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

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

Objective To investigate the molecular mechanism of sulforaphane(Sul)promoting bone marrow stem cells(BMSCs)differentiating into osteoblasts.Methods BMSCs were divided into the control group(without any treatment),induction group(induction of osteogenic differentiation),and induction+Sul group(induction of osteogenic differentiation with the addition of 40 μmol/L of Sul).The adenovirus-shRNA-Mock,-shRNA-TET1,-shRNA-TET2,and-shRNA-TET3 were transfected into BMSCs as the shRNA-Mock group,shRNA-TET1 group,shRNA-TET2 group,and shRNA-TET3 group.BMSCs were cultured in cell culture medium containing osteogenic differentiation induction medium and 40 μmol/L of Sul,and then transfected with adenovirus-shRNA-TET1,-shRNA-TET2,-shRNA-TET3,and-shRNA-Mock as the induction+Sul+shRNA-TET1 group,induction+Sul+shRNA-TET2 group,induction+Sul+shRNA-TET3 group,and induction +Sul+shRNA-Mock group.The mRNA and protein expression levels of Runx2 after BMSCs differentiated into osteoblasts were determined by qPCR and Western blot.The DNA content of Runx2 promoter region bound to Histone H3 after BMSCs differentiated into osteoblasts was determined by chromatin immunocoprecipitation(ChIP).The methylation level of Runx2 promoter region of BMSCs differentiated into osteoblasts was determined by HpaⅡenzyme and MspⅠenzyme digestion combined with qPCR.The degree of BMSCs differentiated into osteoblasts was determined by alizarin red staining.Results Compared with the induction group,the mRNA and protein expression levels of Runx2 in the induction+Sul group were significantly increased(P<0.05);the content of DNA in the Runx2 promoter region bound to Histone H3 was increased(P<0.05),the methylation level of Runx2 promoter region was reduced(P<0.05),and the alizarin red staining score was elevated(P<0.05).Compared with the induction+Sul group,the content of DNA in the Runx2 promoter region bound to Histone H3 in the induction+Sul+shRNA-TET1 group was decreased(P<0.05),the methylation level of Runx2 promoter region was increased(P<0.05),and the alizarin red staining score was decreased(P<0.05).While there was no significant change among the induction+Sul+shRNA-TET2 group,induction+Sul+shRNA-TET3 group,induction+Sul+shRNA-Mock group(P>0.05).Conclusion Sul can promote the differentiation of BMSCs into osteoblasts through promoting DNA demethylation of Runx2 promoter region by TET1.

OBJECTIVE: To investigate the clinical efficacy and advantages of Tianji orthopedic robot assisted cannulated screw internal fixation for femoral neck fracture. METHODS: The clinical data of 41 patients with femoral neck fracture who underwent internal fixation with cannulated screws from January 2019 to January 2022 were retrospectively analyzed. According to different surgical methods, they were divided into Tianji robot group and traditional cannulated screw fixation group (traditional operation group). Among them, there were 18 patients in Tianji robot group including 8 males and 10 females with age of (56.00±4.22) years old, Garden typeⅠ (4 cases), type Ⅱ (11 cases), type Ⅲ (2 cases), and type Ⅳ (1 case). There were 23 patients in the traditional operation group, including 10 males and 13 females, aged (54.87±4.81) years old;there were 5 cases of Garden typeⅠ, 14 cases of type Ⅱ, 3 cases of type Ⅲ and 1 case of type Ⅳ. The operation time, intraoperative blood loss, fluoroscopy times, guide needle placement times, operation costs and other indicators were observed and compared between two groups. Harris score was used to evaluate hip joint function 12 months after operation. RESULTS: The wounds of all patients healed in Grade A without complications. There were significant differences between two groups in terms of operation time, times of intraoperative fluoroscopy, times of guide needle placement, amount of intraoperative bleeding, and operation cost (P<0.05). All 41 patients were followed up for at least 12 months. The fractures of both groups were healed. There was no infection, screw loosening, fracture displacement and femoral head necrosis in Tianji robot group during follow-up;Screw loosening occurred in 2 patients in the traditional operation group during follow-up. At 12 months after operation, Harris hip joint function score of Tianji robot group was higher than that of traditional operation group in daily activity, lameness, joint activity score and total score (P<0.05). CONCLUSION Tianji robot assisted nail placement is a better method for the treatment of femoral neck fracture, which improves the surgical efficiency, is more accurate, has higher success rate of one-time nail placement, shorter operation time, less radiation, and has better hip joint function recovery after surgery.
Male ; Female ; Humans ; Middle Aged ; Robotics ; Retrospective Studies ; Femoral Neck Fractures/surgery* ; Bone Screws ; Fracture Fixation, Internal/methods* ; Treatment Outcome

AIM:To observe the effect of implantable collamer lens V4c(ICL V4c)implantation on high myopia, and the changes in anterior segment morphology.METHODS:A prospective study was conducted on 100 patients(200 eyes)with high myopia who were treated with ICL V4c implantation in the hospital from February 2018 to March 2021. The best corrected visual acuity(BCVA), uncorrected visual acuity(UCVA), intraocular pressure, higher-order aberration, anterior segment morphology [iridocorneal angle(ICA), central anterior chamber depth(ACD), anterior chamber volume(ACV), central corneal thickness(CCT)and K-value(K)], photopic and scotopic contrast sensitivity before operation and 6 and 12mo after operation were comparatively analyzed.RESULTS:All patients were followed-up. UCVA and BCVA were significantly improved at 6 and 12mo after operation(P<0.05). Total higher-order aberration, horizontal coma and vertical coma showed no significant difference before and after operation(P>0.05). Spherical aberration, ICA, ACD and ACV at 6 and 12mo after operation were significantly smaller than those before operation(P<0.05). Under photopic state, the contrast sensitivity of 3.0 and 6.0 c/d was significantly higher at 6 and 12mo after operation when compared with that before operation(P<0.05). Under scotopic state, the contrast sensitivity of 6.0 c/d was significantly higher at 6 and 12mo after operation when compared with that before operation(P<0.05); there was no significant difference in CCT, K, or intraocular pressure before and after operation(P>0.05).CONCLUSION:Although ICA, ACD and ACV in patients with high myopia are reduced after ICL V4c implantation, the operation can effectively improve visual acuity and visual quality.

AIM: To investigate the application value of Worst lacrimal probe combined with modified lacrimal duct intubation in anastomosis of complex canalicular laceration.METHODS: Retrospective study. A total of 68 cases(68 eyes)with complex traumatic canalicular laceration treated in the ophthalmology department of the Second Affiliated Hospital of Zunyi Medical University from March 1, 2019 to March 31, 2021 were selected. They were divided into two groups according to the surgical methods, with 36 patients(36 eyes)who were treated with the Worst lacrimal probe to find the broken end of lacrimal duct combined with improved lacrimal duct threading intubation in group A, and 32 patients(32 eyes)who were treated with microscope to find the broken end of lacrimal duct and two-way intubation anastomosis canaliculus intubation in group B. The clinical efficacy, success rate of intraoperative search for the broken end of lacrimal duct, searching time, operation time, the degree of pain, postoperative ocular foreign body sensation and complications were compared between the two groups.RESULTS: The total effective rate of clinical efficacy in patients of group A was higher than that in group B(94% vs. 38%), the success rate of intraoperative search for broken end of lacrimal duct was higher than that in group B(100% vs. 47%), the searching time and operation time were shorter than those in group B, and the score of pain degree was lower than that in group B(all P<0.05). The postoperative follow-up for 6mo-1a showed that the ocular foreign body sensation score, the incidence of lacrimal punctum rupture and morphological change, and the degree of tear overflow in group A were all lower than those in group B(all P<0.05).CONCLUSION: Worst lacrimal probe combined with modified lacrimal duct intubation for the treatment of complex traumatic canalicular laceration can find the broken end of lacrimal duct more accurately, shorten the operation time, reduce the pain and foreign body sensation of patients, improve clinical efficacy and reduce the incidence of complications.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

OBJECTIVE: To investigate the regulatory effect and mechanism of DNA methyltransferase 3A (DNMT3a) in hydroquinone-induced hematopoietic stem cell toxicity. METHODS: Cells (HSPC-1) were divided into 4 groups, that is A: normal HSPC-1; B: HQ-intervented HSPC-1; C: group B + pcDNA3 empty vector; D: group B + pcDNA3- DNMT3a. RT-qPCR and Western blot were used to detect the expression levels of DNMT3a and PARP-1 mRNA and protein, respectively. Cell morphology was observe; Cell viability and apoptosis rate of HSPC-1 were detected by MTT and flow cytometry, respectively. RESULTS: Compared with group A, the expression levels of DNMT3a mRNA and protein in HSPC-1 of group B were decreased, while PARP-1 mRNA and protein were increased (P<0.05); there was no significant difference in the above indexes between group C and group B; compared with group B, the expression levels of DNMT3a mRNA and protein showed increased, while PARP-1 mRNA and protein were decreased significantly in cells of group D transfected with DNMT3a (P<0.05). Cells in each group were transfected with DNMT3a and cultured for 24 h, HSPC-1 in group A showed high density growth and mononuclear fusion growth, while the number of HSPC-1 in group B and C decreased and grew slowly. Compared with group B and C, the cell growth rate of group D was accelerated. The MTT analysis showed that cell viability of HSPC-1 in group B were lower than that of group A at 24 h, 48 h and 72 h (P<0.05); after transfected with DNMT3a, the cell viability of HSPC-1 in group D were higher than that of group B at 24 h, 48 h and 72 h (P<0.05). The apoptosis rate of cells in group B was significantly higher than that of group A (P<0.001), while the apoptosis rate in group D was lower than that of group B (P<0.001). CONCLUSION DNMT3a may be involved in the damage of hematopoietic stem cells induced by hydroquinone, which may be related to the regulation of PARP-1 activity by hydroquinone-inhibited DNMT3a.
Apoptosis ; Cell Proliferation ; DNA Methyltransferase 3A ; Hematopoietic Stem Cells/drug effects* ; Humans ; Hydroquinones/toxicity* ; Poly (ADP-Ribose) Polymerase-1 ; RNA, Messenger/metabolism*

OBJECTIVE: To compare treatment effect of monolateral and circular external fixator in infectious tibial nonunion and to explore external fixation structure with better osteogenic ability and fewer complications. METHODS: A retrospective analysis was performed on 150 patients with infectious tibial nonunion admitted from January 2010 to December 2014. Patients who met the inclusion and exclusion criteria were divided into monolateral fixator group and circular fixator group according to the type of external fixation. Demographic and perioperative data of the two groups were collected. New bone quality was assessed by pixels ratio, treatment effect was assessed by complications. Notes for treatment was explored by case analysis. RESULTS: A total of 64 patients with infectious mid-tibial nonunion were included, 26 in monolateral fixator group and 38 in circular fixator group. There was no difference in demographic data between two groups. The pixel ratio of new bone between two groups was from 0.91 to 0.97 with an average of (0.94±0.03), and from 0.93 to 0.97 with an average of(0.95±0.02), respectively, with no statistical significance (P>0.05). The external fixation index was from 34.1 to 50.6 with an average of (42.3±8.3) days /cm in monolateral fixator group and from 44.5 to 56.1 with an average of (45.8±10.3) days/cm in the circular fixator group, and the difference was not statistically significant (P>0.05). There were 7 cases (26.9%) of complications in monolateral fixator group and 5 cases (13.2%) in circular fixator group, the difference was not statistically significant (P>0.05), but 5 cases of foot ptosis in monolateral fixator group and none in circular fixator group. The time of weight bearing in monolateral fixator group was later than that in circular fixator group, and the difference was statistically significant (P<0.05). CONCLUSION Monolateral and circular fixators can achieve equivalent bone formation in the treatment of infected tibial nonunion. Circular fixator is recommended for patients with severe osteoporosis or concomitant medical diseases requiring early weight bearing. Hydroxyapatite coated screws are recommended if a monolateral external fixator is selected when the expected enlarged length is long and the fixation time is long and close monitoring of the ankle movement is required to avoid foot droop.
Humans ; Tibial Fractures/surgery* ; Retrospective Studies ; External Fixators ; Tibia/surgery* ; Treatment Outcome ; Hydroxyapatites

This article reports a patient with extensive high-pressure injection injury of the hand caused by mistaken injection of polyurethane material into the index finger, who was diagnosed and treated in the Department of Orthopedics of Huzhou Central Hospital in 2019. Both the digital artery and digital nerve were involved, and the polyurethane involved the right palm along the flexor tendon sheath of the index finger and wrist. Due to the lack of X-ray development, the scope of the first debridement was small, and the blood supply to the fingertip was poor. Finally, the patient's right index finger was amputated due to infection and necrosis. MR or B-ultrasound should be perfected before operation to clarify the extent of polyurethane involvement. The initial thorough debridement or multiple debridements are necessary to improve the prognosis. If the blood supply of the fingers is poor, the blood supply can be reconstructed by skin flap transplantation.
Finger Injuries/surgery* ; Humans ; Polyurethanes/adverse effects* ; Plastic Surgery Procedures ; Skin Transplantation ; Surgical Flaps/surgery* ; Treatment Outcome