Objective:To investigate the expression of Cullin associated NEDD8 dissociated protein 1 in colorectal cancer and its effect on the biological behavior of colorectal cancer.Method:A total of 70 pairs of colorectal cancer and paired normal tissue specimens were collected from Jun to Dec 2017 at the Department of Gastrointestinal Surgery at Peking University People's Hospital. Immunohistochemistry was used to detect the expression of Cullin associated NEDD8 dissociated protein 1 and analyze its relationship with clinical pathological indicators and prognosis. CCK8, colony formation assay, transwell assay, and wound healing assay were used to evaluate the effects of Cullin associated NEDD8 dissociated protein 1 on the proliferation, migration, and invasion ability of colon cancer cells.Result:Compared with normal tissues, Cullin associated NEDD8 dissociated protein 1 was highly expressed in colorectal cancer (Immunohistochemistry score: 3.685±1.257 vs. 2.000±0.851, Z=6.536, P<0.001). The expression level of Cullin associated NEDD8 dissociated protein 1 was significantly correlated with T stage ( χ2=5.67, P=0.017), N stage ( χ2=7.20, P=0.007), and pathology stage ( χ2=4.66, P=0.031). Patients with high expression of Cullin associated NEDD8 dissociated protein 1 had a worse prognosis than those with low expression ( χ2=4.80, P=0.037). Knocking down Cullin associated NEDD8 dissociated protein 1 significantly reduced the proliferation, colony formation, and invasive migration ability of DLD1 cells (all P<0.05). Conclusion:Cullin associated NEDD8 dissociated protein 1 is significantly overexpressed in colorectal cancer and has a promoting effect on the occurrence and development of colorectal cancer.

Objective:To investigate the expression of Cullin associated NEDD8 dissociated protein 1 in colorectal cancer and its effect on the biological behavior of colorectal cancer.Method:A total of 70 pairs of colorectal cancer and paired normal tissue specimens were collected from Jun to Dec 2017 at the Department of Gastrointestinal Surgery at Peking University People's Hospital. Immunohistochemistry was used to detect the expression of Cullin associated NEDD8 dissociated protein 1 and analyze its relationship with clinical pathological indicators and prognosis. CCK8, colony formation assay, transwell assay, and wound healing assay were used to evaluate the effects of Cullin associated NEDD8 dissociated protein 1 on the proliferation, migration, and invasion ability of colon cancer cells.Result:Compared with normal tissues, Cullin associated NEDD8 dissociated protein 1 was highly expressed in colorectal cancer (Immunohistochemistry score: 3.685±1.257 vs. 2.000±0.851, Z=6.536, P<0.001). The expression level of Cullin associated NEDD8 dissociated protein 1 was significantly correlated with T stage ( χ2=5.67, P=0.017), N stage ( χ2=7.20, P=0.007), and pathology stage ( χ2=4.66, P=0.031). Patients with high expression of Cullin associated NEDD8 dissociated protein 1 had a worse prognosis than those with low expression ( χ2=4.80, P=0.037). Knocking down Cullin associated NEDD8 dissociated protein 1 significantly reduced the proliferation, colony formation, and invasive migration ability of DLD1 cells (all P<0.05). Conclusion:Cullin associated NEDD8 dissociated protein 1 is significantly overexpressed in colorectal cancer and has a promoting effect on the occurrence and development of colorectal cancer.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Objective To investigate the effect of glycine N-methyl transferase (GNMT)on intrauterine adhesion (IUA)fibrosis and its related mechanism.Methods In vivo experiment:A total of 36 healthy female SD rats (SPF grade,6～8 weeks old and weighing from 180～220 g)were subjected in this study.IUA model of SD rats and IUA model of GNMT overexpressed rats were established.RT-qPCR and immunofluorescence assay were applied to detect GNMT expression level in normal uterus and model group.RT-qPCR and Western blotting were used to detect the mRNA and protein levels of fibrosis-related molecules and the activation of TGF-β1/Smad3 signaling pathway in each group.The number of endometrial glands in each group was observed by HE staining.Masson staining was used to analyze the severity of endometrial fibrosis in each group.In vitro experiment:transformed human endometrial stromal cells (THESCs)fibrotic phenotype model was constructed using TGF-β1,and THESCs stably transfected with GNMT overexpression lentvirus were treated with TGF-β1.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of fibrosis-related molecules.The expression of TGF-β1/Smad3 signaling pathway was detected by Western blotting.TGF-β1/Smad3 signaling pathway was activated by TGF-β1/Smad signaling pathway activator (SRI-011381),and the expression of TGF-β1/Smad3 signaling pathway and key molecular proteins of fibrosis phenotype was measured with Western blotting.Results In vivo experiment,the mRNA and protein expression levels of GNMT were significantly decreased in the IUA rats than the control rats (P<0.05).Overexpression of GNMT decreased the mRNA and protein levels of fibrosis related molecules,Collagen Ⅰ,Collagen Ⅲ and FN in the IUA rats (P<0.05),and decreased the phosphorylation levels of TGF-β1 and its downstream Smad3 protein (P<0.05).HE and Masson staining showed that overexpression of GNMT could increase the number of endometrial glands and reduce the severity of fibrosis in the IUA rats (P<0.05).In vitro experiments:overexpression of GNMT decreased the mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ and FN associated with fibrotic phenotype of THESCs (P<0.05),and reduced the phosphorylation level of Smad3 protein,downstream of TGF-β1 (P<0.05).After activation of TGF-β1/Smad3 signaling pathway,the protein levels of TGF-β1/Smad3 signaling pathway and downstream fibrosis phenotype molecules,Collagen Ⅲ and FN,were significantly decreased in the LV-GNMT+SRI-011381 group.Conclusion Overexpression of GNMT can inhibit endometrial fibrosis by regulating TGF-β1/Smad3 signaling pathway,thus achieving therapeutic effect on IUA.

Objective:To evaluate the clinical effect of modified posterior pharyngeal flap surgery in the treatment of velopharyngeal insufficiency.Methods:Clinical data of patients with cleft lip and palate diagnosed with velopharyngeal insufficiency and undergoing modified posterior pharyngeal flap surgery in Peking University School and Hospital of Stomatology from January 2018 to May 2022 were retrospectively analyzed. The traditional posterior pharyngeal flap surgery was improved by combining the modern concept and method of soft palate muscle reconstruction, and performed modified posterior pharyngeal flap surgery to correct velopharyngeal insufficiency. Preoperative and postoperative follow-up were performed including speech evaluation (classifying as none, mild, moderate, moderate to severe hypernasality and nasal emission), nasopharyngeal fiberscope (classifying velopharyngeal insufficiency as mild, moderate, or severe), lateral cephalometric radiographs (resting position and /i/ position), and the Nasal Obstruction Symptom Evaluation (NOSE) scale. The recovery of velopharyngeal function and nasal ventilation after the operation were statistically analyzed. The difference of resting velar length (RVL), effective working length (EWL) and angel of velar lifting (AVL) before and after the operation was compared by paired t-test to evaluate the clinical effect of surgery. P<0.05 indicates a statistically significant difference. Results:A total of 83 patients with velopharyngeal insufficiency were enrolled, including 44 males and 39 females, aged (13.04±11.31) years (4-53 years). 83 patients were followed up for 6-18 months after surgery, and all patients had primary wound healing without postoperative bleeding, perforation, or posterior pharyngeal flap detachment; 78 cases achieved complete velopharyngeal closure, the surgical success rate was 94%, three patients still had mild hypernasality and nasal emission after surgery, one patient still had moderate hypernasality and nasal emission after surgery, and one patient had severe hypernasality after surgery. The RVL was (29.27±6.01) mm before the operation and (36.88±6.51) mm after the operation.The EWL of the soft palate was (18.53±5.04) mm before the operation and (25.76±5.17) mm after the operation.The angel of velar lifting was 11.42°±11.65° before the operation and 15.91°±8.54° after operation. The differences were statistically significant ( P<0.01). 98%(81/83) patients had subjective nasal obstruction symptom in the short period after surgery (within one month), the nasal obstruction symptom evaluation (NOSE) score was 8.61±3.64. The long-term postoperative follow-up showed that the NOSE score was 3.06±2.92, and the difference was statistically significant ( P<0.01). Conclusion:Modified posterior pharyngeal flap surgery can significantly increase the resting velar length and effective working length, improve the movement ability of the soft palate, acquire functional reconstruction of velopharyngeal closure, improve speech function and achieve effectively surgical results.

Objective To investigate the influencing factors of vancomycin in the area under curve for 24 h(AUC0-24h)in patients after orthopedic surgery,and to predictive and analyze a good pharmacokinetic model for AUC0-24h Methods Patients who underwent orthopedic surgery and used vancomycin in The Sixth Affiliated Hospital of Xinjiang Medical University from January 2018 to December 2022 were included,and the basic information,the medication,the blood and biochemical indexes of the patients were collected to analyze the factors affecting postoperative vancomycin AUC0-24h in orthopedic surgery.The AUC0-24h was calculated using the first-level pharmacokinetic formula,the JavaPK? for Desktop(JPKD)and the vancomycin daily dose elimination rate formula.Results 91 patients were finally included,and the cystatin C(OR=189.168,P=0.005)and the single dose(OR=19.160,P＜0.001)were independent protective factors for vancomycin AUC0 24 h in postoperative orthopedic patients,and the retinol binding protein was an independent risk factor for vancomycin AUC0-24h(OR=0.910,P＜0.05).By predicting and analyzing the model of vancomycin AUC0 24h in postoperative orthopedic patients,the absolute percentage error of both JPKD software and vancomycin daily dose elimination rate formula were lower than 30％.The intraclass correlation efficient between the AUC0 24h of the JPKD software and vancomycin daily dose elimination rate formula,and the AUC0 24h of the first-level pharmacokinetic formula were 0.781 and 0.524,respectively.Conclusion Cystatin C is an important factor influencing vancomycin AUC0-24h in postoperative orthopedic patients,and JPKD software is more suitable for predicting vancomycin AUC0-24h after orthopedic surgery than the vancomycin daily dose elimination rate formula method.

Objective:To evaluate the clinical effect of modified posterior pharyngeal flap surgery in the treatment of velopharyngeal insufficiency.Methods:Clinical data of patients with cleft lip and palate diagnosed with velopharyngeal insufficiency and undergoing modified posterior pharyngeal flap surgery in Peking University School and Hospital of Stomatology from January 2018 to May 2022 were retrospectively analyzed. The traditional posterior pharyngeal flap surgery was improved by combining the modern concept and method of soft palate muscle reconstruction, and performed modified posterior pharyngeal flap surgery to correct velopharyngeal insufficiency. Preoperative and postoperative follow-up were performed including speech evaluation (classifying as none, mild, moderate, moderate to severe hypernasality and nasal emission), nasopharyngeal fiberscope (classifying velopharyngeal insufficiency as mild, moderate, or severe), lateral cephalometric radiographs (resting position and /i/ position), and the Nasal Obstruction Symptom Evaluation (NOSE) scale. The recovery of velopharyngeal function and nasal ventilation after the operation were statistically analyzed. The difference of resting velar length (RVL), effective working length (EWL) and angel of velar lifting (AVL) before and after the operation was compared by paired t-test to evaluate the clinical effect of surgery. P<0.05 indicates a statistically significant difference. Results:A total of 83 patients with velopharyngeal insufficiency were enrolled, including 44 males and 39 females, aged (13.04±11.31) years (4-53 years). 83 patients were followed up for 6-18 months after surgery, and all patients had primary wound healing without postoperative bleeding, perforation, or posterior pharyngeal flap detachment; 78 cases achieved complete velopharyngeal closure, the surgical success rate was 94%, three patients still had mild hypernasality and nasal emission after surgery, one patient still had moderate hypernasality and nasal emission after surgery, and one patient had severe hypernasality after surgery. The RVL was (29.27±6.01) mm before the operation and (36.88±6.51) mm after the operation.The EWL of the soft palate was (18.53±5.04) mm before the operation and (25.76±5.17) mm after the operation.The angel of velar lifting was 11.42°±11.65° before the operation and 15.91°±8.54° after operation. The differences were statistically significant ( P<0.01). 98%(81/83) patients had subjective nasal obstruction symptom in the short period after surgery (within one month), the nasal obstruction symptom evaluation (NOSE) score was 8.61±3.64. The long-term postoperative follow-up showed that the NOSE score was 3.06±2.92, and the difference was statistically significant ( P<0.01). Conclusion:Modified posterior pharyngeal flap surgery can significantly increase the resting velar length and effective working length, improve the movement ability of the soft palate, acquire functional reconstruction of velopharyngeal closure, improve speech function and achieve effectively surgical results.

Objective·To assess the effect of veno-arterial extracorporeal membrane oxygenation(VA-ECMO)treatment on the mortality rate of patients suffering from cardiogenic shock and cardiac arrest in hospital.Methods·A total of 19 patients with cardiogenic shock or cardiac arrest who were treated with VA-ECMO treatment in Suzhou Kowloon Hospital,Shanghai Jiao Tong University School of Medicine from September 2017 to March 2022 were included in the retrospective study.Patients were divided into extracorporeal cardiopulmonary resuscitation(ECPR)group(n=9)and VA-ECMO for cardiogenic shock(E-CS)group(n=10)according to whether cardiac arrest had occurred.The general demographic data,clinical data,Sequential Organ Failure Assessment(SOFA)scores,postoperative complications and prognostic indicators of the two groups of patients were collected.Univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the correlation between each covariate and hospital mortality.Results·Among the included patients,there were 15 males(78.9％),with an average age of 46.5(34.5,61.6)years.The incidence of postoperative complications was as follows:bleeding(47.4％),AKI(36.8％),infection(31.6％),limb ischemia(15.8％)and cerebrovascular accident(5.3％).The duration of VA-ECMO was 4.0(2.0,6.8)days,and the intensive care duration was 11.5(5.8,26.2)days;the ECMO withdrawal success rate was 63.2％,and the hospital mortality was 63.2％.The results of univariate Cox proportional hazard regression analysis showed that AKI(prior to VA-ECMO initiation),postoperative complications of infection and limb ischemia were correlated with the hospital mortality of patients(all P＜0.05).The results of multivariate Cox proportional hazard regression analysis showed that AKI(prior to VA-ECMO initiation),postoperative complications of infection and limb ischemia were also independent risk factors for the hospital mortality of patients(all P＜0.05).Conclusion·For patients with cardiogenic shock and cardiac arrest treated with VA-ECMO,AKI(prior to VA-ECMO initiation),postoperative infection and limb ischemia are independently associated with higher hospital mortality.

Objective    To compare the outcomes following emergency surgery or conservative treatment for patients with acute type A aortic intramural hematoma (IMH). Methods    Clinical data of consecutive patients diagnosed with acute type A aortic IMH in our hospital from September 2014 to December 2018 were retrospectively analyzed. The patients who met our surgical indications received surgery (an operation group) and other patients received strict conservative treatment (a conservative treatment group). Results    Finally 127 patients were enrolled, including 112 males and 15 females with an average age of 53.6±13.0 years. Of 127 patients, 85 (66.9%) patients accepted emergency surgery and 42 (33.1%) patients accepted strict conservative treatment. There was no difference between the two groups in early mortality or complications (P>0.05). The 5-year survival rate was 90.4% in the operation group and 74.3% in the conservative treatment group (P=0.010). A maximum aortic diameter in the ascending aorta and aortic arch≥45 mm and maximum thickness of IMH in the same section≥8 mm were risk factors for IMH-related death in patients undergoing conservative treatment (P<0.001). Conclusion    The mortality associated with emergency surgery for patients with acute type A aortic IMH is satisfactory. In clinical centers with well-established surgical techniques and postoperative management, emergency surgical treatment may provide a better outcome than conservative treatment for patients with acute type A aortic IMH.