Search

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-β1 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-β1 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-β1 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-β1 signalling activation to ameliorate myocardial fibrosis.

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

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.

Here, we describe a family case carrier with 3q29 microduplication, a 1.56Mb and 1.68 Mb duplicate region, that was identified by CNV-seq. Different from the common clinical traits of previously reported cases, this family of individuals shows an apparently normal phenotype.

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.通过整理甘肃武威、居延出土汉简中灸法相关内容，对其临床应用情况和特色进行了总结。武威汉简主要记载了灸法禁忌，涉及年龄禁忌和时日禁忌；居延汉简主要记载灸背部腧穴的方法，临床强调依腧穴施灸、单穴施灸，并对施灸量有明确要求，初步呈现了汉代甘肃等西北地区灸法的应用和发展情况，对促进出土汉简灸法文献的研究具有一定的指导意义。.

Objectives: In this study, we aimed to identify the family members carried the same microdeletion and to discover the symptoms of a familial 16p11.2 microdeletion were greatly different. Case Report: The son, a 6-years-old boy, displayed scoliosis, mental retardation, and language retardation. The mother displayed mild mental retardation, but no scoliosis or language retardation or genital tract malformation. Pedigree research revealed that the mother, her son, and her fetus carried the same 16p11.2 microdeletion through CNV-sequencing, Whole Exon Sequencing, and PCR, but the father was normal. And her fetal displayed no scoliosis by ultrasound. After birth, the baby displayed genital tract malformation, but no scoliosis or mental retardation.Conclusions: This finding uncovered that the symptoms of 16p11.2 microdeletion syndrome are greatly different, even in the same segment microdeletion.

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.

BACKGROUND: Endometrial cancer (EC) is the most common gynecologic cancer and the fourth most common cancer among women in the United States (US). Although early-onset endometrial cancer (EOEC, diagnosed under age 50) is relatively uncommon, several studies have reported the incidence of EOEC has been increasing in recent decades. Because few studies have examined differences in incidence trends across race/ethnicity between EOEC and late-onset endometrial cancer (LOEC, diagnosed at age 50 or older), we compared the incidence trends between EOEC and LOEC in the US by race/ethnicity across two decades. METHODS: We used the CiNA Analytic File, 1995-2018, Public Use, obtained from the North American Association of Central Cancer Registries (NAACCR) and identified 930,176 invasive endometrial cancer cases (ICD-O-3 site code C54.1, excluding histology codes 9050-9055, 9140, and 9590-9992), of which 12.6% were EOEC and 87.4% LOEC. We examined the characteristics of these cases including race/ethnicity, year of diagnosis, tumor stage and grade by EOEC and LOEC status. We calculated the yearly race/ethnicity-specific age-adjusted incidence rates (AAIR) and the average annual percent change (AAPC) in the AAIRs for EOEC and LOEC respectively. RESULTS: Compared with LOEC cases, women with EOEC were less likely to be non-Hispanic (NH) White, more likely to be Hispanic or NH Asian/Pacific Islander (API), and less likely to have advanced stage or poorly differentiated grade. The AAIRs were highest in NH Whites in 1995 for both EOEC and LOEC. By 2018, the highest AAIR was found in Hispanics for EOEC and in NH Blacks for LOEC, resulting from faster increases in EC risk among the non-white groups. AAIRs for EOEC and LOEC increased over the study period, with the overall AAPC being three times as high for EOEC as LOEC (AAPC 1.72 vs. 0.57). For EOEC, the largest increases were observed in NH Blacks (AAPC=3.52) followed by Hispanics (AAPC=2.77) and NH API (AAPC=2.06). For LOEC, the largest increases were observed in NH APIs (AAPC=2.42) followed by NH Blacks (AAPC=2.28) and Hispanics (AAPC=1.71). For both EOEC and LOEC, the AAPCs were highest in NH Blacks and lowest in NH Whites. CONCLUSIONS: The faster increases in EOEC incidence among NH Black, Hispanic, and NH API women likely reflect racial/ethnic differences in the prevalence and trends of endometrial cancer risk factors. This indicates that these higher-risk populations might benefit from targeted surveillance and interventions. Future studies should evaluate whether these differences across race/ethnicity are attributable to specific tumor characteristics, biomarkers, or other sociodemographic factors. Citation Format: Talar S. Habeshian, Lihua Liu, Juan-Juan Zhang, Margaret Du, Immaculata De Vivo, Veronica W. Setiawan. Rising incidence and racial disparities of early-onset endometrial cancer in the United States, 1995-2018 [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C119.

In previous studies, crude Houttuynia cordata polysaccharides showed beneficial effects on acute lung injury in vivo, a syndrome in which anti-complementary activities played an important role. Anti-complementary activity-guided fractionation of H. cordata polysaccharides led to the isolation of two highly branched homogeneous polysaccharides, HC-PS1 and HC-PS3, with a molecular weight of 274 530 and 216 384 Da, respectively. The polysaccharides were purified by chromatography on DEAE-cellulose and Superdex columns. Their structural characterization was performed by IR, GC-MS, methylation, NMR, and SEM analysis. Both HC-PS1 and HC-PS3 are composed of eight types of monosaccharides, including rhamnose, arabinose, mannose, glucose, glucuronic acid, galactose, galacturonic acid, and xylose. The main linkages of the sugar residues in HC-PS1 include terminal Rhap, terminal and 1,5-linked Araf; 1,3,6-linked and 1,4,6-linked Manp; terminal, 1,4-linked, 1,3-linked, 1,3,6-linked and 1,4,6-linked and 1,3,4,6-linked Glcp; and terminal, 1,4-linked and 1,6-linked Galp. The main monosaccharide linkages in HC-PS3 are similar to that of HC-PS1, except the additional 1,3,4-linked Manp and the absence of 1,3,6-linked Glcp. HC-PS1 and HC-PS3 were found to inhibit complement activation through both the classical and alternative pathways with 50% inhibition concentrations of 0.272 – 0.318 mg/mL without interfering with the coagulation system. Preliminary mechanism studies indicated that both HC-PS1 and HC-PS3 inhibited the activation of the complement system by interacting with C2, C4, and C5. The results suggest that HC-PS1 and HC-PS3 could be valuable for the treatment of diseases associated with the excessive activation of the complement system.

Following the idea of L -fuzzy generalized neighborhood systems as introduced by Zhao et al., we will give the join-complete lattice structures of lower and upper approximation operators based on L -fuzzy generalized neighborhood systems. In particular, as special approximation operators based on L -fuzzy generalized neighborhood systems, we will give the complete lattice structures of lower and upper approximation operators based on L -fuzzy relations. Furthermore, if L satisfies the double negative law, then there exists an order isomorphic mapping between upper and lower approximation operators based on L -fuzzy generalized neighborhood systems; when L -fuzzy generalized neighborhood system is serial, reflexive, and transitive, there still exists an order isomorphic mapping between upper and lower approximation operators, respectively, and both lower and upper approximation operators based on L -fuzzy relations are complete lattice isomorphism.

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)-β, 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-β, 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-β 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-β 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-β signaling in irradiated fibroblasts. The results suggest the potential application of miR-26a in the treatment of RIF.

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.

The estrogen-related receptor (ERR) gene is a member of the nuclear receptor subfamily. Previous studies have indicated that ERR plays important roles in regulating insect growth and development. How ERR is associated with ant caste specificities remains unclear. In this study, we attempted to identify the role of ERR in the regulation of different adult caste specificities of Polyrhachis vicina Roger. Significant variations were detected in the ants including PvERR expressions, some physiological indexes and morphological traits including survival rate, body weight, body length, head width and abdominal appearance by different techniques. The results revealed that when PvERR expressions is up-regulated, boundaries of the abdominal segments were indistinct on the ventral side of the abdomen in males. Down-regulation of PvERR expressions caused abdominal swelling in males and a distended ventral abdomen in females and workers. Variation in PvERR expressions led to a remarkable decline in ant survival rates, particularly for males. These results indicated that different caste adults appeared to have different degrees of sensitivity in physiological response and morphological changes caused by variation in PvERR expressions. Thus, our data demonstrate that PvERR plays an important role in regulating the different adult caste specificities of P. vicina.

Along with increasing mobility of populations, TB in migrating population is one of the main reasons for aggravating epidemics of TB. TB in migrating population is more serious than that in common people, with more factors influencing its epidemics and more challenging detection and management. The migrating population with TB is characterized by high mobility, low socioeconomic status, poor living conditions in areas with heavy TB burden, insufficient knowledge about health, poor accessibility of health-care service, and prolonged delay for diagnosis and treatment of TB. The morbidity and mortality of TB in migrating populations are higher than those in urban residents and the migrating population is the high-risk population of TB. TB in migrating population constitutes a great challenge to prevention and control of TB.

Objective: To study the relationship of peripheral blood TLRs and Tespa1 expression levels with cytokines and oxidative stress in patients with chronic urticaria. Methods: A total of 68 patients who were diagnosed with chronic urticaria and treated in Songzi People’s Hospital clinic between June 2014 and April 2017 were selected as the CU group of the research, and 80 healthy volunteers who received physical examination were selected as the control group. TLR2, TLR7 and Tespa1 mRNA expression in peripheral blood mononuclear cells as well as the levels of Th1/Th2 cytokines and oxidative stress indexes in serum were detected. Results: TLR2 and TLR7 mRNA expression in peripheral blood mononuclear cells of CU group were significantly higher than those of control group while Tespa1 mRNA expression was significantly lower than that of control group. Serum IFN-γ, IL-2, TNF-α, T-AOC, SOD and GSH-Px levels of CU group were significantly lower than those of control group, negatively correlated with peripheral blood TLR2 and TLR7 mRNA expression, and positively correlated with Tespa1 mRNA expression; serum IL-4, IL-5, IL-10, IL-31 and MDA levels were significantly higher than those of control group, positively correlated with peripheral blood TLR2 and TLR7 mRNA expression, and negatively correlated with Tespa1 mRNA expression. Conclusions: The changes in peripheral blood TLR2, TLR7 and Tespa1 expression in patients with chronic urticaria can cause the changes in Th1/Th2 immune response and the activation of oxidative stress.

Transversus abdominis plane (TAP) block reduces opiate requirements and pain scores in abdominal surgery, but the effect has not been evaluated in hernia surgery. The aim of this study was to evaluate the efficacy of TAP block in hernia surgery.A meta-analysis of randomized clinical trials (RCTs) evaluating the effect of TAP block in adults undergoing hernia surgery was performed. The primary outcomes were morphine requirements 24 hours after surgery and the number of rescue analgesia patients. Secondary outcomes were pain scores on rest and on movement at 24 hours after surgery, postoperative nausea and vomiting and general postoperative complications.The search strategy yielded 231 articles after duplicates have been removed, and finally 8 RCTs with a total of 791 patients were included. In patients who received a TAP block, the cumulative morphine utilization was significantly reduced at 24 hours (weighted mean difference [WMD] -11.40 mg, -22.41 to -0.39; P=0.04). The number of patients needing a rescue analgesia (relative risk: 0.35, 0.22 to 0.55; P0.001), the pain scores on rest 24 hours after surgery (WMD: -0.29, -0.55 to -0.04; P=0.02) and the pain scores on movement or coughing 24 hours after surgery (WMD: -0.70, -1.33 to -0.06; P=0.03) were all lower in patients who received a TAP block. There was also significant reduction in the postoperative nausea and vomiting, and the general postoperative complications in TAP block group.Within a heterogeneous group of RCTs, TAP block reduces postoperative morphine requirements and the severity of pain after hernia surgery.

A concise, efficient one-pot synthesis of functionalized chromeno[4,3-b]pyridine derivatives via a three-component reaction of 4-oxo-4H-chromene-3-carbaldehydes, malononitrile or cyanoacetates, and aromatic amines under catalyst-free conditions in an environmentally friendly medium (ethanol-water, 3:1 v/v) is described. This synthesis involves a group-assisted purification process, which avoids traditional recrystallization and chromatographic purification methods.

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.

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.

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.

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

Postgraduate Training is an important pathway to train and make innovative talents. How to establish an effective internal quality assurance system for graduate education, improve the quality of training, strengthen the training of innovation ability, and apply the theory of continuous improvement to all aspects of graduate work, and train the professional and practical senior talents who can meet the needs of the job and continue to pursue further education. This is an urgent problem for graduate education.

Active power filters (APF) can compensate for harmonics and reactive power. The traditional APF PI control has difficulty in parameter setting, and has the characteristics of control lag, and the control accuracy of current is low. The control of three-level APF needs to consider multiple objectives. Finite Control Set Model Predictive Control (FCS-MPC) is a newly proposed method that can increase constraints and multi-objective control. According to the limited switching state, it tracks the reference current and has dynamic Fast response and good compensation results. In this paper, the finite set model predictive control algorithm of three-level APF is studied, and the results show that the harmonic content of the power grid is low, which meets the relevant requirements.

Objective: To assess the levels of serum cytokines, T lymphocyte subsets and STAT3 in patients with herpes zoster as well as the intervention effect of mouse nerve growth factor. Methods: A total of 102 patients with herpes zoster were selected as observation group and received mouse nerve growth factor intervention, and 100 cases of normal people who received physical examination in our hospital during the same period as the healthy control group. The levels of serum Th1/Th2 cytokines, IgG subclass and complements and T lymphocyte subsets as well as STAT3 function of observation group before and after treatment and healthy control group were detected. Results: Serum IL-2 and γ-IFN levels of observation group after treatment were higher than those before treatment while IL-4, IL-5, IL-10 and TNF-α毩 levels were lower than those before treatment (P

BACKGROUND The use of trastuzumab has proven to be a successful strategy in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer; however, it is associated with an increased risk of cardiac dysfunction. We performed an up-to-date, comprehensive meta-analysis to clarify the risk of congestive heart failure (CHF) in patients with early breast cancer receiving different durations of adjuvant trastuzumab with the longest-term follow-up. METHODS Eligible studies included randomized control trials of HER2-positive early breast cancer patients with or without trastuzumab in adjuvant chemotherapy. Adequate reporting of CHF data were required for inclusion. Statistical analyses were conducted to calculate the overall incidence, relative risk (RR), and 95% confidence interval (CI) by use of a fixed-effects model. RESULTS Six randomized control trials including 18,111 patients were identified. The overall incidence of high-grade CHF in patients treated with trastuzumab versus placebo was 1.44% (95% CI, 0.79%-2.64%) and the RR was 3.19 (95% CI, 2.03-5.02; p < .00001). In subgroup analysis, the difference in CHF incidence failed to achieve significance. The RR for 8 mg/kg trastuzumab (high dose) was greater than that for 4 mg/kg (low dose) (RR, 6.79, 95% CI, 2.03-22.72, p = .0001; versus RR, 2.64; 95% CI, 1.61-4.32; p = .002). Additionally, higher RRs were observed for patients receiving trastuzumab for 1 year (RR, 3.29; 95% CI, 2.07-5.25) and 2 years (RR, 9.54; 95%CI, 2.19-41.43), but not 9 weeks (RR, 0.50; 95% CI, 0.05-5.49) compared with control groups. No evidence of publication bias was observed. CONCLUSION Adjuvant trastuzumab therapy was strongly associated with an increased risk of significant CHF in patients with early breast cancer, particularly in 2-year use. IMPLICATIONS FOR PRACTICE This comprehensive meta-analysis evaluated the risk of congestive heart failure with a usage profile of adjuvant trastuzumab in patients with early breast cancer. Before initiating treatment with trastuzumab, a risk-benefit analysis for individual patients should be critically evaluated, considering that the prognosis is closely related to drug dose and duration of use. Cardiac function should be monitored throughout the treatment period and also during follow-up. Thus, early identification of trastuzumab-related cardiac dysfunction can allow effective medical intervention, elimination of symptoms, recovery of function, and continuation of trastuzumab therapy.

To explore the antagonistic effect of vitamin E (VE) on male reproductive toxicity induced by di-2-ethylhexyl phthalate (DEHP) in pubertal SD rats and its underlying mechanisms.Thirty 5-week-old male SD rats were randomly divided into five groups of equal number, corn oil control, low-dose (10 mg/kg/d), medium-dose (100 mg/kg/d) and high-dose DEHP exposure (500 mg/kg/d), and VE intervention (high-dose DEHP + VE ［100 mg/kg/d］), and treated respectively for 30 successive days. At 3 days after treatment, the testes of the animals were harvested for determination of the oxidative stress index, serum reproductive hormone levels, cauda epididymal sperm parameters, and expressions of cell apoptosis-related genes and proteins.Compared with the control group, the rats of the medium- and high-dose DEHP groups showed significant decreases in the levels of such serum reproductive hormones as follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T), sperm parameters as average path velocity (VAP), straight line velocity (VSL), curvilinear velocity (VCL), straightness (STR), linearity (LIN) and wobble (WOB), and the activities of superoxide dismutase (SOD) and glutathione peroxide (GSH-Px), but significant increases were observed in the latter two groups in the content of malondialdehyde (MDA)(［3.32±0.87］ nmol/mg pro vs ［2.13±0.49］ nmol/ mg pro), mRNA expressions of Bad, Bax, Cytochrome C, Caspase-3 and the Bax/Bcl-2 ratio, and protein expressions of Cytochrome C and Caspase-3. In comparison with the high-dose DEHP group, the VE intervention group exhibited remarkably increased serum LH and T levels, sperm VAP, VSL, VCL, STR and WOB, and activities of SOD and GSH-Px, but markedly decreased mRNA expressions of Bad, Bax, Cytochrome C, Caspase-3 and the Bax/Bcl-2 ratio as well as the protein expressions of Cytochrome C and Caspase-3 in the testis tissue (P0.05).Exposure to DEHP induces androgen secretion disorders, causes oxidative damage to the testicular tissue, activates the mitochondrial apoptosis pathway in the testis, and ultimately reduces the quality of epididymal sperm, while VE can protect the rat testis from DEHP-induced reproductive toxicity.目的： 探索维生素E（VE）对青春期邻苯二甲酸二异辛酯（DEHP）暴露致雄性大鼠生殖毒性的干预作用以及其机制。方法： 将30只35日龄雄性SD大鼠(体重96~122 g)随机分为对照组（玉米油），低［10 mg/(kg·d）］、中［100 mg/(kg·d）］、高［500 mg/(kg·d）］DEHP组，以及VE干预组［（500 mg/(kg·d） DEHP+100 mg/(kg·d） VE］，各组给予相应食物30 d。在染毒干预结束后，分别检测大鼠睾丸组织氧化应激指标、附睾尾部精子参数、血清生殖激素水平、凋亡相关靶基因及蛋白的表达。结果： 与对照组比较，中、高DEHP组血清中FSH、LH和T水平明显降低，精子运动参数VAP、VCL明显降低， SOD和GSH-Px活力显著降低，Bak、Bax基因表达和Bax/Bcl-2基因表达比值显著升高，细胞色素C mRNA表达及细胞色素C和Caspase-3蛋白表达均显著上调(P均0.05)；高DEHP组MDA含量［(3.32±0.87) nmol/mg pro vs (2.13±0.49) nmol/mg pro］明显升高, 精子运动参数VAP、VCL、VSL、STR、LIN、WOR均明显降低(P0.05)。与高DEHP组比较，VE干预组的LH和T水平明显升高；VAP、VSL、VCL、STR和WOB明显升高；SOD和GSH-Px活力显著升高；MDA含量明显降低；Bak、Bax基因表达和Bax/Bcl-2基因表达比值显著降低；细胞色素C、Caspase-3 mRNA表达及蛋白表达均显著下调(P均0.05)。结论： 青春期DEHP暴露可抑制生殖激素分泌或释放，导致雄性大鼠睾丸组织氧化损伤，激活细胞线粒体凋亡通路，也可导致附睾精子质量下降；而VE对DEHP所诱导的雄性生殖毒性具有一定的拮抗作用。.

The mechanism of cisplatin resistance is complex. Previous studies have indicated that chloride voltage-gated channel 3 (CLCN3) is associated with drug resistance; however, the mechanisms are not fully understood. Therefore, the present study explored the involvement of CLCN3 in cisplatin resistance in human glioma U251 cells. The effects of combined cisplatin treatment and CLCN3 suppression on cultured U251 cells were investigated. The decreased viability of cisplatin-treated U251 cells indicated the cytotoxic effects of CLCN3 silencing. Expression of the apoptosis-related gene TP53 and caspase 3 activation were enhanced in cisplatin-treated U251 cells. Furthermore, the ratio of BCL2/BAX expression was decreased. Notably, CLCN3 suppression promoted cisplatin-induced cell damage in U251 cells. Thus, the combined use of cisplatin and CLCN3 antisense had additive effects in U251 cells. In addition, the present results indicated that CLCN3 suppression decreased lysosome stabilization in U251 cells treated with cisplatin. To conclude, the present results indicated that CLCN3 suppression can sensitize glioma cells to cisplatin through lysosomal dysfunction.

In the winter-wheat and summer-maize multiple cropping system in lime concretion black soil of Huanghuaihai Plain, the effects of three tilling methods (conventional tillage, rotary tillage, subsoiling tillage) in wheat season coupling with three nitrogen treatments (120 kg·hm在黄淮砂姜黑土区冬小麦-夏玉米复种两熟种植体系中,研究了小麦季3种耕作方式(常规翻耕、旋耕和深松)结合夏玉米播前3个施氮量(120、225和330 kg·hm

Poor prognosis and chemotherapy tolerance are the main obstacles encountered in the treatment of cholangiocarcinoma. Chloroquine (CQ), an antimalarial agent, is able to induce sustained endoplasmic reticulum (ER) stress by functioning as an autophagy inhibitor. The present study indicated that CQ had the ability to induce apoptosis in QBC939 cholangiocarcinoma cells. Furthermore, using western blotting, Hoechst staining and flow cytometry, it was demonstrated that CQ induced the apoptosis of QBC939 cholangiocarcinoma cells. Analysis by a polymerase chain reaction (PCR) array and confirmation via quantitative PCR technology indicated that the expression levels of growth arrest and DNA damage 153 [C/EBP homologous protein (CHOP)], a key molecule involved in ER stress-induced apoptosis, and its downstream death receptors were increased following CQ stimulation. It was considered that the upregulation of CHOP may mediate CQ-induced extrinsic pathways and autophagy-dependent apoptosis; therefore, the role of autophagy in cholangiocarcinoma treatment was elucidated based on the data demonstrating that CQ regulates the ER-autophagy network in tumor cells. Furthermore, it was considered that CQ may become a novel and effective strategy for the treatment of cholangiocarcinoma.

Increasing evidence suggests that mitochondrial respiratory chain complex I participates in carcinogenesis and cancer progression by providing energy and maintaining mitochondrial function. However, the role of complex I in ovarian cancer is largely unknown. In this study we showed that metformin, considered to be an inhibitor of complex I, simultaneously inhibited cell growth and induced mitochondrial-related apoptosis in human ovarian cancer cells. Metformin interrupted cellular energy metabolism mainly by causing damage to complex I that impacted mitochondrial function. Additionally, treatment with metformin increased the activation of sirtuin 3 (SIRT3), a mitochondrial deacetylase. We demonstrated that SIRT3 overexpression aggravated metformin-induced apoptosis, energy stress and mitochondrial dysfunction. Moreover, treatment with metformin or SIRT3 overexpression increased activation of AMP-activated protein kinase (AMPK), a major sensor of cellular energy status. AMPK compensated for energy loss by increasing glycolysis. The impact of this was assessed by reducing glucose levels in the media or by using inhibitors (2-deoxyglucose, Compound C) of glycolysis and AMPK. The combination of these factors with metformin intensified cytotoxicity through further downregulation of ATP. Our study outlines an important role for SIRT3 in the antitumor effect of mitochondrial complex I inhibitors in human ovarian cancer cells. This effect appears to be mediated by induction of energy stress and apoptosis. Strategies that target the mitochondria could be enhanced by modulating glycolysis to further aggravate energy stress that may increase the antitumor effect.

Two novel enediyne-derived natural products, amycolamycins A and B (1 and 2), were characterized from a locust-associated actinomycete Amycolatopsis sp. HCa4. Amycolamycins A and B contain a unique 2-(cyclopenta[a]inden-5-yl)oxirane core with suspected enediyne polyketide biosynthetic origin. Sequencing and analysis of the acm biosynthetic gene cluster allowed us to propose the biosynthetic pathway of 1 and 2. Moreover, amycolamycin A (1) was selectively cytotoxic to the M231 breast cancer cell line.

The micromorphology of a seed is linked to its dispersal and germination, but evolutionary and ecological aspects in Orchidaceae remain unclear. We investigated the seed characters of Paphiopedilum and Cypripedium that might be associated with life form and involved in possible ecological adaptations. A phylogenetic comparative analysis of nine seed micromorphological characters was performed in 24 species from two genera with close phylogenetic relationships but significant differences in their ecological characteristics. Species within Paphiopedilum had larger embryos and a smaller percentage of air space (AS) than those of Cypripedium species. Compared with 16 terrestrial species, two epiphytic Paphiopedilum species had larger embryos and smaller AS. Those larger embryos might ensure more successful seedling establishment while the higher amount of air space in both terrestrial Paphiopedilum and Cypripedium may increase seed buoyancy and enable them to disperse over longer distances. Whereas AS and seed length (SL) are phylogenetically conservative, most other characters examined here had weak signals, indicating clear convergent evolution. Across species, SL was positively correlated with AS, indicating a high degree of seed size–dispersal coordination. These findings may imply a trade-off of seed characters in relation to the possible ecological adaptations required for seedling establishment versus dispersal.

The novel propeller type compound, 2,4,6-tri(anthracen-9-yl)-1,3,5-triazine (TAT) with C3 symmetry was synthesized by using 9-anthryl lithium with 1,3,5-trichlorotriazine or 2-chloro-4,6-dimethoxy-1,3,5-triazine in the presence of palladium catalyst in 22–48% yield. Another two propeller-like compounds, 2-(anthracen-9-yl)-4,6-dimethoxy-1,3,5-triazine (3) and 2,4-di(anthracen-9-yl)-6-methoxy-1,3,5-triazine (4) were obtained at the same time. The propeller type structures of TAT, 3 and 4 were confirmed by crystal analysis and theoretical calculations. The intramolecular C–C bond rotations between the anthryl groups and the triazine units in molecules TAT, 3 and 4 were regarded as the key factor to understand their spectroscopic behaviors in fluid medium and rigid solution.

A concise and efficient one-pot synthesis of functionalized [1,8]naphthyridine derivatives via a three-component domino reaction of glutaraldehyde, malononitrile, and β-ketoamides, under catalyst-free conditions in an environmentally friendly medium (ethanol) is described. The main advantages of this protocol are short reaction times, practical simplicity, high yields, catalyst-free conditions, cheap and benign solvents, and high regio- and stereo-selectivities.

A novel bridged pentacyclic skeleton has been constructed via the six-component domino reaction of glutaraldehyde, malononitrile, cyclic 1,3-dicarbonyl compounds and amines under microwave irradiation. In this one-pot transformation, 11 new bonds and five new rings have been formed. The main advantages of this protocol are short reaction time (within 30 min), practical simplicity, high regioselectivity, benign solvents, atom-economy, and environmental friendliness.