Ecological stoichiometry of leaf-litter-fine roots in mixed plantations in mountainous area of Southern Ningxia, China.

The southern mountainous areas in Ningxia are representative regions of the Loess Plateau, with extremely fragile ecological environment. Large area of pure plantations established during the project of Grain for Green has suffered from poor nutrient availability and biodiversity loss, while planting mixed plantations is commonly consi-dered as an effective way to improve the ecological benefits. We selected Robinia pseudoacacia + Picea asperata mixed plantation, R. pseudoacacia + Armeniaca sibirica mixed plantation, A. sibirica pure plantation and R. pseudoa-cacia pure plantation located ina Ningnan mountainous area as test objects. Based on the theory and method of ecological stoichiometry, we measured the C, N and P contents of leaves, litter and fine roots to understand nutrient cycling characteristics of different plantations. The results showed that there was significant difference in foliar stoichiometry of each tree species within the four plantations. P. asperata leaves had the highest C content in the R. pseudoacacia + P. asperata mixed plantation, and R. pseudoacacia leaves had the highest N and P contents in the R. pseudoacacia + A. sibirica mixed plantation. N content of R. pseudoacacia and A. sibirica leaves was significantly higher in mixed plantation compared with that in pure plantation. There was no significant difference in litter biomass, litter C, N, P contents and stoichiometric ratios between the pure and mixed plantations of R. pseudoacacia. Litter biomass in A. sibirica pure plantation was significantly higher than that in R. pseudoacacia + A. sibirica mixed plantation, while litter C content was significantly lower than that in the mixed plantation. Fine root biomass decreased with increasing soil depth in the four plantations, with total fine root biomass being the highest in the R. pseudoacacia + A. sibirica mixed plantation. N content and N:P of fine roots in the R. pseudoacacia + A. sibirica mixed plantation were higher than those in R. pseudoacacia and A. sibirica pure plantations. There was significant negative correlation between N content in leaves and fine roots of R. pseudoacacia + A. sibirica mixed plantation. There were significant negative correlations between the N content of leaves and litter, as well as between the P content of leaves and fine roots in the R. pseudoacacia + P. asperata mixed plantation. P content between litter and fine roots in A. sibirica pure plantation was significantly negatively correlated. Nutrient status of mixed plantations was better than pure plantations in the Ningnan mountainous area, with the mixed plantation of R. pseudoacacia and A. sibirica being the best. Mixed planting reduced nutrient limitation on plant growth to a certain extent.

Incidence of constipation and associated factors in the period of lockdown during COVID-19 pandemic: protocol for a systematic review and meta-analysis.

INTRODUCTION: The lifestyle and habit changes that have emerged as a result of quarantine measures may have had a negative impact on defecation habits. However, there is a lack of data on combined estimates of its occurrence and prevalence. METHODS AND ANALYSIS: We will conduct a systematic search for observational studies on PubMed/MEDLINE, Web of Science, Cochrane Library, EMBASE, CNKI, SinoMed, VIP China Science and Technology Journal database, Chinese Biomedical Databases and Wanfang Data. The search will include literature published from the inception of the databases to September 2022. Two authors will independently screen articles and extract data based on predefined inclusion and exclusion criteria. The risk of bias in the included studies will be evaluated using the Newcastle-Ottawa Scale for observational studies. Statistical analysis will be performed using Review Manager software V.5.4 and STATA V.16.0 software. Heterogeneity among studies will be assessed using the Q statistical test and I2 statistical tests. In case of significant heterogeneity, subgroup analysis and sensitivity analysis will be conducted to explore the source of heterogeneity. Sensitivity analyses will also be performed to assess the reliability of the study findings. If feasible, a meta-analysis will be conducted. Otherwise, a descriptive synthesis will be performed using a best-evidence synthesis approach. The primary outcome of interest will be the prevalence of constipation. The secondary outcomes will involve examining the association of risk factors. To evaluate potential publication bias, we will use both the Begg funnel plot and Egger's weighted regression statistics. Furthermore, to accurately assess the quality of evidence for our primary outcome, we will employ the Grading of Recommendations Assessment, Development and Evaluation system. ETHICS AND DISSEMINATION: This systematic review protocol will only consider published studies available in databases and will not include individual patient data. Therefore, ethical approval is not required, and the findings will be published in a peer-reviewed journal. PROSPER REGISTRATION NUMBER: CRD42022366176.

Quantitative risk-benefit profiles of oral contraceptives, insulin sensitizers and antiandrogens for women with polycystic ovary syndrome: A model-based meta-analysis.

Oral contraceptives (OCs), insulin sensitizers, and antiandrogens (AAs), alone or in combination, are commonly used for treating non-fertility indications in polycystic ovary syndrome (PCOS). However, unclear risk-benefit profiles jeopardize their appropriate clinical applications. This study aimed to quantitatively evaluate the effects of the aforementioned medications and to compare their risk-benefit profiles. Randomized controlled trials published until 14th March 2022 were searched in PubMed and Embase. A model-based meta-analysis was developed to examine the time-effect profiles of each medication. The maximal percentage change of the effect (Emax) and time to achieve half of Emax (T50) were estimated. Primary outcomes included menstruation, hirsutism score, free androgen index (FAI), body mass index (BMI), insulin sensitivity, and lipid profiles. Overall, 200 studies (9,685 patients and 385 arms) were identified for modeling. OCs performed exceptionally well in improving menstruation (Emax: 149%; T50: 7.44 weeks), hirsutism score (Emax: 66.2%; T50: 26.2 weeks), and FAI (Emax: 75.7%; T50: 0.51 weeks). However, OCs elevated the triglyceride (TG) level (Emax: 12.6%; T50:1.19 weeks). After 12-week OC treatment, the TG level of approximately 30% of patients, whose baselines were normal, exceeded the reference limit. This suggested that OC-induced dyslipidemia should be routinely monitored. The maximal BMI-lowering effect of metformin was similar to that of placebo (Emax: 3.80%); however, metformin had a shorter T50 (6.67 weeks versus 12.9 weeks). Further, active lifestyle intervention plus placebo significantly decreased BMI (Emax: 8.78%). Adding metformin to active lifestyle intervention accelerated the BMI-lowering effect within 24 weeks, whereas with the extension of this addition beyond 24 weeks, BMI did not reduce further, which indicated that benefits were limited from this prolonged addition. AAs were less potent in reducing hirsutism score (Emax: 40.2% versus 66.2%) and FAI (Emax: 34.5% versus 75.7%) compared to OCs. OC plus metformin combined OC-derived androgen-suppressing effects and metformin-derived insulin-sensitizing effects, and partially relieved the OC-induced TG increase (Emax: 9.76%). Baseline dependency was found in most clinical responses, implying that pharmacotherapies tailored based on baselines achieved more clinical improvements. This study presents new quantitative evidence on pharmacotherapies for PCOS. Currently, long-term risk-benefit profiles and emerging therapies are inadequately reported and require more further research.

Estrogen-related receptor functions via the 20-hydroxyecdysone and IIS/TOR signaling pathways to regulate the development and morphology changes of ant Polyrhachis vicina Roger (Hymenoptera, Formicidae).

Estrogen-related receptor (ERR) is a key regulator of insect growth, development, and metabolic processes in insects; however, the molecular mechanisms underlying its effects are not fully understood. We investigated roles of 20-hydroxyecdysone (20E) and insulin/insulin-like signaling/target of rapamycin (IIS/TOR) signaling pathways in the effects of PvERR on larval development, metamorphosis, and adult growth in ant Polyrhachis vicina Roger. PvFOXO expression levels depended on caste and developmental stage. PvERR RNAi significantly reduced the expression levels of IIS/TOR signaling pathway genes and 20E signaling pathway genes in fourth-instar larvae, pupae, females, and workers and significantly increased the expression levels of IIS/TOR signaling pathway genes PvFOXO and PvAkt in males. PvFOXO RNAi resulted in developmental defects and increased mortality. After PvFOXO RNAi, the expression of PvERR, 20E signaling pathway genes, and IIS/TOR signaling pathway genes decreased significantly in pupae, females, and workers and increased significantly in fourth-instar larvae. Exogenous 20E attenuated expression changes induced by PvFOXO RNAi in a sex- and stage-specific manner. These results indicate that ERR interacts with 20E and IIS/TOR signaling pathways to regulate caste determination, metamorphosis, and male fertility in P. vicina and that correlations between PvERR and PvFOXO are caste- and stage-specific.

Feasibility analysis of rapid gene detection using intraoperative frozen tissues: comparison of intraoperative frozen tissues with paraffin-embedded tissues in epidermal growth factor receptor gene mutation detection of lung adenocarcinoma.

BACKGROUND: Epidermal growth factor receptor (EGFR) is the driver gene with the highest frequency of mutations in lung adenocarcinoma and can guide the development of targeted therapies. The detection of routine gene mutations must be performed after the preparation of paraffin samples in a standard polymerase chain reaction (PCR) laboratory, which is time-consuming. The Idylla™ EGFR fully automatic PCR system for rapid detection requires no special detection environment and completes the process in only 2.5 h. It has been applied to tissues embedded in paraffin. METHODS: The Idylla™ EGFR automated PCR system was used to detect EGFR gene mutations in intraoperative frozen fresh tissues and paraffin-embedded tissues from 47 enrolled patients with lung adenocarcinoma. The gold standard amplification refractory mutation system (ARMS) method for gene mutation detection was used for verification, and the concordance between the three detection results was compared, to investigate the feasibility of detecting rapid gene mutations in intraoperative frozen samples. RESULTS: The EGFR mutation rate in 47 fresh samples of lung adenocarcinoma was 61.7% (29/47), which is consistent with the mutation level of lung adenocarcinoma in the Asian population (38.8-64.0%). The concordance rate between the Idylla™ frozen tissues and paraffin-embedded tissues was 91.4% (43/47) when compared to the ARMS method, while the coincidence rate between the two methods was 93.6% (44/47). The three methods had a total consistency rate of 89.4% (42/47). CONCLUSIONS: The Idylla™ EGFR fully automatic PCR system directly detects EGFR mutations in fresh tissues. The operation is simple, the detection time is short, and the accuracy is high. The detection time is reduced to 1/4-1/3 of the original time while meeting clinical standards for detecting the gene status of patients, thus saving crucial time for individualized and accurate treatment of patients. The method has promising clinical application prospects.

Melatonin effects on sleep quality of COVID-19 patients: a protocol for systematic review and meta-analysis of randomised controlled trials with trial sequential analysis.

INTRODUCTION: Sleep disturbance is one of the common complaints of patients with COVID-19 infection. Melatonin is a physiological indoleamine involved in circadian rhythm regulation and it is currently used for secondary sleep disorders caused by various diseases. Some clinical randomised controlled trials (RCTs) have obtained a small amount of evidence and controversial results in support of their therapeutic effect on sleep disorders, but no studies have summarised and evaluated RCTs in all current databases to obtain conclusive results. Therefore, the aim of this systematic review and meta-analysis was to determine the efficacy and safety of melatonin in the treatment of sleep disturbances in patients with COVID-19. METHODS AND ANALYSIS: We will search for RCT-type studies of melatonin in the treatment of sleep disturbances in patients with COVID-19. From inception to October 2022 will be available on PubMed/MEDLINE, Web of Science, Embase, CINAHL, PsycINFO, LILACS, SCOPUS, Cochrane Central Register of Controlled Trials, ICTRP, Wanfang Data, VIP database and CNKI, VIP database, China Biomedical Literature Database to search for eligible studies. There are no language and geographical restrictions. Two authors will independently screen and select eligible studies, assess methodological quality and perform data extraction. Two additional authors will independently extract data from each study. Then, meta-analysis will then be carried out using a fixed-effects or random-effects model, using the mean difference for continuous outcomes and the relative risk for dichotomous outcomes. Risk of bias assessment will be assessed using the Cochrane risk-of-bias tool. Heterogeneity between studies was assessed by Cochrane Q-test and I2. The quality of evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Funnel plots, Begg's test and Egger's test will be used to assess the risk of publication bias. Subgroup analysis, data synthesis, meta-analysis and overall incidence of adverse events will be performed using Review Manager V.5.4 software and Stata software. Trial sequential analysis will be performed if appropriate. ETHICS AND DISSEMINATION: This study is an extraction review of data from existing studies, and thus it is unnecessary to obtain ethical approval. The results of this systematic review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022359221.

The Inhibitory Effect of Phycocyanin Peptide on Pulmonary Fibrosis In Vitro.

Phycocyanin is an excellent antioxidant with anti-inflammatory effects on which recent studies are growing; however, its specific target remains unclear. Linear tetrapyrrole compounds such as bilirubin have been shown to lead to the induction of heme oxygenase 1 expression in vivo, thus achieving antioxidant and anti-inflammatory effects. Phycocyanin is bound internally with linear tetrapyrrole phycocyanobilin in a similar structure to bilirubin. We speculate that there is probably a way of inducing the expression of heme oxygenase 1, with which tissue oxidative stress and inflammation can be inhibited, thus inhibiting pulmonary fibrosis caused by oxidative damage and inflammation of lung. By optimizing the enzymatic hydrolysis process, phycocyanobilin-bound phycocyanin peptide were obtained, and its in vitro antioxidant, anti-inflammatory, and anti-pulmonary fibrosis activities were investigated. The results show that the phycocyanobilin peptide was able to alleviate oxidative and inflammatory damage in cells through the Keap1-Nrf2-HO-1 pathway, which in turn relieved pulmonary fibrosis symptoms.

Circulating circular RNA profiles associated with celiac disease seropositivity in children with type 1 diabetes.

Introduction: The frequency of celiac disease autoantibody (CDAb) positivity in type 1 diabetes (T1D) has increased due to unclear mechanisms, including autoimmune injury. Circular ribonucleic acids (circRNAs) participate in autoimmune diseases, but the roles of circRNAs in T1D with CDAbs are currently unknown. This study aimed to determine the frequency of CDAbs in Chinese children with T1D and describe the relationship between CDAbs and circRNAs. Materials and methods: Eighty patients diagnosed with T1D were screened for CDAbs and CD-predisposing genes, and circRNAs in peripheral blood mononuclear cells (PBMCs) were collected from 47 patients. The Gene Expression Omnibus (GEO) database was searched for candidate circRNAs in related studies on T1D PBMCs. Data on clinical characteristics (i.e., blood glucose control, residual islet function, and daily insulin dosage) and immunophenotypes (i.e., islet autoantibodies and immune cell subsets) were collected. Results: In total, 35.0% of patients were positive for CDAbs. CD-predisposing genes accounted for 52.5% of the genes, and no significant difference in frequency was found between the CDAb-positive (CDAb+) and CDAb-negative (CDAb-) groups. In addition, among the differentially expressed circRNAs from the GEO database, five highly conserved circRNAs homologous to humans and mice were screened, and only the expression of hsa_circ_0004564 in the CDAb+ group significantly decreased (CDAb+ vs. CDAb-:1.72 ± 1.92 vs. 11.12 ± 8.59, p = 6.0 × 10-6), while the expression of hsa_circ_0004564 was upregulated in the general T1D population. Moreover, its parental gene RAPH1 was significantly upregulated (CDAb+ vs. CDAb-:1.26 ± 0.99 vs. 0.61 ± 0.46, p = 0.011). Importantly, the positive correlation between hsa_circ_0004564 and CD3+ cells was validated in children with T1D after adjustments for CDAbs (p = 0.029), while there were no correlations between hsa_circ_0004564 and clinical characteristics or other immune cell subsets (i.e., CD4+ T cells, CD8+ T cells, and natural killer cells). Conclusion: This study highlights the importance of screening for CD in Chinese children with T1D, considering the high prevalence of CDAb positivity and CD-predisposing genes. The profile of candidate circRNAs in children with T1D with CDAbs was different from that in previous reports on general T1D patients from the GEO database. Moreover, hsa_circ_0004564 and its parental gene RAPH1 may be new targets for studying immune mechanisms in children with T1D and CD.

[Discussion on moxibustion practice of the Han medical bamboo slips unearthed in Wuwei and Juyan regions of Gansu province].

Through collecting the relevant moxibustion records of Han medical bamboo slips unearthed in Wuwei and Juyan regions of Gansu province, the situation and characteristics of clinical practice of moxibustion were summarized. In Wuwei Han medical bamboo slips, the contraindications of moxibustion were recorded, with age and time involved. Juyan Han medical bamboo slips mainly recorded the methods of moxibustion at the acupoints located on the back of the body, with clear emphasis and requirement of acupoint selection, single acupoint moxibustion and moxibustion quantity (the numbers of moxa cone) included. These records on bamboo slips initially display the practice and development of moxibustion in Gansu and other northwestern regions of China in the Han Dynasty, providing a certain instruction for the literature research of moxibustion of the excavated Han medical bamboo slips.

Bellidifolin Inhibits SRY-Related High Mobility Group-Box Gene 9 to Block TGF-ß Signalling Activation to Ameliorate Myocardial Fibrosis.

Myocardial fibrosis is the main morphological change of ventricular remodelling caused by cardiovascular diseases, mainly manifested due to the excessive production of collagen proteins. SRY-related high mobility group-box gene 9 (SOX9) is a new target regulating myocardial fibrosis. Bellidifolin (BEL), the active component of G. acuta, can prevent heart damage. However, it is unclear whether BEL can regulate SOX9 to alleviate myocardial fibrosis. The mice were subjected to isoproterenol (ISO) to establish myocardial fibrosis, and human myocardial fibroblasts (HCFs) were activated by TGF-ß1 in the present study. The pathological changes of cardiac tissue were observed by HE staining. Masson staining was applied to reveal the collagen deposition in the heart. The measurement for expression of fibrosis-related proteins, SOX9, and TGF-ß1 signalling molecules adopted Western blot and immunohistochemistry. The effects of BEL on HCFs, activity were detected by CCK-8. The result showed that BEL did not affect cell viability. And, the data indicated that BEL inhibited the elevations in α-SMA, Collagen I, and Collagen III by decreasing SOX9 expression. Additionally, SOX9 suppression by siRNA downregulated the TGF-ß1 expression and prevented Smad3 phosphorylation, as supported by reducing the expression of α-SMA, Collagen I, and Collagen III. In vivo study verified that BEL ameliorated myocardial fibrosis by inhibiting SOX9. Therefore, BEL inhibited SOX9 to block TGF-ß1 signalling activation to ameliorate myocardial fibrosis.

A comparison of capillary electrophoresis and next-generation sequencing in the detection of immunoglobulin heavy chain H and light chain κ gene rearrangements in the diagnosis of classic hodgkin's lymphoma.

This study aimed to compare the application value of capillary electrophoresis and next-generation sequencing for immunoglobulin (IG) gene rearrangement in the diagnosis of classic Hodgkin's lymphoma. Twenty paraffin-embedded specimens from patients with classic Hodgkin's lymphoma were screened. For gene rearrangement detection, the ABI 3500 Genetic Analyzer and ABI Ion GeneStudio S5 Plus sequencing system were used, respectively, and the results were compared. Five cases with monoclonal rearrangements (25%, 5/20) were detected by Capillary Electrophoresis, and positivity for the FR1, FR2, FR3, and IGк loci was 5%, 10%, 10%, and 15%, respectively; 12 cases with monoclonal rearrangements (60%, 12/20) were detected by Next-generation Sequencing where the positivity of the above corresponding loci were 35%, 45%, 50%, and 30%, respectively. Among the 20 samples, 6 IGк clonal rearrangements were detected, and the usage frequency (66.7%) of IGкJ4 was the highest in the IGкJ subgroup. The usage frequency of IGкV1 and IGкV3 in the GкV sub-group was 33.3% and 33.3%, respectively. Twelve immunoglobulin heavy chain (IGH) clonal rearrangements were detected among the 20 samples, and the order of usage frequency in the IGH joining region J (IGHJ) subgroup was IGHJ4 > IGHJ5 > IGHJ6 > IGHJ3. The gene with the highest usage frequency in the IGH variable (IGHV) subgroup was IGHV3 (50%) and the percentage of IGHV mutations ranged from 0% ± 11.45% with an average frequency of 3.34%. Compared with Capillary Electrophoresis, Next-generation Sequencing showed a higher positivity in the detection of gene clonal rearrangements, was more accurate in the interpretation of results.

Guidelines on the treatment with integrated traditional Chinese medicine and western medicine for severe coronavirus disease 2019.

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

Vitellogenin regulates estrogen-related receptor expression by crosstalk with the JH and IIS-TOR signaling pathway in Polyrhachis vicina Roger (Hymenoptera, Formicidae).

The Estrogen-related receptor (ERR) can regulate the growth and development, metabolism, reproduction, and other physiological activities of insects, but its specific mechanism of action is still unclear. The aim of this study was to explore the relationship between expression of ERR and Vitellogenins (Vg) and the juvenile hormone (JH) and insulin/insulin-like growth factor/target of rapamycin (IIS/TOR) signaling pathways in Polyrhachis vicina Roger. P. vicina was used as the experimental model to clone the PvVg gene, perform double-stranded RNA synthesis and delivery and observe the effects of pharmacological treatments. The full-length PvVg cDNA product is 5586 bp. Higher PvVg mRNA expression was seen in the pupa and adults, and varying levels were seen in the different body parts of three different castes. RNA interference of PvVg expression led to disturbed development, an abnormal phenotype, and high mortality. PvVg RNAi also led to a reduction in mRNA levels of PvERR, ultraspiracle (PvUSP), forkhead box protein O (PvFOXO) and PvTOR genes in fourth instar larval, but a significant increase was seen in pupa and females. No significant change was seen in workers and males. After PvVg knockdown, application of exogenous JHIII reduced the expression of these genes in pupa and females, increased expression in workers, and decreased PvUSP mRNA expression in males. Both protein and mRNA expression levels of PvFOXO were affected by PvVg RNAi. PvERR RNAi increased PvVg expression in pupa and females and Kruppel-homolog 1 (PvKr-h1) and PvFOXO expression in males. The results of this study suggest that there is an interaction between PvERR and PvVg, and that crosstalk with the JH and IIS/TOR signaling pathways can affect development and reproduction. This effect is caste and developmental stage specific. We also speculate that the FOXO/USP complex participates in JH regulation of PvVg in P. vicina.

MicroRNA-26 regulates the expression of CTGF after exposure to ionizing radiation.

Radiation-induced fibrosis (RIF) is a serious complication that occurs after irradiation and which is caused by the deposition of extracellular matrix (ECM) proteins such as collagen. However, the underlying mechanisms, including the expression of the cytokines, that promote the RIF process, are not yet fully understood. MicroRNAs (miRNAs) have recently been suggested to act as post-transcriptional repressors for many genes; however, their role in the process of RIF remains to be elucidated. Our previous study showed that ionizing radiation increased the type I collagen expression through the activation of transforming growth factor (TGF)-ß, while miR-29 repressed this increase. This study aimed to investigate the mechanisms by which the expression of connective tissue growth factor (CTGF), a downstream mediator of TGF-ß, is controlled by miRNAs post-transcriptionally after exposure to ionizing radiation. The expression of CTGF in NIH-3T3 cells and mouse embryonic fibroblasts was increased by ionizing radiation. However, this increase was suppressed with a specific inhibitor of TGF-ß receptor. Among the predictable miRNAs that target the CTGF gene, the expression of miR-26a was downregulated after exposure to ionizing radiation and this regulation was negatively mediated by TGF-ß signaling. miR-26a negatively regulated the CTGF expression at the post-transcriptional level; however, ionizing radiation suppressed this negative regulation. In addition, the overexpression of miR-26a inhibited the expression of CTGF and type I collagen after irradiation. In conclusion, miR-26a modulates the expression of CTGF via TGF-ß signaling in irradiated fibroblasts. The results suggest the potential application of miR-26a in the treatment of RIF.

Alström syndrome with a novel mutation of ALMS1 and Graves' hyperthyroidism: A case report and review of the literature.

BACKGROUND: Alström syndrome (AS, OMIM ID 203800) is a rare disease involving multiple organs in children and is mostly reported in non-Chinese patients. In the Chinese population, there are few reports on the clinical manifestations and pathogenesis of AS. This is the first report on the association between AS and Graves' hyperthyroidism. CASE SUMMARY: An 8-year-old Chinese girl was diagnosed with AS. Two years later, Graves' hyperthyroidism developed with progressive liver dysfunction. The patient's clinical data were collected; DNA from peripheral blood of the proband, parents and sibling was collected for gene mutation detection using the second-generation sequencing method and gene panel for diabetes. The association between the patient's genotype and clinical phenotype was analyzed. She carried the pathogenic compound heterozygous mutation of ALMS1 (c.2296_2299del4 and c.11460C>A). These stop-gain mutations likely caused truncation of the ALMS1 protein. CONCLUSION: The manifestation of hyperthyroidism may suggest rapid progression of AS.

Endometrial autophagy is essential for embryo implantation during early pregnancy.

Embryo implantation is an essential and complex process in mammalian reproduction. However, little evidence has indicated the involvement of autophagy during embryo implantation. To determine the possible role of autophagy in uterine of pregnant mice during the peri-implantation stage, we first examined the expression of autophagy-related markers ATG5 and LC3 on day 4, 5, and 6 of pregnancy (D4, D5, and D6, respectively). Compared with expression on D4, downregulation of the autophagy-related markers was observed on D5 and D6, the days after the embryo attached to the receptivity endometrium. Further examination showed that autophagy-related markers ATG5, ATG12, LC3, cathepsin B, and P62 at the implantation site were significantly decreased when comparing with the inter-implantation site. Fewer number of autophagosomes at the implantation site were also observed by transmission electron microscopy. To confirm the functional role of autophagy during embryo implantation in mice, we administered the autophagy inhibitor 3-methyladenine and chloroquine to mice. After treated with 3-methyladenine, the expression of decidual markers HOXA10 and progesterone receptor were significantly reduced. Furthermore, a reduction in implantation sites and increase in the HOXA10 and PR protein levels were observed in response to chloroquine treatment. In addition, impaired uterine decidualization and dysregulation of the PR and HOXA10 protein levels was observed after autophagy inhibited by 3-methyladenine and chloroquine in in vivo artificial decidualization mouse model. In the last, LC3 and P62 were also observed in normal human proliferative, secretory, and decidua tissues. In conclusion, endometrial autophagy may be essential for embryo implantation, and it may be associated with endometrial decidualization during early pregnancy. KEY MESSAGE: • Autophagy-related markers were significantly decreased at implantation site. • Autophagy inhibition results in abnormal decidualization. • Autophagy is essential for embryo implantation.

The LINC00365/SCGB2A1 (Mammaglobin B) Axis Down-Regulates NF-κB Signaling and Is Associated with the Progression of Gastric Cancer.

PURPOSE: A lack of early diagnostic biomarkers and therapeutic targets has led to poor prognosis for gastric cancer patients. However, the analysis of cancer-associated genomic data has been shown to be effective in identifying potential markers. Recently, the long non-coding RNA LINC00365 and SCGB2A1 gene (as known as mammaglobin B) were predicted to be co-expressed in gastric cancer based on the Gene Expression Omnibus database. However, their precise role in gastric cancer tumors is still not clear. METHODS: The expressions of LINC00365 and SCGB2A1 in gastric cancer tissues were investigated using qPCR and their expressions were detected in a gastric cancer tissue microarray by in situ hybridization and immunohistochemical staining. The functions of LINC00365 in BGC-823 and MGC-803 gastric cancer cells were tested using the MTT assay, flow cytometry, colony formation assay, EDU staining, immunofluorescence and luciferase assay. RESULTS: We found that LINC00365 and SCGB2A1 mRNA were both expressed at low levels in 30 cases of gastric cancer. Gastric cancer tissue microarray analysis indicated that LINC00365 and SCGB2A1 were expressed at low levels in tumor tissue, and low expression of both factors correlated with shorter survival time. Functional studies showed that LINC00365 overexpression significantly inhibited gastric cancer cell viability through the impairment of proliferation rather than the promotion of apoptosis. Furthermore, overexpressed LINC00365 upregulated SCGB2A1 in gastric cancer cell lines. Immuno-fluorescence and luciferase assay analysis indicated that LINC00365 overexpression inhibited the NF-κB pro-survival signaling pathway. Consistent with the effects of LINC00365, SCGB2A1 upregulation also reduced cell survival and inactivated NF-κB. CONCLUSION: Collectively, our findings revealed that SCGB2A1 may be the target coding protein regulated by LINC00365 in gastric cancer. LINC00365 and SCGB2A1 may function as tumor suppressors and may serve as potential prognostic and therapeutic markers in gastric cancer treatment.

Phenotypic characterization of macrophages in the BMB sample of human acute leukemia.

Macrophages within tissues display a strong plastic ability in respond to environmental cues in both physiologic influences and disease. However, the macrophage phenotype and its distribution in the bone marrow biopsies (BMB) samples of human acute leukemia (AL) remain poorly understood. In this study, 97 BMB samples of patients with acute leukemia and 30 iron-deficiency anemias (IDA) as control group were evaluated with immunohistochemistry. In comparison with controls, the counts of CD68+, CD163+, and CD206+macrophages were remarkably increased in BMB samples of acute leukemia (P < 0.01), as well as their infiltration density was roaring up-regulation (P < 0.01). The expression levels of CD68+, CD163+, and CD206+macrophages were decreased in patients with complete remission, but there still existed statistically significant contrast to the control group (P < 0.01). The ratios of the CD163-positive cells or CD206-positive cells to CD68-positive cells were most prevalent in the BMB samples of human acute leukemia compared with the control group (P < 0.01), which support that macrophages were polarized to M2 macrophages.

MiRNA-574-3p inhibits cell progression by directly targeting CCND2 in colorectal cancer.

Colorectal cancer (CRC) remains the candidate for one of the typical types of malignant tumors of in gastrointestinal tract all around the world, which leads to tremendous death and ranks as the top leading death of cancer. Recently, microRNAs have emerged as double-edged sword in numerous cancers. This investigation aims to discuss the regulative role of microRNA-574-3p (miR-574-3p), elucidating its molecular mechanism and clinical significance in CRC. Herein, it revealed to us that miR-574-3p was lowly expressed in CRC tissues in comparison with the matched paracarcinoma tissues. In addition, transfection of SW480 and HT29 cells with miR-574-3p mimics prohibited the post-transcriptional expression of Cyclin D2 (CCND2), which then significantly blocked cell growth and cell migration, yet triggered cell apoptosis. Also, dual-luciferase reporter assays proved the role of CCND2 as the targeted gene for miR-574-3p. miR-574-3p overexpression prohibited the activity of CCND2 in SW480 and HT29 cells. Silencing of CCND2 in SW480 and HT29 CRC cell lines leading to reduced cell proliferative and migrative rates, and enhanced apoptotic rate. The suppressive effects of elevation of miR-574-3p on the proliferation of the human CRC cells and promotive effects on cell apoptosis by targeting CCND2 were further illustrated in the in vitro studies. Thus, we hypothesize that miR-574-3p may be served as a prospective therapeutic candidate for CRC.

Chaetomadrasins A and B, Two New Cytotoxic Cytochalasans from Desert Soil-Derived Fungus Chaetomium madrasense 375.

Two new cytochalasans, Chaetomadrasins A (1) and B (2), along with six known analogues (3-8), were isolated from the solid-state fermented culture of desert soil-derived Chaetomium madrasense 375. Their structures were clarified by comprehensive spectroscopic analyses, and the absolute configurations of Compounds 1 and 2 were confirmed by electronic circular dichroism (ECD) and calculated ECD. For the first time, Chaetomadrasins A (1), which belongs to the chaetoglobosin family, is characterized by the presence of all oxygen atoms in the form of Carbonyl. Chaetomadrasin B (2) represents the first example of chaetoglobosin type cytochalasan characterized by a hydroxy unit and carbonyl group fused to the indole ring. Compounds 1 and 2 displayed moderate cytotoxicity against HepG2 human hepatocellular carcinoma cells.