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1.
Discov Oncol ; 15(1): 168, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750182

ABSTRACT

BACKGROUND: Studies evaluating the effectiveness of immune checkpoint inhibitors (ICI) for endometrial cancer (EC) are limited. This study aimed to assess the efficacy of PD-1/PD-L1 inhibitors as monotherapy for EC by conducting a meta-analysis. The predictive significance of MMR status, a biomarker for ICI response, also required further investigation. METHODS: A systematic literature search was conducted in English databases until September 2023. The analysis included objective response rate (ORR), disease control rate (DCR), adverse events (AEs), and odds ratios (OR), along with their corresponding 95% confidence intervals (CI). RESULTS: There were twelve trials totaling 685 individuals. PD-1/PD-L1 inhibitor monotherapy resulted in an ORR for 34% (95% CI = 24-44%) of the pooled EC patients. Subgroup analysis revealed a significantly higher ORR in dMMR EC (45%) compared to pMMR EC (8%), with an OR of 6.36 (95% CI = 3.64-11.13). The overall DCR was 42%, with dMMR EC at 51% and pMMR EC at 30% (OR = 2.61, 95% CI = 1.69-4.05). Grade three or higher adverse events (AEs) occurred in 15% of cases (95% CI = 9-24%) of the pooled incidence of AEs, which was 68% (95% CI = 65-72%). CONCLUSIONS: This meta-analysis provides significant evidence for the effectiveness of PD-1/PD-L1 inhibitors as monotherapy for EC. Notably, dMMR EC patients demonstrated superior treatment efficacy with PD-1/PD-L1 inhibitor immunotherapy. Further research is required to explore subclassifications of EC based on dMMR molecular subtypes, enabling improved treatment strategies and outcomes for EC patients.

2.
Environ Pollut ; 346: 123625, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38401636

ABSTRACT

The blood-testis barrier (BTB) plays a vital role in mammalian spermatogenesis by separating the seminiferous epithelium into an adluminal and a basal compartment. Cadmium (Cd) is a toxic heavy metal that is widely present in the environment. We observed that Cd can induce BTB disruption, leading to apoptosis of testicular cells. However, the molecular mechanisms contributing to BTB injury induced by Cd have not yet been fully clarified. Vimentin (Vim) is an important desmosome-like junction protein that mediates robust adhesion in the BTB. In this study, we investigated how Vim responds to Cd. We found that Cd treatment led to a significant decrease in Vim expression, accompanied by a marked increase in LC3-II expression and a higer number of autophagosomes. Interestingly, we also observed that Cd-induced autophagy was associated with decreased Vim activity and enhanced apoptosis of testicular cells. To further investigate the role of autophagy in Vim regulation under Cd exposure, we treated cells with an autophagy inhibitor called 3-MA. We found that 3-MA treatment enhanced Vim expression and improved the disruption of the BTB under Cd exposure. Additionally, the inhibition of Vim confirmed the role of autophagy in modulating Vim expression. These results reveal a previously unknown regulatory mechanism of Cd involving the interplay between a heavy metal and a protein.


Subject(s)
Blood-Testis Barrier , Cadmium , Male , Animals , Cadmium/toxicity , Cadmium/metabolism , Vimentin/metabolism , Blood-Testis Barrier/metabolism , Testis/metabolism , Spermatogenesis/physiology , Autophagy , Mammals
3.
Ecotoxicol Environ Saf ; 273: 116095, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38367604

ABSTRACT

The male reproductive dysfunction accounts for 50% of infertile couples in the world. Cadmium (Cd) is one of the most harmful heavy metals to both the environment and inhabitants. Accumulating data suggest that Cd could cause male infertility. Sertoli cell (SC) is a somatic cell of testis and a key regulator of spermatogenesis by providing physical and nutritional support for developing sperm. Many studies showed that Cd induced dysfunction of SCs was directly related to male reproductive damage. However, the mechanism of SCs injury caused by Cd remains to be clarified. We found that Cd treatment caused a significant increase of apoptosis in SCs cells, accompanied by a marked increase in the production of ROS. These results were associated with the formation of mitochondria-containing autophagosomes and increased expression of LC3-II in vitro. Interestingly, our results showed that Cd did not promote but inhibited the fusion of mitochondria-containing autophagosomes with lysosomes by reducing the function of lysosomes. Together, this study provides insight into the negative effects of Cd, which interferes with autophagic flux and induces the apoptosis of SCs.


Subject(s)
Cadmium , Sertoli Cells , Male , Humans , Cadmium/metabolism , Sertoli Cells/metabolism , Semen , Autophagy , Apoptosis
4.
J Gene Med ; 26(1): e3568, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37455244

ABSTRACT

BACKGROUND: The present study aims to develop a metabolic gene signature to evaluate the survival rate of ovarian cancer (OC) patients and analyze the potential mechanisms of metabolic genes in OC because the difficulty in early detection of OC often leads to poor treatment outcomes. METHODS: A non-negative matrix factorization algorithm was applied to determine molecular subtypes according to metabolism genes. To build a risk prognosis model, least absolute shrinkage and selection operator multivariate Cox analysis was carried out with weighted correlation network analysis (WCGNA). Glycolytic flux and mitochondrial function were evaluated by conducting seahorse analysis. RESULTS: On the basis of metabolism-related genes, the two subtypes of OC samples present in The Cancer Genome Atlas database were distinguished. An analysis of WGCNA identified 1056 genes. Lastly, a 10-gene signature (CMAS, ADH1B, PLA2G2D, BHMT, CACNA1C, AADAC, ALOX12, CYP2R1, SCN1B and ME1) was constructed that demonstrated promising performance in predicting outcome in patients with OC. The RiskScore of the gene signature was linked to microenvironment cell infiltration and immune checkpoint. Higher RiskScores were associated with poorer results for OC patients. Seahorse analysis shows the influence of CMAS in cell energy metabolism. CONCLUSIONS: In the present study, a novel marker for evaluating the survival of OC patients was developed through the creation of a gene signature incorporating metabolism-related genes. Our knowledge of immunotherapy and microenvironment cell infiltration may be enriched by evaluating metabolism-related gene modification patterns.


Subject(s)
Ovarian Neoplasms , Vaccines , Humans , Female , Ovarian Neoplasms/genetics , Ovarian Neoplasms/therapy , Machine Learning , Energy Metabolism , Algorithms , Tumor Microenvironment/genetics
5.
Front Endocrinol (Lausanne) ; 14: 1265525, 2023.
Article in English | MEDLINE | ID: mdl-38075052

ABSTRACT

Ovarian cancer is a highly malignant gynecological cancer influenced by the immune microenvironment, metabolic reprogramming, and cellular senescence. This review provides a comprehensive overview of these characteristics. Metabolic reprogramming affects immune cell function and tumor growth signals. Cellular senescence in immune and tumor cells impacts anti-tumor responses and therapy resistance. Targeting immune cell metabolism and inducing tumor cell senescence offer potential therapeutic strategies. However, challenges remain in identifying specific targets and biomarkers. Understanding the interplay of these characteristics can lead to innovative therapeutic approaches. Further research is needed to elucidate mechanisms, validate strategies, and improve patient outcomes in ovarian cancer.


Subject(s)
Ovarian Neoplasms , Humans , Female , Cellular Senescence , Research Design , Tumor Microenvironment
6.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 48(3): 472-480, 2023 Mar 28.
Article in English, Chinese | MEDLINE | ID: mdl-37164931

ABSTRACT

Schizophrenia is a chronic mental disease. With the change of medical model, quality of life has gradually become an important prognostic indicator for patients with schizophrenia. People with schizophrenia have a lower quality of life than the general population or people with other chronic diseases, Sociodemographic factors such as age, gender, employment, education level, income and living situation; clinical factors such as psychiatric symptoms, medication compliance and insight; and psychosocial factors such as social support, cognition, stigma, self-esteem and needs are the main influencing factors for schizophrenia patients. Medication and psychological interventions such as social skills training, family intervention, cognitive correction and cognitive behavioral therapy can be used to improve the quality of life of patients with schizophrenia. Understanding the factors affecting the quality of life of schizophrenia patients and the improvement measures helps to provide reference for improving their quality of life.


Subject(s)
Cognitive Behavioral Therapy , Schizophrenia , Humans , Schizophrenia/drug therapy , Quality of Life/psychology , Social Stigma , Cognition
7.
Front Public Health ; 11: 1097098, 2023.
Article in English | MEDLINE | ID: mdl-37200989

ABSTRACT

Aims: Suicide ideation, self-harm, and suicide are common in patients with schizophrenia, but the reported prevalence vary largely across studies. Improved prevalence estimates and identification of moderators of the above self-directed violence are needed to enhance recognition and care, and to guide future management and research. This systematic review aims to estimate the pooled prevalence and identify moderators of suicide ideation, self-harm, and suicide among patients diagnosed with schizophrenia in China. Methods: Relevant articles published until September 23, 2021, were searched using PubMed, EBSCO, Web of Science, Embase, Science Direct, CNKI, CBM, VIP, and Wanfang databases. Eligible studies published in English or Chinese which reported the prevalence of suicide ideation, self-harm, or suicide among Chinese patients with schizophrenia were collected. All studies passed a quality evaluation. This systematic review was registered with PROSPERO (registration number CRD42020222338). PRISMA guidelines were used in extracting and reporting data. Random-effects meta-analyses were generated using the meta package in R. Results: A total of 40 studies were identified, 20 of which were evaluated as high-quality studies. Based on these studies, the prevalence of lifetime suicide ideation was 19.22% (95% CI: 7.57-34.50%), prevalence of suicide ideation at the time of investigation was 18.06% (95% CI: 6.49-33.67%), prevalence of lifetime self-harm was 15.77% (95% CI: 12.51-19.33%), and prevalence of suicide was 1.49% (95% CI: 0.00-7.95%). Multivariate meta-regression analysis revealed that age (ß = - 0.1517, p = 0.0006) and dependency ratio (ß = 0.0113, p < 0.0001) were associated with the lifetime prevalence of self-harm. Study assessment score (ß = 0.2668, p < 0.0001) and dependency ratio (ß = 0.0050, p = 0.0145) were associated with the lifetime prevalence of suicide ideation. Results of the spatial analysis showed that the prevalence of self-directed violence varied greatly across different provinces. Conclusion: This systematic review provides estimates of the prevalence of self-directed violence among Chinese patients with schizophrenia and explores its moderators and spatial patterns. Findings also have important implications for allocating prevention and intervention resources to targeted high-risk populations in high prevalence areas.


Subject(s)
Schizophrenia , Self-Injurious Behavior , Humans , Suicide, Attempted , Schizophrenia/epidemiology , Prevalence , East Asian People , Self-Injurious Behavior/epidemiology
8.
Front Nutr ; 10: 1086507, 2023.
Article in English | MEDLINE | ID: mdl-36860691

ABSTRACT

Background: Hypertension is a major public health concern that strongly influences the quality of life of people worldwide. Keshan disease (KD) is an endemic cardiomyopathy related to low selenium, threatening residents in rural areas of 16 provinces in China. Furthermore, the prevalence of hypertension in the KD-endemic areas has been increasing annually. However, hypertension research associated with KD has only focused on endemic regions, and no studies have compared hypertension prevalence between endemic and non-endemic areas. Therefore, this study investigated the prevalence of hypertension to provide a basis for preventing and controlling hypertension in the KD-endemic areas, even in rural areas. Methods: We extracted blood pressure information from cardiomyopathy investigation data from a cross-sectional study of the KD-endemic and non-endemic areas. The hypertension prevalence between the two groups was compared using the Chi-square test or Fisher s exact test. Additionally, Pearson's correlation coefficient was employed to evaluate the relationship between the per capita gross domestic product (GDP) and hypertension prevalence. Results: There was a statistically significant increase of hypertension prevalence in the KD-endemic areas (22.79%, 95% confidence interval [CI]: 22.30-23.27%) over the non-endemic areas (21.55%, 95% CI: 21.09-22.02%). In the KD-endemic areas, more men had hypertension than women (23.90% vs. 21.65%, P < 0.001). Furthermore, the hypertension prevalence was higher in the north than in the south in the KD-endemic areas (27.52% vs. 18.76%, P < 0.001), non-endemic areas (24.86% vs. 18.66%, P < 0.001), and overall (26.17% vs. 18.68%, P < 0.001). Finally, the prevalence of hypertension positively correlated with per capita GDP at province level. Conclusions: The increasing hypertension prevalence is a public health problem in the KD-endemic areas. Healthy diets, such as high consumption of vegetables and seafoods, and foods that are rich in selenium, might help prevent and control hypertension in the KD-endemic areas and other rural areas in China.

9.
Transl Res ; 256: 73-86, 2023 06.
Article in English | MEDLINE | ID: mdl-36586533

ABSTRACT

Liquid biopsy has the advantage of diagnosing diseases in a non-invasive manner. Seminal plasma contains secretions from the bilateral testes, epididymides, seminal vesicles, bulbourethral glands, and the prostate. These organs are relatively small and contain delicate tubes that are prone to damage by invasive diagnosis. Cell-free seminal nucleic acids test is a newly emerged item in liquid biopsy. Here, we present a comprehensive overview of all known cell-free DNA and cell-free RNAs (mRNA, miRNA, lncRNA, circRNA, piRNA, YRNA, tsRNA, etc.) and discuss their roles as biomarker candidates in liquid biopsy. With great advantages, including high stability, sensitivity, representability, and non-invasiveness, cell-free DNA/RNAs may be developed as promising biomarkers for the screening, diagnosis, prognosis, and follow-up of diseases in semen-secreting organs. Moreover, RNAs in semen may participate in important processes, including sperm maturation, early embryo development, and transgenerational disease inheritance, which may be developed as potential treatment targets for future clinical use.


Subject(s)
Cell-Free Nucleic Acids , Semen , Male , Humans , Spermatozoa , Biomarkers , Reproduction
11.
J Microbiol ; 60(5): 496-510, 2022 May.
Article in English | MEDLINE | ID: mdl-35362894

ABSTRACT

Bacterial leaf streak caused by Xanthomonas oryzae pv. oryzicola (Xoc) is one of the most destructive diseases affecting rice production worldwide. In this study, we extracted and purified phenazine substances from the secondary metabolites of Lysobacter antibioticus 13-6. The bacteriostatic mechanism of phenazine substances against Xoc was investigated through physiological response and transcriptomic analysis. Results showed that phenazine substances affects the cell membrane permeability of Xoc, which causes cell swelling and deformation, blockage of flagellum synthesis, and imbalance of intracellular environment. The changes in intracellular environment affect the physiological and metabolic functions of Xoc, which reduces the formation of pathogenic factors and pathogenicity. Through transcriptomic analysis, we found that among differentially expressed genes, the expression of 595 genes was induced significantly (275 up-regulated and 320 down-regulated). In addition, we observed that phenazine substances affects three main functions of Xoc, i.e., transmembrane transporter activity, DNA-mediated transposition, and structural molecular activity. Phenazine substances also inhibits the potassium ion transport system that reduces Xoc resistance and induces the phosphate ion transport system to maintain the stability of the internal environment. Finally, we conclude that phenazine substances could retard cell growth and reduce the pathogenicity of Xoc by affecting cell structure and physiological metabolism. Altogether, our study highlights latest insights into the antibacterial mechanism of phenazine substances against Xoc and provides basic guidance to manage the incidence of bacterial leaf streak of rice.


Subject(s)
Oryza , Xanthomonas , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Lysobacter , Oryza/microbiology , Phenazines/metabolism , Phenazines/pharmacology , Plant Diseases/microbiology , Plant Diseases/prevention & control
12.
World J Microbiol Biotechnol ; 38(4): 71, 2022 Mar 08.
Article in English | MEDLINE | ID: mdl-35258706

ABSTRACT

The present study aimed to evaluate transcriptional activator-like effector (TALE) genes in 86 Xanthomonas oryzae pv. oryzicola strains collected from 8 rice-growing regions in Yunnan, and to examine the relationship between TALE genotypes and virulence in 6 differential rice lines. Besides, the geographical areas, distribution of these genotypes were studied in detail. Genetic diversity was analyzed through the number and size of putative TALE genes based on TALE gene avrXa3 as a probe. We found that X. oryzae pv. oryzicola strains consist of variable number (13-27) of avrXa3-hybridizing fragments (putative TALE genes). Test strains were classified into 8 genotypes (G1-G8) with major genotypes G3 and G7 widely distributed in Yunnan. Pathogenicity of X. oryzae pv. oryzicola was evaluated by inoculating 6 differential rice lines with a single resistance gene into 9 pathotypes clusters (I-IX), the dominant Genotypes G3 and G7 consist of pathotypes I, II, and IV. Furthermore, we also detected the known TALE target genes expression in susceptible rice cultivar (cv. nipponbare) after inoculating 8 genotypes-representative X. oryzae pv. oryzicola strain. Correlation between the numbers of putative TALE genes of X. oryzae pv. oryzicola and relevant target genes in nipponbare confirmed up-regulation. Altogether, this study has given insights into the population structure of X. oryzae pv. oryzicola that may inform strategies to control BLS in rice.


Subject(s)
Oryza , Xanthomonas , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , China , DNA, Bacterial/genetics , Oryza/genetics , Plant Diseases , Plant Leaves/metabolism , Transcription Activator-Like Effectors/metabolism , Virulence/genetics , Xanthomonas/genetics
13.
3 Biotech ; 11(10): 434, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34603912

ABSTRACT

Bacterial leaf streak (BLS) caused by Xanthomonas oryzae pv. oryzicola (Xoc), impacts the production of rice. However, several rice cultivars displayed resistance to Xoc in the field, but scarce information is available about the role of endophytic microbiota in disease resistance. In the present study, the endophytic bacterial communities of resistant and susceptible rice cultivars "CG2" and "IR24", respectively, were analyzed using high throughput 16S rRNA gene amplified sequencing and culture dependent method was further used for bacterial isolation. A total of 452,716 high-quality sequences representing 132 distinct OTUs (Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes) and 46 isolates of 16 genera were explored from rice leaves infected with Xoc. Community diversity of endophytic bacteria were higher in the leaves of the resistant cultivars compared to susceptible cultivars upon Xoc infection. Strikingly, this diversity might contribute to natural defense of the resistant cultivar against pathogen. Pantoea, which is pathogen antagonist, was frequently detected in two cultivars and higher abundance were recorded in resistant cultivars. Different abundance genus includes endophytic isolates with marked antagonistic activity to Xoc. The increased proportions of antagonistic bacteria, may contribute to resistance of rice cultivar against Xoc and the Pantoea genus was recruited by Xoc infection play a key role in suppressing the development of BLS disease in rice. Taken together, this work reveals the association between endophytic bacteria and BLS resistance in rice and identification of antagonism-Xoc bacterial communities in rice. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02979-2.

14.
J Trace Elem Med Biol ; 68: 126832, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34364066

ABSTRACT

PURPOSE: The prevalence of Keshan disease (KD) is low and has reached controlled or eliminated levels even in counties that had a high KD prevalence in the past. Few nationwide surveys on selenium levels in KD areas have been conducted in the past 2 decades. We conducted a cross-sectional study to investigate the selenium levels and their association with KD control and prevention in areas where KD is prevalent. METHODS: We collected 2143 human-hair, 698 soil, 701 rice, 607 flour, 521 corn, and 330 other-food samples from 49 counties with KD and 19 non-KD counties of nine KD provinces of China. The selenium content of samples was examined with hydride generation atomic fluorescence spectrometry. The difference in selenium levels between the KD and non-KD areas was analyzed. Cochran-Armitage trend tests were used to evaluate the association between selenium levels and KD control. RESULTS: The selenium levels in human hair, soil, staple foods, and other foods in the KD areas (0.2996 mg/kg, 0.1380 mg/kg, 0.0190 mg/kg and 0.0076 mg/kg, respectively) were lower than those in the non-KD areas (0.3700 mg/kg, 0.1930 mg/kg, 0.0240 mg/kg and 0.0165 mg/kg, respectively). The Cochran-Armitage tests showed that there was a trend for the selenium standard ratio in the counties to increase in the order of KD uncontrolled, to controlled, to eliminated (Z = 2.229, P < 0.05). CONCLUSION: The residents in the KD areas were found to be selenium-deficient. Improving the supply of staple foods containing selenium levels exceeding 0.025 mg/kg and abundant foodstuffs might contribute to KD control and prevention.


Subject(s)
Cardiomyopathies , Enterovirus Infections , Selenium , China , Cross-Sectional Studies , Humans , Selenium/analysis , Soil
15.
Infect Genet Evol ; 94: 105008, 2021 10.
Article in English | MEDLINE | ID: mdl-34284137

ABSTRACT

Bacterial leaf streak caused by Xanthomonas oryzae pv. oryzicola (Xoc) is a devastating disease of rice worldwide, including China. The second messenger c-di-GMP plays an important role in the transduction of intercellular signals. However, little is known about the function of EAL domain protein in c-di-GMP that regulates the virulence in Xoc. In this study, the function of EAL domain protein encoded by pde (FE36_09715) gene in the regulation of c-di-GMP was investigated. Results of this study, showed that the deletion of pde gene led to a significant reduction in the virulence of Xoc and was positively related to the reduction of exopolysaccharides production, biofilm formation, and flagellar motility. However, these significantly impaired properties from the ∆pde mutant strain were partially recovered in the complementary strain. In addition, the deletion of pde gene in Xoc strain YM15 had no visible effect on the colony morphology, amylase, and protease activities of Xoc. It is concluded that, as a regulator for the c-di-GMP level, the pde gene plays an important role in partial biological processes in Xoc and is essential for its virulence.


Subject(s)
Biofilms , Flagella/physiology , Genes, Bacterial , Plant Diseases/microbiology , Polysaccharides, Bacterial/genetics , Xanthomonas/genetics , Gene Deletion , Polysaccharides, Bacterial/biosynthesis , Virulence , Xanthomonas/pathogenicity
16.
Am J Physiol Endocrinol Metab ; 319(2): E291-E304, 2020 08 01.
Article in English | MEDLINE | ID: mdl-32603600

ABSTRACT

Several studies have reported that health problems occur in assisted reproductive technology (ART)-conceived offspring. Recently, investigations have demonstrated that paternal environmental conditions influence offspring health. However, it is unclear whether the factors that cause male infertility per se affect offspring health and contribute to health problems in ART-born children. Scrotal heat stress represents a common cause for oligoasthenozoospermia, and in these cases, in vitro fertilization-embryo transfer (IVF-ET) is typically recommended for those individuals trying to conceive. We exposed C57BL/6J male mice to frequent and mild scrotal heat stress (fmSHS) (39°C for 30 min once weekly for 5 consecutive wk). Sperm was subjected to IVF-ET with oocytes of untreated C57BL/6J females to produce offspring mice. Glucose intolerance and insulin resistance was observed in the male offspring mice derived from fmSHS-exposed fathers. Islets, after evaluation, remained unchanged. Genes involved in glucose metabolism, especially, those in insulin signaling pathways, showed dysregulation in the liver of the fmSHS-derived male offspring. Differentially methylated regions were found in the sperm of fmSHS-exposed mice by whole genome bisulfite sequencing. Interestingly, abnormal methylation of some genes with altered expression in offspring was observed in both the sperm of fmSHS fathers and the liver of their male offspring. Our results suggest that the factors that cause male infertility can affect male offspring health by an epigenetic mechanism.


Subject(s)
Epigenesis, Genetic/physiology , Glucose/metabolism , Hot Temperature , Infertility, Male/genetics , Paternal Exposure/adverse effects , Scrotum/physiopathology , Animals , DNA Methylation , Embryo Transfer , Female , Fertilization in Vitro , Glucose Intolerance/etiology , Glucose Intolerance/pathology , Infertility, Male/etiology , Insulin Resistance/genetics , Islets of Langerhans/pathology , Male , Mice , Mice, Inbred C57BL , Nuclear Receptor Subfamily 4, Group A, Member 1/genetics , Signal Transduction/genetics
17.
Reprod Biomed Online ; 40(5): 617-626, 2020 May.
Article in English | MEDLINE | ID: mdl-32276888

ABSTRACT

RESEARCH QUESTION: Frequent and mild scrotal heat stress (fmSHS) often occurs in humans. The aim of this study was to determine the impact of fmSHS on natural fertility, the IVF-embryo transfer (IVF-ET) process and the offspring sex ratio. DESIGN: Male mice were randomly divided into four groups: no scrotal heat stress (SHS) (controls) and those subjected to SHS at 37°C, 39°C or 41°C for 30 min once a week for 5 consecutive weeks. The testis, epididymis and sperm quality were assessed to evaluate the effects of different degrees of SHS, to establish an fmSHS model. Then, natural fertility, IVF-embryo transfer (IVF-ET) results, embryo development, offspring sex ratio and the X/Y chromosome-bearing sperm ratio were examined. RESULTS: SHS at 39°C and 41°C caused mild impairment to spermatozoa, leading to a phenotype similar to oligoasthenozoospermia in humans. Given that most SHS conditions in humans are close to body temperature, SHS of 39°C was adopted to build the fmSHS model. fmSHS reduced the fertilization rate, impaired on-time development and reduced the implantation rate of the embryos in the IVF-ET process, but it did not affect the development or function of blastocysts. The fmSHS mice produced more Y chromosome-bearing spermatozoa and propagated more male offspring. CONCLUSIONS: fmSHS not only reduced the fertilization ability of spermatozoa but also influenced their function beyond fertilization, in addition to changing the offspring sex ratio. These results may help to shed new light on the infertility treatment of males with scrotal heat risk and the health concerns of offspring propagated from these fathers.


Subject(s)
Embryo Implantation/physiology , Embryonic Development/physiology , Fertility/physiology , Heat-Shock Response/physiology , Scrotum/physiology , Spermatozoa/physiology , Animals , Body Temperature/physiology , DNA Fragmentation , Female , Fertilization in Vitro , Male , Mice , Semen Analysis , Sex Ratio , Sperm Motility/physiology
18.
Am J Gastroenterol ; 115(3): 473-480, 2020 03.
Article in English | MEDLINE | ID: mdl-32142484

ABSTRACT

OBJECTIVES: Severe acute pancreatitis (SAP) is still a big challenge. Accumulated data showed that overexpression of cyclooxygenase-2 (COX-2) in acute pancreatitis and experimental pancreatitis could be attenuated with COX-2 inhibitors. This study was aimed to evaluate whether the occurrence of SAP could be prevented by selective COX-2 inhibitors. METHODS: A total of 190 patients with predicted SAP were randomized into convention group or convention plus COX-2 inhibitors (C+COX-2-Is) group. Besides conventional treatment to all patients in 2 groups, parecoxib (40 mg/d intravenous injection for 3 days) and celecoxib (200 mg oral or tube feeding twice daily for 7 days) were sequentially administrated to the patients in the C+COX-2-Is group. The primary outcome was predefined as the occurrence of SAP. The serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) for all of the patients were measured. RESULTS: The occurrence of SAP in the C+COX-2-Is group was decreased 47.08% compared with the convention group, 21.05% (20/95) vs 39.78% (37/93), P = 0.005. A reduction of late local complications was also shown in the C+COX-2-Is group, 18.95% (18/93) vs 34.41% (32/95), P = 0.016. The serum levels of IL-6 and TNF-α were significantly lower in the C+COX-2-Is group than those in the convention group, P < 0.05. Parecoxib relieved abdominal pain more rapidly and decreased the consumption of meperidine. An incremental reduction of cost for 1% decrease of SAP occurrence was RMB475. DISCUSSION: Sequential administration of parecoxib and celecoxib in patients with predicted SAP obtained about half-reduction of SAP occurrence through decreasing serum levels of TNF-α and IL-6. This regimen presented good cost-effectiveness.


Subject(s)
Celecoxib/therapeutic use , Cyclooxygenase 2 Inhibitors/therapeutic use , Isoxazoles/therapeutic use , Pancreatitis/prevention & control , Administration, Oral , Adolescent , Adult , Aged , Drug Administration Schedule , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Injections, Intravenous , Male , Middle Aged , Pancreatitis/diagnosis , Prospective Studies , Severity of Illness Index , Treatment Outcome , Young Adult
19.
Transl Cancer Res ; 9(2): 726-734, 2020 Feb.
Article in English | MEDLINE | ID: mdl-35117418

ABSTRACT

BACKGROUND: This study aimed to evaluate the correlation of A-kinase-interacting protein 1 (AKIP1) with C-X-C motif chemokine ligand (CXCL) 1 and CXCL2, and their associations with clinical characteristics and prognosis in cervical cancer patients. METHODS: One hundred and fifty early-stage cervical cancer patients treated with surgical resection were reviewed and tumor tissue samples were obtained. Expression of AKIP1, CXCL1 and CXCL2 was detected by immunohistochemistry (IHC). Data of tumor features were retrieved, and disease-free survival (DFS) as well as overall survival (OS) were calculated. RESULTS: AKIP1 expression was positively correlated with CXCL1 and CXCL2 expression in cervical cancer tissue (both P<0.001). AKIP1 expression was positively correlated with tumor size (P=0.040), lymph node (LYN) metastasis (P=0.034) and International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.021); CXCL1 expression was positively associated with tumor size (P=0.048); and CXCL2 expression was positively correlated with LYN metastasis (P=0.026). As for DFS and OS, AKIP1 high expression was correlated with worse DFS (P=0.016) and OS (P=0.007), CXCL1 high expression was associated with poor DFS (P=0.029) but not OS (P=0.118). No correlation of CXCL2 expression with DFS (P=0.141) or OS (P=0.125) was found. CONCLUSIONS: AKIP1 positively correlates with CXCL1/CXCL2, and associates with advanced tumor features as well as unfavorable survival profiles in cervical cancer patients.

20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(3): 463-468, 2018 May.
Article in Chinese | MEDLINE | ID: mdl-30014652

ABSTRACT

OBJECTIVE: To investigate drug knowledge of middle school students in HIV prone areas in Liangshan of Sichuan Province. METHODS: Students were randomly selected from the middle schools located in the HIV prone areas in Liangshan. A questionnaire survey was conducted. Drug knowledge of the respondents and associated factors were analyzed. RESULTS: Of the 10 749 respondents,10.1% had wrong knowledge about drugs. The respondents of male gender and minority ethnicity in the region and those who were in a lower grade,had poor academic records,more sisters,and a schoolmate taking drugs,and lived in a family with HIV infected member were more likely to had poor drug knowledge. By contrast,the respondents who had a peasant father,lived with both parents,resided in a city or township,self-rated in the middle and low 1/3 of wealth,lived in a community with >50% school attendance,and had a family member taking drugs were less likely to have wrong drug knowledge. CONCLUSION: Middle school students in the HIV prone areas in Liangshan have poor drug knowledge. Socioeconomic factors influence the drug knowledge of students,which require systematic interventions.


Subject(s)
Health Knowledge, Attitudes, Practice , Illicit Drugs , Students , China , Female , HIV Infections , Humans , Male , Schools , Socioeconomic Factors , Surveys and Questionnaires
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