Hematologic malignancies, including leukemia, lymphoma, and multiple myeloma, are hazardous diseases characterized by the uncontrolled proliferation of cancer cells. Dysregulated cell cycle resulting from genetic and epigenetic abnormalities constitutes one of the central events. Importantly, cyclin-dependent kinases (CDKs), complexed with their functional partner cyclins, play dominating roles in cell cycle control. Yet, efforts in translating CDK inhibitors into clinical benefits have demonstrated disappointing outcomes. Recently, mounting evidence highlights the emerging significance of WEE1 G2 checkpoint kinase (WEE1) to modulate CDK activity, and correspondingly, a variety of therapeutic inhibitors have been developed to achieve clinical benefits. Thus, WEE1 may become a promising target to modulate the abnormal cell cycle. However, its function in hematologic diseases remains poorly elucidated. In this review, focusing on hematologic malignancies, we describe the biological structure of WEE1, emphasize the latest reported function of WEE1 in the carcinogenesis, progression, as well as prognosis, and finally summarize the therapeutic strategies by targeting WEE1.
Humans ; Protein-Tyrosine Kinases/physiology* ; Hematologic Neoplasms/drug therapy* ; Cell Cycle Proteins/antagonists & inhibitors* ; Nuclear Proteins/antagonists & inhibitors* ; Cyclin-Dependent Kinases ; Molecular Targeted Therapy ; Animals

OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

Objective Performing physical tasks in the low-pressure environment of space poses a significant physiological challenge for astronauts.This study investigates the localized thermophysiological effects of typical physical tasks on different body segments and analyzes the mechanisms by which low-pressure environments influence human task performance.The findings aim to provide a theoretical basis for the thermal control design of spacesuits,focusing on both localized thermoregulation and overall task performance.Methods Two typical physical tasks—15 kg weighted walking and 25 kg load-carrying—were conducted in a simulated low-pressure composite environment chamber.The chamber was set to an altitude-equivalent pressure of 57 kPa(4500 m),with a temperature of 26℃and humidity of 40％.Six non-acclimatized adult male participants were recruited.After environmental stabilization,12-point skin temperatures were recorded throughout the tasks,and localized temperature data were statistically analyzed.Results Under low-pressure conditions,different body regions exhibited distinct thermal responses over time depending on the task type,while the same body region showed varied responses under different task conditions.During walking,temperatures in the primary active regions(thighs and calves)decreased,with most other body regions(except the pelvis and feet)gradually cooling as the task progressed.In contrast,during load-carrying,temperatures in the primary active regions(back and upper arm muscles)increased significantly.Conclusion Astronauts performing different tasks in low-pressure environments experience distinct localized thermophysiological effects.Therefore,spacesuit thermal control systems should not only account for task intensity and metabolic differences but also adapt localized heating/cooling based on task-specific thermal profiles.This approach enables targeted intelligent thermal regulation,enhancing operational support in specific mission scenarios.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

AIM To investigate the effects of diosgenin on autophagy of human osteosarcoma cells.METHODS Human osteosarcoma MG63 and U2OS cells with or without exposure to diosgenin had their proliferation detected by MTT assay,their ultrastructure observed by transmission electron microscopy,their expression of autophagy protein Beclin1 observed by immunofluorescence staining,and their expressions of autophagy molecular markers LC3,Beclin1 and PI3K/Akt/mTOR signaling pathway related proteins detected by Western blot.The MG63 and U2OS cells cotreated with diosgenin and PI3K pathway inhibitor LY294002 had the expression of Beclin1 mRNA detected by RT-qPCR.The MG63 and U2OS cells cotreated with autophagy inhibitor 3-methyladenine(3-MA)had their inhibition rate of proliferation detected by MTT assay,their expression of cleaved-caspase3 protein detected by Western blot,and their expression of caspase3 mRNA detected by RT-qPCR.RESULTS Upon osteosarcoma MG63 and U2OS cells,diosgenin inhibited their proliferation,promoted the generation of autophagosomes,increased the protein expression of LC3 Ⅱ and Beclin1(P<0.05,P<0.01),reduced the protein expression of LC3 I(P<0.01),and inhibited the protein phosphorylation level of PI3K/Akt/mTOR pathway(P<0.05,P<0.01),whose effects were offset by the intervention with autophagy inhibitors in terms of the reduced proliferation inhibition and down-regulated expressions of caspase3 mRNA and cleaved-caspase3 protein(P<0.01).CONCLUSION Diosgenin can inhibit the proliferation of osteosarcoma cells and induce their autophagy leading to their death and autophagy apoptosis,which may be related to the activation of PI3K/Akt/mTOR signaling pathway and up-regulation of the expression of LC3 Ⅱ and Beclin1 proteins.

Objective To evaluate the value of miniprobe endoscopic ultrasound(EUS)in guiding endoscopic treatment of small-diameter(maximum diameter less than 1 cm)and low-grade(G1 grade)rectum neuroendocrine neoplasm(R-NEN),and to provide evidence and clues for its clinical application and further research.Methods The clinical data of 85 cases of low-grade(G1 grade)R-NEN with a maximum diameter of less than 1 cm who underwent endoscopic treatment in our center from January 2014 to December 2020 were retrospectively analyzed.The patients were divided into the EUS group(37 cases)and control group(48 cases)according to whether EUS was performed before endoscopic treatment.The positive rate of incision margin,the incidence of complications,the recurrence rate,the hospital stay,the cost of hospitalization and endoscopic therapy were compared between the two groups.Results The positive rate of incision margin in the EUS group was significantly lower than that in control group(P<0.05).There was no significant difference in the incidence of complications,tumor recurrence rate,hospital stay or hospital costs between the two groups(P>0.05).There was statistically significant difference in the endoscopic therapy between the two groups(P<0.05).Conclusion Evaluating the lesion depth of small-diameter and low-grade(G1 grade)R-NEN before surgery by miniprobe EUS and selecting endoscopic surgery according to its results of can significantly reduce the residual risk of resection margin tumors.

Objective To construct an artificial intelligence assisted diagnosis model based on deep learning for dynamically recognizing gastric lesions and their locations under gastroscopy in real time,and to evaluate its ability to detect and recognize gastric lesions and their locations.Methods The gastroscopy videos of 104 patients in our hospital was retrospectively analyzed,and the video frames were manually annotated.The annotated picture frames of lesion category were divided into the training set and the validation set according to the ratio of 8∶2,and the annotated picture frames of location category were divided into the training set and the validation set according to the patient sources at the ratio of 8∶2.These sets were utilized for training and validating the respective models.YoloV4 model was used for the training of lesion recognition,and ResNet152 model was used for the training of location recognition.The accuracy,sensitivity,specificity,positive predictive value,negative predictive value and location recognition accuracy of the auxiliary diagnostic model were evaluated.Results A total of 68 351 image frames were annotated,with 54 872 frames used as the training set,including 41 692 frames for lesion categories and 13 180 frames for location categories.The validation set consisted of 13 479 frames,comprising 10 422 frames for lesion categories and 3 057 frames for location categories.The lesion recognition model achieved an overall accuracy of 98.8%,with a sensitivity of 96.6%,specificity of 99.3%,positive predictive value of 96.3%,and negative predictive value of 99.3% in validation set.Meanwhile,the location recognition model demonstrated an top-5 accuracy of 87.1% .Conclusion The artificial intelligence assisted diagnosis model based on deep learning for real-time dynamic recognition of gastric lesions and their locations under gastroscopy has good ability in lesion detection and location recognition,and has great clinical application prospects.

Objective To analyze the clinical and imaging features of hemichorea associated with non-ketotic hyperglycemia(HC-NH)and to explore the perfusion of cerebral blood flow in the patients.Methods A retrospective study was conducted on 23 HC-NH patients diagnosed in Henan Provincial People's Hospital from January 2018 to December 2023.The clinical manifesta-tions,imaging features and prognosis were collected and analyzed,and the correlation with cere-bral blood flow hypoperfusion was investigated.Results The symptoms were all lateral involun-tary movements,of which 4 cases presented only single upper limb(1 case was left upper limb,the other 3 cases were right upper limb),and 19 cases had both upper and lower limbs involved(10 cases were left limb,and 9 cases were right limb).After the onset of the symptoms,the blood glucose level was 19.72±4.72 mmol/L,glycated hemoglobin level was(13.60±3.68)％,but all of patients were negative to urine ketone bodies.Hyperdense lesions in the contralateral basal ganglia region on CT images were observed in 6 cases.Strip or patchy hyperintensity was seen on T1-weighted MR images.All patients had ipsilateral stenosis of the vessels and regional hypoperfu-sion of cerebral blood flow as shown by MR perfusion-weighted imaging.All symptoms were re-lieved after actively controlling blood glucose,improving blood circulation,and symptomatic man-agement.Conclusion HC-NH is quite rare in clinical practice,and its occurrence may be related to cerebral blood flow hypoperfusion triggered by basal nucleus degeneration.

Objective To investigate the expression of FBXW12 in pancreatic cancer and elucidate its impact on cancer cell migration and invasion.Methods The present study utilized the GEPIA 2 database to analyze the differential expression of FBXW12 between pancreatic cancer tissues and normal tissues.Clinical data from 31 pancreatic cancer patients who underwent radical resection at Linyi People's Hospital from June 2016 to December 2022 were collected.Immunohistochemical staining was conducted to assess FBXW12 expression in both cancerous and adjacent normal tissues obtained during surgery,with subsequent follow-up for survival prognosis.Western blot and polymerase chain reaction(PCR)techniques were employed to determine FBXW12 protein expression levels in pancreatic cancer cell lines.The impact of FBXW12 on cancer cell invasion and migration was evaluated using Transwell cell invasion and scratch test.Results The results from the analysis of the GEPIA 2 database revealed a significant downregulation of FBXW12 mRNA expression in pancreatic cancer tissues compared to normal pancreatic tissues(P＜0.05).Immunohistochemical analysis demonstrated a positive expression rate of FBXW12 protein in pancreatic cancer tissues at 75.19％(23/31),whereas adjacent normal tissues exhibited a higher positive expression rate at 93.55％(29/31),indicating a statistically significant difference in FBXW12 expression between pancreatic cancer and adjacent normal tissues(P＜0.05).Additionally,the expression level of FBXW12 in pancreatic cancer tissues was found to be closely associated with lymph node metastasis(P＜0.05),patients with low expression of FBXW12 have a worse prognosis(P＜0.05).Furthermore,transfection with FBXW12 overexpression plasmid resulted in a significant decrease in the invasion and migration abilities of pancreatic cancer cells.Conclusion FBXW12 is low expressed in pancreatic cancer and is associated with the occurrence and development of pancreatic cancer.