The effects and mechanisms of heat stress on mammalian oocyte and embryo development.

The sum of nonspecific physiological responses exhibited by mammals in response to the disruption of thermal balance caused by high-temperature environments is referred to as heat stress (HS). HS affects the normal development of mammalian oocyte and embryos and leads to significant economic losses. Therefore, it is of great importance to gain a deep understanding of the mechanisms underlying the effects of HS on oocyte and embryonic development and to explore strategies for mitigating or preventing its detrimental impacts in the livestock industry. This article provides an overview of the negative effects of HS on mammalian oocyte growth, granulosa cell maturation and function, and embryonic development. It summarizes the mechanisms by which HS affects embryonic development, including generation of reactive oxygen species (ROS), endocrine disruption, the heat shock system, mitochondrial autophagy, and molecular-level alterations. Furthermore, it discusses various measures to ameliorate the effects of HS, such as antioxidant use, enhancement of mitochondrial function, gene editing, cultivating varieties possessing heat-resistant genes, and optimizing the animals'rearing environment. This article serves as a valuable reference for better understanding the relationship between HS and mammalian embryonic development as well as for improving the development of mammalian embryos and economic benefits under HS conditions in livestock production.

[Investigation of tick - borne Rickettsia in selected areas of Liupanshui City, Guizhou Province in 2023].

OBJECTIVE: To investigate the prevalence of tick-borne rickettsial infections in selected areas of Liupanshui City, Guizhou Province, 2023, so as to provide insights into the management of tick-borne rickettsioses in the city. METHODS: Ticks were captured from the body surface of bovines and sheep in Gaoxing Village, Dashan Township, Liupanshui City, Guizhou Province during the period between April and June, 2023, and tick species were identified using morphological and molecular biological techniques. In addition, tick-borne Rickettsia was identified using a nested PCR assay, including spotted fever group rickettsiae (SFGR), Coxiella spp., Anaplasma spp., Ehrlichia spp., and Orientia spp., and positive amplified fragments were sequenced and aligned with known sequences accessed in the GenBank database. RESULTS: A total of 200 ticks were collected and all tick species were identified as Rhipicephalus microplus. Nestle PCR assay combined with sequencing identified ticks carrying Candidatus Rickettsia jingxinensis (40.50%), Coxiella burnetii (1.50%), and Coxiella-like endosymbionts (27.00%), and Anaplasma spp., Ehrlichia spp. or Orientsia spp. was not detected. CONCLUSIONS: R. microplus carried Candidatus R. jingxinensis, C. burnetii, and Coxiella-like endosymbionts in selected areas of Liupanshui City, Guizhou Province. Intensified monitoring of tickborne rickettsial infections is needed in livestock and humans to reduce the damages caused by rickettsioses.

MRI-based bone marrow radiomics for predicting cytogenetic abnormalities in multiple myeloma.

AIM: To develop a radiomics signature applied to magnetic resonance imaging (MRI)-images to predict cytogenetic abnormalities in multiple myeloma (MM). MATERIALS AND METHODS: Patients with newly diagnosed MM were enrolled retrospectively from March 2019 to September 2022. They were categorised into the high-risk cytogenetics (HRC) group and standard-risk cytogenetics (SRC) group. The patients were allocated randomly at a ratio of 7:3 into training and validation cohorts. Volumes of interest (VOI) was drawn manually on fat suppression T2-weighted imaging (FS-T2WI) and copied to the same location of the T1-weighted imaging (T1WI) sequence. Radiomics features were extracted from two sequences and selected by reproducibility and redundant analysis. The least absolute shrinkage selection operation (LASSO) algorithm was applied to build the radiomics signatures. The performance of the radiomics signatures to distinguish HRC with SRC was evaluated by ROC curves. The area under the curve (AUC), specificity, and sensitivity were also calculated. RESULTS: A total of 105 MM patients were enrolled in this study. The four and 11 most significant and relevant features were selected separately from T1WI and FS-T2WI sequences to build the radiomics signatures based on the training cohort. Compared to the T1WI sequence, the radiomics signature based on the FS-T2WI sequence achieved better performance with AUCs of 0.896 and 0.729 in the training and validation cohorts respectively. A sensitivity of 0.833, specificity of 0.667, and Youden index of 0.500 were achieved for the FS-T2WI radiomics signature in the validation cohort. CONCLUSIONS: The radiomics signature based on MRI provides a non-invasive and convenient tool to predict cytogenetic abnormalities in MM patients.

[Pathogenic characteristics and influence factors of bloodstream infection-induced severe sepsis in pediatric intensive care unit].

Objective: To summarize the pathogenic characteristics of bloodstream infection (BSI)-induced severe sepsis and analyze the influence factors in pediatric intensive care unit (PICU). Methods: Pediatric patients who were diagnosed with severe sepsis caused by BSI in the PICU of Children's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2016 to December 2021 were retrospectively selected and divided into survival group and death group according to their discharge outcomes. Clinical characteristics, laboratory parameters, pathogenic characteristics and drug resistance of the patients were collected. The characteristics of pathogens, clinical and laboratory indicators were summarized, and the influencing factors of death in children with severe sepsis caused by BSI were analyzed based on binary multivariate logistic regression. Results: A total of 132 patients, aged [M (Q1, Q3)] 36 (10, 119) months, with BSI-induced severe sepsis were enrolled in this study, including 81 males and 51 females. There were 38 cases aged 36 (15, 120) months in the death group, including 23 males and 15 females. There were 94 cases, aged 36 (8, 108) months, in the survival group, including 58 males and 36 females. A total of 132 strains of pathogens were isolated, including 87 strains (65.9%) of Gram-negative bacteria. The top 5 pathogens were Klebsiella pneumoniae (24 cases, 18.2%), Escherichia coli (17 cases, 12.9%), Acinetobacter baumannii (13 cases, 9.8%), Pseudomonas aeruginosa (10 cases, 7.6%) and Staphylococcus aureus (10 cases, 7.6%). The proportion of multi-drug resistant bacteria in hospital-acquired BSI was higher than that in community-acquired BSI [52.9% (36/68) vs 15.6% (10/64), P=0.001]. The proportions of community-acquired infection were 58.5% (55/94) and 23.7% (9/38) in the survival and death groups, respectively, the difference was statistically significant (P<0.001). The proportion of central venous catheter insertion before bloodstream infection in the death group was higher than that in the survival group [63.2% (24/38) vs 42.6% (40/94), P=0.034]. According to the binary multivariate logistic regression analysis, hospital-acquired infection (OR=4.80, 95%CI: 1.825-12.621, P=0.001), absolute neutrophil count (ANC) (OR=0.93, 95%CI: 0.863-0.993, P=0.030) and decreased albumin (OR=0.89, 95%CI: 0.817-0.977, P=0.014) were risk factors for death. Conclusions: The common pathogen of BSI-induced severe sepsis in PICU is Gram-negative bacteria. The proportion of multi-drug resistant organisms of BSI obtained in hospitals is high. Children with severe sepsis due to BSI with nosocomial acquired infection, ANC and decreased albumin have a high risk of death.

Intraperitoneal PD-1 monoclonal antibody for the treatment of advanced primary liver cancer with malignant ascites: a single-arm, single-center, phase Ib trial.

BACKGROUND: Advanced primary liver cancer patients with malignant ascites have a poor prognosis and lack effective treatment plans. This phase Ib study aims to explore the safety and clinical efficacy of intraperitoneal anti-programmed cell death protein 1 (PD-1) antibody in these patients. PATIENTS AND METHODS: Patients received sintilimab 100 mg intraperitoneally plus best supportive care on days 1, 8, and 15 in three cycles of 4 weeks. The course was repeated every 28 days until intolerable toxicity had developed or disease progression. The primary endpoint was safety, while the secondary endpoints were objective response rate (ORR), ascites control rate (ACR), and overall survival (OS). RESULTS: From February 2021 through November 2022, a total of 21 patients (14 hepatocellular carcinoma and 7 cholangiocarcinoma) were enrolled to receive intraperitoneal sintilimab. Twelve patients had adverse events (AEs). The most common grade 3 AEs were fatigue, rash, and abdominal pain. No grade ≥4 AEs occurred in any patients. ORR was only evaluated in 13 patients, including partial response in 4, stable disease in 7, and progressive disease in 2. A reduction in the median maximum diameter of the tumor after treatment was observed; however, there was no statistical significance among patients. The objective remission rate of ascites was 43.75%, and the median OS for all 21 patients was 17.6 weeks. CONCLUSIONS: This exploratory study represents the first trial to demonstrate the safety and clinical efficacy of intraperitoneal anti-PD-1 antibody administration. No unexpected safety concerns were identified. A large, multicenter, prospective study is needed to confirm the promising clinical efficacy.