The dysregulation of cyclin-dependent kinase 12 (CDK12), which may result from genomic alterations or modulation by upstream effectors, is implicated in cancer oncogenesis and progression. CDK12 overexpression or activation is sufficient to induce tumor initiation, recurrence, and therapeutic resistance. However, CDK12 may also exert tumor-suppressive functions in a context-dependent manner. Therefore, caution is warranted when targeting CDK12 in future clinical trials. A comprehensive elucidation of the dual roles and underlying mechanisms of CDK12 in carcinogenesis is urgently needed to advance precision oncology. This review provides an overview of the current understanding of the dysregulation and biological roles of CDK12 in cancer. Subsequently, we systematically summarize the functions and mechanisms of the oncogenic and tumor-suppressive roles of CDK12 in different contexts. Finally, we discuss the potential of CDK12 as a novel therapeutic target and its implications in clinical oncology, offering insights into future directions for innovative cancer treatment strategies.

Objective To investigate the effect of acupuncture on the morphology of the dry eye rabbit's cornea and the nuclear factor κB(NF-κB)signaling pathway of the corneal tissue to analyze the mechanism of acupuncture on dry eyes.Methods Twenty-four healthy New Zealand rabbits,without restriction on sex,were randomly divided into four groups,including a blank group,a model group,an acupuncture group,and a sham acupuncture group,with 6 in each group.Rabbits in the blank group were not treated;rabbits in the other three groups were treated with scopolamine hydro-bromide 2.0 mg·kg-1 by subcutaneous injection at 8:00,11:00,14:00 and 18:00 each day for 35 consecutive days un-til the end of the experiment.Rabbits in the sham acupuncture group were treated with sham acupuncture on the 22nd day after successful modeling by quickly pricking acupoints(Jingming BL1,Cuanzhu BL2,Sizhukong SJ23,Taiyang EX-HN5 and Tongziliao GB1)with a blunt acupuncture needle,once a day,for a total of 14 days.Rabbits in the acupuncture group were treated with acupuncture at the same acupoints as the sham acupuncture group after successful modeling.The corneal fluorescence staining was conducted on Days 0,21,28 and 35 after modeling.On Day 35,corneal confocal microscope ex-aminations were conducted.Then,the rabbits were sacrificed,the corneal morphological changes were observed by light microscope and transmission electron microscope,and the expression of corneal NF-κB protein was detected by Western blot.Results Compared with the model group,the score of rabbit corneal fluorescein staining in the acupuncture group and blank group decreased on the 28th and 35th days after modeling,and the differences were statistically significant(all P＜0.05).The results of the confocal microscope examination on Day 35 after modeling showed that,compared with other groups,there were a large number of globular immune cells and activated stromal cells with unclear boundaries and irregu-lar sizes in the stromal layer and inflammation in the area with irregular intercellular space in the model group and the sham acupuncture group.In the acupuncture group,the morphology of stromal layer cells improved,the cells were slightly acti-vated,and there were no obvious abnormalities in the corneal nerve morphology.On the 35th day after modeling,the re-sults of the light microscope showed that,the surface of the corneal tissue in the model group and the sham acupuncture group showed hyperkeratinized flat epithelial cells,lymphocyte infiltration,increased number of focal epithelial cell layers,and epithelial cell detachment.In the acupuncture group,there were 4-6 layers of epithelial cells in the corneal epitheli-um,and epithelial shedding decreased.In addition,the lymphocyte infiltration decreased compared with the model group.On the 35th day after modeling,the results of the transmission electron microscope showed that abnormal microvilli oc-curred and epithelial cells were absent in the corneal epithelial cells of rabbits in the model group and the sham acupuncture group,the cell space was widened,the rough endoplasmic reticulum was severely expanded,and desmosomes were dis-banded with mitochondrial swelling.In the acupuncture group,the microvilli structure of epithelial cells was sparse and short,local deletion was still observed,the rough endoplasmic reticulum was slightly expanded,and no obvious swelling of mitochondria was observed.On the 35th day after modeling,the Western blot examination results showed that,compared with the blank group,the expression of p-NF-κB p65 was up-regulated in both the model group and sham acupuncture group(both P＜0.05);compared with the model group and sham acupuncture group,the expression of p-NF-κB p65 in the acupuncture group was down-regulated(both P＜0.05).Conclusion Acupuncture can inhibit the NF-κB signaling path-way to play an anti-inflammatory role and relieve corneal inflammation and injury of dry eye rabbit models.

Objective To explore the regulatory effect of miR-204-5p on biological behaviors of bladder cancer cells and its molecular mechanism.Methods Survival analysis and correlation analysis were performed using TCGA database to explore the association of miR-204-5p expression with survival outcomes and clinicopathological parameters of bladder cancer patients.The expression level of miR-204-5p was detected in bladder cancer and adjacent tissues and in normal uroepithelial cells and bladder cancer cells.In cultured bladder cancer cells,the effects of miR-204-5p overexpression and knockdown on cell proliferation,migration,invasion,and apoptosis were analyzed.Transcriptome sequencing,bioinformatics analysis and dual-luciferase assay were carried out to confirm targeted inhibition of RAB22A by miR-204-5p to promote malignant biological behaviors of bladder cancer cells.Results Patients with high miR-204-5p expressions had lowered median survival time and poor prognosis(P<0.05).The expression of miR-204-5p was significantly up-regulated in bladder cancer tissues and cells(P<0.05).In bladder cancer cells,miR-204-5p overexpression significantly promoted cell proliferation,migration and invasion and reduced cell apoptosis.Transcriptome sequencing,bioinformatics analysis and dual-luciferase assay all suggested that RAB22A was a key downstream factor of miR-204-5p.Overexpression of miR-204-5p significantly inhibited RAB22A expression in bladder cancer cells,and overexpression of RAB22A partially reversed miR-204-5p overexpression-induced enhancement of bladder cancer cell proliferation.Conclusion High expression of miR-204-5p promotes proliferation,migration and invasion and reduces apoptosis of bladder cancer cells by negatively regulating RAB22A expression.

Objective To explore the regulatory effect of miR-204-5p on biological behaviors of bladder cancer cells and its molecular mechanism.Methods Survival analysis and correlation analysis were performed using TCGA database to explore the association of miR-204-5p expression with survival outcomes and clinicopathological parameters of bladder cancer patients.The expression level of miR-204-5p was detected in bladder cancer and adjacent tissues and in normal uroepithelial cells and bladder cancer cells.In cultured bladder cancer cells,the effects of miR-204-5p overexpression and knockdown on cell proliferation,migration,invasion,and apoptosis were analyzed.Transcriptome sequencing,bioinformatics analysis and dual-luciferase assay were carried out to confirm targeted inhibition of RAB22A by miR-204-5p to promote malignant biological behaviors of bladder cancer cells.Results Patients with high miR-204-5p expressions had lowered median survival time and poor prognosis(P<0.05).The expression of miR-204-5p was significantly up-regulated in bladder cancer tissues and cells(P<0.05).In bladder cancer cells,miR-204-5p overexpression significantly promoted cell proliferation,migration and invasion and reduced cell apoptosis.Transcriptome sequencing,bioinformatics analysis and dual-luciferase assay all suggested that RAB22A was a key downstream factor of miR-204-5p.Overexpression of miR-204-5p significantly inhibited RAB22A expression in bladder cancer cells,and overexpression of RAB22A partially reversed miR-204-5p overexpression-induced enhancement of bladder cancer cell proliferation.Conclusion High expression of miR-204-5p promotes proliferation,migration and invasion and reduces apoptosis of bladder cancer cells by negatively regulating RAB22A expression.

Objective:To summarize the age, gender difference, cause, location, time, treatment and prognosis of femoral intertrochanteric fracture complicated with pseudoaneurysm, and analyze the influence of different treatment methods on the occurrence of femoral intertrochanteric fracture complicated with pseudoaneurysm.Methods:Using the method of systematic literature review, a total of 76 literatures were retrieved from multiple databases at home and abroad, and 45 literatures were screened out through the second screening of title, abstract and full text. The patients with intertrochanteric fracture complicated with pseudoaneurysm were selected as the research objects, and the duplicate cases were deleted; the age, gender, onset age, etiology, location, treatment and prognosis of the disease were retrospectively analyzed.Results:A total of 54 cases of femoral intertrochanteric fracture related pseudoaneurysms were selected from 45 literatures, including 25 males and 27 females, and 2 cases had no gender; aged from 43 to 94 years old, and 4 cases were younger than 60 years old, 6 between 61 and 70, 17 between 71 and 80, and 25 between 81 and 90. Forty-five cases occurred in deep femoral artery, 3 cases in superficial femoral artery, 1 case in superior gluteal artery, 1 case of medial circumflex artery, 1 case of lateral circumflex femoral artery, 1 case of femoral artery, and 2 cases of unknown location. The occurrence time of pseudoaneurysm: 17 cases within 1 week after fracture, 8 cases from 1 week to 3 weeks, 19 cases from 3 weeks to 3 months, 2 cases more than 3 months, and 8 cases unknown. The causes of pseudoaneurysm: among the 54 patients, 41 cases had definite causes, including 21 cases of vascular injury caused by fracture block; 20 cases of iatrogenic injury, of which the incidence of direct injury of blood vessels by screw or drill was the highest, accounting for 55% (11/20). Twenty-two cases were treated with vascular embolization, 10 cases with surgical sutures, 8 cases with surgical ligation, 4 cases with resection of pseudoaneurysm, 5 cases with covered stent, and 4 cases with thrombin injection. There were 42 cases who had follow-up data, and no recurrence and other complications were found during the follow-up period.Conclusion:The peak age of femoral intertrochanteric fracture complicated with pseudoaneurysm was 71-90 years old. The incidence of femoral intertrochanteric fracture complicated with pseudoaneurysm was more often within 1 week after fracture and 3 weeks to 3 months after fracture, due to fracture fragments and iatrogenic vascular injury caused by the location of the profundus femoris artery. Treatment options include vascular embolization, surgical ligation, suture or resection of pseudoaneurysm, covered stent and thrombin injection, and the prognosis is generally good.

Objective:To investigate the effect of mechano-growth factor（MGF）on osteoclast activity and its mechanism.Methods:The RAW264.7 precursor osteoclast cell line was cultured with 25 ng/ml macrophage-colony stimulating factor（M-CSF）and 30 ng/ml receptor activator of NF-κB ligand（RANKL），and identified by tartrate resistant acid phosphatase（TRAP）staining after 7 days of culture. Western blot anslysis was used to determine the effect of 45 ng/ml MGF on the phosphoinositide-3-kinase/protein kinase B（PI3K/AKT）signaling pathway in separated osteoclasts，including levels of AKT，phosphorylation（p）-AKT，lactation mammalian target of rapamycin（mTOR），p-mTOR and TRAP at 0，4，8 and 12 hours. Real-time fluorescence quantitative PCR was used to expressions of TRAP in osteoclasts at 0，4，8 and 12 hours. The PI3K/Akt phosphorylation inhibitor LY294002（20 μmol/L）combined with MGF（45 ng/ml）was used to act on osteoclasts，and expression levels of Akt，p-Akt，mTOR，p-mTOR and TRAP were detected by Western blot at 0，4，8 and 12 hours.Results:After culturing RAW264.7 cells with M-CSF and RANKL for 7 days，a large number of osteoclasts with positive TRAP staining can be obtained. Western blot analysis showed expression levels of Akt and mTOR did not change significantly over time（ P>0.05），expression levels of p-Akt and p-mTOR increased continuously from（2.18±0.34）pg/ml and（0.83±0.10）pg/ml at 0 hour to（3.86±0.36）pg/ml and（1.56±0.19）pg/ml at 12 hours（ P<0.05），and expression level of TRAP decreased significantly over time，from（5.66±0.47）pg/ml at 0 hour to（3.76±0.38）pg/ml at 12 hours（ P<0.05）. Real-time fluorescence quantitative PCR analysis of expression of TRAP in osteoclasts showed that MGF inhibited the expression of TRAP in osteoclasts，which decreased from 1.02±0.06 at 0 hour to 0.53±0.11 at 12 hours（ P<0.05）. After acting LY294002 combined with MGF on osteoclasts，Western blot analysis showed expression levels of Akt and mTOR did not change significantly over time（ P>0.05），expression levels of p-AKT and p-mTOR decreased significantly from（3.28±0.18）pg/ml and（3.29±0.22）pg/ml at 0 hour to（2.06±0.34）pg/ml and（2.04±0.20）pg/ml at 12 hours（ P<0.05），and expression level of TRAP had no significant difference over time（ P>0.05）. Conclusions:MGF inhibits osteoclast activity by inhibiting the expression of TRAP in osteoclasts through PI3K/Akt signaling pathway. LY294002 inhibits the expression of PI3K/Akt signaling pathway in osteoclasts，further verifying the mechanism of MGF inhibiting osteoclast activity，and this finding puts forward new ideas for clinical prevention and treatment of osteoporosis.

Objective:To compare the outcomes of combined lingual mucosal graft with buccal mucosal graft urethroplasty and combined lingual mucosal graft with ADM (acellular dermal matrix) urethroplasty for the treatment of repair failed hypospadias.Methods:From February 2017 to February 2019, 26 patients with failed hypospadias repairs were treated with combined lingual mucosal graft with buccal mucosal graft urethroplasty (14 cases in Group A), and combined lingual mucosal graft with ADM urethroplasty (12 cases in Group B). The mean age of Group A was (29.5±1.2) years (range 18.0-41.0 years), and (26.5±0.8) years (range 20.0-38.0 years) in Group B. The previous operation times was mean (3.6±0.7)(range 2-5 times) and (4.6±0.8)(range 3-5 times) in Group A and Group B respectively. Operation method: All patients were nasally intubated, the remaining curvature was corrected, the fibrous tissue or scar was removed, and the defected urethra was measured. In Group A, the lingual mucosa was spread and fixed to the corpora cavernosa over the midline as the urethral plate, the buccal mucosa was covered the lingual mucosa as ventral urethra, both the mucosa lateral edges was sutured. In Group B, the lingual mucosa was harvested and fixed to the corpora cavernosa the same as in Group A, the ADM was made appropriate length and width, covered and sutured with the lingual mucosa. The lingual mucosa was harvested mean (5.0±0.2)cm(range 4-6cm)long, mean (1.2±0.2)cm (range 1.0-1.5cm)wide and mean (5.0±0.2)cm(range 5-6cm)long, mean (1.2±0.2)cm (range 1.0-1.5cm)wide in Group A and Group B respectively( P<0.05). In Group A, the buccal mucosa was harvested mean (4.1±0.2)cm(range 3.5-5.5cm)long, mean (1.2±0.2)cm wide. Criteria for successful repair of hypospadias were set as: ①The appearance of the penis is nearly normal; ②The penis curvature was corrected; ③Urethra orifice in normal position; ④Urine flow line is normal. The outcomes of the two groups were analyzed and compared, statistical analysis was done using SPSS 18.0 software. Results:The mean follow-up time was (16.3±1.6)(8-24) months. The age, number of preoperative surgeries, number of previous oral mucous membranes, and length of urethral defects were no statistically significant differences between the two groups in A and B( P>0.05). The length of oral mucosa was harvested during the operation between group A and Group B were statistically significant differences( P<0.05). The incidence of oral complications in group A and B: Oral pain 7/14, 1/12; The feeling of tension in mouth 8/14, 1/12; The numbness in the oral 8/14, 1/12, A and Group B were statistically significant differences( P<0.05). The incidence of urethral complications in group A and Group B: the urethra fistula 1/14, 4/12; the urethral stricture 2/14, 6/12, there were statistically significant differences between the two groups ( P<0.05). Penile curvature 2/14, 1/12, ( P>0.05). The success rate was 12/14 and 5/12 in Group A and B respectively, with statistical difference( P<0.05). Conclusions:Combined lingual mucosal graft with buccal mucosal graft urethroplasty could be a good choice for repeated failed hypospadias repairs. Combined lingual mucosal graft with ADM urethroplasty has many complications and less success, should be performed in caution.

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in

OBJECTIVE: To explore the application of the"five-line division method "in selecting the surgical approach for occupying lesions in the saddle area and its adjacent areas. METHODS: Based on the natural anatomic structures, 5 lines (alpha, beta, theta line and lambda, epsilon line) were drawn on the images of the craniocerebral axial plane crossing the middle of the saddle area and the craniocerebral median sagittal plane, thus dividing the saddle area and its adjacent areas into 6 regions in the axial plane (1, 2, 3, 1', 2', and 3' regions) and into 4 regions in the sagittal plane (I, II, III, and IV regions). Based on these divisions, the large space-occupying lesions in the saddle area and adjacent areas were classified and their respective surgical approaches were determined after reviewing the commonly used approaches in the saddle area and clinical experiences. We collected the data of 116 patients undergoing surgeries for space-occupying lesions involving the saddle and the adjacent areas in our hospital between September, 2014 and August, 2017, and analyzed their classifications and the corresponding surgical approaches based on the "five- line division method " to compare the consistency between the hypothetic approaches and the approaches adopted in the actual surgeries. RESULTS: The actual surgical approaches adopted in the 116 cases were all selected under the guidance of experts in our hospital. The hypothetic surgical approaches selected based on the"five- line division method "showed a good consistency with the actually adopted approaches. CONCLUSIONS The"five-line division method "can spatially classify the commonly seen space-occupying lesions involving the saddle area and its adjacent area to provide assistance in the selection of surgical approaches for such lesions.
General Surgery/methods* ; Humans

Objective: To evaluate the treatment of complex acetabular fractures involving the posterior column by anterograde lag screws via the ilioinguinal approach. Methods: A retrospective study was conducted of the 8 patients with complex acetabular fracture involving the posterior column who had been treated at Department of Orthopaedics, The Second Affiliated Hospital to Inner Mongolia Medical University from January 2017 to June 2018. They were 5 males and 3 females, aged from 35 to 62 years (average, 43.5 years). According to the Letournel-Judet classification, 3 cases were T-shaped fractures, 4 anterior column plus posterior hemitransverse fractures and one both column fracture. The interval from injury to operation averaged 8 days (from 7 to 17 days). The anterior acetabulum was fixated by a reconstruction plate and the posterior column by antegrade lag screws, all through the ilioinguinal approach. The quality of fracture reduction, fracture union time, function of the affected hip and complications were recorded. Results: By the Matta imaging criteria, the quality of fracture reduction was rated as excellent in 7 cases and as fine in one. Intraoperative major hemorrhage or injury to sciatic nerve occurred in none of the patients. This cohort obtained an average follow-up of 8 months (from 6 to 18 months). All fractures united well after an average of 10 weeks (from 8 to 12 weeks). The function of affected hip evaluated by the improved Merle d’Aubigne & Postel criteria at the last follow-up was excellent in 7 cases and fine in one. Follow-ups revealed no incidence of deep vein thrombosis or heterotopic ossification. Conclusions For patients with complex acetabular fracture involving the posterior column, internal fixation of the anterior acetabulum with a reconstruction plate through the ilioinguinal approach and fixation of the posterior column with antegrade lag screws also through the ilioinguinal approach can result in fine therapeutic effects, because complications like ectopic ossification and sciatic nerve injury related to the Kocher-Langenbeck approach can be prevented. This treatment is particularly suitable for the patients whose condition of the soft tissues at the posterior pelvis is poor.