ABSTRACT
Gastric cancer is highly prevalent in China, yet early diagnosis and overall survival rates are low. The primary treatment strategy is comprehensive therapy centered on surgery. Studies indicate that neoadjuvant chemotherapy can enhance radical resection rates and extend survival in locally advanced gastric cancer. Combining VEGFR inhibitors with chemotherapy improves efficacy in digestive system tumors, while PD-1/PD-L1 inhibitors combined with anti-angiogenesis agents or chemotherapy show synergistic effects. This report presents a case of gastric adenocarcinoma (cT3N1M0) treated with SOX, apatinib mesylate, and camrelizumab as neoadjuvant therapy, followed by D2 distal gastrectomy and postoperative adjuvant therapy with the same regimen. The patient completed all treatment cycles successfully. Post-neoadjuvant therapy, only focal residual cancer cells were found in the lamina propria (pT1a). During postoperative adjuvant therapy follow-up, gastroscopic biopsy indicated a pathological complete response with no recurrence or metastasis. The patient primarily experienced dyspepsia, oropharyngeal pain, capillary proliferation, mild bone marrow suppression, nausea, and vomiting as side effects. Therefore, SOX combined with apatinib mesylate and camrelizumab shows promise for treating resectable locally advanced gastric cancer.
Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Pyridines , Stomach Neoplasms , Humans , Stomach Neoplasms/drug therapy , Pyridines/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Gastrectomy , Male , Middle Aged , Neoadjuvant Therapy , Treatment Outcome , Adenocarcinoma/drug therapyABSTRACT
The inflammatory status of patients is closely related to their nutritional status, and the impact of inflammatory status on patients with pyloric stenosis remains unclear. The present study aimed to investigate the impact of inflammatory status on the prognosis of patients with gastric cancer with early pyloric stenosis who underwent radical resection. A retrospective analysis included 242 patients with gastric cancer who underwent radical resection at the Affiliated Hospital of Southwest Medical University between July 2016 and December 2020. All patients were diagnosed with early pyloric stenosis. Correlation analysis was used to assess variations among different factors, and survival analysis was conducted to evaluate differences in overall survival (OS). To identify independent prognostic indicators, both univariate and multivariate Cox regression analyses were performed, addressing potential multicollinearity using Lasso analysis. Propensity score matching (PSM) was employed to eliminate potential confounding factors. Additionally, a prognostic risk model and nomogram based on inflammatory indicators were developed to comprehensively explore their impact on prognosis. Initial survival analysis revealed significant associations between neutrophil-to-lymphocyte ratio (NLR; χ2=10.522, P<0.001), systemic immune-inflammation index (SII; χ2=6.733, P=0.025), systemic inflammation response index (SIRI; χ2=15.490, P<0.001) and OS of the patients, while there was no significant survival difference among patients with different platelet-to-lymphocyte ratio (PLR; χ2=2.561, P=0.050). SIRI not only had the highest area under the curve but was also found to be an independent prognostic indicator (hazard ratio=1.851, P=0.046) in the present study. Following PSM on SIRI, a total of 174 patients were included in the subsequent analysis. Time-receiver operating characteristic and survival curves for SIRI after PSM consistently demonstrated its robust prognostic predictive capability. Furthermore, the prognostic risk model based on SIRI and the nomogram incorporating SIRI both exhibited high prognostic value. Inflammatory status was significantly associated with the prognosis of patients with gastric cancer with early pyloric stenosis who underwent radical resection. The NLR, SII and SIRI could all predict patient outcomes. Moreover, SIRI exhibited the highest prognostic value among the inflammatory indices and has been identified as an independent prognostic factor in the present study.
ABSTRACT
BACKGROUND: ATPase activity and the antioxidant function of intestinal tissue can reflect intestinal cell metabolic activity and oxidative damage, which might be related to intestinal function. However, the specific influence of intestinal ATPase activity and antioxidant function on growth performance, feed conversion efficiency, and the intestinal microbiota in sheep remains unclear. RESULTS: This study analyzed the correlation between ATPase activity and antioxidant function in the jejunum of 92 Hu sheep and their growth performance and feed conversion efficiency. Additionally, individuals with the highest (H group) and lowest (L group) jejunum MDA content and Na+ K+-ATPase activity were further screened, and the effects of jejunum ATPase activity and MDA content on the morphology and microbial community of sheep intestines were analyzed. There was a significant correlation between jejunum ATPase and SOD activity and the initial weight of Hu sheep (P < 0.01). The H-MDA group exhibited significantly higher average daily gain (ADG) from 0 to 80 days old and higher body weight (BW) after 80 days. ATPase and SOD activities, and MDA levels correlated significantly and positively with heart weight. The jejunum crypt depth and circular muscle thickness in the H-ATP group were significantly higher than in the L-ATP group, and the villus length, crypt depth, and longitudinal muscle thickness in the H-MDA group were significantly higher than in the L-MDA group (P < 0.01). High ATPase activity and MDA content significantly reduced the jejunum microbial diversity, as indicated by the Chao1 index and observed species, and affected the relative abundance of specific taxa. Among species, the relative abundance of Olsenella umbonata was significantly higher in the H-MDA group than in the L-MDA group (P < 0.05), while Methanobrevibacter ruminantium abundance was significantly lower than in the L-MDA group (P < 0.05). In vitro culture experiments confirmed that MDA promoted the proliferation of Olsenella umbonata. Thus, ATPase and SOD activities in the jejunum tissues of Hu sheep are predominantly influenced by congenital factors, and lambs with higher birth weights exhibit lower Na+ K+-ATPase, Ca2+ Mg2+-ATPase, and SOD activities. CONCLUSIONS: The ATPase activity and antioxidant performance of intestinal tissue are closely related to growth performance, heart development, and intestinal tissue morphology. High ATPase activity and MDA content reduced the microbial diversity of intestinal tissue and affect the relative abundance of specific taxa, representing a potential interaction between the host and its intestinal microbiota.
Subject(s)
Adenosine Triphosphatases , Antioxidants , Gastrointestinal Microbiome , Jejunum , Animals , Jejunum/microbiology , Jejunum/enzymology , Antioxidants/metabolism , Gastrointestinal Microbiome/physiology , Adenosine Triphosphatases/metabolism , Sheep , Male , Malondialdehyde/metabolism , Superoxide Dismutase/metabolismABSTRACT
BACKGROUND: Human hematopoietic organoids have a wide application value for modeling human bone marrow diseases, such as acute hematopoietic radiation injury. However, the manufacturing of human hematopoietic organoids is an unaddressed challenge because of the complexity of hematopoietic tissues. METHODS: To manufacture hematopoietic organoids, we obtained CD34+ hematopoietic stem and progenitor cells (HSPCs) from human embryonic stem cells (hESCs) using stepwise induction and immunomagnetic bead-sorting. We then mixed these CD34+ HSPCs with niche-related cells in Gelatin-methacryloyl (GelMA) to form a three-dimensional (3D) hematopoietic organoid. Additionally, we investigated the effects of radiation damage and response to granulocyte colony-stimulating factor (G-CSF) in hematopoietic organoids. RESULTS: The GelMA hydrogel maintained the undifferentiated state of hESCs-derived HSPCs by reducing intracellular reactive oxygen species (ROS) levels. The established hematopoietic organoids in GelMA with niche-related cells were composed of HSPCs and multilineage blood cells and demonstrated the adherence of hematopoietic cells to niche cells. Notably, these hematopoietic organoids exhibited radiation-induced hematopoietic cell injury effect, including increased intracellular ROS levels, γ-H2AX positive cell percentages, and hematopoietic cell apoptosis percentages. Moreover, G-CSF supplementation in the culture medium significantly improved the survival of HSPCs and enhanced myeloid cell regeneration in these hematopoietic organoids after radiation. CONCLUSIONS: These findings substantiate the successful manufacture of a preliminary 3D hematopoietic organoid from hESCs-derived HSPCs, which was utilized for modeling hematopoietic radiation injury and assessing the radiation-mitigating effects of G-CSF in vitro. Our study provides opportunities to further aid in the standard and scalable production of hematopoietic organoids for disease modeling and drug testing.
Subject(s)
Granulocyte Colony-Stimulating Factor , Hematopoietic Stem Cells , Organoids , Humans , Organoids/metabolism , Organoids/drug effects , Hematopoietic Stem Cells/metabolism , Hematopoietic Stem Cells/drug effects , Hematopoietic Stem Cells/cytology , Granulocyte Colony-Stimulating Factor/pharmacology , Human Embryonic Stem Cells/cytology , Human Embryonic Stem Cells/metabolism , Reactive Oxygen Species/metabolism , Regeneration/drug effects , Cell Differentiation/drug effects , Antigens, CD34/metabolismABSTRACT
Cotton Verticillium wilt is mainly caused by the fungus Verticillium dahliae, which threatens the production of cotton. Its pathogen can survive in the soil for several years in the form of microsclerotia, making it a destructive soil-borne disease. The accurate, sensitive, and rapid detection of V. dahliae from complex soil samples is of great significance for the early warning and management of cotton Verticillium wilt. In this study, we combined the loop-mediated isothermal amplification (LAMP) with CRISPR/Cas12a technology to develop an accurate, sensitive, and rapid detection method for V. dahliae. Initially, LAMP primers and CRISPR RNA (crRNA) were designed based on a specific DNA sequence of V. dahliae, which was validated using several closely related Verticillium spp. The lower detection limit of the LAMP-CRISPR/Cas12a combined with the fluorescent visualization detection system is approximately ~10 fg/µL genomic DNA per reaction. When combined with crude DNA-extraction methods, it is possible to detect as few as two microsclerotia per gram of soil, with the total detection process taking less than 90 min. Furthermore, to improve the method's user and field friendliness, the field detection results were visualized using lateral flow strips (LFS). The LAMP-CRISPR/Cas12a-LFS system has a lower detection limit of ~1 fg/µL genomic DNA of the V. dahliae, and when combined with the field crude DNA-extraction method, it can detect as few as six microsclerotia per gram of soil, with the total detection process taking less than 2 h. In summary, this study expands the application of LAMP-CRISPR/Cas12a nucleic acid detection in V. dahliae and will contribute to the development of field-deployable diagnostic productions.
Subject(s)
CRISPR-Cas Systems , Nucleic Acid Amplification Techniques , Plant Diseases , Soil Microbiology , Nucleic Acid Amplification Techniques/methods , Plant Diseases/microbiology , Ascomycota/genetics , Ascomycota/isolation & purification , Molecular Diagnostic Techniques/methods , Gossypium/microbiology , DNA, Fungal/genetics , DNA, Fungal/isolation & purification , Verticillium/geneticsABSTRACT
Incontinentia pigmenti (IP) is a rare X-linked dominant neuroectodermal dysplasia that primarily affects females. The only known causative gene is IKBKG, and the most common genetic cause is the recurrent IKBKGâ³4-10 deletion resulting from recombination between two MER67B repeats. Detection of variants in IKBKG is challenging due to the presence of a highly homologous non-pathogenic pseudogene IKBKGP1. In this study, we successfully identified four pathogenic variants in four IP patients using a strategy based on single-tube long fragment read (stLFR) sequencing with a specialized analysis pipeline. Three frameshift variants (c.519-3_519dupCAGG, c.1167dupC, and c.700dupT) were identified and subsequently validated by Sanger sequencing. Notably, c.519-3_519dupCAGG was found in both IKBKG and IKBKGP1, whereas the other two variants were only detected in the functional gene. The IKBKGâ³4-10 deletion was identified and confirmed in one patient. These results demonstrate that the proposed strategy can identify potential pathogenic variants and distinguish whether they are derived from IKBKG or its pseudogene. Thus, this strategy can be an efficient genetic testing method for IKBKG. By providing a comprehensive understanding of the whole genome, it may also enable the exploration of other genes potentially associated with IP. Furthermore, the strategy may also provide insights into other diseases with detection challenges due to pseudogenes.
ABSTRACT
This retrospective cohort study aimed to determine the prevalence of anemia among patients with gynecological cancer prior to any treatment and to identify contributing factors associated with anemia in this group. We retrospectively analyzed data from female patients aged 18 and above, diagnosed with various forms of gynecological cancer at The Affiliated Hospital of Southwest Medical University between February 2016 and March 2021. Anemia was assessed based on the most recent CBC results before any cancer treatment. Eligibility was based on a definitive histopathological diagnosis. Key variables included demographic details, clinical characteristics, and blood counts, focusing on hemoglobin levels. Statistical analysis was conducted using logistic regression models, and anemia was defined as hemoglobin levels below 12 g/dL for women, according to WHO criteria. Of the 320 participants, a significant prevalence of anemia was found. Correlations between anemia and factors like age, educational level, and biological markers (iron, folic acid, and vitamin B12 levels) were identified. In our study, we found that the prevalence of anemia among patients with gynecological cancer prior to any treatment was 59.06%, indicating a significant health concern within this population. The study highlights a significant prevalence of anemia in patients with gynecological cancer, emphasizing the need for regular hemoglobin screening and individualized management. These findings suggest the importance of considering various characteristics and clinical variables in anemia management among this patient group. Further studies are needed to explore the long-term effects of these factors on patient outcomes and to develop targeted interventions.
Subject(s)
Anemia , Genital Neoplasms, Female , Humans , Female , Anemia/epidemiology , Retrospective Studies , Middle Aged , Prevalence , Genital Neoplasms, Female/epidemiology , Genital Neoplasms, Female/complications , Adult , Aged , Hemoglobins/analysis , Hemoglobins/metabolism , Risk FactorsABSTRACT
Metastatic colon cancer remains an incurable disease, and it is difficult for existing treatments to achieve the desired clinical outcome, especially for colon cancer patients who have received first-line treatment. Although immune checkpoint inhibitors (ICIs) have demonstrated durable clinical efficacy in a variety of solid tumors, their response requires an inflammatory tumor microenvironment. However, microsatellite-stable (MSS) colon cancer, which accounts for the majority of colorectal cancers, is a cold tumor that does not respond well to ICIs. Combination regimens open the door to the utility of ICIs in cold tumors. Although combination therapies have shown their advantage even for MSS colon cancer, it remains unclear whether combination therapies show their advantage in patients with pretreated metastatic colon cancer. We report a patient who has achieved complete remission and good tolerance with sintilimab plus bevacizumab and platinum-based chemotherapy after postoperative recurrence. The patient had KRAS mutation and MSS-type colon cancer, and his PD-1+CD8+ and CD3-CD19-CD14+CD16-HLA-DR were both positive. He has achieved a progression-free survival of 43 months and is still being followed up at our center. The above results suggest that this therapeutic regimen is a promising treatment modality for the management of pretreated, MSS-type and KRAS-mutated metastatic colorectal cancer although its application to the general public still needs to be validated in clinical trials.
Subject(s)
Antibodies, Monoclonal, Humanized , Colonic Neoplasms , Proto-Oncogene Proteins p21(ras) , Male , Humans , Bevacizumab/therapeutic use , Proto-Oncogene Proteins p21(ras)/genetics , Pathologic Complete Response , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Platinum , Microsatellite Repeats , Tumor MicroenvironmentABSTRACT
As a crucial economic trait, fat deposition is directly related to carcass quality and feed efficiency in sheep. The purpose of this study was to investigate the polymorphisms of the FGB gene related to fat deposition and detect the expression features of the FGB gene in different adipose tissues of sheep by using Sanger sequencing, MassARRAY® SNP technique, and quantitative real-time PCR (qRT-PCR). Results showed that in the intron region of the FGB gene, a SNP g. 3378953 A > T has been identified, and significant association was found between perirenal fat weight, perirenal fat relative weight, mesenteric fat weight, and mesenteric fat relative weight (P < 0.05). Moreover, qRT-PCR analysis showed that FGB was expressed in all three adipose tissues, and FGB gene expression level in the AA genotype was significantly lower than that in the AT or TT genotypes (P < 0.05). Therefore, the FGB gene can be used as a candidate gene to reduce fat deposition in Hu sheep breeding, and the selection of the AA genotype in Hu sheep in production practice is more conducive to improving production efficiency.
Subject(s)
Adipose Tissue , Polymorphism, Single Nucleotide , Animals , Polymorphism, Single Nucleotide/genetics , Adipose Tissue/metabolism , Sheep/genetics , Sheep/physiology , Genotype , Sheep, Domestic/genetics , Sheep, Domestic/physiology , Male , Female , BreedingABSTRACT
BACKGROUD: To investigate the factors influencing fertility quality of life in infertile men, constructing a structural equation model of the factors influencing fertility quality of life in infertile men, and to provide suggested measures for improving fertility quality of life in infertile men. METHODS: It is a Observational study. Infertile men (n = 250) attending a fertility centre in a hospital in Xinjiang, matched 1:2 men with no obvious male factor in the control group (n = 500).The Quality of Fertility Life Scale, the Social Support Scale, the Fertility Stress Scale and the Positive Attention Awareness Scale were used to conduct the survey. The model was constructed by applying the maximum likelihood estimation method in Mplus 8.3 software, to explore the factors influencing the quality of reproductive life of infertile men through path analyses. Differences between the case and control groups were statistically significant (P < 0.05) in terms of total fertility quality of life scores, core entry dimensions, affective responses, physical and mental relationships, selective treatment dimensions, and treatment tolerance. RESULTS: Past medical history, history of exposure to hazardous environments, health insurance reimbursement, social support, fertility stress, and mindfulness are important factors affecting the quality of fertility life of infertile men. CONCLUSION: The quality of fertility life of infertile men is not optimistic. By improving the level of mindfulness, fertility stress, and social support, we propose appropriate measures to improve the quality of fertility life of infertile men. These measures can improve their confidence in clinical diagnosis and infertility treatment, enabling them to cope positively with these challenges.
Subject(s)
Infertility , Quality of Life , Humans , Male , Quality of Life/psychology , Cross-Sectional Studies , Fertility , Infertility/psychology , Surveys and QuestionnairesABSTRACT
Platinum (Pt) supported on high surface area carbon has been the most widely used electrocatalyst in proton exchange membrane fuel cell (PEMFC). However, conventional carbon supports are susceptible to corrosion at high potentials, leading to severe degradation of electrochemical performance. In this work, titanium carbonitride embedded in mesoporous carbon nanofibers (m-TiCN NFs) are reported as a promising alternative to address this issue. Benefiting from the interpenetrating conductive pathways inside the one-dimensional (1D) nanostructures and the embedded TiCN nanoparticles (NPs), m-TiCN NFs exhibit excellent stability at high potentials and interact strongly with Pt NPs. Subsequently, m-TiCN NFs-supported Pt NPs deliver remarkably enhanced oxygen reduction reaction (ORR) activity and durability, with negligible activity decay and less than 5% loss of electrochemical surface areaï¼ECSAï¼ after 50 000 cycles. Moreover, the fuel cell assembled by this catalyst delivers a maximum power density of 1.22 W cm-2 and merely 3% loss after 30 000 cycles of accelerated durability tests under U.S. Department of Energy (DOE) protocols. The improved ORR activity and durability are attributed to the superior corrosion resistance of the m-TiCN NF support and the strong interaction between Pt and m-TiCN NFs.
ABSTRACT
This study aimed to scrutinize the relationship between physical exercise and hypertension, taking into account multiple variables such as age, body mass index (BMI), family history, smoking, and alcohol consumption in the Southern Sichuan population, China, using a retrospective approach based on hospital record data. This retrospective study analyzed data from 946 participants obtained from a hospital electronic medical record system. The data included information regarding participants' lifestyle factors, family history, and a clinical diagnosis of hypertension. Univariate and multivariate logistic regression models were employed to identify the association between lifestyle factors and hypertension. The study found a hypertension prevalence of 38.5% in the analyzed population. Multivariate analyses identified significant factors associated with hypertension as age (odds ratio [OR]: 1.045, 95% confidence interval [CI]: 1.036-1.054), BMI (OR: 1.107, 95% CI: 1.084-1.132), smoking (OR: 2.299, 95% CI: 1.674-3.157), alcohol consumption (OR: 0.644, 95% CI: 0.478-0.867), and physical exercise (OR: 0.682, 95% CI: 0.506-0.920). Findings from this hospital record-based retrospective study reinforce the multifactorial nature of hypertension. They highlight the significance of physical exercise, along with maintaining optimal BMI and encouraging healthy habits like nonsmoking and moderate alcohol consumption in hypertension prevention. Our findings also underscore the need for future prospective studies to establish causality and explore the generalizability of these results beyond the Southern Sichuan population.
Subject(s)
Exercise , Hypertension , Humans , Prospective Studies , Retrospective Studies , Health Behavior , Hypertension/epidemiologyABSTRACT
Human pluripotent stem cell (hPSC)-derived red blood cells (RBCs) possess great potential for compensating shortages in transfusion medicine. For better RBC generation from hPSCs, we compared the cell seeding density in the embryoid body formation-based hPSC induction protocol. In the selection of low- and high-density inoculation conditions, we found that low-density culture performed better in the final RBC product with more cell output and increased average cellular hemoglobin content. An elaborate study using flow cytometry demonstrated that low inoculation density promoted endothelial-to-hematopoietic transition, followed by improved hematopoietic progenitor formation and erythrocyte generation. The improved transformation from glycolysis to mitochondrial oxidation and reduced apoptosis might be responsible for this effect. Hints from RNA sequencing suggested that molecules involved in microenvironment interaction and metabolic regulation might respond for the different developmental potential. The possible mediators between outer message and intracellular response could be the nutrition sensors FOXO, PRKAA1 (AMPK), and MTOR genes. It is possible that low inoculation density triggered metabolic regulation signals, promoted mitochondrial oxidation, and resulted in enhanced cell amplification and hematopoietic differentiation. The low cell culture density will improve RBC generation from hPSCs.
Subject(s)
Cell Differentiation , Erythrocytes , Pluripotent Stem Cells , Humans , Erythrocytes/cytology , Erythrocytes/metabolism , Pluripotent Stem Cells/cytology , Pluripotent Stem Cells/metabolism , Cell Count , Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/metabolism , Mitochondria/metabolismABSTRACT
Ticks are one of the most important vectors that can transmit pathogens to animals and human beings. This study investigated the dominant tick-borne bacteria carried by ticks and tick-borne infections in forestry populations in Arxan, Inner Mongolia, China. Ticks were collected by flagging from May 2020 to May 2021, and blood samples were collected from individuals at high risk of acquiring tick-borne diseases from March 2022 to August 2023. The pooled DNA samples of ticks were analyzed to reveal the presence of tick-borne bacteria using high-throughput sequencing of the 16S rDNA V3-V4 region, and species-specific polymerase chain reaction (PCR) related to sequencing was performed to confirm the presence of pathogenic bacteria in individual ticks and human blood samples. All sera samples were examined for anti-SFGR using ELISA and anti-B. burgdorferi using IFA and WB. A total of 295 ticks (282 Ixodes persulcatus and 13 Dermacentor silvarum) and 245 human blood samples were collected. Rickettsia, Anaplasma, Borrelia miyamotoi, and Coxiella endosymbiont were identified in I. persulcatus by high-throughput sequencing, while Candidatus R. tarasevichiae (89.00%, 89/100), B. garinii (17.00%, 17/100), B. afzelii (7.00%, 7/100), and B. miyamotoi (7.00%, 7/100) were detected in I. persulcatus, as well the dual co-infection with Candidatus R. tarasevichiae and B. garinii were detected in 13.00% (13/100) of I. persulcatus. Of the 245 individuals, B. garinii (4.90%, 12/245), R. slovaca (0.82%, 2/245), and C. burnetii (0.41%, 1/245) were detected by PCR, and the sequences of the target genes of B. garinii detected in humans were identical to those detected in I. persulcatus. The seroprevalence of anti-SFGR and anti-B. burgdorferi was 5.71% and 13.47%, respectively. This study demonstrated that Candidatus R. tarasevichiae and B. garinii were the dominant tick-borne bacteria in I. persulcatus from Arxan, and that dual co-infection with Candidatus R. tarasevichiae and B. garinii was frequent. This is the first time that B. miyamotoi has been identified in ticks from Arxan and R. solvaca has been detected in humans from Inner Mongolia. More importantly, this study demonstrated the transmission of B. garinii from ticks to humans in Arxan, suggesting that long-term monitoring of tick-borne pathogens in ticks and humans is important for the prevention and control of tick-borne diseases.
Subject(s)
Coinfection , Ixodes , Tick-Borne Diseases , Animals , Humans , Forestry , Seroepidemiologic Studies , Ixodes/microbiology , Tick-Borne Diseases/epidemiology , Tick-Borne Diseases/microbiologyABSTRACT
Introduction: Currently in China, there is a lack of well-defined and viable incentive mechanisms at the governmental and hospital levels to support the development of young medical talents, thereby hindering their growth Existing studies primarily investigate the current state and trajectory of incentives, yet they inadequately address the distinctive characteristics of various stakeholders involved in medical talent incentive processes, particularly the lack of research on incentive mechanisms with Chinese attributes. Methods: This study adopts evolutionary game theory to investigate the dynamics of replication and the strategies for achieving evolutionary stability in the comprehensive development of young medical talents, considering both scenarios with and without supportive policies. Results: In the absence of any supportive policy measures, the evolutionarily stable strategy (ESS) point is O(0,0), the unstable equilibrium point is C(1,1), and the saddle points are A(0,1), B(1,0). The initial state of the system is at the unstable equilibrium point C(1,1), which means that the young medical talents and medical institutions adopt a combination of strategies (actively seeking comprehensive development and taking incentive measures). Under the scenario with supportive policies, the ESS point is C(1,1), the unstable equilibrium point is O(0,0), and the saddle points are A(0,1), B(1,0). The initial state of the system is at the unstable equilibrium point O(0,0), which means that young medical talents and medical institutions adopt (N,N) strategy combinations (inactively seeking comprehensive development, implementing no incentive measure). Discussion: (1) Government incentives play a crucial role in motivating young medical talents to seek comprehensive development. (2) The level of government incentive support for young medical talents should exceed the cost increment of individual efforts. Additionally, the policy support provided by the government to medical institutions should surpass the incentive support offered by these institutions to young medical talents. This will enhance the motivation and encouragement efforts of medical institutions in actively promoting comprehensive development among young medical talents. (3) With the backing of certain government incentive policies, medical institutions implementing incentive measures and young medical talents actively seeking comprehensive development will establish a virtuous cycle of mutual promotion.
Subject(s)
Motivation , Policy , Government , Game Theory , ChinaABSTRACT
In recent years, the microbiome has shown an integral role in cancer immunotherapy and has become a prominent and widely studied topic. A full understanding of the interactions between the tumor microbiome and various immunotherapies offers opportunities for immunotherapy of cancer. This review scrutinizes the composition of the tumor microbiome, the mechanism of microbial immune regulation, the influence of tumor microorganisms on tumor metastasis, and the interaction between tumor microorganisms and immunotherapy. In addition, this review also summarizes the challenges and opportunities of immunotherapy through tumor microbes, as well as the prospects and directions for future related research. In conclusion, the potential of microbial immunotherapy to enhance treatment outcomes for cancer patients should not be underestimated. Through this review, it is hoped that more research on tumor microbial immunotherapy will be done to better solve the treatment problems of cancer patients.
Subject(s)
Microbiota , Neoplasms, Second Primary , Neoplasms , Humans , Neoplasms/therapy , Immunotherapy , Treatment OutcomeABSTRACT
Phosphodiesterase 9A (PDE9A) plays a crucial role in activating the cGMP-dependent signaling pathway and may have important effects on the growth and development of the gastrointestinal tract in Hu sheep. In this study, we analyzed the single nucleotide polymorphisms of PDE9A in 988 Hu sheep and their correlation with growth performance, feed efficiency, and gastrointestinal development. Additionally, we examined the expression level of different PDE9A genotypes in the gastrointestinal tract of Hu sheep by using fluorescence quantitative PCR. The results revealed a moderate level of polymorphism (0.25 < PIC < 0.50) at the g.286248617 T > C mutation site located in the first intron of PDE9A in Hu sheep, with three genotypes: CC, CT, and TT. The weights of the omasum, colon, and cecum were significantly greater in the CC genotype than in the TT genotype (P < 0.05), and the expression level of PDE9A in the tissues of the rumen, ileum, cecum, and colon was notably lower in the CC genotype individuals (P < 0.05). These findings suggest that the polymorphism of PDE9A affects the weight of the stomach, colon, and cecum in Hu sheep through expression regulation. Overall, the results of this study suggest that the g.286248617 T > C mutation site in the first intron of PDE9A can serve as a potential molecular marker for breeding practices related to the gastrointestinal weight of Hu sheep.
Subject(s)
Breeding , Polymorphism, Single Nucleotide , Animals , 3',5'-Cyclic-AMP Phosphodiesterases/genetics , Gastrointestinal Tract , Genotype , Sheep/geneticsABSTRACT
Ventilator-associated pneumonia (VAP) is a serious complication in neonates requiring mechanical ventilation. This study aimed to determine the risk factors associated with the development of VAP in neonates admitted to the neonatal intensive care unit (NICU) of the Affiliated Hospital of Southwest Medical University. In a retrospective observational study, neonates admitted to the NICU from 1 January 2019, to 31 December 2021, requiring ventilation for more than 48 h were included. Neonates who died within 48 h of NICU admission, those without obtainable consent, or identified with a genetic syndrome were excluded. Various neonatal and clinical variables were evaluated. Univariate and multivariate analyses were performed to determine risk factors associated with VAP. Of the total neonates included, several risk factors were identified for VAP, such as being a premature infant and use of dexamethasone and sedatives. Moreover, reintubation was found to decrease the risk of VAP. Some factors like gestational age, birth weight, Apgar scores at 5 min, and other parameters were found not significantly associated with the development of VAP. The study identified several risk factors associated with the development of VAP in neonates. Recognizing these risk factors could help in the prevention and early management of VAP, thus improving the prognosis for these patients. Further studies are needed to validate these findings and explore the mechanistic links between these factors and VAP.
Subject(s)
Pneumonia, Ventilator-Associated , Infant, Newborn , Infant , Humans , Pneumonia, Ventilator-Associated/epidemiology , Pneumonia, Ventilator-Associated/drug therapy , Pneumonia, Ventilator-Associated/etiology , Retrospective Studies , Respiration, Artificial/adverse effects , Birth Weight , Risk FactorsABSTRACT
Ovarian cancer (OC) is one of the most common and recurring malignancies in gynecology. Patients with relapsed OC always develop "cascade drug resistance" (CDR) under repeated chemotherapy, leading to subsequent failure of chemotherapy. To overcome this challenge, amphiphiles (P1) carrying a nitric oxide (NO) donor (Isosorbide 5-mononitrate, ISMN) and high-density disulfide are synthesized for encapsulating mitochondria-targeted tetravalent platinum prodrug (TPt) to construct a nanocomposite (INP@TPt). Mechanism studies indicated that INP@TPt significantly inhibited drug-resistant cells by increasing cellular uptake and mitochondrial accumulation of platinum, depleting glutathione, and preventing apoptosis escape through generating highly toxic peroxynitrite anion (ONOO-). To better replicate the microenvironmental and histological characteristics of the drug resistant primary tumor, an OC patient-derived tumor xenograft (PDXOC) model in BALB/c nude mice was established. INP@TPt showed the best therapeutic effects in the PDXOC model. The corresponding tumor tissues contained high ONOO- levels, which were attributed to the simultaneous release of O2â¢- and NO in tumor tissues. Taken together, INP@TPt-based systematic strategy showed considerable potential and satisfactory biocompatibility in overcoming platinum CDR, providing practical applications for ovarian therapy.
ABSTRACT
Introduction: The adverse effects of high glucose on embryos can be traced to the preimplantation stage. This study aimed to observe the effect of high glucose on early-stage embryos. Methods and results: Seven-week-old ICR female mice were superovulated and mated, and the zygotes were collected. The zygotes were randomly cultured in 5 different glucose concentrations (control, 20mM, 40mM, 60mM and 80mM glucose). The cleavage rate, blastocyst rate and total cell number of blastocyst were used to assess the embryo quality. 40 mM glucose was selected to model high glucose levels in this study. 40mM glucose arrested early embryonic development, and the blastocyst rate and total cell number of the blastocyst decreased significantly as glucose concentration was increased. The reduction in the total cell number of blastocysts in the high glucose group was attributed to decreased proliferation and increased cell apoptosis, which is associated with the diminished expression of GLUTs (GLUT1, GLUT2, GLUT3). Furthermore, the metabolic characterization of blastocyst culture was observed in the high-glucose environment. Discussion: The balance of glycolysis and oxidative phosphorylation at the blastocyst stage was disrupted. And embryo development arrest due to high glucose is associated with changes in glycolysis and oxidative phosphorylation, as well as abnormalities in the TCA cycle and amino acid metabolism.