Black rice diet alleviates colorectal cancer development through modulating tryptophan metabolism and activating AHR pathway.

Consumption of dietary fiber and anthocyanin has been linked to a lower incidence of colorectal cancer (CRC). This study scrutinizes the potential antitumorigenic attributes of a black rice diet (BRD), abundantly rich in dietary fiber and anthocyanin. Our results demonstrate notable antitumorigenic effects in mice on BRD, indicated by a reduction in both the size and number of intestinal tumors and a consequent extension in life span, compared to control diet-fed counterparts. Furthermore, fecal transplants from BRD-fed mice to germ-free mice led to a decrease in colonic cell proliferation, coupled with maintained integrity of the intestinal barrier. The BRD was associated with significant shifts in gut microbiota composition, specifically an augmentation in probiotic strains Bacteroides uniformis and Lactobacillus. Noteworthy changes in gut metabolites were also documented, including the upregulation of indole-3-lactic acid and indole. These metabolites have been identified to stimulate the intestinal aryl hydrocarbon receptor pathway, inhibiting CRC cell proliferation and colorectal tumorigenesis. In summary, these findings propose that a BRD may modulate the progression of intestinal tumors by fostering protective gut microbiota and metabolite profiles. The study accentuates the potential health advantages of whole-grain foods, emphasizing the potential utility of black rice in promoting health.

Association between serum uric acid and female infertility: a cross-sectional study of National Health and Nutrition Examination Survey (NHANES) 2013-2018.

BACKGROUND: Female infertility is a major problem for women of reproductive-age worldwide. Oxidative stress and inflammation are involved in processes related to female infertility. Serum uric acid levels, an indicator of oxidative stress and inflammation, have rarely been reported to be associated with female infertility. This study aimed to investigate the relationship between serum uric acid levels and female infertility. METHODS: This cross-sectional study included women aged 18-44 years from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2018. All data were extracted from NHANES questionnaires and laboratory measurements. Weighted univariable and multivariable logistic regression analyses were utilized to explore the relationship between serum uric acid and female infertility. Stratified analyses were performed based on body mass index (BMI, < 25 kg/m2 and ≥ 25 kg/m2) and age (≤ 30 years and > 30 years). The odds ratio (OR) with 95% confidence interval (CI) was used to report associations. RESULTS: A total of 2,884 women were included, of which 352 (13.30%) had infertility. Women with high serum uric acid concentrations were related to higher odds of infertility (OR = 1.20, 95%CI: 1.03-1.39) after adjusting for confounders. Compared with serum uric acid concentrations ≤ 3.72 mg/dL, women with uric acid concentrations of 4.43-5.13 mg/dL (OR = 1.65, 95%CI: 1.02-2.67) and > 5.13 mg/dL (OR = 1.86, 95%CI: 1.10-3.13) were related to higher odds of infertility. Stratified analyses showed that high serum uric acid concentrations were associated with higher odds of infertility in women with a BMI < 25 kg/m2 (OR = 1.41, 95%CI: 1.04-1.93), but not in women with a BMI ≥ 25 kg/m2 (P = 0.056). In addition, high serum uric acid concentrations were associated with higher odds of infertility in women aged > 30 years (OR = 1.23, 95%CI: 1.04-1.45), but not in women aged ≤ 30 years (P = 0.556). CONCLUSION: Women with high serum uric acid concentrations were associated with higher odds of infertility, and this association may vary by BMI and age.

The Role of Traditional Chinese Formula Ding-Kun Pill (DKP) in Expected Poor Ovarian Response Women (POSEIDON Group 4) Undergoing In Vitro Fertilization-Embryo Transfer: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: The primary objective of the study was to assess traditional Chinese formula DKP supplementation in terms of efficacy and safety on reproductive outcomes of expected poor ovarian responder (POR, POSEIDON Group 4) undergoing in vitro fertilization-embryo transfer (IVF-ET). Design Setting and Participants: Women eligible for IVF-ET were invited to participate in this randomized, double-blind, placebo-controlled, superiority trial at academic fertility centers of ten public hospitals in Chinese Mainland. A total of 462 patients (35-44 years) equally divided between DKP and placebo groups with antral follicle count (AFC) <5 or anti-müllerian hormone (AMH) <1.2 ng/ml were randomized. Interventions: All participants were given DKP or 7 g placebo twice daily on the previous menstrual cycle day 5 until oocyte retrieval, which took approximately 5 to 6 weeks. Main Outcome Measure: The primary outcome was the ongoing pregnancy defined as more than 20 gestational weeks of an intrauterine living fetus confirmed by pelvic ultrasonography. Results: Demographic characteristics were equally distributed between the study populations. Intention-to-treat (ITT) analysis revealed that ongoing pregnancy rate (OPR) was not significantly different between DKP and placebo groups [26.4% (61/231) versus 24.2% (56/231); relative risk (RR) 1.09, 95% confidence interval (CI) 0.80 to 1.49, P = 0.593]. No significant differences between groups were observed for the secondary outcomes. The additional per protocol (PP) analysis was in line with ITT results: OPR in DKP group was 27.2% (61/224) versus 24.1% (55/228) in placebo group [RR 1.13, 95%CI (0.82 to 1.55), P = 0.449]. After subgroup analysis the findings concluded that POR population of 35-37 years had a significantly higher OPR after 5-6 weeks of oral DKP (41.8%, 33/79) versus placebo (25.4%, 18/71) [RR 1.65, 95% CI (1.02 to 2.65), P = 0.034, P for interaction = 0.028]. Conclusion: This well-designed randomized controlled trial (RCT) offers new high-quality evidence to supplement existing retrospective literature concerning DKP performance in expected PORs. DKP could be recommended as a safe and natural remedy for expected PORs (aged 35-37 years) who fulfill the POSEIDON group 4 criteria. However, additional interventional clinical studies are undoubtedly required to be conducted in the future to validate this hypothesis. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR1900026614.

Salbutamol combined with budesonide in treatment of pediatric bronchial asthma and its effect on eosinophils.

BACKGROUND: The aim of this study was to investigate and discuss the salbutamol combined with budesonide in treatment of pediatric bronchial asthma (BA) and its effect on eosinophils (EOS). METHODS: Ninety-eight BA children admitted and treated in our hospital from July 2016 to June 2017 were collected and divided into control group (N.=49) and observation group (N.=49) according to random number table. The children in control group were treated with budesonide and those in observation group were treated with salbutamol combined with budesonide. The clinical efficacy, pulmonary functions and levels of T-lymphocyte subsets (including cluster of differentiation 3 (CD3)+, CD4+, CD8+ and CD4+/CD8+) in the immune system between two groups were compared after the treatment; the levels of eosinophil cationic protein (ECP) and eotaxin in the children were compared before the treatment and at 1, 4 and 8 weeks after the treatment; the changes in EOS counts in blood and induced sputum of the children before and after the treatment were compared, and the EOS apoptosis rate was compared at 1, 4 and 8 weeks after the treatment. RESULTS: The effective rate of treatment in observation group was significantly higher than that in control group (P<0.05). After the treatment, the indexes of pulmonary function in observation group were obviously better than those in control group (P<0.05). Compared with those in control group, the levels of CD3+, CD4+ and CD4+/CD8+ of the children in observation group were elevated remarkably, while the CD8+ level was lowered (P<0.05). The levels of ECP and eotaxin in the two groups were decreased after the treatment compared with those before the treatment, and the levels in observation group were superior to those in control group (P<0.05). After the treatment, the EOS counts of both groups of children were lower than those before the treatment, and the decrease in observation group was more notable than that in control group. At 1, 4 and 8 weeks after the treatment, the EOS apoptosis rate in observation group was obviously higher than that in control group (P<0.05). CONCLUSIONS: The treatment of salbutamol combined with budesonide for pediatric BA has significant therapeutic effects; it can restore the pulmonary functions rapidly and improve the immunity of the lung, reduce the levels of eotaxin, ECP and EOS of the child patients and promote EOS apoptosis.

A newly identified missense mutation in CLCA2 is associated with autosomal dominant cardiac conduction block.

BACKGROUND: Progressive cardiac conduction defect (PCCD), also known as Lenegre-Lev disease, is one of the most common heart conduction abnormalities. Previous studies have screened for known mutation sites that cause heart block in a 68-person family with a history of PCCD, revealed no mutations. OBJECTIVE: To screen pathogenic genes of the PCCD family and to study the function of the gene mutations related to heart block diseases. METHODS: Whole exome sequencing (WES) was performed on two PCCD patients and one non-PCCD family member to find the related pathogenic gene. After family co-segregation and preliminary functional analysis, we identified the mutant gene CLCA2. To study the function of this gene, we constructed mutant-gene mice using CRISPR-Cas9 technology, and electrocardiogram monitoring was performed after genotype verification. RESULTS: The CLCA2 c.G1725T mutation was identified and co-segregated with the phenotype. The analysis showed that the CLCA2 c.G1725T mutation is harmful and mainly affects protein glycosylation. Immunofluorescence staining revealed that CLCA2 was highly expressed in the sinoatrial node (SAN) tissues. Electrocardiogram monitoring of the mice revealed that CLCA2 point mutations induced mild conduction block and ectopic pacemakers. CONCLUSION: Our findings indicate that a novel heterozygous missense mutation c.G1725T of the CLCA2 gene may be associated with heart block disease and the mutation in this gene may lead to sinus node lesions and conduction blocking.

The spleen may be an important target of stem cell therapy for stroke.

Stroke is the most common cerebrovascular disease, the second leading cause of death behind heart disease and is a major cause of long-term disability worldwide. Currently, systemic immunomodulatory therapy based on intravenous cells is attracting attention. The immune response to acute stroke is a major factor in cerebral ischaemia (CI) pathobiology and outcomes. Over the past decade, the significant contribution of the spleen to ischaemic stroke has gained considerable attention in stroke research. The changes in the spleen after stroke are mainly reflected in morphology, immune cells and cytokines, and these changes are closely related to the stroke outcomes. Autonomic nervous system (ANS) activation, release of central nervous system (CNS) antigens and chemokine/chemokine receptor interactions have been documented to be essential for efficient brain-spleen cross-talk after stroke. In various experimental models, human umbilical cord blood cells (hUCBs), haematopoietic stem cells (HSCs), bone marrow stem cells (BMSCs), human amnion epithelial cells (hAECs), neural stem cells (NSCs) and multipotent adult progenitor cells (MAPCs) have been shown to reduce the neurological damage caused by stroke. The different effects of these cell types on the interleukin (IL)-10, interferon (IFN), and cholinergic anti-inflammatory pathways in the spleen after stroke may promote the development of new cell therapy targets and strategies. The spleen will become a potential target of various stem cell therapies for stroke represented by MAPC treatment.

[Molecular genetic study of a family featuring cardiac conduction block].

OBJECTIVE To explore the genetic mechanism for a family affected with cardiac conduction block. METHODS Affected family members were screened for potential mutations of known candidate genes. As no pathogenic mutation was found, two patients and one healthy member from the family were further analyzed by exomic sequencing followed by Sanger sequencing. The pathogenicity of suspected mutation was analyzed using bioinformatics software. RESULTS Sequencing of the full exome has identified a c.G1725T mutation in the CLCA2 gene. Sanger sequencing has detected the same mutation in all five patients, but not in the normal member from the family. Bioinformatics analysis indicated that the mutation has resulted in substitution of the 575th amino acid cysteine (C) by tryptophan (W). The site is highly conserved and becomes pathogenic with the mutation. CONCLUSION The heterozygous c.G1725T mutation in exon 11 of the CLCA2 gene probably underlies the disease and fit the autosomal dominant pattern of inheritance.

Relation between qualitative and quantitative 3-dimensional ultrasound and ki-67 expression in breast cancer.

To investigate the relation between quantitative blood flow parameters on 3-dimensional (3D) color histogram, 3D ultrasound characteristics and Ki-67 expression in breast cancer. Three-dimensional ultrasound characteristics and histological classifications of 76 breast tumors in 75 confirmed cases were analyzed. Relations of tumor volume (V), vascularization index (VI), flow index (FI) and vascularization-flow index (VFI) on 3D color histogram to Ki-67 expression were studied by statistical methods. VI and VFI measurements of tumors in positive Ki-67 expression group were obviously increased compared with the negative expression group (P<0.05). V and FI measurements of positive expression group were higher than those of the negative expression group, but the difference was not significant (P>0.05). Cases showing positive expression of Ki-67 were more likely to have lymph node metastases (P<0.05), and Ki-67 expression positively correlated with histological classification (P<0.05). However, the two groups did not show significant differences in the findings of "sun-like symptom" (P>0.05). Qualitative and quantitative 3D ultrasound characteristics correlated with positive expression of Ki-67 in breast cancer. Quantitative analysis with 3D color histogram more accurately evaluates blood supply of breast tumors, providing references for predicting biological behaviors and prognosis of breast cancer.

Differentiation of rat iPS cells and ES cells into granulosa cell-like cells in vitro.

Premature ovarian failure (POF) is an ovarian defect characterized by the premature depletion of ovarian follicles before 40 years of age, representing one major cause of female infertility. Stem cells provide the possibility of a potential treatment for POF. In this study, rat embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) were co-cultured with granulosa cells (GCs) to differentiate to GC-like cells. The level of estradiol (E2) analyzed by radioimmunoassay showed that the E2 concentration of the culture supernatant of co-cultured rat iPSCs and ESCs increased in a time-dependent manner, compared with the GCs group that has an opposite trend. The expression of follicle-stimulating hormone receptor (FSHR) was confirmed by immunostaining. These results indicated that rat iPSCs and ESCs were effectively induced to GC-like cells through indirect cell-to-cell contact. Real-time polymerase chain reaction was performed to analyze the expression level of marker genes in POF, including BMP15, FMR1, FSHR, INHA, AMH, NOBOX, FOXO3, EIF2B, FIGLA, and GDF9. The BMP15, FSHR, INHA, AMH, NOBOX, and GDF9 genes were significantly up-regulated in iPSCs and ESCs co-cultured with GCs in comparison with cells that were not co-cultured. Thus, here we demonstrated an available method to differentiate rat iPSCs and ESCs into GC-like cells in vitro for the possible cell therapy of POF.

[Impacts on repeated common cold for the adults with different constitutions treated by acupoint application in the dog days and the three nine-day periods after the winter solstice].

OBJECTIVE: To observe the impacts on repeated common cold for the adults with different constitutions treated by acupoint application in the dog days (the three periods of the hottest days) and the three nine-day periods after the winter solstice (the three periods of the coldest days). METHODS: One hundred and fifty-two cases of repeated common cold were divided into four zones according to the body constitution. Each zone was sub-divided into a group of the dog days + the three nine-day periods of the coldest days (group A), and a simple group of the dog periods (group B). In both groups, Dazhui (GV 14), Feishu (BL 13), Tiantu (CV 22), Danzhong (CV 17), Zhongfu (LU 1) and Shenshu (BL 23) were selected. In group A, the acupoint application was given on the 1st or 2nd day of the first, second and third periods of the hottest days in 2010, as well as the 1st or 2nd day of the first, second and third periods of the coldest days in 2010 separately. In group B, the acupoint application was only given on the 1st or 2nd day of the first, second and third periods of the hottest days in 2010. The follow-up visit was conducted before the acupoint application in the three periods of the coldest days in 2010 and before the acupoint application in the three periods of the hottest days in 2011. Additionally, the frequency of disease attack and the symptom score in sickness were taken as the observation indices for the efficacy assessment in both groups. RESULTS: (1) In both groups, the attack frequency was reduced obviously in half a year after the three periods of the hottest days for the patients of qi deficiency constitution, yang deficiency constitution and qi stagnation constitution and the clinical symptom score were reduced apparently (all P<0.01), which were superior to those for the patients of phlegm damp constitution (P<0.01, P<0.05). For the patients of phlegm damp constitution, only the clinical symptom score was reduced (P<0.01). (2) In group A, the improvements were received in the attack frequency and the clinical symptom score in half a year after the three periods of the coldest days for the patients of those four constitutions as compared with those before treatment (all P<0.01). In group B, the attack frequency and the clinical symptom score were all back to the level as those before treatment. (3) In group A, in half a year after the three periods of the coldest days, the efficacy for reducing the attack frequency and the improvements in the clinical symptoms were better than those in group B (all P<0.01). CONCLUSION: The acupoint application in the dog days and the three nine-day periods after the winter solstice reduces the attack frequency and relieves the clinical symptoms of common cold for the adults of individual constitutions to different extents. The efficacy can be further improved in the treatment with the acupoint application in the three nine-day periods after the winter solstice half a year after the acupoint application in the dog days.

[Observation of the therapeutic effect on COPD of cold phlegm blocking the lung type at stable stage treated with acupoint sticking therapy in different season].

OBJECTIVE: To systematically observe the clinical effect on chronic obstructive pulmonary disease (COPD) at the stable stage, differentiated as cold phlegm blocking the lung type, treated with acupoint sticking therapy during the dog days and the three nine-day periods after the winter solstice so as to propose the latest clinical idea and theoretic evidence for the treatment of COPD. METHODS: One hundred and fifty cases of COPD at stable stage, which were in accordance with the inclusive standard were randomly divided into three groups, named group A (treatment in dog days and the three nine-day periods after the winter solstice), group B (treatment in dog days) and group C (treatment in the three nine-day periods after the winter solstice), 50 cases in each group. The ingredients (Semen Brassicae, Euphoribia Kansui, Asarum, Rhizome Corydalis, Cinnamon, ginger juice) and doses of herbal medicine plaster were same in each group. The herbal plaster was applied to Feishu (BL 13), Shenshu (BL 23), Dazhui (GV 14), Tiantu (CV 22), Danzhong (CV 17) and Zhongfu (LU 1). In group B, the treatment was given once on the 1st day of each dog-day period, totally 3 treatments were included. In group C, the treatment was given once on the 1st day of each nine-day periods after the winter solstice, totally, 3 treatments were involved. In group A, the treatment was given once on the 1st day of each dog-day period and each nine-day periods after the winter solstice separately, totally 6 treatments were required. The therapeutic effect was evaluated in 4 aspects, named comprehensive clinical efficacy, survival quality (the scores for symptoms, activity limitation and influence on daily life), the attach frequency and pulmonary function. RESULTS: The total effective rate was 88.0% (46/50) in group A, which was superior to 76.0% (38/50) in group B and 70.0% (35/50) in group C separately (P < 0.01, P < 0.001). The results of the attack frequency, clinical symptom score and pulmonary function indices after treatment were all improved apparently as compared with those before treatment in each group (all P < 0.01). All the above indices in group A were improved much apparently as compared with the other two groups (P < 0.01, P < 0.001). Except for the level of forced vital capacity (FVC), the results of clinical symptom score and the other pulmonary function indices in group B were all improved significantly as compared with group C (P < 0.05, P < 0.001). CONCLUSION: Acupoint sticking therapy during different season of the year achieves a superior clinical efficacy for the patients with COPD at stable stage. This therapy can reduce the attack frequency and improve the survival quality and pulmonary function for the patients. It is concluded that the efficacy of the treatment in dog days and the three nine-day periods after the winter solstice is superior to simple dog-day treatment and the treatment in the three nine-day periods after the winter solstice, and the efficacy of dog days treatment is better than that in the three nine-day periods after the winter solstice.

[Fetal posterior cranial fossa in the second and third trimester].

OBJECTIVE: To examine the normal range of the width of posterior cranial fossa (WPCF) in the second and third trimester by ultrasonography, and to investigate its relationship with fetal congenital and chromosome abnormality. METHODS: WPCF of 2484 fetus (gestational age from 14 to 41 weeks) was measured by ultrasonograph routinely, and the infants were followed up. RESULTS: In 2848 fetus, 2772 were normal and 76 were abnormal. WPCF increased before 32 weeks, decreased after 33 weeks, the largest value of WPCF was 13.4 mm. The occurrence rate of WPCF> or =8 mm in normal fetus was 8.84%, and that in abnormal fetus was 17.46%. Most fetuses with chromosome abnormality had normal WPCF in the second trimester, but some fetuses with remarkable broadening in the late stage. Some abnormal fetuses (such as water head, Dandy-Walker's syndrome etc) showed significant extension of WPCF. CONCLUSION: WPCF increases before 32 weeks, decreases after 33 weeks;and can be easily measured during 29 - 32 weeks. WPCF of some fetus with chromosome abnormality or with congenital abnormality is remarkably broadened in the late stage. The fetus of WPCF> or =10 mm should be followed up closely, and antenatal diagnosis should be done if WPCF is more than 14 mm.

[Synthesis and spectral characterization of 4-amino-4'-chlorobenzophenone].

4-nitro-4'-chlorobenzophenone has been synthesized from p-nitrobenzol chloride and chlorobenzene in the presence of catalyst anhydrous AlCl3 and 4-amino-4'-chlorobenzophenone as an important organic intermediate was prepared by reduction of 4-nitro-4'-chlorobenzophenone with Na2S2. With the aid of orthogonal experiments the optimum reaction conditions were determined: reaction temperature 92 degrees C, time 2.5 h, 4-nitro-4'-chlorobenzophenone:Na2S2 = 1:1.7 (mol), yield 85.80%, purity 98.08%, m.p. 177-179 degrees C. The molecular structure of the title compound has been characterized by Elemental Analysis (EA), 1H and 13C Nuclear Magnetic Resonance Spectrometry (NMR), Infrared Spectroscopy (IR), and Mass Spectroscopy (MS), and the main infrared absorption peaks and nuclear magnetic spectral bands of this compound were assigned. The mass spectral fragmentations of the product's important fragment ions were elucidated. The result provides useful information for developing substitutes of non-cancer-causing forbidden dye intermediate.

Microwave-assisted solid-phase organic synthesis (MASPOS) as a key step for an indole library construction.

[reaction: see text] Microwave-assisted solid-phase organic synthesis (MASPOS) has been demonstrated to significantly facilitate the Cu(II)- or Pd(II)-mediated ring closure of the resin-bound 2-alkynylanilides. Under microwave irradiation at 200 degrees C [for Cu(OAc)(2), NMP] or 160 degrees C [for Pd(MeCN)(2)Cl(2), THF] for 10 min, 1-acyl-2-alkyl-5-arenesulfamoylindoles were obtained, after cleavage from the resin, in 95-99% purities and in 65-82% overall yields via a 5-step synthetic sequence.