Salvage camrelizumab for an intractable NK/T cell lymphoma patient with two instances of intestinal perforation: a case report and literature review.

BACKGROUND: The prognosis of natural killer/T cell lymphoma (NKTCL) with multifocal small intestine involvement complicated by intestinal perforation is extremely poor. There is no evidence-based treatment strategy for this intractable condition. CASE PRESENTATION: A 30-year-old male was admitted to our hospital in April 2017 and presented with recurrent fever for three months and multiple painless subcutaneous nodules in the abdominal wall. An excision biopsy of the subcutaneous nodules in the abdominal wall revealed NKTCL. The patient was diagnosed with stage IVB NKTCL with skin and multifocal small intestinal involvement according to the imaging results. The first intestinal perforation occurred due to tumor infiltration before the initial treatment. The second intestinal perforation occurred after receiving two cycles of chemotherapy with a modified SMILE regimen. The histone deacetylase inhibitor (HDACi) chidamide was administered as a single-agent therapy after recovery from the second intestinal perforation. Complete remission was achieved. Unfortunately, five months later, the patient was confirmed to have relapsed and received the salvage chemotherapy. The patient suffered from disease progression again after the fourth cycle of chemotherapy. At this point, from May 29, 2018, the patient started to receive injections of the anti-programmed death 1 (PD-1) antibody camrelizumab as a salvage treatment. Two months after the initial anti-PD-1 antibody camrelizumab injection, the response was partial remission. Disease progression was confirmed in March 2021, with a progression-free survival time of 34 months. CONCLUSIONS: NKTCL patients with multifocal small intestine involvement have a high risk of intestinal perforation. The possible etiologies of bowel perforation include tumor infiltration, tumor necrosis in response to therapy, and acute inflammation. The anti-PD-1 antibody camrelizumab may be a new candidate agent for treating this type of intractable NKTCL. Further observations are necessary to identify the efficacy and safety of new agents in the future.

An approach combining bioinformatics and machine learning to identify eight autophagy-related biomarkers and construct molecular mechanisms underlying COVID-19 and major depressive disorders.

OBJECTIVE: A lack of objective biomarkers is preventing the screening and diagnosis of COVID-19 combined with major depression disorder (COVID-19-MDD). The purpose of this study was to identify diagnostic biomarkers and gene regulatory mechanisms associated with autophagy; a crucial process significantly involved in the pathogenesis of COVID-19-MDD. MATERIALS AND METHODS: In this study, differentially expressed genes (DEGs) were screened using GSE98793 from the GEO2R analysis (GEO) database, and intersected with the COVID-19-related gene (CRGs) and autophagy-related genes (ARGs) to obtain common genes involved in. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these common genes were performed. Subsequently, the transcription factor (TF)-gene regulatory network and comorbidity network were constructed. In addition, 10 drug candidates were screened using the DSigDB database. To identify diagnostic markers, we used LASSO regression. RESULTS: In total, 13 common genes were screened, which were primarily enriched in lysosomes, endoplasmic reticulum membranes, and other endomembrane systems also associated with autophagy. Additionally, these genes were involved in neurological cell signaling and have a functional role in pathways related to vascular endothelial growth factor, tyrosine kinase, autophagy, inflammation, immunity, and carcinogenesis. Tumors and psychiatric disorders were the most highly linked diseases to COVID-19. Finally, ten drug candidates and eight diagnostic markers (STX17, NRG1, RRAGD, XPO1, HERC1, HSP90AB1, EPHB2, and S1PR3) were screened. CONCLUSIONS: This is the first study to screen eight diagnostic markers and construct a gene regulatory network for COVID-19-MDD from the perspective of autophagy. The findings of our study provide novel insights into the diagnosis and treatment of COVID-19-MDD.

CircRNA-PTPRA promoted the progression of atherosclerosis through sponging with miR-636 and upregulating the transcription factor SP1.

OBJECTIVE: Atherosclerosis (AS) is the leading cause of death for humans worldwide, and some circular RNAs (circRNAs) have been demonstrated to play important roles in its progression. In this study, we mainly investigated the functions and molecular mechanisms of circRNA-PTPRA (circPTPRA) in AS. PATIENTS AND METHODS: The expressions of circPTPRA and miR-636 were detected in serum samples of AS patients (n=30) and healthy controls (n=30) by RT-PCR. Then levels of circPTPRA were detected after ox-LDL treatment into vascular smooth muscle cell (VSMCs), macrophage and endothelial cells. LV-sh circPTPRAs were constructed and infected into VSMCs. CCK-8 assay was performed to measure cell proliferation abilities, flow cytometry (FACS) was performed to measure cell-cycle distribution and TUNEL staining was performed to detect cell apoptosis. Western blot (WB) was performed to detect protein levels of SP1, Cyclin D1, Cyclin E, Bax, Bad, Cleaved Caspase3. Luciferase reporter assay was performed to verify the potential binding sites of circPTPRA and miR-636, miR-636 and SP1. RESULTS: RT-PCR showed that circPTPRA was upregulated in serum samples of AS patients, which was increased by ox-LDL in VSMCs. CircPTPRA inhibition repressed cell proliferation, improved cell-cycle distribution in G0/G1 phase and promoted cell apoptosis. MiR-636, a potential target for circPTPRA, was reduced in serum samples of AS patients and Luciferase reporter assay confirmed that circPTPRA could directly sponge with miR-636 in VSMCs. Furthermore, miR-636 inhibition promoted proliferation and repressed apoptosis of VSMCs, while miR-636 overexpression reversed these results. SP1, a transcription factor that played some roles in the progression of AS, was predicted to be a target of miR-636. MiR-636 inhibition increased SP1 while miR-636 overexpression repressed SP1 expression, Luciferase reporter assay proved that miR-636 could target at SP1 in VSMCs. Moreover, the repressed cell proliferation and promoted cell apoptosis abilities in LV-sh SP1 were reversed following with miR-636 inhibitor transfection. In addition, the repressed cell proliferation and promoted cell apoptosis abilities in VSMCs with LV-sh circPTPRAs were reversed following with miR-636 inhibitor transfection, which suggested that circPTPRA regulated cell proliferation and apoptosis through miR-636/SP1 axis in AS. CONCLUSIONS: According to the results, we found that circPTPRA was upregulated in serum samples of AS patients, which promoted cell proliferation and inhibited cell apoptosis through repressing miR-636 and upregulating SP1 signaling axis. Our results uncovered a potential role of circPTPRA, which might be a marker and therapeutic target for AS patients.

Risk factors for disease progression in patients with mild to moderate coronavirus disease 2019-a multi-centre observational study.

OBJECTIVES: Since December 2019, the novel coronavirus disease 2019 (COVID-19) that emerged in Wuhan city has spread rapidly around the world. The risk for poor outcome dramatically increases once a patient progresses to the severe or critical stage. The present study aims to investigate the risk factors for disease progression in individuals with mild to moderate COVID-19. METHODS: We conducted a cohort study that included 1007 individuals with mild to moderate COVID-19 from three hospitals in Wuhan. Clinical characteristics and baseline laboratory findings were collected. Patients were followed up for 28 days for observation of disease progression. The end point was the progression to a more severe disease stage. RESULTS: During a follow up of 28 days, 720 patients (71.50%) had recovered or were symptomatically stable, 222 patients (22.05%) had progressed to severe disease, 22 patients (2.18%) had progressed to the critically ill stage and 43 patients (4.27%) had died. Multivariate Cox proportional hazards models identified that increased age (hazard ratio (HR) 2.56, 95% CI 1.97-3.33), male sex (HR 1.79, 95% CI 1.41-2.28), presence of hypertension (HR 1.44, 95% CI 1.11-1.88), diabetes (HR 1.82, 95% CI 1.35-2.44), chronic obstructive pulmonary disease (HR 2.01, 95% CI 1.38-2.93) and coronary artery disease (HR 1.83, 95% CI 1.26-2.66) were risk factors for disease progression. History of smoking was protective against disease progression (HR 0.56, 95% CI 0.34-0.91). Elevated procalcitonin (HR 1.72, 95% CI 1.02-2.90), urea nitrogen (HR 1.72, 95% CI 1.21-2.43), α-hydroxybutyrate dehydrogenase (HR 3.02, 95% CI 1.26-7.21) and D-dimer (HR 2.01, 95% CI 1.12-3.58) at baseline were also associated with risk for disease progression. CONCLUSIONS: This study identified a panel of risk factors for disease progression in individuals with mild to moderate COVID-19.

Association between maximum mouth opening and area of bony fusion in simulated temporomandibular joint bony ankylosis.

The aim of this study was to investigate the quantitative association between active/passive maximum mouth opening (AMMO/PMMO) and the severity of simulated temporomandibular joint (TMJ) bony ankylosis. Twenty-eight male sheep were divided randomly and equally into surgical and control groups. Surgical group animals underwent bilateral TMJ osteotomy during which left lateral pterygoid muscle function was blocked. Control animals did not undergo surgery. Body weight, AMMO/PMMO, and TMJ morphological features were evaluated preoperatively and at 12 and 24 weeks post-surgery. In the surgical group, only the right TMJ complexes with maintained lateral pterygoid muscle function developed TMJ bony ankylosis. The AMMO/PMMO and end-feel distance in the surgical group were significantly lower than those in the control group (P < 0.001, both) at 12 and 24 weeks post-surgery. Moreover, AMMO (r = -0.940 and -0.952, P < 0.001, both) and PMMO (r = -0.944 and -0.953, P < 0.001, both) were negatively correlated with the area (mm2) of bony fusion post-surgery. These findings may be useful for the clinical treatment of early mandibular condyle fracture, with the use of occlusal pads/open-mouth plates to relax the lateral pterygoid muscle and block its function. When bony ankylosis developed in the TMJ, the greater the area of bony fusion, the more limited were AMMO/PMMO.

Influence of miR-199a on rats with non-small cell lung cancer via regulating the HIF-1α/VEGF signaling pathway.

OBJECTIVE: Micro-ribonucleic acids (miRNAs) are involved in the occurrence of various cancers, and the hypoxia-inducible factor 1-α (HIF-1α) is the main regulator of cell proliferation induced by hypoxia. The relationships of miR-199a and HIF-1α expressions with non-small cell lung cancer (NSCLC) remain unclear, so they were explored in this work. MATERIALS AND METHODS: On the basis of establishing the rat model of NSCLC, the messenger RNA (mRNA) expressions of miR-199a, HIF-1α and the vascular endothelial growth factor (VEGF) were analyzed in NSCLC rats, and the correlations of miR-199a with the mRNAs of HIF-1α and VEGF and cancer staging were investigated. To further study the role of miR-199a in NSCLC cell proliferation via the HIF-1α/VEGF signaling pathway, NSCLC cells were treated with the signaling pathway inhibitor and transfected with miR-199a mimics, respectively. Also,  the roles of the inhibitor PX-478 and miR-199a mimics in the expressions of miR-199a, HIF-1α, and VEGF proteins, as well as their influences on cell proliferation ability were detected. RESULTS: In NSCLC rats, the expression of miR-199a was substantially decreased (p<0.01), but the expressions of HIF-1α and VEGF were notably raised (p<0.01). MiR-199a was negatively correlated with the expression of VEGF. As cancer developed, the expression of miR-199a was gradually lowered, but the expressions of HIF-1α and VEGF were gradually increased. Both HIF-1α/VEGF signaling pathway inhibitor PX-478 and miR-199a mimics significantly reduced the expressions of HIF-1α and VEGF proteins (p<0.01) and suppressed the cell proliferation activity. CONCLUSIONS: MiR-199a prevents the proliferation of NSCLC cells via the targeted down-regulation of the HIF-1α/VEGF signaling pathway.

SNHG16 promotes the progression of osteoarthritis through activating microRNA-93-5p/CCND1 axis.

OBJECTIVE: This study aims to investigate whether SNHG16 (small nucleolar RNA host gene 16) can promote the progression of osteoarthritis (OA) by regulating the microRNA-93-5p/Cyclin D1 (CCND1) axis, thereby finding new therapeutic targets for the treatment of OA. PATIENTS AND METHODS: A total of 23 OA patients and 23 patients undergoing lower extremity amputation were enrolled in this study. We collected their cartilage tissues from knee joint for isolating chondrocytes. The relative levels of SNHG16, CCND1 and microRNA-93-5p in cartilage tissues of OA patients and controls were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The regulatory effect of SNHG16 on proliferative potential of chondrocytes was evaluated by Cell Counting Kit-8 (CCK-8) and colony formation assay, respectively. Cell cycle progression was examined using flow cytometry. Dual-Luciferase reporter gene assay was conducted to verify the binding between SNHG16 with microRNA-93-5p and microRNA-93-5p with CCND1. Rescue experiments were performed to elucidate whether SNHG16 regulated CCND1 expression by targeting microRNA-93-5p. RESULTS: The expressions of SNHG16 and CCND1 upregulated, while microRNA-93-5p downregulated in cartilage tissues of OA patients relative to controls. Correlation regression analyses showed a negative expression correlation between SNHG16 and microRNA-93-5p, as well as CCND1 and microRNA-93-5p in OA patients. On the contrary, SNHG16 expression was positively correlated to CCND1 expression in OA. The knockdown of SNHG16 suppressed viability, cloning ability and cell cycle progression, but induced apoptosis in chondrocytes. Dual-Luciferase reporter gene assay showed that SNHG16 could bind to microRNA-93-5p. SNHG16 knockdown markedly upregulated the expression of microRNA-93-5p. Moreover, the knockdown of microRNA-93-5p reversed the inhibited viability due to SNHG16 knockdown. Transfection of microRNA-93-5p mimics markedly inhibited CCND1 expression. Importantly, CCND1 overexpression reversed the inhibitory effect of SNHG16 knockdown on chondrocyte viability. CONCLUSIONS: SNHG16 promotes the development of OA by regulating microRNA-93-5p/CCND1 axis.

Low expression of lncRNA MEG3 promotes the progression of oral squamous cell carcinoma by targeting miR-21.

OBJECTIVE: The aim of this study was to explore whether maternally expressed gene 3 (MEG3) could facilitate the proliferation and migration of oral squamous cell carcinoma (OSCC) cells by selectively binding to miR-21, thereby participating in the progression of OSCC. PATIENTS AND METHODS: The expression levels of MEG3 and miR-21 in OSCC tissues and normal control tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The effects of MEG3 and miR-21 on cell proliferation and migration were examined by cell counting kit-8 (CCK-8), transwell, and scratch assay, respectively. Meanwhile, cell cycle was detected using flow cytometry. The binding relationship between miR-21 and MEG3 was confirmed by dual luciferase assay. In addition, MEG3 and miR-21 were simultaneously knock-down to figure out whether MEG3 could regulate the proliferation and migration of OSCC cells through targeted binding to miR-21. RESULTS: QRT-PCR results indicated that MEG3 expression in OSCC tissues was remarkably lower than that of normal control tissues. However, the expression of miR-21 was significantly higher in OSCC tissues. Meanwhile, it was found that inhibiting MEG3 expression in OSCC cell lines could significantly promote cell proliferation and migration, while the simultaneous inhibition of miR-21 showed the opposite effect. Dual Luciferase assay results revealed that MEG3 could selectively bind to miR-21. In addition, we demonstrated that the knockdown of MEG3 in Tca-8113 and CAL-27 cells partially reversed the inhibitory effect of downregulated-miR-21 on cell proliferation and migration. These results further suggested that MEG3 might regulate OSCC cell proliferation via selectively binding to miR-21. CONCLUSIONS: Low expression of MEG3 can promote the proliferation and migration of OSCC cells through targeted binding to miR-21.

MiR-124a inhibits proliferation and invasion of rheumatoid arthritis synovial fibroblasts.

OBJECTIVE: To investigate the impact of miR-124Aa on the proliferation, invasion and cytokine excretion of rheumatoid arthritis synovial fibroblasts (RASFs) in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: RASFs were separated for in-vitro culture, and transfected using lipidosome that connected with chemically synthesized miR-124a mimic or miR-124a inhibitor. Then, MTT, transwell chamber, and flow-cytometry were used to detect the impact on the proliferation, invasion, and apoptosis of RASFs; RT-PCR and Western-blotting were employed to measure the effect of miR-124a on the expressions of matrixmetalloproteinase3/13 (MMP3/13) and interleukin1ß (IL-1ß) of RASFs. RESULTS: miR-124a significantly suppresses the proliferation of RASFs, while inhibits the invasion of RASFs. The flow cytometry indicated that miR-124a showed no significant effect on the apoptosis of RASFs. Finally, miR-124a downregulates the expressions of MMP3/13 and IL-1ß. CONCLUSIONS: MiR-124a is of great significance for the onset of RA by inhibiting the proliferation and invasion of RASFs possibly through downregulating the expression of MMP3/13 and IL-1ß.

Sestrin2 aggravates oxidative stress of neurons by decreasing the expression of Nrf2.

OBJECTIVE: Oxidative injury is an essential part of the pathological changes of cerebral ischemia-reperfusion. Sestrin2 (Sesn2), a conserved antioxidant protein, is activated under stress to protect cells against oxidative stress. This study mainly explored the function and mechanism of Sesn2 during cerebral ischemia-reperfusion injury in rats. MATERIALS AND METHODS: Oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary neurons was established. MTS and LDH (lactate dehydrogenase) kit were used to detect cell viability and cell damage by colorimetric method. The superoxide dismutase (SOD) kit and malondialdehyde (MDA) kit were used to access the level of SOD and MDA in neurons. To establish a model of middle cerebral artery occlusion (MCAO) in adult male Sprague-Dawley (SD) rats, the process of cerebral ischemia-reperfusion injury in animals was simulated. Western blot and immunofluorescence were utilized to further examine the relationship between the expression of Sesn2 and Nrf2 (nuclear factor E2 related factor 2). RESULTS: Sesn2 aggravated neuronal damage and enhanced cell viability in OGD/R model. Intraventricular injection of Sesn2 siRNA lentivirus aggravated nerve function damage in MCAO model, increased cerebral infarction area and water content. Sesn2 overexpression resulted in the increase of total, nuclear levels of Nrf2, as well as the downstream proteins of Nrf2, sulfiredoxin1 (Srx1) and thioredoxin1 (Trx1). On the contrary, after knockdown of Sesn2, we obtained the opposite result. Knockdown of Sesn2 reduced Nrf2, Srx1 and Trx1 levels in rat cerebral cortex in MCAO model. CONCLUSIONS: Sesn2 promoted the transfer of nuclear Nrf2 to the cytoplasm, it decreased the expressions of Nrf2 and its downstream proteins, Srx1 and Trx1. Meanwhile, it increased the cerebral ischemia-reperfusion injury by changing the distribution of Nrf2.

Correlations of SOX9 expression with serum IGF1 and inflammatory cytokines IL-1α and IL-6 in skin lesions of patients with acne.

OBJECTIVE: To study the correlations of sex determining region Y-box 9 (SOX9) expression with serum type-1 insulin-like growth factor (IGF-1), interleukin-1α (IL-1α), and interleukin-6 (IL-6) in skin lesion tissues of patients with acne. PATIENTS AND METHODS: Six patients with acne who were treated for the first time in our outpatient clinic from June 2017 to July 2017 were selected as observation group, and 6 normal subjects were selected as control group. The expression of SOX9 was detected by immunohistochemistry. The protein expressions of IGF-1, IL-1α, and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). SOX9 was detected by quantitative polymerase chain reaction (qPCR). RESULTS: Compared with that in control group, the expression of SOX9 in observation group was significantly increased (p < 0.05). Compared with those in control group, the expressions of IGF-1, IL-1α and IL-6 in observation group were significantly increased (p < 0.05). Compared with that in control group, the mRNA expression of SOX9 in observation group was significantly increased (p < 0.05). SOX9 was positively correlated with IGF-1, IL-1α and IL-6. CONCLUSIONS: The expressions of SOX9, IGF-1, IL-1α, and IL-6 in skin lesion tissues of patients with acne are increased, and SOX9 is positively correlated with IGF-1, IL-1α, and IL-6 and can be used as a target for the treatment of acne inflammation.

Combinatory effect of mesenchymal stromal cells transplantation and quercetin after spinal cord injury in rat.

OBJECTIVE: To investigate the synergistic effects of quercetin (Qu) administration and transplantation of human umbilical cord mesenchymal stromal cells (HUMSCs) following spinal cord injury (SCI). MATERIALS AND METHODS: HUMSCs were isolated, cultured and certificated via flow cytometry. Sixty Sprague-Dawley (SD) female rats were used and SCI models were made. All rats were divided into five experimental groups: culture medium treated group (n=28); HUSMCs + quercetin-treated group (n = 28); HUMSCs treated group (n=28); quercetin-treated group (n = 28); sham group (n = 20). Basso, Beattie, and Bresnahan (BBB) were used to assess neurological function recovery. Axons at the injury epicenter of the injury were checked by immunohistochemical analysis. Cystic cavity was measured and rat cytokine Luminex custom 8-plex kits (for interleukin (IL)-4, IL-1ß, IL-6, IL-10, interferon (IFN)-γ, tumor necrosis factor (TNF)-ß1) were checked. RESULTS: The combination treatment with Qu and delayed transplantation of HUMSCs after rat SCI improved neurological functional recovery, increased axonal preservation, promoted macrophage polarization, decreased the size of the cystic cavity, reduced the proinflammatory cytokines, including IL-1ß and IL-6. Also, it increased anti-inflammatory cytokines, including IL-4, IL-10, and transforming growth factor (TGF)-ß1. CONCLUSIONS: We showed that HUMSCs transplantation in combination with Qu was a potential strategy for reducing secondary damage and promoting functional recovery following SCI.

Cauliflower-like Neoplasm of Duodenal Papilla in a Liver Transplant Recipient: What Should We Think and Do? A Case Report.

BACKGROUND: With the continuous improvement of liver transplantation technology, the survival rate of liver transplantation has been improved, but recurrent or de novo malignancy remains one of the major factors affecting the long-term survival of liver transplant recipients. CASE REPORT: A 45-year-old Chinese man had a plastic biliary stent placed on account of biliary anastomotic stenosis after 3 years of piggyback liver transplantation. He came to our hospital because of recurrent fever and jaundice for 2 weeks, and his carcinoembryonic antigen-199 had increased. The patient's duodenal papillary was cauliflower-like at endoscopic retrograde cholangiopancreatography to replace the biliary stent. He was initially suspected of having duodenal papillary carcinoma after liver transplantation. However, the pathology from endoscopic retrograde cholangiopancreatography and endoscopic ultrasound-guided biopsy showed inflammation. While awaiting the result of biopsy, his CA-199 decreased significantly after anti-infection and symptomatic treatment. The patient was diagnosed with biliary anastomotic stenosis and duodenal papillitis. He was discharged uneventfully; to date, there is no evidence of malignant tumor. CONCLUSIONS: We report this case to provide helpful information to clinicians about the management of the duodenal papilla cauliflower-like neoplasm after liver transplantation, which should be considered as inflammatory first. Perhaps our view can avoid the risk of bringing an excessive medical treatment and unnecessary economic burden to patients and their families.

Increased expression of miR-330-3p: a novel independent indicator of poor prognosis in human breast cancer.

OBJECTIVE: Previous study has reported that miR-330-3p was highly expressed in breast cancer (BC) patients. However, the effect of miR-330-3p in BC progression remains largely unclear. The purpose of this study was to investigate the clinical significance of miR-330-3p expression in BC. PATIENTS AND METHODS: The expression of miR-330-3p was detected by quantitative Real-time PCR in BC tissues and matched normal breast tissues. The association of miR-330-3p expression with clinicopathological factors of BC patients was also analyzed by x2-test. Prognosis value of patients with BC was assessed by Kaplan-Meier method and Cox proportional hazards model, respectively. RESULTS: Quantitative real-time PCR analysis showed that the expression level of miR-330-3p was significantly higher in BC specimens than that in corresponding noncancerous tissues (p < 0.01). The levels of miR-330-3p were positively correlated with the status of TNM stage (p = 0.011) and lymph node metastasis (p = 0.006). Kaplan-Meier analysis revealed that 5-year overall survival of BC patients with high miR-330-3p expression was shorter compared to those patients with low miR-330-3p expression (p < 0.0001). Moreover, univariate and multivariate regression analysis demonstrated that miR-330-3p was an independent prognostic factor in BC. CONCLUSIONS: Our data suggest that miR-330-3p upregulation maybe concurrently associated with prognosis in patients with BC, suggesting that miR-330-3p may be a potential prognostic biomarker and therapeutic target for patients with BC.

Immunomodulatory effects of T helper 17 cells and regulatory T cells on cerebral ischemia.

The aim of the present study was to analyze the relationship between cerebral ischemia and immune effects. A total of 70 Kunming mice were randomly divided into two groups: a model group (60 mice) and a sham group (10 mice). The model group was divided into six subgroups (10 mice per group) which were categorized according to the following time periods of treatment: 6 h, 12 h, 24 h, 48 h, 72 h and 5 days. The temporary middle cerebral artery occlusion (tMCAO) mouse model was established using intracavitary suture. The degree of brain injury was evaluated by detecting the neurological deficit score (NDS). Following cerebral ischemia reperfusion, the edema of the brain tissue was aggravated, and the infarction area was increased. At 48 h, the volume of the cerebral infarction reached a peak (44.4±3.2%) and then it decreased. The NDS score gradually decreased, and the nerve function was gradually restored. At 6 h, the NDS score was 4.6±0.55, whereas at the 5 d time point, it was significantly decreased (P less than 0.05) to 2.2±0.45. Flow cytometry analysis indicated that the percentage of Th17 cells increased gradually following ischemia. At 24 h, the percentage of Th17 cells reached its maximum value (0.70±0.10%) compared with the sham and the 5 d groups (P less than 0.05). At 24 h, the percentage of Th17 cells reached the lowest value (0.9±0.29%), whereas at the 5 d time point it increased significantly (3.2±0.49%) compared with the normal level (P less than 0.05). The secretion of Th17 and Treg-associated cytokines was consistent with the number of Th17 and Treg cells following ischemia. However, the levels of IL-17A in the brain tissues and the serum indicated a tendency to increase following the prolongation of ischemia. This marker reached the maximum levels on day 5. The IL-17 brain level was 77.9±5.11pg/ml, whereas the serum level was 29.44±3.06pg/ml. The changes in the secretion of the Th17 and Treg-related inflammatory cytokines were consistent with the changes in the cell ratio of Th17 and Treg cells. A significant correlation was noted between the two groups and the degree of ischemic brain injury. The results suggested that the functional status of Th17/Treg cells was imbalanced following cerebral ischemia.

Genetic study of early-onset Graves' disease in the Chinese Han population.

Graves' disease (GD) is a complex autoimmune disorder in which genetic and environmental factors are both involved in the pathogenesis. Early-onset patients have a shorter exposure time to environmental factors and are, therefore, good models to help understand the genetic architecture of GD. Based on previous studies of early-onset GD, 11 single nucleotide polymorphisms (SNPs) and their related SNPs (R2 > .6), SNPs located within a ±1-Mb region of the FOXP3 gene, and 20 validated GD-risk SNPs were selected and screened for genotyping in 3735 GD and 4893 control patients to investigate whether early-onset GD is a subtype of GD with distinct susceptibility genes. Ultimately, we did not confirm the reported genetic markers of early-onset GD in our Chinese Han population but found that a GD-risk SNP located in the human leukocyte antigen class I region-rs4947296-was more strongly correlated with early-onset GD than non-early-onset GD. In addition, heterogeneity analysis of GD patients suggests that it may be more reasonable to define early-onset GD as an onset age ≤20 years.

Analgesic effect of dezocine in different doses on elderly patients undergoing abdominal operation under general anesthesia and its influence on stress response to postoperative tracheal extubation.

OBJECTIVE: To study the analgesic effect of dezocine in different doses on elderly patients undergoing abdominal operation under general anesthesia and to investigate the influence of dezocine on stress response to postoperative tracheal extubation. PATIENTS AND METHODS: A total of 76 elderly patients undergoing abdominal operation under general anesthesia and postoperative analgesia in our hospital from January 2015 to January 2016 were selected, and patients treated with fentanyl were selected as the control group (fentanyl: 10 µg/kg, n=19). The patients were randomly divided into low-dose group (dezocine: 0.05 mg/kg, n=19), medium-dose group (dezocine: 0.1 mg/kg, n=19) and high-dose group (dezocine: 0.15 mg/kg, n=19). The patients in each group were intravenously injected with 0.1 mg/kg tropisetron. The tracheal catheter was withdrawn from patients in each group; the heart rate (HR), respiratory rate (RR), mean arterial pressure (MAP) and saturation of pulse oxygen (SpO2) of patients in each group before and at 10 min after tracheal extubation were recorded in detail; moreover, the visual analogue scale (VAS) score, Ramsay sedation score, occurrence rate of adverse reactions, Bruggrmann comfort scale (BCS) score and times of pressing analgesia pump after operation of patients in the four groups were evaluated at 4, 8, 12, 24 and 48 h after operation. RESULTS: Compared with those before operation, there were no statistically significant differences in HR, RR, MAP and SPO2 of patients in low-dose group, medium-dose group and high-dose group at 10 min after tracheal extubation, and HR, RR, MAP and SPO2 of patients in control group were significantly increased after tracheal extubation (p<0.05). The VAS scores of patients in low-dose group within 48 h were significantly higher than those in control group, medium-dose group and high-dose group (p<0.05). The Ramsay sedation scores of patients in low-dose group and medium-dose group were significantly lower than those in control group and high-dose group (p<0.05), and the BCS score of patients in low-dose group was lower than those in medium-dose group, high-dose group, and control group (p<0.05). Besides, the occurrence rates of postoperative adverse reactions of patients in control group and low-dose group were higher than those in medium-dose group and high-dose group (p<0.05), the times of pressing analgesia pump after operation of patients in low-dose group were more than those in control group, medium-dose group and high-dose group (p<0.05), and the times were reduced successively in low-dose group, medium-dose group, and high-dose group. Finally, the results of correlation analysis showed that the dose of dezocine was positively correlated with the Ramsay sedation score, but negatively correlated with the VAS score of patients. CONCLUSIONS: Dezocine can effectively enhance the analgesic effect on elderly patients receiving abdominal operation under general anesthesia in a dose-dependent manner. Moreover, dezocine can significantly reduce the stress response of elderly patients to postoperative tracheal extubation, and reduce the occurrence rate of adverse complications after abdominal operation under general anesthesia.

The mechanism of miR-23a in regulating myocardial cell apoptosis through targeting FoxO3.

OBJECTIVE: Myocardial cell apoptosis represents important pathologic basis of ischemia-reperfusion injury (I/R). MiR-23a is related to myocardial hypertrophy and cardiac remodeling by regulating myocardial cell growth and apoptosis. This study intended to observe the regulating effect of miR-23a in myocardial cell and related target, and investigate its clinical significance to I/R injury. MATERIALS AND METHODS: The rats were divided into sham group and myocardial I/R group. Myocardial cell cycle and miR-23a expression were tested. H2O2 was applied to treat H9c2 rat myocardial cell to simulate oxidative stress during I/R. The cells were divided into blank group, NC group, miR-23a mimic group, H2O2 group, and miR-23a + H2O2 group. ROS content and cell apoptosis were detected by flow cytometry. MiR-23a, FoxO3a, and BIM gene expression were determined by qRT-PCR. FoxO3a and BIM protein levels were measured by Western blot. RESULTS: Compared with sham group, myocardial apoptosis increased, while miR-23a expression was significantly downregulated in I/R group. H2O2 treatment markedly increased ROS levels in H9c2 cells and elevated apoptosis. The overexpression of mMiR-23a effectively reduced cell apoptosis induced by H2O2 treatment. H2O2 treatment significantly decreased miR-23a expression, while markedly elevated the levels of FoxO3a and BIM. The overexpression of miR-23a apparently impeded the induction of FoxO3a and BIM by H2O2. CONCLUSIONS: The downregulation of miR-23a plays a negative role in oxidative stress and cell apoptosis induced by I/R. The overexpression of miR-23a is of significance to alleviate cell apoptosis through inhibiting FoxO3a and downstream target BIM expression.

miR-340 suppresses tumor growth and enhances chemosensitivity of colorectal cancer by targeting RLIP76.

OBJECTIVE: Colorectal cancer (CRC) is a common human malignancy and is the second leading cause of cancer deaths worldwide with a dismal prognosis. Previous investigations have shown that miR-340 can modulate the metabolism of CRC cells. The aim of this report is to study the role of miR-340 in the development and progression of CRC. PATIENTS AND METHODS: The level of miR-340 in CRC cells was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. CRC cell lines were used as model cell lines and the anti-tumor effect of miR-340 in vitro was examined. The luciferase reporter assay was performed. The level of miR-340 was restored in CRC cells by the usage of the miR-340 mimic. Re-expression of RLIP76 in CRC cells was then constructed. Moreover, the target gene of miR-340 was identified through the experiment of in vivo xenograft model. RESULTS: The aberrant downregulation of miR-340 is correlated with advanced stage of CRC. Furthermore, the ectopic overexpression of miR-340 in CRC cell lines resulted in growth inhibition, apoptosis and enhanced chemosensitivity in vitro and in vivo, which was mediated by directly targeting RLIP76. CONCLUSIONS: miR-340 acts as a tumor suppressor in CRC and is involved in the chemoresistance of CRC.

Liver Transplant Recipient With Tumefactive Demyelinating Lesions: A Case Report and Literature Review.

Tumefactive demyelinating lesions (TDLs) that may resemble brain neoplasms or abscesses are uncommon but noteworthy. A solid knowledge of how to distinguish TDLs from malignancy or infection is a key step to avoid unnecessary medical or surgical interventions. Almost all the intracranial demyelination diseases after liver transplantation (LT) refer to central pontine myelinolysis or extrapontine myelinolysis; TDLs after LT have never been reported. In 2005, a 45-year-old Chinese male underwent orthotopic LT due to "acute on chronic liver failure" in our hospital. He took triple anti-rejection drugs including tacrolimus, mycophenolate mofetil, and corticosteroids after LT. In 2010, he was admitted for right limb weakness, and the head magnetic resonance imaging and magnetic resonance spectroscopy revealed the lesions were more likely to be TDLs. His symptoms disappeared after he was administered corticosteroid therapy which proved the diagnosis. Five years later, he was admitted again to hospital with dizziness and double version. The magnetic resonance image and magnetic resonance spectroscopy showed that the new solitary lesion in the cerebellum may in fact be the new TDL. He received corticosteroid therapy and was discharged after symptoms improved. Herein, to our knowledge, we reported the first case of TDL after LT. We reported this case to provide helpful information to clinicians about intracranial demyelination diseases after LT which maybe are not always central pontine myelinolysis or extrapontine myelinolysis.