% (N = 179) of the 463 admissions of the cardiology and orthopedics departments were not justified by the C-AEP, respectively. Age (OR = 0.717), self-pay (OR = 3.752), admission via outpatient sector (OR = 5.332), and readmission (OR = 2.501) were identified as factors affecting the appropriateness of admissions in the cardiology department. Age (OR = 0.930), self-pay (OR = 2.597), admission during 12:00-17:59 (OR = 3.211), and admission via outpatient sector (OR = 7.060) were determined to be associated with appropriateness of admission in the orthopedics department. The main reason for inappropriateness was premature admission for both departments. CONCLUSIONS: The magnitude of inappropriate admissions was considerable in the departments. To improve appropriateness, the results suggest that further interventions should be focused on both external and internal factors.

Nanoparticle Delivery of miR-34a Eradicates Long-term-cultured Breast Cancer Stem Cells via Targeting C22ORF28 Directly.

Rationale: Cancer stem cells (CSCs) have been implicated as the seeds of therapeutic resistance and metastasis, due to their unique abilities of self-renew, wide differentiation potentials and resistance to most conventional therapies. It is a proactive strategy for cancer therapy to eradicate CSCs. Methods: Tumor tissue-derived breast CSCs (BCSC), including XM322 and XM607, were isolated by fluorescence-activated cell sorting (FACS); while cell line-derived BCSC, including MDA-MB-231.SC and MCF-7.SC, were purified by magnetic-activated cell sorting (MACS). Analyses of microRNA and mRNA expression array profiles were performed in multiple breast cell lines. The mentioned nanoparticles were constructed following the standard molecular cloning protocol. Tissue microarray analysis has been used to study 217 cases of clinical breast cancer specimens. Results: Here, we have successfully established four long-term maintenance BCSC that retain their tumor-initiating biological properties. Our analyses of microarray and qRT-PCR explored that miR-34a is the most pronounced microRNA for investigation of BCSC. We establish hTERT promoter-driven VISA delivery of miR-34a (TV-miR-34a) plasmid that can induce high throughput of miR-34a expression in BCSC. TV-miR-34a significantly inhibited the tumor-initiating properties of long-term-cultured BCSC in vitro and reduced the proliferation of BCSC in vivo by an efficient and safe way. TV-miR-34a synergizes with docetaxel, a standard therapy for invasive breast cancer, to act as a BCSC inhibitor. Further mechanistic investigation indicates that TV-miR-34a directly prevents C22ORF28 accumulation, which abrogates clonogenicity and tumor growth and correlates with low miR-34 and high C22ORF28 levels in breast cancer patients. Conclusion: Taken together, we generated four long-term maintenance BCSC derived from either clinical specimens or cell lines, which would be greatly beneficial to the research progress in breast cancer patients. We further developed the non-viral TV-miR-34a plasmid, which has a great potential to be applied as a clinical application for breast cancer therapy.

Diabetes Increases Morbidities of Colonic Diverticular Disease and Colonic Diverticular Hemorrhage: A Systematic Review and Meta-Analysis.

Colonic diverticular disease (CDD) and colonic diverticular hemorrhage (CDH) are the most common disorders in hospital admissions and outpatient health clinic visits. However, risk factors of CDD and CDH are complicated and need to be discussed. Diabetes mellitus (DM) has been related with CDD and CDH, but the associations remain ambiguous. Therefore, we performed a literature search for studies involving the associations among DM, morbidity of CDD, and incidence of CDH. Relative risks or odds ratios with their corresponding 95% confidence intervals (CIs) were combined and weighted to produce summary effect size. Sensitivity analysis and subgroup analysis were further performed. We selected 17 studies that involved a total of 8212 patients with diabetes, 381,579 controls without diabetes. We found that patients with DM had approximately 1.201 times higher CDD morbidity in prospective studies (95% CI, 1.135-1.270) with no significant heterogeneity (Q = 0.42, P = 0.519, I = 0%). DM was associated with a 52.8% increase in risk of CDH (95% CI, 14%-104%); we did not find significant heterogeneity among these studies (Q = 12.94, P = 0.114, I = 38.2%). This meta-analysis confirms that DM is an important risk factor for morbidities of CDD and CDH.

POMC maintains tumor-initiating properties of tumor tissue-derived long-term-cultured breast cancer stem cells.

The identification and understanding of the molecular network of cancer stem cells (CSCs) have had a profound impact on our view of carcinogenesis and treatment strategy. Unfortunately, a major problem is that serial passages of CSCs from clinical solid tumor specimens currently are not available in any lab, and thus, reported data are difficult to confirm and intensively interrogated. Here, we have generated two tumor tissue-derived breast CSC (BCSC) lines that showed prolonged maintenance over 20 serial passages in vitro, while retaining their tumor-initiating biological properties. We then deciphered the intrinsic mechanism using analyses of mRNA expression array profiles. It has been determined that pro-opiomelanocortin (POMC) is closely related with protein phosphorylation mediated by G-protein-coupled estrogen receptor (GPER) in BCSC. Following, knockdown of POMC inhibits properties of mammosphere formation, CD44+ CD24- population, CD44 expression, and clonogenicity ability in BCSC. We found that inhibition of POMC attenuates phosphorylation of AKT2 and GSK3ß in BCSC. Further in vivo investigations demonstrated that POMC interference regulates proliferation of BCSC-bearing tumors. Combination of the clinical results that POMC positive expression is frequently upregulated in human breast cancer and POMC positivity correlated with a poor prognosis, POMC is a potential therapeutic target for BCSC. In conclusion, we have successfully established two long-term-cultured BCSC from clinical specimens. We further indicated that POMC acts as a potential therapeutic target and prognostic marker for future treatment of BCSC.