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 explore the advantages and effectiveness of the independently developed intelligent orthopedic robot-assisted distal locking of femoral intramedullary nails. METHODS: Thirty-two adult cadaveric femur specimens were randomly divided into two groups, with 16 specimens in each group. The experimental group used the intelligent orthopedic robot to assist in the distal locking of femoral intramedullary nail holes, while the control group used the traditional method of manual locking under X-ray fluoroscopy. The locking time, fluoroscopy times, and the success rate of first locking were recorded and compared between the two groups. RESULTS: The locking time of the experimental group was (273.94±38.67) seconds, which was shorter than that of the control group [(378.38±152.72) seconds], and number of fluoroscopies was (4.56±0.81) times, which was less than that of the control group [(8.00±3.98) times]. The differences were significant [ MD=73.054 (-37.187, 85.813), P=0.049; MD=1.969 (-1.437, 2.563), P=0.002]. The first locking success rate of the experimental group was 100% (16/16), which was significantly higher than that of the control group (68.75%, 11/16) ( P=0.043). CONCLUSION The efficiency of distal locking of femoral intramedullary nails assisted by the intelligent orthopedic robot is significantly higher than that of the traditional manual locking method under fluoroscopy, as it can markedly reduce the time required for distal locking of femoral intramedullary nails, decrease intraoperative radiation exposure, and increase the success rate of locking.
Humans ; Fracture Fixation, Intramedullary/instrumentation* ; Bone Nails ; Fluoroscopy ; Femur/diagnostic imaging* ; Femoral Fractures/surgery* ; Robotic Surgical Procedures/instrumentation* ; Cadaver ; Adult ; Robotics ; Male

PURPOSE: Deep vein thrombosis (DVT) of the left and right lower extremities was treated in the same way, but the left and right extremities received different levels of attention. This study aimed to investigate the differences between the right and left lower extremity deep vein thrombosis (LEDVT). METHODS: Clinical characteristics of LEDVT patients from July 2020 to June 2022 were retrospectively analyzed to compare the incidence of LEDVT on different limbs, demographics, predisposing factors, and anatomical characteristics. The exclusion criteria were bilateral LEDVT and recurrent thrombosis. Measured data was analyzed using independent samples t-test or Mann-Whitney test. Count data were analyzed by Chi-square test. A p < 0.05 was considered a statistically significant difference. RESULTS: There were 478 patients included in this study and the ratio of left to right LEDVT on the left and right limbs was 3.16:1 (363:115). Left LEDVT predominantly affected female, with the major aged > 50 years (50 - 60 years: 16.80%; > 60 years: 57.30%). The primary predisposing factor was iliac vein compression syndrome, with iliofemoral thrombosis being the main type. Male patients with LEDVT on the right limb were predominant and the age of onset was usually ≤ 60 years (52.17%). The main predisposing factor was recent surgery or trauma (< 30 days) and femoropopliteal thrombosis was the main type. In more detail, the left iliac vein was compressed mainly in the proximal segment, and the right iliac vein was compressed mainly in the intermediate and distal segments. Recent surgery or trauma to the locomotor system and genitourinary system often induced LEDVT. CONCLUSION The incidence of LEDVT on the left is significantly higher than that on the right. LEDVT on different sides has different characteristics, which is crucial for prevention and diagnosis in the relevant population so there are also differences in treatment of the affected limbs.
Humans ; Venous Thrombosis/etiology* ; Male ; Female ; Middle Aged ; Lower Extremity/blood supply* ; Retrospective Studies ; Adult ; Aged ; Age Factors ; Sex Factors ; Risk Factors ; Acute Disease ; Incidence ; Aged, 80 and over ; Young Adult ; Adolescent

OBJECTIVE: Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke (IS). However, the lipid profiles associated with IS have been poorly studied. We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling. METHODS: Serum lipidomic profiling was performed using LC-MS in 20 patients with IS and 20 age- and sex-matched healthy controls. Univariate and multivariate analyses were simultaneously performed to identify the differential lipids. Multiple testing was controlled for using a false discovery rate (FDR) approach. Enrichment analysis was performed using MetaboAnalyst software. RESULTS: Based on the 294 lipids assayed, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used to distinguish patients with IS from healthy controls. Fifty-six differential lipids were identified with an FDR-adjusted P less than 0.05 and variable influences in projection (VIP) greater than 1.0. These lipids were significantly enriched in glycerophospholipid metabolism (FDR-adjusted P = 0.009, impact score = 0.216). CONCLUSIONS Serum lipid profiles differed significantly between patients with IS and healthy controls. Thus, glycerophospholipid metabolism may be involved in the development of IS. These results provide initial evidence that lipid molecules and their related metabolites may serve as new biomarkers and potential therapeutic targets for IS.
Humans ; Pilot Projects ; Lipidomics ; Male ; Female ; Biomarkers/blood* ; Middle Aged ; Ischemic Stroke/blood* ; Aged ; China ; Lipids/blood* ; Adult ; Case-Control Studies ; East Asian People

A molecularly imprinted electrochemical sensor for rapid detection of tenuazonic acid(TeA)was developed based on the Au-MoS2/MOF(Fe2+/Fe3+)high-efficiency catalytic cycle amplification strategy,using p-aminobenzoic acid(PABA)as the functional monomer,and TeA as the template molecule.The molecularly imprinted polymer(MIP)was prepared on the surface of Au-MoS2/MOF(Fe2+/Fe3+)modified electrode through electropolymerization.By introducing flower-like MoS2 nanoflakes(MoS2 NFs)as a co-catalyst into a mixed-valence structured Fe-MOF(Fe2+/Fe3+),the H2O2 electrochemical signal of the MIP/Au-MoS2/MOF(Fe2+/Fe3+)/GCE was significantly enhanced.Under optimal conditions,the sensor exhibited good selectivity and high sensitivity toward TeA.A linear relationship(R2=0.992)was observed between the electrochemical response and TeA concentration in the range of 0.001-10 μg/kg,with a detection limit of 0.3 ng/kg.The developed method was successfully applied to determination of TeA in fruit samples,with recoveries ranging from 90.8%to 110.8%,and relative standard deviations from 1.9%to 8.4%.

OBJECTIVE To provide a reference for the definition of the legal attributes of the provincial Chinese herbal pieces processing norms and the improvement of legal expression for the drug standards in Drug Administration Law. METHODS Based on the legal evolution of local drug standards in China， the composition of national drug standards for Chinese herbal pieces and the composition of current provincial Chinese herbal pieces processing norms were analyzed； at the same time， based on the method of legal interpretation， the legal connotation of the provincial Chinese herbal medicine processing norms in Drug Administration Law was investigated. RESULTS & CONCLUSIONS In the practice of drug supervision， the provincial Chinese herbal pieces processing norms are essentially local drug standards. The newly revised Drug Administration Law defines the drug standards specifically， but does not stipulate the legal attribute of drug standards for the provincial Chinese herbal pieces processing norms， and there are certain legislative technical defects. It is suggested that when amending the Drug Administration Law， the legal attributes of the drug standards of the provincial Chinese herbal medicine processing norms should be clarified.

Humans ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Mutation/genetics* ; Colorectal Neoplasms/genetics* ; Proto-Oncogene Proteins B-raf/metabolism*

Rosai-Dorfman disease(RDD)is a rare non-Langerhans cell histiocytosis.The etiology and pathogenesis of RDD have not been fully explained,and its occurrence is even rarer in the maxillofacial region.This paper reported a patient who was first misdiagnosed as facial inflammation caused by oral disease and finally diagnosed as RDD.Clinical features,diagnosis,treatment,and prognosis were discussed based on the literature.This work provides reference for fu-ture diagnosis and differentiation of RDD in cheek.

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence rate.However,the mechanisms governing tumor initiation and recurrence are poorly understood.Here,we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution.Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response(IR),bone remodeling(BR),tooth development(TD),epithelial development(ED),and cell cycle(CC)signatures.Of note,we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence,which was dominated by the EZH2-mediated program.Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids.These data described the tumor subpopulation and clarified the identity,function,and regulatory mechanism of CC ameloblastoma cells,providing a potential therapeutic target for ameloblastoma.

Purpose To investigate the clinicopathologic,immunophenotypic features,genetic alterations and prognosis of melanotic Xp11 neoplasms/melanotic TFE3-rearrangement neo-plasms.Methods Five cases were selected from the Depart-ment of Pathology,Union Hospital,Huazhong University of Sci-ence and Technology from November 2018 to July 2023.The clinicopathologic,immunohistochemical,FISH assays,next-generation sequencing(NGS)and follow-up details were collect-ed.Results There were 1 male and 4 females,with their ages ranging from 16 to 59 years(mean 28.2 years).The maximum diameters of the masses were 3-6 cm(average 4.7 cm).The tumors located in right kidneys(3 cases),tubal interstitium(1 case)and pelvis(1 case).Microscopically,most tumors shared similar morphology such as nested,acinar structures sep-arated by a delicate vascular network.Epithelioid tumor cells presented with clear to granular eosinophilic cytoplasm.Lym-phocytic infiltration was seen in the background;melanin depo-sition was noted in the cases;neoplastic necrosis was detected in 4 cases.Mitotic activity was low with 5 cases showing＜3/10 HPF.Intravascular tumor thrombus was detected in 2 cases,no lymphovascular and nerve invasions were detected in other 3 ca-ses.Immunohistochemically,all 5 cases expressed TFE3 dif-fusely,and expressed HMB45,Melan A to varying degrees,CK(AE1/AE3),CK7,EMA,PAX8,TFEB,S-100,SOX10,SMA,desmin were all non-reactive in the 5 cases.The Ki67-la-beling index was＜20％.TFE3 separation signal in 4 cases were detected by FISH,1 case was interpreted as negative due to atypical signal which was confirmed by next-generation se-quencing(NGS)assay as RBM10-TFE3.Clinical follow-up was available for five patients for 2-60 months,in which four pa-tients were alive with no evidence of disease after initial resec-tion,and one patient with thoracic spine metastasis was currently in stable condition.Conclusion Melanotic Xp1 1 neoplasms/melanotic TFE3-rearrangement neoplasms has unique morpholog-ic,immunophenotypic and genetic characteristics.It might be reclassified into a distinctive malignant mesenchymal tumor enti-ty.