ObjectiveTo explore the role of β-catenin in the proinvasive consequences of hypoxia in hepatocellular carcinoma (HCC).MethodsWe established in vitro and in vivo hypoxic models using the highly metastatic MHCC97 and the stable red fluorescent protein-expressing MHCC97-R cells.The role of β-catenin in hypoxia-mediated aggressiveness was investigated by β-catenin knockdown.ResultsHypoxia caused a pronounced arrest of proliferation in MHCC97 cells,suppressed tumor growth in MHCC97-R xenografts,but promoted in vitro invasiveness and in vivo metastasis.β-Catenin-silencing by short hairpin significantly inhibited the enhanced invasiveness of MHCC97 cells due to hypoxia,reduced the increase in distant metastasis by hepatic arterial ligation,but failed to further restrain cell proliferation.Conclusionβ-Catenin in HCC cells plays an essential role in the hypoxia-induced metastatic potential.A reduction of βcatenin expression inhibited the proinvasive consequences of hypoxia in HCC.

Objective To study the desired therapeutic effect of vaginoplasty using sigmoid colon or peritoneum for entire vaginal atre-sia.Methods From May 2015 to October 2015,8 patients with complete vaginal atresia in our hospital performed vaginoplasty using sigmoid colon or peritoneum successfully.The operation methods,prognosis and therapeutic effect and quality of sexual life of two groups were com-pared and analyzed to investigate a perfect operative method and ideal nursing.Results Laparoscopic vaginoplasty using the peritoneum compared with that using sigmoid colon has advantages of shorter time of operation,less bleeding,less trauma and quicker recovery.However, artificial vagina using sigmoid colon was much more similar to a natural vagina in morphological and physiological characteristics,merely ac-companied by excessive mucus discharge during the postoperative period.At lower risk of vaginal adhesion and stenosis,laparoscopically as-sisted vaginoplasty using sigmoid colon graft also puts high technical requirements.Two patients normally developed uterus menstruate regular-ly.Four patients without uterus and 2 patients with rudimentary uterus experienced good sexual intercourse after vaginoplasty.Conclusion Patients with complete colpatresia who have normal womb should creat a patent and functional vagina until adolescence to restore its physio-logical and reproductive function.Anatomical reconstructive treatment of vaginal agenesis for patients with absent or hypoplastic uterus can be postponed till the late teens or in the adult.Both laparoscopic sigmoid vaginoplasty and peritoneal vaginoplasty achieve a minimal-invasive, cosmetic,natural lubricous, smooth artificial vagina for patient’ s sex life satisfactory.

Objective To explore the clinical efficacy and safety of hyper-early embolotherapy in treatment of intracranial ruptured aneurysm.Methods A retrospective analysis was made on 33 patients with intracranial ruptured aneurysm.Preoperative Hunt-Hess grade:grade Ⅰ-Ⅱ in 16 patients,gradeⅢin 5 patients,grade Ⅳ in 9 patients,grade Ⅴ in 3 patients.All patients were confirmed with subarachnoid hemorrhage (SAH) by angiography and then underwent embolization under general anesthesia by detachable coils within 6 h from onset.Results After operation,25 patients (75.8％) recovered well,4 patients (12.1％) were with mild disability with paralysis and aphasia,4 patients (12.1％) were dead (1 patient for intraoperative aneurysm rupture,1 patient for postoperative pneumonia,1 patient for infection of hematoma at puncture site and 1 patient for postoperative gastrointestinal bleeding).Followed up 1-6 months,no rebleeding occurred.Conclusions Hyper-early embolotherapy could avoid rebleeding of the aneurysm,and relieve the vasespasm,without increasing the intra-operative rebleeding rate.Moreover hyper-early embolotherapy could greatly decrease the mortality of poor-grade SAH patients.

Objective To investigate the clinical effect of percutaneous hollow screw combined with tension band internal fixation for comminuted patellar fracture after arthroscopic reduction.Methods 105 patients with comminuted patellar fracture in our hospital from April 2013 to September 2017 were selected and divided into observation group (n =53) and control group (n =52) according to different treatment schemes.The control group was treated with conventional open reduction and Kirschner wire combined with tension band internal fixation,while the observation group was treated with arthroscopic assisted reduction and percutaneous cannulated screw combined with wire tension band internal fixation.The operation status and postoperative fracture healing time of the two groups were compared.One-year follow-up was performed after operation.The incidence of complications,the excellent and good rate of operation,and the preoperative and postoperative pain scores (VAS) and knee were compared.Hospital for special surgery knee score (HSS),Activity of Daily Life Scale (ADL),quality of life score (the Mos 36-item Short Form Health Survey,SF-36) were compared.Results The observation group had fewer fluoroscopy times during operation,shorter incision length and shorter healing time after operation than the control group (P ＜ 0.05);the incidence of complications in the observation group was 3.85％,lower than 20.00％ in the control group,and the excellent and good rate of operation was 96.15％,higher than 82.00％ in the control group (P ＜ 0.05);the VAS scores of the two groups were lower than those of the control group one year after operation,and the scores of HSS,ADL and SF-36 were lower than those of the control group.The preoperative improvement was higher in the observation group than in the control group (P ＜ 0.05).Conclusions Arthroscopic reduction combined with percutaneous hollow screw and tension band internal fixation for patellar comminuted fracture can reduce surgical trauma and accelerate the rehabilitation of patients.It can reduce the incidence of complications,relieve pain,improve knee function,daily living ability and quality of life,and the effect is remarkable.

BACKGROUND:Currently,there is a lack of large sample studies to analyze the bone metabolism level of patients with femoral head necrosis of different etiologies and stages,which is not conducive to the development of better necrosis-promoting repair strategies. OBJECTIVE:To study the bone metabolism of patients with osteonecrosis of the femoral head with different etiologies and Association Research Circulation Osseous(ARCO)stages. METHODS:A retrospective study was performed on 401 patients diagnosed with osteonecrosis of the femoral head as the trial group,and 81 healthy subjects as the control group.The trial group could be divided into three groups according to different etiologies:steroid-induced osteonecrosis of the femoral head,alcoholic osteonecrosis of the femoral head and traumatic osteonecrosis of the femoral head,and were divided into stages Ⅱ/Ⅲ/Ⅳ according to different ARCO stages.Seven bone metabolism-related indicators of all subjects were collected,including bone metabolism-regulating hormone 25-hydroxyvitamin D and bone conversion markers:N-terminal propeptide of type Ⅰ procollagen,degradation product of type Ⅰ collagen,n-terminal middle molecular fragment of osteocalcin,general biochemical markers of bone metabolism:serum calcium,serum phosphorus,serum alkaline phosphatase.The bone metabolism levels of each group were compared and the independent factors associated with osteonecrosis of the femoral head were determined by binary Logistic regression analysis. RESULTS AND CONCLUSION:Compared with the control group,levels of degradation product of type Ⅰ collagen,N-terminal propeptide of type Ⅰ procollagen,n-terminal middle molecular fragment of osteocalcin,serum phosphorus and alkaline phosphatase in the trial group were significantly increased(all P＜0.05).Based on the presence or absence of the disease,according to binary Logistic regression analysis,degradation product of type Ⅰ collagen,N-terminal propeptide of type Ⅰ procollagen,and n-terminal middle molecular fragment of osteocalcin were independent factors associated with osteonecrosis of the femoral head.The levels of degradation product of type Ⅰ collagen and N-terminal propeptide of type Ⅰ procollagen in three groups of patients with different etiologies were higher than normal reference values.The bone metabolism-regulating hormone 25-hydroxyvitamin D and serum calcium in the alcoholic osteonecrosis of the femoral head group were higher than those in the other two groups(P＜0.05).The level of bone metabolism-regulating hormone 25-hydroxyvitamin D in steroid-induced and traumatic osteonecrosis of the femoral head groups was lower than the normal value.There were no significant differences in seven bone metabolism-related indicators in patients with ARCO stages Ⅱ,Ⅲ and Ⅳ osteonecrosis of the femoral head(all P＞0.05),but degradation product of type Ⅰ collagen and N-terminal propeptide of type Ⅰ procollagen in these three groups were higher than normal reference values.Bone metabolism-regulating hormone 25-hydroxyvitamin D in patients with ARCO stage Ⅱ and ARCO stage Ⅳ was lower than the normal reference value.It is concluded that the bone metabolism level of osteonecrosis of the femoral head patients was abnormal.The degradation product of type Ⅰ collagen and N-terminal propeptide of type Ⅰ procollagen of osteonecrosis of the femoral head patients with different etiologies and ARCO stages were all higher than the normal reference value,and they were in a state of high bone turnover.Degradation product of type Ⅰ collagen,N-terminal propeptide of type Ⅰ procollagen and n-terminal middle molecular fragment of osteocalcin may be risk factors for the pathogenesis of osteonecrosis of the femoral head.

BACKGROUNDAltered immunoresponse is associated with tumorigenesis and cancer progression. This study assessed the levels of tumor-infiltrating CD3 + or CD8 + T lymphocytes and interleukin-2 (IL-2) protein in radically resected non-small cell lung cancer (NSCLC) tissues to predict overall survival (OS) of the patients.

METHODSParaffin-embedded tissue specimens from 129 NSCLC patients were retrospectively collected for immunostaining of CD8 + , CD3 + , and IL-2 expression. Clinicopathological and survival data were collected and analyzed using the Chi-squared test, Kaplan-Meier curves, and the log-rank test or the Cox regression model.

RESULTSThe data showed a significant inverse association between CD8 + T lymphocyte levels and IL-2 expression (r = -0.927; P = 0.000) and between the levels of CD8 + and CD3 + T lymphocytes (r = -0.722; P = 0.000), but a positive association between CD3 + T lymphocyte levels and IL-2 expression (r = 0.781; P = 0.000) in NSCLC tissues. Furthermore, the levels of CD3 + and CD8 + T lymphocytes and IL-2 expression were associated with tumor stage (P = 0.023, 0.006, and 0.031, respectively) and the level of CD8 + T lymphocytes was associated with the patient gender (P = 0.024). In addition, the levels of CD8 + T lymphocytes were associated with an unfavorable 5-year OS, whereas patients with high levels of CD3 + T lymphocytes in tumor lesions and IL-2-expressing tumors had significantly better 5-year OS rates than patients with low levels.

CONCLUSIONSThe levels of CD8 + T cells in tumor lesions and IL-2 expression were both independent predictors of OS for these NSCLC patients. Thus, the detection of tumor-infiltrating CD3 + or CD8 + T lymphocytes and IL-2 expression could be useful to predict the prognosis of radically resected NSCLC patients.

CD3 Complex ; metabolism ; CD8-Positive T-Lymphocytes ; metabolism ; Female ; Humans ; Immunohistochemistry ; Interleukin-2 ; metabolism ; Lung Neoplasms ; immunology ; metabolism ; Lymphocytes, Tumor-Infiltrating ; metabolism ; Male ; Prognosis

Objective To explore the clinical significance and mechanisms of chromatin licensing and DNA repli-cation factor 1(CDT1)in lung adenocarcinoma).Methods The gene expression samples of lung adenocarcinoma tissue and normal lung tissue were downloaded from the TCGA database,and perform differential analysis,GO a-nalysis,independent prognosis analysis,and correlation analysis with immunotherapy using R language.CDT1 ex-pression in lung adenocarcinoma and normal tissues was detected by PCR in clinical samples.The changes of cell proliferation and cycle in si-CDT1 knockdown group and si-NC control group were detected by flow cytometry.The invasive ability of each group was detected by Transwell.The expressions of CDT1,TPX2 and p53 in each group were detected by Western blot.Results The TCGA data analysis revealed CDT1 as a differentially expressed gene.GO analysis indicated that CDT1 was closely associated with the cell cycle.The high expression of CDT1 in lung adenocarcinoma tissues was validated in clinical samples.CDT1 could serve as an independent factor for predicting the prognosis of lung adenocarcinoma and had predictive value for immunotherapy in lung adenocarcinoma.Knock-down of CDT1 resulted in a significant decrease in cell proliferation ability compared to the control group,and cells were noticeably arrested in the G1 phase.Transwell assay results demonstrated a significant reduction in invasive capacity in the CDT1 knockdown group.Knockdown of CDT1 led to a significant decrease in TPX2 expression and a significant increase in p53 expression,while overexpression of CDT1 yielded the opposite effect.Conclusion Re-sults demonstrate the elevated expression of CDT1 in lung adenocarcinoma,its association with prognostic signifi-cance,and its impact on lung adenocarcinoma's occurrence and development by influencing TPX2 and p53.

Objective:To investigate the effect and molecular mechanism of high concentration of IL-17A on osteoclast differentiation by inhibiting autophagy of osteoclast precursor cells through PI3K/Akt pathway.Methods:With RANKL (50 ng/ml) inducing osteoclast precursor cells (osteoclast we cells, OCPs), osteoclast differentiation model is set up. In osteoclast differentiation model of high levels of IL-17A (100 ng/ml), RAW264.7 cells were divided into negative control CTR-N group, CTR-R group with RANKL, IL-17A group, IL-17A+LY294002 group. BMMs were divided into negative control CTR-N group with M-CSF, CTR-R group, IL-17A group and IL-17A+LY294002 group with M-CSF and RANKL. IL-17A was applied to OCPs, and tartrate-resistant acid phosphatase (TRAP) staining was used to observe the number of osteoclast differentiation. The number of autolysosomes was observed under transmission electron microscope. RAW264.7 was treated with IL-17A. Western blot was used to detect the relative expression levels of p-Akt/Akt, p-mtor/mTOR, p-PI3K/PI3K, p-ULK1/ULK1, Cleaved-caspase3/caspase3, Beclin1/β-actin. The apoptosis rate of RAW264.7 cells treated with IL-17A was detected by flow cytometry. OCPs were treated with IL-17A and PI3K inhibitor LY294002, and TRAP staining was used to observe the number of osteoclast differentiation.Results:The TRAP staining showed that the positive ratio for RAW264.7 cells CTR-N group, CTR-R group, IL-17A group was 1.33%±0.58%, 100%±3.01%, 51.11%±4.02% with that of IL-17A significantly lower than CTR-R group ( t=16.970, P<0.05). The positive rates of BMMs in the CTR-N group, CTR-R group and IL-17A group were 1.67%±0.58%, 100%±1.01% and 50.33%±2.52%, respectively, with that of IL-17A group significantly lower than CTR-R group ( t=31.770, P<0.05). Transmission electron microscopy showed that the number of autophagosomes in RAW264.7 cells in CTR-R group and IL-17A group were 3.67±1.53 and 0.67±0.58, respectively, with significant difference between the groups ( t=3.182, P<0.05). While in BMMs cells CTR-R group and IL-17 the numbers of autophagosome were 3.00±1.00 and 0.33±0.58 with significant difference ( t=4.000, P<0.05); Western blot results showed 0.69±0.03、0.69±0.13、1.47±0.13、0.78±0.04、0.66±0.10、0.82±0.03 for RAW264.7 cells CTR-R group Akt/Akt, p-mTOR/mTOR, p-PI3K/PI3K, p-ULK1/ULK1, Cleaved caspase3/caspase3, Beclin1/β-Actin and 0.89±0.04、1.14±0.18、1.87±0.04、0.53±0.09、0.93±0.02、0.54±0.03 for RAW264.7 cells IL-17A group p-Akt/Akt, p-mTOR/mTOR, p-PI3K/PI3K, p-ULK1/ULK1, Cleaved caspase3/caspase3, Beclin1/β-Actin with significant difference ( t=6.708; t= 3.497; t=5.424; t=4.542; t=4.638; t=11.220, all P<0.05); Flow cytometry detection showed that in CTR-R group, IL-17A RAW264.7 cells apoptosis rates of group A were 6.92%±0.62%, 12.12%±0.69%, with significant difference between the two groups ( t=9.747, P<0.05); After using LY294002 TRAP staining, it showed a positive result of 9.00%±2.00%, 158.33%±3.51%, 100%±2.65% and 128.99%±4.01% for CTR-N, CTR-R, IL-17A and IL-17A+LY294002 in RAW264.7 cells respectively with significant difference between IL-17A+LY294002 group and the IL-17A in group A ( t=10.470, P<0.05). For BMMs cells CTR-N, CTR-R group, IL-17A in group, IL-17A+LY294002 group, the positive rate was 8.01%±0.99%, 151.67%±4.51%, 100%±3.61%, with significant difference between IL-17A+LY294002 group and IL-17A group ( t=6.535, P<0.05). Conclusion:High concentration of IL-17A inhibits osteoclast differentiation by inhibiting autophagy of osteoclast precursor cells through PI3K/Akt pathway.

OBJECTIVE: To assess the association of 7 single nucleotide polymorphisms (SNPs) including rs13278062 (TNFRSF10A), rs3750846 (ARMS2-HTRA1), rs429358 (APOE), rs5817082 (CEPT), rs2043085 (LIPC), rs1626340 (TGFBR1), and rs8135665 (SLC16A8) identified through genome-wide association study (GWAS) with age-related macular degeneration (AMD) among ethnic Han Chinese from Sichuan, China. METHODS: A cohort of 576 AMD patients and 572 healthy controls were enrolled in a case-control study. The SNPs were genotyped by a Mass array MALDI-TOF System. On the premise that the genotype distribution of each SNP locus in both groups satisfied Hardy-Weinberg equilibrium, the genetic pattern was analyzed and the scores of allele and genotype frequencies ware compared. RESULTS: There was a significant association between TNFRSF10A rs13278062 and AMD under the heterozygous model (P = 0.000, OR = 1.529, 95%CI = 1.196-1.954) and the dominant model (P = 0.002, OR = 1.459, 95%CI = 1.154-1.865), suggesting that subjects carrying rs13278062GT and rs13278062TT + GT are more likely to develop the AMD, whereas no significant difference was observed for rs13278062 under other models. No association was detected with the other six SNPs and AMD under various genetic models. CONCLUSION This case-control association study has indicated that TNFRSF10A rs13278062 is associated with AMD under the heterozygous and dominant models, suggesting that the TNFRSF10A variant may be involved in the development of AMD among ethnic Han Chinese population.
Case-Control Studies ; Gene Frequency ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; High-Temperature Requirement A Serine Peptidase 1/genetics* ; Humans ; Macular Degeneration/genetics* ; Polymorphism, Single Nucleotide

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.