OBJECTIVETo investigate the effect of ADAM10 inhibitor GI254023X on the proliferation and apoptosis of multiple myeloma H929 cell line and its mechanisms.

METHODSH929 cells were treated with different concentrations of GI254023X, the proliferation-inhibitive curve was assayed and plotted by CCK-8 method, the cell viability and apoptosis were detected by flow cytometry with Annexin V/7-AAD double staining. The cleavage of Notch1 protein (cleaved notch1) was determined by Western blot. The transcripts of Notch1 target gene Hes-1 were detected by real-time PCR.

RESULTSThe GI254023X inhibited the proliferation of H929 cells in the time- and dose- dependent manners. As compared with the control group, the apoptosis of cells increased along with enhancement of GI254023X concentration; The expression of cleaved Notch1 was down-regulated after the treatment with GI254023X. The levels of Hes-1 mRNA transcripts in H929 cells was reduced in GI254023X treated group.

CONCLUSIONGI254023X can remarkably inhibit the proliferation and induce the apoptosis of H929 cells. Its mechanism may be associated with inbihition of Notch1 activation.

ADAM Proteins ; ADAM10 Protein ; Amyloid Precursor Protein Secretases ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Dipeptides ; Down-Regulation ; Humans ; Hydroxamic Acids ; Membrane Proteins ; Multiple Myeloma ; Receptor, Notch1

Objective : To investigate the effects of Lin28 overexpression on the proliferation and osteogenic differentiation of human dental pulp stem cells (hDPSCs) through mTOR signaling pathway. Methods : After transfecting lentiviral vectors of Lin28 gene in hDPSCs , the relative expression of Lin28 was detected by Real⁃time PCR. CCK⁃8 assay was applied to detect the effect on cell proliferation. qRT⁃PCR was used to research the expression levels of alkaline phosphatase (ALP) , osteopontin (OPN) and osteocalcin (OCN) . Western blot assay was processed to investigate the effects on the relative expression levels of ALP and OPN proteins. Alizarin red staining was utilized to detect the mineralized nodules. Results : Compared with the control group , the cell proliferation of transfection group was promoted (P < 0. 05) ; The mRNA and protein expression levels of ALP , OPN and OCN in transfection group were significantly lower than those in control group (P < 0. 05) , the expression level of ALP apparently decreased after the addition of mTOR inhibitor rapamycin (P < 0. 05) ; Alizarin red staining showed that the size and number of mineralized nodules formed in transfection group were markedly declined compared with empty carrier group (P < 0. 05) . Conclusion Overexpression of Lin28 can inhibit the osteogenic differentiation of hDP⁃ SCs through suppress mTOR signaling pathway.

[Objective] To explore the correlation between the 5-factor modified frailty index (mFI-5) and acute kidney injury (AKI) after laparoscopic radical nephrectomy in elderly patients with renal cancer, so as to provide reference for the prevention and treatment of postoperative AKI. [Methods] A retrospective analysis was conducted on the clinical data of 214 elderly patients (≥60 years) who underwent laparoscopic radical nephrectomy at our hospital during Dec.2018 and Dec.2021.Patients were divided into frail group (n=75, mFI-5≥2) and non-frail group (n=139, mFI-5<2). The incidence of AKI and sub items of mFI-5 were compared between the two groups.According to the occurrence of AKI, patients were divided into AKI group (n=77) and non-AKI group (n=137). Univariate and multivariate logistic analyses were conducted to identify risk factors of AKI.Receiver operating characteristic (ROC) curves were plotted to test the effectiveness of mFI-5 in predicting AKI. [Results] The incidence of AKI was significantly higher in the frail group than in the non-frail group (64.00% vs. 20.86%, P<0.05). Univariate analysis showed that the incidence of AKI was related to gender, diabetes, hypertension, nonfunctional independent status, weakness and split kidney glomerular filtration rate (GFR). Multivariate logistic regression analysis showed that male (OR=2.454, 95%CI: 1.193—5.047), complicated weakness (OR=6.580, 95%CI: 3.380—12.811), and low split kidney GFR (OR=0.945, 95%CI: 0.911—0.980) were independent risk factors of AKI (P<0.05). The area under the ROC curve of AKI predicted by mFI-5 was 0.711. [Conclusion] Preoperative mFI-5 score is an effective predictor of AKI in elderly patients undergoing laparoscopic radical nephrectomy.As patients with frailty have a higher risk of AKI, preoperative evaluation and monitoring should be strengthened and timely intervention should be taken to improve the prognosis.

AIM: To describe the clinical features of congenital isolated inferior rectus(IR)palsy with compensatory head posture of facial rotation and to analyze the effect of surgical treatment.

METHODS: Fifteen patients with IR muscle palsy further presenting with abnormal compensatory head posture of facial rotation were retrospectively identified from May 2014 to July 2018. Changes in the degree of facial rotation in patients were evaluated using an orthopedic goniasmometer. Variations in vertical and horizontal deviations were measured through prism and alternate cover tests, and changes in cyclotropia of pre- and postoperation were assessed by objective evaluation of eye torsion with fundus photography. IR resection was the main surgical treatment.

RESULTS: Among the 15 patients, 13 who were subjected to IR muscle resection or IR muscle resection combined with superior rectus muscle recession showed good results after surgery. These results included improved underaction of IR, coordination of eye movement, disappearance of abnormal facial rotation of compensatory head position, and total correction of vertical and horizontal deviation and cyclodeviation. Furthermore, each 1 mm resection of IR can correct 1.54±0.93° incyclotropia. In the other two patients with small vertical deviation who were done by inferior oblique myectomy, the improvement in facial rotation was unsatisfied, and eye motion remained uncoordinated.

CONCLUSION: Congenital isolated IR muscle palsy characterized by compensatory head posture of facial rotation is the main compensatory head posture. The resection of IR is effective and perfect. Mild overcorrection and undercorrection do not influence curative effect.

Infant, Newborn ; Humans ; Macrophage Activation Syndrome/diagnosis*

Objective: To observe the pathological changes of brain tissue in neonatal rats after hypoxic-ischemic brain damage(HIBD), the distribution and expression changes of endoplasmic reticulum stress(ERS) related factors includingactivated transcription factor 6(ATF6), inositol demand factor 1(IRE1) and double-stranded RNA-activated protein kinase-likeendoplasmic reticulum kinase(PERK) in brain tissue. Methods : Seven-day-old newborn rats were divided into sham operation group(Sham group) and hypoxic-ischemic brain damage group(HIBD group). The modified rice method was used to establish the HIBD model. Hematoxylin-eosin(HE) staining was performed on the brain tissue at the 72 h point of modeling to observe the pathological changes of the brain, Nissl staining was used to observe the neuron damage in the cortex and hippocampus, and immunohistochemistry was used to detect the expression of ATF6, IRE1 and PERK in the cerebral cortex and hippocampus of rats in each group. The models were sacrificed at 6 h, 24 h, and 72 h respectively, Western blot was used to detect the protein expression of ATF6, IRE1, and PERK at each time point at 6 h, 24 h, and 72 h. Results: 72 hours after HIBD, HE staining showed that no nerve cell injury was observed in the Sham group, while nerve cell injury was observed in the brain tissue of the HIBD group, and the main injury sites were the cerebral cortex and hippocampus. Nissl staining showed that the proportion of damaged neurons in the cortex and hippocampus of the HIBD group was higher than that in the Sham group, and the difference was statistically significant(P<0.001). Immunohistochemical staining showed that compared with the Sham group, the number of ATF6, IRE1, and PERK positive cells(brown-yellow) in the cerebral cortex and hippocampus of the HIBD group increased(P<0.001). In the HIBD group, the expression of ATF6 in the cytoplasm and nucleus of nerve cells increased, and the expression of IRE1 in the nucleus and PERK in the cytoplasm increased. The relative protein expression levels of ATF6, IRE1, and PERK at each time point in the HIBD group were higher than those in the Sham group, and the differences were statistically significant(allP<0.05). Conclusion The brain damage of neonatal rats after hypoxic-ischemic brain injury is mainly in the cerebral cortex and hippocampus, and the expression of ER stress factors in cerebral cortex and hippocampus is increased, suggesting that ER stress related factors are involved in its pathological injury.

【Objective】 To investigate the feasibility of prostatic exosomal protein (PSEP) detection kit in the diagnosis of histological prostatitis (HP) in patients with benign prostatic hyperplasia (BPH), and to explore the correlation between PSEP and other clinical parameters. 【Methods】 A total of 104 patients with BPH or BPH plus HP treated during Nov.2021 and Nov.2022 were involved. The patients were instructed to fill out the International Prostate Symptom Score (IPSS) scale independently before surgery. Clinical data such as prostate volume, residual urine volume, free prostate specific antigen (fPSA), total prostate specific antigen (tPSA), and fPSA/tPSA were collected. Preoperative midstream morning urine was collected for PSEP detection. 【Results】 The sensitivity and specificity of PSEP in the diagnosis of BPH were 93.51% and 70.37%, respectively, which were highly consistent with the postoperative pathological diagnosis results (Kappa=0.663). Serum PSEP level was positively correlated with tPSA level (r=0.242, P=0.040). 【Conclusion】 PSEP has a high clinical diagnostic value in the diagnosis of HP, which can provide a reliable basis for the diagnosis of HP in BPH patients and improve the diagnosis rate.

Objective:To observe the effect of braces combined with insoles on scoliosis and walking performance in patients with adolescent idiopathic scoliosis (AIS). Methods:From September, 2019 to September, 2020, 42 subjects with AIS were selected and randomly divided into brace group (n = 21) and brace combined with insole group (n = 21). Both groups received two-month routine rehabilitation, including braces for 22 to 23 hours a day and gymnastics for 30 minutes a day. The brace combined with insole group additionally wore insoles, at least eight hours a day for two months. Meanwhile, 32 even-aged adolescents were recruited as healthy controls. Firstly, gait and plantar pressure of 42 patients and 32 healthy adolescents were compared to find out abnormal indicators. Secondly, the scoliosis and above abnormal indicators were compared between the brace group and the brace combined with insole group Results:The center of pressure excursion index (CPEI) was higher in AIS group than in the healthy group (F = 3.120, P < 0.05), and there was no significant difference in walking speed, gait cycle and phase between two groups (P>0.05). An obvious imbalanced pressure was observed between the medial and lateral heel of the single foot and the bilateral foot in AIS patients (P < 0.05). After treatment, the Cobb's angle decreased in AIS patients (t > 7.552, P < 0.001), however, no difference was found between the brace group and the brace combined with insole group (t = 0.459, P > 0.05); the CPEI decreased (t = 2.209, P < 0.05), and the pressure in medial and lateral heel as well as the left and right foot tended to be balanced (t > 2.306, P < 0.05) in the brace combined with insole group, and were better than that of the brace group (|t| > 2.319, P < 0.05). Conclusion:Plantar pressure distribution shows obvious local and global asymmetric changes in AIS patients. The efficacy of insoles on the scoliosis is limited, but the insole can effectively improve the abnormal biomechanics and balance the force.

OBJECTIVETo assess the effects of warm ischaemia time (WIT) on renalfunction after laparoscopic partial nephrectomy (LPN) for renal masses in patients.

METHODSFrom January 2010 to December 2012, 39 patients treated with LPN for a single T1 renal tumor were enrolled in this prospective study. There were 24 male and 15 female patients. Their age was (58 ± 10) years old, and their body mass index was (27 ± 3) kg/m(2). The mean operation time was (132 ± 12) minutes, and the mean WIT was (29 ± 8) minutes. Clinical parameters, the single glomerular filtration rates (sGFR) were compared before the operation and after 3 and 12 months in order to observer the effects on renal function and find the factors predicting the renal function impairment.

RESULTSThere were significant differences between 3, 12 months after the operation ((26.8 ± 5.6) ml/min and (28.6 ± 5.6) ml/min, respectively) and preoperation ((31.9 ± 6.3) ml/min) in sGFR (F = 4.882 and 5.511, both P < 0.05). And there were significant negative correlations between the sGFR in 3 and 12 months after the operation and WIT (r = -0.569, P = 0.000 and r = -0.448, P = 0.004) . The preoperative sGFR (β = 0.260, 95%CI:0.089-0.431) and WIT (β = 0.369, 95%CI:0.189-0.555) were independent predictors for function decline of the operated kidney (both P < 0.05). The analysis showed that the effects of WIT within 30 minutes on renal function is relatively small. Longer WIT was associated with lower postoperative sGFR values (F = 22.128 and 20.552, both P = 0.000) .

CONCLUSIONSFor the LPN operation, the longer of the WIT, the more serious of renal function damage. sGFR is an accurate measurement to assess the renal damage. Every effort should be made to minimise WIT during LPN, and the limit of 30 minutes should be not exceeded.

Aged ; Female ; Humans ; Kidney ; physiopathology ; Kidney Function Tests ; Kidney Neoplasms ; surgery ; Laparoscopy ; Male ; Middle Aged ; Nephrectomy ; Operative Time ; Prospective Studies ; Warm Ischemia ; adverse effects