Clinical efficacy and adverse reactions analysis of PD-1/PD-L1 inhibitors in advanced esophageal squamous cell carcinoma.

OBJECTIVE: The aim of this study was to investigate the clinical efficacy and associated adverse reactions of Programmed Death Receptor-1 (PD-1)/PD-L1 inhibitors in the management of patients with advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: In this retrospective study, 54 patients with advanced ESCC treated with PD-1/PD-L1 inhibitors in our hospital from January 2021 to January 2023 were identified as the research subjects. Using propensity score matching at a 1:1 ratio, patients only receiving chemotherapy were recruited as controls. The clinical effectiveness of PD-1/PD-L1 was evaluated by comparing the objective response rate (ORR) and disease control rate (DCR). Progression-free survival (PFS) and overall survival (OS) were analyzed for treatment outcome assessments. Adverse events (AEs) between the two groups were recorded and compared. RESULTS: Patients treated with PD-1/PD-L1 inhibitors had a higher rate of ORR (33.33%) and disease control (85.19%), compared to controls with an objective response rate of 20.37% and a disease control rate of 59.26%. The two groups showed similar ORR results, while the incorporation of PD-1/PD-L1 inhibitors resulted in significantly increased DCR when compared to the controls. The median OS was 22 months (95% CI: 1,629 months) for the control group and 31 months (95% CI: 28NA) for the study group, suggesting OS benefits offered by PD-1/PD-L1 inhibitor treatment (HR=0.479, 95% CI: 0.284, 0.809). The median PFS was 15 months (95% CI: 1,223 months) for the control group and 23 months (95% CI: 1,926) for the study group, indicating more PFS benefits provided by PD-1/PD-L1 inhibitors (HR=0.662, 95% CI: 0.436, 1.005). Adverse events and their severity were recorded during patient follow-up, and no grade 5 adverse events were reported in either group. The incidence of grade 3 or higher adverse events between the two groups was similar, while PD-1/PD-L1 inhibitors appeared to significantly reduce the incidence of gastrointestinal reactions in patients. CONCLUSIONS: PD-1/PD-L1 inhibitors integrated with chemotherapy provide significant benefits in the management of patients with advanced ESCC without increasing adverse events.

Fruit Intake and Alzheimer's Disease: Results from Mendelian Randomization.

Alzheimer's disease (AD) is the leading cause of dementia in old age, recognized as a global health priority. To explore causal effects of fresh fruit intake and dried fruit intake on AD liability, this study utilized GWAS from the UK Biobank and FinnGen to conduct Mendelian randomization (MR) analysis, and used inverse variance weighted (IVW), MR-Egger, and weighted median approaches for MR estimates, and visual inspections judged result stability. Results suggested little evidence of a potential causal relationship between fresh fruit intake and AD (OR=0.97, 95%CI=0.50-1.91, P=0.939), while significant, robust causality was indicated between dried fruit intake and AD (OR=4.09, 95%CI=2.07-8.10, P<0.001). Stability evaluations showed no heterogeneity or pleiotropy affecting interpretability and credibility of primary analyses. In conclusion, we strengthened evidence for positive causality from dried fruit intake to AD liability, with causality from fresh fruit intake on AD risk was not demonstrated.

Effect of music intervention during hemodialysis: a comprehensive meta-analysis.

Aggravating disease and the accompanying increase in the frequency of hemodialysis interventions worsen the quality of life of patients leading to poor physical and psychological outcomes. Music-based interventions have been suggested to improve both the physical and psychological prognoses for patients undergoing hemodialysis. Two meta-analyses on the impact of music-based interventions on anxiety in patients undergoing hemodialysis failed to evaluate the impact of these interventions on other physiological outcomes. Therefore, in this study, we gather evidence on the effects of music-based interventions on physical and psychological outcomes in patients with chronic kidney disease undergoing hemodialysis. To determine the influence of music-based interventions on anxiety, pain, heart rate, and blood pressure (systolic, diastolic) in patients with chronic kidney disease undergoing hemodialysis, we performed a systematic literature search adhering to PRISMA guidelines on the EMBASE, CENTRAL, Scopus, and MEDLINE academic databases. We performed meta-analyses to consolidate the evidence on the influence of music-based interventions on the physical and psychological outcomes of patients with chronic kidney disease undergoing hemodialysis. From 1,402 studies, we found eight eligible studies with 597 (264 women, 287 men) patients with chronic kidney disease undergoing hemodialysis (mean age, 56.9 ± 10.8 years). Among these patients, 298 received the music-based intervention and 299 were included as controls. Our meta-analysis revealed a small-to-medium effect of the music-based intervention to reduce pain levels (Hedge's g, -0.75), anxiety (-0.16), heart rate (-0.15), and systolic (-0.14) and diastolic blood pressure (-0.11) in patients with chronic kidney disease receiving hemodialysis as compared to the values of the same variables in the control group. The evidence from our analyses supports the beneficial impact of music-based interventions to alleviate anxiety and pain, and to reduce heart rate and blood pressure in these patients.

MicroRNA-1-3p inhibits the growth and metastasis of ovarian cancer cells by targeting DYNLT3.

OBJECTIVE: The purpose of this study was to explore the role of microRNA-1-3p in the progression of ovarian cancer (OVC) and its possible molecular mechanisms. PATIENTS AND METHODS: For the purpose of exploring the specific mechanism of the oncogene dynein light chain Tctex-type 3 (DYNLT3) in OVC, bioinformatics techniques were applied to predict miRNAs that might bind to DYNLT3, and then microRNA-1-3p was selected. After measuring the expression levels of microRNA-1-3p and DYNLT3 in 60 pairs of OVC tissue samples, the Pearson correlation analysis was used to calculate the expression correlation of microRNA-1-3p and DYNLT3. In addition, Dual-Luciferase reporting assay was used to verify the combination of the two in OVC cells. Furthermore, microRNA-1-3p NC, microRNA-1-3p mimics, and microRNA-1-3p mimics+ DYNLT3-OE (overexpression) were transfected into ES-2 and SKOV-3 cells, respectively. Subsequently, real-time quantitative polymerase chain reaction (qPCR) was performed to examine microRNA-1-3p level in each group of cells, followed by cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) test, and transwell assay to verify the impact of microRNA-1-3p on the proliferation, migration ability, and invasiveness of OVC cells. Finally, the mRNA and protein levels of DYNLT3 were examined by qPCR and Western blot in OVC, respectively. RESULTS: Bioinformatics prediction results showed that a total of three possible miRNAs bound to the oncogene DYNLT3. Then, microRNA-1-3p was selected for further validation. qPCR results revealed that microRNA-1-3p was down-regulated in OVC tissues and cells, while DYNLT3 was up-regulated in OVC tissues. In addition, Pearson correlation analysis indicated that microRNA-1-3p was negatively correlated with DYNLT3 expression, and the Dual-Luciferase reporter assay confirmed that microRNA-1-3p was able to bind directly to the 3'-UTR of DYNLT3. Besides, microRNA-1-3p-mimics transfection remarkably decreased the mRNA and protein expressions of DYNLT3. On the contrary, transfection of microRNA-1-3p-mimics remarkably inhibited the proliferation, migration ability, and invasiveness of OVC cells. Moreover, the transfection of microRNA-1-3p-mimics+DYNLT3-OE partially reversed the inhibitory effect of microRNA-1-3p-mimics on the proliferative, migrate ability, and invasiveness of OVC cells. CONCLUSIONS: MicroRNA-1-3p is under expressed either in OVC tissues or in cell lines, and overexpression of microRNA-1-3p may inhibit proliferative and migrate ability and invasiveness of OVC cells by modulating DYNLT3, which make microRNA-1-3p a potential therapeutic target for OVC.

Therapeutic effects of chimeric antigen receptor T cells (CAR-T) on relapse/refractory diffuse large B-cell lymphoma (R/R DLBCL): a meta-analysis.

OBJECTIVE: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL). This study aimed to systematically evaluate the efficacy of chimeric antigen receptor T cells (CAR-T) in treating relapse/refractory DLBCL (R/R DLBCL) and associated complete-remission rate (CR). MATERIALS AND METHODS: PubMed, Cochrane Library, CNKI, VIP, CBM, and Wanfang databases were searched, and literature was collected up to January 2019. According to inclusion criteria and exclusion criteria, two researchers independently reviewed and screened literature, extracted required data and crossly checked them. This meta-analysis was conducted using RevMan 5.3 software. RESULTS: This study finally included 13 English literatures and 263 cases. There was no heterogeneity among all these studies, therefore, fixed effect model was used. Meta-analysis findings showed that total CR rate of R/R DLBCL treated with CAR-T was 46.8% (95% CI: 0.408-0.533). Subgroup analysis showed that CR rate of CD28 group was slightly higher [52.5%, with 95% confidence interval (CI): 0.441-0.602] compared to that of 4-1BB group (41.5%, with 95% CI: 0.324-0.510). CR rate of CD19 group was slightly higher (49.2%, with 95% CI: 0.429-0.556) compared to that of CD20 group (42.2%, with 95% CI: 0.231-0.639). Funnel chart of total CR rate, co-stimulatory factor, and target antigen demonstrated fundamental symmetry. Moreover, age, HSCT administration, CAR-T cell counts, and drug pre-treatment also affected immunotherapy on CAR-T on R/R DLBCL. CONCLUSIONS: CAR-T treatment for R/R DLBCL demonstrated evident curative effect and high complete remission rate. CAR-T cell immunotherapy would be expected to become mainstream therapy for hematolymph system tumors.

MicroRNA-1271 inhibits the progression of papillary thyroid carcinoma by targeting IRS1 and inactivating AKT pathway.

OBJECTIVE: The important role of microRNA-1271 (miR-1271) has been identified in human diseases and cancers. However, the biological function of miR-1271 remains ambiguous in papillary thyroid carcinoma (PTC). Therefore, the specific role of miR-1271 was investigated in PTC. PATIENTS AND METHODS: The expressions of miR-1271 and insulin receptor substrate 1 (IRS1) were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay. The protein expression of the genes was measured by Western blot analysis. The function of miR-1271 was investigated using methyl thiazolyl tetrazolium (MTT) and transwell assays. The Dual-Luciferase assay was used to observe the relationship between miR-1271 and IRS1. RESULTS: MiR-1271 was downregulated in PTC tissues. Moreover, overexpression of miR-1271 suppressed migration, invasion and proliferation of PTC cells. Furthermore, IRS1 was indicated as a direct target gene of miR-1271 and knockdown of IRS1 inhibited cell migration, invasion and proliferation in PTC. In addition, miR-1271 inhibited the progression of PTC by targeting IRS1. Besides that, miR-1271 blocked the epithelial-mesenchymal transition (EMT) and protein kinase B (AKT) pathway in PTC. CONCLUSIONS: MiR-1271 inhibited the progression of PTC by targeting IRS1 and blocking EMT and AKT pathway.

LncRNA KCNQ1OT1 is overexpressed in non-small cell lung cancer and its expression level is related to clinicopathology.

OBJECTIVE: The aim of this study was to explore the expression of long non-coding RNA (lncRNA) KCNQ1OT1 in non-small cell lung cancer (NSCLC), and to elucidate its clinical significance. PATIENTS AND METHODS: The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of lncRNA KCNQ1OT1 in NSCLC tissues and para-cancer tissues (5 cm or above away from the tumor). The relation between lncRNA KCNQ1OT1 expression and the clinical-pathological data was analyzed by the multivariate logistic regression analysis. Furthermore, the survival analysis was performed by the Kaplan-Meier method. RESULTS: The expression of lncRNA KCNQ1OT1 increased significantly in NSCLC tissues than that of in para-cancer tissues. According to the median expression of lncRNA KCNQ1OT1, NSCLC patients were divided into two groups, including high expression group and low expression group. Meanwhile, the lncRNA KCNQ1OT1 expression was correlated with tumor size, tumor node metastasis (TNM) staging, and lymph node metastasis of NSCLC patients. Both univariate analysis and multivariate analysis indicated that the high expression of lncRNA KCNQ1OT1 was closely related to TNM staging and lymph node metastasis. In addition, the Kaplan-Meier analysis showed that the overall survival and progression-free survival time of patients with higher lncRNA KCNQ1OT1 expression were significantly worse than those with lower lncRNA KCNQ1OT1 expression. CONCLUSIONS: LncRNA KCNQ1OT1 might contribute to the development of NSCLC.

MiR-875 can regulate the proliferation and apoptosis of non-small cell lung cancer cells via targeting SOCS2.

OBJECTIVE: To investigate the effect of miR-875 on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cancer cell line A549 and the related mechanism. PATIENTS AND METHODS: 30 paired tumor tissue and the adjacent tissue were collected. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) has been performed to detect the expression of miR-875 in NSCLC tissues and adjacent normal tissues. Moreover, suppressor of cytokine signaling 2 (SOCS2) has been predicted as a target of miR-875, and Dual-Luciferase reporter assay has been performed to confirm the targeting relationship; furthermore, the expression of SOCS2 in tumor tissue and the adjacent tissue were compared. Next, human NSCLC cell line A549 cells were cultured and transfected with miR-875 inhibitor with or without SOCS2 siRNA, and the proliferation and apoptosis of the cells were evaluated by Cell Counting Kit (CCK-8) and flow cytometry methods. Finally, the relative protein expression of Wnt and ß-catenin were analyzed by Western blot analysis. RESULTS: MiR-875 was significantly up-regulated in NSCLC tissues compared with the adjacent tissues. SOCS2 was confirmed as a target of miR-875, and the expression of SOCS2 was markedly decreased in NSCLC tissues. Moreover, the knockdown of miR-875 inhibited the proliferation and promoted the apoptosis of A549 cells, while transfection of SOCS2 siRNA can block miR-875 inhibitor-induced anti-proliferative effects. Finally, the transfection of miR-875 inhibitor decreased the expression of Wnt and ß-catenin, and SOCS2 siRNA can reverse the effect. CONCLUSIONS: MiR-875 may regulate the proliferation and apoptosis of NSCLC cells via targeting SOCS2, suggesting that miR-875 has the potential to become a therapeutic target for the treatment in NSCLC.

Association of elective cesarean delivery with metabolic measures in childhood: A prospective cohort study in China.

BACKGROUND AND AIMS: Cesarean delivery may increase the risk of childhood obesity, a precursor of metabolic syndrome (MetS). We aimed to investigate the association of elective cesarean delivery (ElCD) with MetS and its components in a Chinese birth cohort. METHODS AND RESULTS: This cohort included 1467 children (737 delivered by ElCD and 730 by spontaneous vaginal delivery [SVD]) who were followed up at the age of 4-7 years in 2013. MetS was defined as the presence of ≥3 components: central obesity, hypertriglyceridemia, low high-density lipoprotein (HDL), high fasting glucose, and hypertension. Of the 1467 children, 93 (6.3%) were categorized as having MetS: 50 (6.8%) delivered by ElCD and 43 (5.9%) by SVD. After multivariable adjustment, ElCD was not associated with MetS (adjusted odds ratio [AOR] 1.15, 95% confidence interval [CI] 0.74, 1.78) or certain components including hypertriglyceridemia, low HDL, and high fasting glucose but was associated with central obesity (AOR 1.33, 95% CI 1.02, 1.72) and hypertension (AOR 1.50, 95% CI 1.15, 1.96), as well as higher levels of total cholesterol (3.43 vs. 3.04 mmol/L; P < 0.001), low-density lipoprotein-cholesterol (1.77 vs. 1.67 mmol/L, P = 0.002), fasting glucose (5.08 vs. 5.02 mmol/L, P = 0.022), systolic (97.57 vs. 94.69 mmHg, P < 0.001)/diastolic blood pressure (63.72 vs. 62.24 mmHg, P < 0.001), and BMI (15.46 vs. 14.83 kg/m2, P < 0.001) than SVD. CONCLUSIONS: ElCD is not associated with MetS in early to middle childhood but is associated with its components including central obesity and hypertension, as well as various continuous indices.

MiRNA-485-5p, inhibits esophageal cancer cells proliferation and invasion by down-regulating O-linked N-acetylglucosamine transferase.

OBJECTIVE: Previous reports suggest that miRNA-485-5p is dysregulated and contributes to tumorigenesis in some cancer types. Nevertheless, the biological role of miRNA-485-5p in esophageal cancer (EC) is not well understood. Additionally, we found that the expression of miR-485-5p in EC tissues was aberrant. PATIENTS AND METHODS: Quantitative RT-PCR (qRT-PCR) was used to demonstrate the expression of miRNA-485-5p in EC cell lines. Cell counting kit-8 (CCK-8) assay and transwell assay indicated that miRNA-485-5p overexpression inhibited cell proliferation, migration, and invasion in EC cell lines. Additionally, Western blotting, dual-luciferase reporter assay, and rescue assay predicted that O-linked N-acetylglucosamine transferase (OGT) was a direct target of miRNA-485-5p. Moreover, we showed that miRNA-485-5p regulated EC tumorigenesis by down-regulating OGT expression in vitro and in vivo. RESULTS: The upregulation of miR-485-5p (fold change = 44 and 26 in ECA109 and TE-1, respectively; p<0.001) was showed by qRT-PCR. Compared with the control groups, the expression miR-485-5p significantly suppressed the proliferation, migration, and invasion of EC cells. The bioinformatic analysis predicted that the 3' untranslated region (UTR) of OGT contains one miR-485-5p target sequences. Western blotting and dual-luciferase reporter assay showed that activation of OGT 3'UTR was increased by co-transfection with miR-485-5p. Finally, CCK-8 assay predicted that the rescue effects of OGT expression on miR-485-5p induced inhibition of cell growth and tumor weight in Eca109 and TE1 cells. CONCLUSIONS: Our results suggest that miRNA-485-5p is a suppressor of EC tumorigenesis and could serve as a novel candidate for therapeutic applications in EC treatment.

MicroRNA-101-5p inhibits the growth and metastasis of cervical cancer cell by inhibiting CXCL6.

OBJECTIVE: The objective of this study is to explore the biological roles of microRNA-101-5p (miR-101-5p) in the growth and metastasis of cervical cancer. PATIENTS AND METHODS: The levels of miR-101-5p and chemokine (C-X-C motif) ligand 6 (CXCL6) in cervical cancer tissues and cells were detected using the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay. The proliferation, colony formation, migration, and invasion assays were conducted using miR-101-5p transfected cervical cancer cell. The expression of CXCL6 was measured by the immunoblotting assay. Xenograft model was constructed to reveal the precise roles of miR-101-5p in the growth of cervical cancer cell in vivo. RESULTS: MiR-101-5p was down-regulated in cervical cancer tissues when compared to the normal controls. The levels of miR-101-5p were higher in cervical cancer cells (SiHa, Caski, C-4-I, C-33 A) than that in the human cervical surface epithelial cell line, HcerEpic. Over-regulation of miR-101-5p inhibited the aggressiveness phenotypes of a cervical cancer cell in vitro. Furthermore, over-regulation of miR-101-5p reduced the tumor growth of cervical cancer cell in vivo. CXCL6 was the target protein of miR-101-5p in cervical cancer as demonstrated by luciferase reporter assay. The mRNA level of CXCL6 was negatively associated with the miR-101-5p level in cervical cancer tissue. Finally, the rescue experiments suggested that the inhibitory role of miR-101-5p was mediated by regulating the expression of CXCL6 in cervical cancer. CONCLUSIONS: These findings indicated that the over-regulation of miR-101-5p suppressed the progression of cervical cancer by targeting CXCL6 and might function as a potential therapeutic target for cervical cancer.

Correction to: Effects of growth hormone on pregnancy rates of patients with thin endometrium.

Unfortunately, there are errors that occurred in the name and manufacture of the growth hormone (GH) received by the patients in the GH group on page two, Table 1 and figure 1 on page three.

Effects of growth hormone on pregnancy rates of patients with thin endometrium.

PURPOSE: To investigate whether growth hormone (GH) could improve pregnancy rates of patients with thin endometrium by clinical study and laboratory experiments. MATERIALS AND METHODS: Ninety-three patients were randomized to either the GH-received group (40) or the routine exogenous administration of estrogens control group (53) for clinical study. The human endometrial carcinoma cell line RL95-2 was used for testing the role of GH with Western blot and real-time PCR by exposure to various concentrations of GH (0.1 nM,1 nM,10 nM,100 nM). RESULTS: Patients treated with GH had a significantly (P < 0.05) greater endometrium thickness on day 3 (7.87±0.72 vs 6.34±0.86), higher implantation rates (24.4% vs 10.5%) and greater clinical pregnancy rates (42.5% vs 18.9%) compared with the control group. No adverse events were associated with the use of GH. Administration of GH significantly up-regulated the expression of VEGF, ItgB3 and IGF-I expression in RL95-2 cells at both mRNA and protein levels (P < 0.05). AG490, an inhibitor of JAK2, nearly completely inhibited the up-regulative effect of GH through the JAK2-STAT5 pathway, and GH-induced effects could be mediated through autocrine IGF-I together with its hepatic counterpart. IGF-I mRNA was detected in the RL95-2 cells. CONCLUSION: GH may improve pregnancy outcomes of patients with thin endometrium who undergo frozen embryo transfer by acting on human endometrial cells to promote proliferation and vascularization and to up-regulate receptivity-related molecular expression.

miR-582-5p is a potential prognostic marker in human non-small cell lung cancer and functions as a tumor suppressor by targeting MAP3K2.

OBJECTIVE: Emerging evidence has shown that microRNAs (miRNAs) play important roles in tumor development and progression. The aim of the present study was to investigate the role of miR-582-5p in non-small cell lung cancer (NSCLC) and to determine the molecular mechanisms underlying its action. PATIENTS AND METHODS: Using quantitative RT-PCR, we detected miR-582-5p expression in NSCLC cell lines and primary tumor tissues. The association of miR-582-5p expression with clinicopathological factors and prognosis was statistically analyzed. The effect of miR-582-5p on proliferation was evaluated by CCK-8. Cell migration and invasion were assessed by transwell assay. miR-582-5p target genes were confirmed using luciferase activity, RT-PCR and Western blot assays. RESULTS: We found that miR-582-5p expression was significantly downregulated in NSCLC cell lines and clinical specimens. Low miR-582-5p expression was significantly associated with lymph node metastasis (p = 0.012) and advanced TNM stage (p = 0.004). Kaplan-Meier assay showed that patients with low expression of miR-582-5p had a shorter overall survival than those with high expression of miR-582-5p (p = 0.0033). Functional experiments demonstrated that overexpression of miR-582-5p suppressed the proliferation, migration and invasion of NSCLC cells in vitro. We identified MAP3K2 as a direct target gene of miR-582-5p in NSCLC cells. In addition, ectopic expression of MAP3K2 restored the effects of miR-582-5p on NSCLC cell proliferation, migration and invasion. CONCLUSIONS: We showed that miR-582-5p inhibits NSCLC metastasis by targeting MAP3K2 expression and could be used as an independent prognostic biomarker for patients with NSCLC.

Microbial community reshaped in gastric cancer.

Patients with gastric cancer harbor distinct microbiota in the stomach. It features with lowered biodiversity, discrete structure, and varied composition. Some bacteria from gastric microbiota are potentially carcinogenic as they are enriched or depleted in gastric cancer. Distinct profile of microbial community in gastric cancer is possibly resulted from altered caused by pathophysiological and environmental factors. H. pylori is a carcinogen colonizing the human stomach. Although persisting for decades, it rarely causes compositional alteration of microbiota. Secretion of acid decreases gradually during the carcinogenic process. Increased pH results in overgrowth of bacteria in gastric fluid. The abundance of a particular taxon, but not the profile of microbiota, is altered in proton pump inhibitor users. Compositions of microbiota vary substantially between individuals, which may account for differential cancer risk. It has been demonstrated that genetic variations contribute to inter-individual variations in gut microbiota. However, their influence on the composition of gastric microbiota requires further exploration. Currently, it appears disrupted homeostasis and inter-individual variations of gastric microbiota are involved in cancer development. Clarifying factors responsible for these changes would reveal how microbiota induces carcinogenesis, benefiting the prevention of gastric cancer.

A modification and validation of quantitative morphometry classification system for osteoporotic vertebral compressive fractures in mainland Chinese.

This study described a modified quantitative morphometry (mQM) system adapted to specific reference values for Mainland Chinese population. The mQM system is validated using the Genant Semiquantative system and is sensitive for detecting vertebral height changes and predicting cement leakage after percutaneous kyphoplasty (PKP) in patients with osteoporotic vertebral compressive fracture (OVCF). INTRODUCTION: OVCF is a manifestation of osteoporosis. To improve clinical management of osteoporosis, the quantitative morphometry (QM) system has been widely used for the early diagnosis and precise classification of OVCF in developed countries. Here, we present an mQM system and validated its use in detecting OVCF in Mainland Chinese. METHODS: Using our mQM system, the pre- and post-operative values of vertebral heights were measured and evaluated in 309 Mainland Chinese who received percutaneous kyphoplasty (PKP) as OVCF treatment. Measurements and classification of fractures from the mQM system were validated by comparing to values obtained by the Genant semiquantative (SQ) method. Moreover, we evaluated the sensitivity of the mQM system by its ability to detect restoration of vertebral heights and predict cement leakage after PKP. RESULTS: The five classification of fractures, No deformity (ND), anterior wedge (AW), posterior wedge (PW), biconcavity (BC), and compression (CP), evaluated by the mQM method shared similar distribution characteristics compared to those obtained by the SQ method. In addition, mQM evaluation showed that the vertebra height of all fracture types showed significant restoration after PKP. The incidence of cement leakage was most common in CP (37.5%), followed by AW (31.6%), BC (26.5%), ND (23.7%), and PW (0.0%). CONCLUSIONS: Our mQM system is suitable for classification of fractures, detection of vertebral height restoration, and correlation of cement leakage after PKP in Mainland Chinese population.

Tacrolimus inhibits proliferation and induces apoptosis by decreasing survivin in scar fibroblasts after glaucoma surgery.

OBJECTIVE: To investigate the effect of tacrolimus on the proliferation of fibroblasts after glaucoma surgery. MATERIALS AND METHODS: Biopsy was applied in this study. Under aseptic conditions, tissues were collected from rabbits, cut into small pieces and cultured. Morphology of fibroblasts was observed under a microscope. Features of fibroblasts were identified via immunocytochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Western blotting and RT-PCR were performed to detect the expressions of related proteins after treatment. Flow cytometry and cell counting kit-8 (CCK-8) assay were employed to examine the proliferation of human Tenon's capsule fibroblasts (HTFs) after tacrolimus treatment. RESULTS: Tacrolimus decreased the levels of survivin and α-smooth muscle actin (α-SMA) after transforming growth factor-ß (TGF-ß) treatment. Besides, it inhibited proliferation and induced apoptosis of HTFs. CONCLUSIONS: Tacrolimus reduces proliferation and promotes apoptosis of HTFs by inhibiting the expression of survivin, which may be a strategy for treating hypertrophic scar after glaucoma surgery.

The influencing mechanism of mTOR signal pathway mediated by mitofusin-2 in development of follicle.

OBJECTIVE: To investigate the influencing mechanism of mammalian target of rapamycin (mTOR) signal pathway mediated by mitofusin-2 (Mfn2) in the development of follicle. MATERIALS AND METHODS: We selected 20 healthy Sprague Dawley (SD) female rats aging between 6 and 8 weeks were divided into the control group and the polycystic ovarian syndrome (PCOS) model group. Rats in PCOS group received the lavage using 0.4 mL 1% carboxymethyl cellulose solution containing letrozole (1 mg/kg/d) consecutively for 20 to 25d. We compared the body weight and ovary weight of rats, and detected levels of sera E2, T, P, FSH and LH through RIA measurement. We also observed the histological morphology of ovary through hematoxylin eosin (HE) staining, as well as the positive expression and location of rMfn2 through immunohistochemistry staining. Finally, we detected the expressions of mTOR, p-Akt, ß-catenin, caspase-3, Bcl-2 and Bax in Mfn2 and mTOR signal pathways in the tissues through RT-PCR and Western blot assay. RESULTS: In the PCOS group, the body weight of rats was lower than that of the control group, but the ovary weight of rats was higher than that in the control group. The levels of T and LH in serum were elevated, the levels of E2, P and FSH were decreased (p < 0.05). In the model group, typical polycystic changes were observed in the rats under the microscope, but no corpus luteum was observed, and a significant decrease was identified in the layers of the granular cell of the follicle. Mfn2 was widely expressed in the granular cells of the ovary, follicular fluid, inner theca cells, corpus luteum, and ovarian stroma. However, the expression in the outer theca cells was relatively low. In the observation group, the positive expression rate of Mfn2 was significantly lower (p < 0.05) than that in the control group. In the PCOS group, the mRNA and protein relative expression levels of mTOR, p-Akt, ß-catenin, and Bcl-2 were significantly lower (p < 0.05) than those in the control group. Conversely, the levels of caspase-3 and Bax were significantly higher (p < 0.05) than those in the control group. CONCLUSIONS: Downregulated expression of Mfn2 may affect the regular development of follicle through the mediation of mTOR signal pathway.

MicroRNA-200c suppressed cervical cancer cell metastasis and growth via targeting MAP4K4.

OBJECTIVE: To dissect the functioning mode of miR-200c on cervical cancer cell metastasis and growth and provide therapeutic targets for cervical cancer. PATIENTS AND METHODS: By quantitative Real-time polymerase chain reaction, the miR-200c expression level in 42 pairs of cervical cancer tissue samples and six cervical cancer-derived cell lines were examined. Using miR-200c mimics, we analyzed the effects of miR-200c over-expression on cell proliferation, invasion, and migration. Dual-luciferase activity assay was recruited to examine the potential target gene MAP4K4 that predicted by several databases. Protein level was studied using Western blot. RESULTS: miR-200c expressed significantly lower in cervical cancer tissue samples and cell lines. And over-expression of miR-200c in cervical cancer cells significantly decreased the cell invasion, migration and proliferation abilities. Dual-luciferase and Western blot confirmed MAP4K4 as a target gene of miR-200c. Furthermore, up-regulation of MAP4K4 counteracted the suppressive effect of miR-200c over-expression on cell growth and metastasis. CONCLUSIONS: miR-200c could suppress cervical cancer cell proliferation and progression via regulating MAP4K4, which might provide a new target for cervical cancer diagnosis and therapy.