Leisure-time physical activity is associated with depressive symptoms in cancer patients: Data from the NHANES 2007-2018.

BACKGROUND: Cancer patients have a higher risk of depression and are associated with severe adverse prognosis. The relationship between leisure-time physical activity (LTPA) and depressive symptoms in cancer patients is currently unclear. Therefore, our study mainly explores the potential association between LTPA and the weekly cumulative time of LTPA with depressive symptoms in cancer patients. METHODS: We included and analyzed 3368 cancer patients (aged >20 years) from the National Health and Nutrition Examination Survey (NHANES) of the United States from 1999 to 2018. The LTPA score was evaluated through a self-report questionnaire, while depressive symptoms were evaluated through the Health Questionnaire-9 (PHQ-9). Multiple logistic regression analysis was used to explore the relationship between LTPA duration and the occurrence of cancer-related depressiive symptoms. Linear correlation was studied using the restricted cubic spline method. RESULTS: According to a fully adjusted multivariate logistic regression model with confounding variables, the odds ratio (OR) between LTPA and depressive symptoms in cancer patients in this study was 0.59 (95 % confidence interval = 0.39, 0.92; P = 0.02). When the LTPA level was ≥300 min/week, the incidence of depressive symptoms was reduced by 59 % (OR = 0.41, 95 % CI = 0.21, 0.83). In addition, the cubic spline method was used to obtain a linear negative correlation between LTPA duration and tumor depressive symptoms. CONCLUSION: LTPA was negatively correlated with cancer-related depressive symptoms, and the cumulative time of LTPA/week was linearly correlated with depressive symptoms. The slope of the benefit curve changed significantly when the cumulative time of LTPA reached 600 min per week, suggesting that appropriately increasing LTPA had significant benefits on mental health of cancer patients.

Anti-rheumatoid arthritis effects of traditional Chinese medicine Fufang Xiaohuoluo pill on collagen-induced arthritis rats and MH7A cells.

Background: Fufang Xiaohuoluo pill (FFXHL) is a commonly used prescription in clinical practice for treating rheumatoid arthritis in China, yet its specific mechanism remains unclear. This study aims to elucidate the pharmacological mechanisms of FFXHL using both in vivo and in vitro experiments. Methods: The collagen-induced arthritis (CIA) rat model was established to evaluate FFXHL's therapeutic impact. Parameters that include paw swelling, arthritis scores, and inflammatory markers were examined to assess the anti-inflammatory and analgesic effects of FFXHL. Human fibroblast-like synoviocytes (MH7A cells) is activated by tumour necrosis factor-alpha (TNF-α) were used to explore the anti-inflammatory mechanism on FFXHL. Results: Our findings indicate that FFXHL effectively reduced paw swelling, joint pain, arthritis scores, and synovial pannus hyperplasia. It also lowered serum levels of TNF-α, interleukin-1ß (IL1ß), and interleukin-6 (IL-6). Immunohistochemical analysis revealed decreased expression of nuclear factor-kappa B (NF-κB) p65 in FFXHL-treated CIA rat joints. In vitro experiments demonstrated FFXHL's ability to decrease protein secretion of IL-1ß and IL-6, suppress mRNA expression of matrix metalloproteinases (MMP) -3, -9, and -13, reduce reactive oxygen species (ROS) levels, and inhibit NF-κB p65 translocation in TNF-α stimulated MH7A cells. FFXHL also suppressed protein levels of extracellular signal-regulated kinase (ERK), c-Jun Nterminal kinase (JNK), p38 MAP kinase (p38), protein kinase B (Akt), p65, inhibitor of kappa B kinase α/ß (IKKα/ß), Toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) induced by TNF-α in MH7A cells. Conclusion: The findings imply that FFXHL exhibits significant anti-inflammatory and antiarthritic effects in both CIA rat models and TNF-α-induced MH7A cells. The potential mechanism involves the inactivation of TLR4/MyD88, mitogen-activated protein kinases (MAPKs), NF-κB, and Akt pathways by FFXHL.

Integrated proteogenomic and metabolomic characterization of papillary thyroid cancer with different recurrence risks.

Although papillary thyroid cancer (PTC) has a good prognosis, its recurrence rate is high and remains a core concern in the clinic. Molecular factors contributing to different recurrence risks (RRs) remain poorly defined. Here, we perform an integrative proteogenomic and metabolomic characterization of 102 Chinese PTC patients with different RRs. Genomic profiling reveals that mutations in MUC16 and TERT promoter as well as multiple gene fusions like NCOA4-RET are enriched by the high RR. Integrative multi-omics analyses further describe the multi-dimensional characteristics of PTC, especially in metabolism pathways, and delineate dominated molecular patterns of different RRs. Moreover, the PTC patients are clustered into four subtypes (CS1: low RR and BRAF-like; CS2: high RR and metabolism type, worst prognosis; CS3: high RR and immune type, better prognosis; CS4: high RR and BRAF-like) based on the omics data. Notably, the subtypes display significant differences considering BRAF and TERT promoter mutations, metabolism and immune pathway profiles, epithelial cell compositions, and various clinical factors (especially RRs and prognosis) as well as druggable targets. This study can provide insights into the complex molecular characteristics of PTC recurrences and help promote early diagnosis and precision treatment of recurrent PTC.

Impact of obese patients in ovarian cancer surgery on postoperative wound complications: A meta-analysis.

The effect of obesity on wound-related outcomes in post-ovarian cancer patients is not clear. A number of studies on the association of fat with post-operation injury in ovarian carcinoma have produced contradictory findings. This study aims to conduct a study of the available data to assess the association of obese individuals with significant surgery results in ovarian cancer. We looked up Cochrane Library, Embase, and PubMed for qualifying research on ovarian cancer operations to determine the primary evidence for evaluating the association of obesity with post-surgical wound injury in ovarian cancer. The odds ratio (OR) was analysed with a fixed effect model if the variability of the study was small; otherwise, the analysis of the data was done with a random effect model. Out of 1259 related trials which were reviewed for eligibility, 6 publications were chosen from 2009 to 2019, 3076 patients who had had an operation for ovarian cancer. Obesity has been linked to an increased rate of wound-related complications in ovarian cancer operations compared to those without obesity (OR, 0.50; 95% CI, 0.37, 0.69 p < 0.0001). Non-obesity was significantly less likely to occur with respect to operation time compared to those with obesity (MD, -48.00; 95% CI, -55.33, -40.68 p < 0.00001). There were no statistically significant differences in the rate of haemorrhage after the operation (OR, 0.26; 95% CI, 0.04, 1.57, p = 0.14). Because of the limited number of trials in this meta-analysis, caution should be exercised in their treatment. More high-quality research with a large sample is required in order to confirm the findings.

Blood-conserving and therapeutic efficacy of intravenous tranexamic acid at different time points after primary total knee arthroplasty with tourniquet application: a randomised controlled trial.

BACKGROUND: The use of a tourniquet in combination with tranexamic acid (TXA) not only ensures clear vision, reduces intraoperative blood loss and shortens operative time but also improves cement-bone inter-digitation in total knee arthroplasty (TKA). However, there is no proof whether the blood flow blocking effect of tourniquet affects the antifibrinolytic effect of TXA, and the optimal timing of TXA administration is still unclear. Therefore, this study aims to investigate the effect of the first dose of TXA administered intravenously before tourniquet compression and release in TKA on perioperative blood loss and therapeutic efficacy in patients. METHODS: In this double-blind trial, 90 patients undergoing primary TKA were randomised into 2 groups: Group A, patients received intravenous TXA 10 min before tourniquet compression (20 mg/kg) and 3, 6 and 24 h later (10 mg/kg), and Group B, patients were treated the same as those in Group A but received intravenous TXA before tourniquet release. The primary outcomes were changes in blood loss, haemoglobin and haematocrit. Secondary outcomes included operation and tourniquet times, blood transfusion rate, subcutaneous petechiae and circumferential changes in the operated limb, visual analogue scale (VAS) score, hospital for special surgery (HSS) score, length of stay (LOS) postoperatively, complications and patient satisfaction. RESULTS: No statistically significant difference was found between the 2 groups with regard to age, sex, weight, body mass index (BMI), Kellgren-Lawrence class, preoperative blood volume, preoperative laboratory values, operation and tourniquet times, transfusion rate, knee circumference, preoperative HSS, or VAS score (P:n.s.). There was no significant difference in intraoperative blood loss (IBL) (52.7 ml vs. 63.4 ml, P = 0.07), hidden blood loss (HBL) (91.4 ml vs. 119.9, P = 0.4) or total blood loss (TBL) (144.1 ml vs. 183.3 ml, P = 0.72) between Groups A and B. Haemoglobin, haematocrit and red blood cell count (RBC) dropped to a low point on postoperative day 3 and then rebounded, returning to normal levels on day 21, and the trend of change between the 2 groups was not statistically significant (P:n.s.). There was no significant difference in subcutaneous ecchymosis incidence, knee swelling rate, HSS score, VAS score, LOS postoperatively, complication rate or patient satisfaction (P:n.s.). CONCLUSION: TXA was administered intravenously prior to tourniquet compression could effectively reduce blood loss in patients who had undergone total knee arthroplasty. However, there was no significant difference in knee swelling rate, subcutaneous bruising and petechiae incidence, knee function, complication rate or satisfaction between patients who TXA was given intravenously before tourniquet compression and release in primary TKA.

Colon-Targeted Release of Gel Microspheres Loaded with Antioxidative Fullerenol for Relieving Radiation-Induced Colon Injury and Regulating Intestinal Flora.

Radiation-induced colitis is a serious clinical problem worldwide. However, the current treatment options for this condition have limited efficacy and can cause side effects. To address this issue, colon-targeted fullerenol@pectin@chitosan gel microspheres (FPCGMs) are developed, which can aggregate on colon tissue for a long time, scavenge free radicals generated in the process of radiation, and regulate intestinal flora to mitigate damage to colonic tissue. First, FPCGMs exhibit acid resistance and colon-targeted release properties, which reduce gastrointestinal exposure and extend the local colonic drug residence time. Second, fullerenol, which has a superior scavenging ability and chemical stability, reduces oxidative stress in colonic epithelial cells. Based on this, it is found that FPCGMs significantly reduce inflammation in colonic tissue, mitigated damage to tight junctions of colonic epithelial cells, and significantly relieved radiation-induced colitis in mice. Moreover, 16S ribosomal DNA (16S rDNA) sequencing results show that the composition of the intestinal flora is optimized after FPCGMs are utilized, indicating that the relative abundance of probiotics increases while harmful bacteria are inhibited. These findings suggest that it is a promising candidate for treating radiation-induced colitis.

Small molecule inhibitors for cancer metabolism: promising prospects to be explored.

BACKGROUND: Abnormal metabolism is the main hallmark of cancer, and cancer metabolism plays an important role in tumorigenesis, metastasis, and drug resistance. Therefore, studying the changes of tumor metabolic pathways is beneficial to find targets for the treatment of cancer diseases. The success of metabolism-targeted chemotherapy suggests that cancer metabolism research will provide potential new targets for the treatment of malignant tumors. PURPOSE: The aim of this study was to systemically review recent research findings on targeted inhibitors of tumor metabolism. In addition, we summarized new insights into tumor metabolic reprogramming and discussed how to guide the exploration of new strategies for cancer-targeted therapy. CONCLUSION: Cancer cells have shown various altered metabolic pathways, providing sufficient fuel for their survival. The combination of these pathways is considered to be a more useful method for screening multilateral pathways. Better understanding of the clinical research progress of small molecule inhibitors of potential targets of tumor metabolism will help to explore more effective cancer treatment strategies.

Berberine inhibits gluconeogenesis in spontaneous diabetic rats by regulating the AKT/MAPK/NO/cGMP/PKG signaling pathway.

This work was aimed to investigate the action mechanism of berberine (BBR) on gluconeogenesis. The effects of BBR were examined in rat primary hepatocytes and confirmed in vivo in spontaneous diabetic rats. Protein levels were assessed by Western blot. Immunofluorescence staining was utilized for visualizing protein expression, while qRT-PCR helped for the determination of gene expression at the mRNA level. Besides, cGMP concentration was measured using ELISA, whereas NO level was assessed by spectrophotometry. BBR inhibited gluconeogenesis by downregulating G6Pase and PEPCK via inhibition of CREB phosphorylation. Moreover, BBR enhanced NO and cGMP concentrations, leading to the activation of the NO/cGMP/PKG signaling via activating AKT1/MAPK axis. The in vivo experiments were consistent with the findings obtained in vitro. Hence, BBR represents a drug candidate for diabetic patients and its mechanism of action may be driven via the AKT/MAPK/NO/cGMP/PKG pathway.

Analysis of Clinical Characteristics of Connective Tissue Disease-Associated Interstitial Lung Disease in 161 Patients: A Retrospective Study.

Objective: This study was conducted to retrospectively analyze the clinical characteristics of CTD-ILD patients to provide strategies for clinical management. Methods: This study collected and analyzed the clinical data and relevant examination results of 161 patients diagnosed with CTD-ILD between 01 January 2018 and 01 January 2021. Results: A total of 161 CTD-ILD patients, 74.53% were females and 25.47% were males, 32.92% were elderly and 67.08% were non-elderly. The main clinical symptoms of CTD-ILD patients were cough (44.72%), decreased activity tolerance (40.37%). RA-ILD was the most common one in the non-elderly and the elderly CTD-ILD patients (48.15% and 50.94%, respectively). Compared with non-elderly, elderly patients with CTD-ILD had a longer duration of CTD (p=0.04). However, fatigue (p=0.005), activity tolerance (p=0.029), the incidence of pulmonary diffusion dysfunction (p=0.047), and systemic immunoinflammatory index (SII, p=0.014) (platelet × NLR) were all decreased. The standard deviation of red blood cell distribution width (RDW) (p=0.024) and immunoglobulin (IgA) (p=0.033) was significantly increased. The smoking index was significantly higher in men than in women with CTD-ILD (p=0.000), but symptoms of reduced activity tolerance were less pronounced than in women (p<0.05). Elderly CTD-ILD patients (p=0.003) and women from non-elderly patients were prone to lower hemoglobin (p=0.000). Among the elderly, the lymphocyte ratio was more significantly elevated in female CTD-ILD patients than in males (p=0.018). In contrast, neutrophil to lymphocyte ratio (NLR) and SII were lower in female (p=0.038) than in male CTD-ILD patients (p=0.043). Conclusion: CTD-ILD mainly affects non-elderly and women. Age may not be involved with decreased activity tolerance and increased lung function impairment in CTD-ILD patients. However, the elderly patients with CTD-ILD, especially the elderly female patients with low inflammation levels and high immune disorders, have a poor prognosis.

Emerging role of circRNAs in cancer under hypoxia.

Circular RNA (circRNA), a recently identified type of non-coding RNAs (ncRNAs), forms a covalently closed loop with neither a 5' cap structure nor a 3' polyadenylated tail. Due to their lack of free ends, circRNAs are not easily cleaved by RNase R, thus avoiding degradation and being more stable than linear RNAs. Recent studies have suggested that circRNAs play a crucial role in regulating gene expression by acting as microRNAs sponges, RNA binding protein sponges and translational regulators. Currently, circRNAs are hot research topics due to their close association with the development of cancer and other diseases. Hypoxia is the most common microenvironment during tumor growth, and hypoxia-inducible factors have different effects on tumor growth and influence important cancer characteristics, including cell proliferation, apoptosis, differentiation, vascularization/angiogenesis, genetic instability, tumor metabolism, tumor immune response, invasion and metastasis. The present review aimed to study the biogenesis and mechanisms of gene regulation of circRNAs in hypoxia, to summarize the latest studies on circRNAs as potential diagnostic and prognostic biomarkers in hypoxia, and to understand the role of circRNAs in the process of tumor drug resistance under hypoxia.

Effects of Lactobacillus plantarum HFY15 on Lupus Nephritis in Mice by Regulation of the TGF-ß1 Signaling Pathway.

Objective: In this study, the Lactobacillus plantarum HFY15 (LP-HFY15) strain isolated from naturally fermented yak yogurt was investigated. An animal model of lupus nephritis was established by pristane to verify the interventional effect of LP-HFY15 on mouse lupus nephritis by regulating the transforming growth factor-ß1 (TGF-ß1) signaling pathway. Materials and Methods: Indexes in mouse serum and tissues were detected by kits, pathological changes in mouse kidney were observed by hematoxylin-eosin (H&E) staining, and quantitative polymerase chain reaction (qPCR) was used to detect TGF-ß 1-related expression in mouse kidney tissue, which further elucidated the mechanism of LP-HFY15. Results: LP-HFY15 decreased the elevation of urinary protein and the levels of interleukin-6 (IL-6), IL-12, tumor necrosis factor alpha (TNF-α), and interferon γ (IFN-γ) in serum and kidney tissue. LP-HFY15 also reduced serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), and raised total protein (TP), and albumin (ALB) levels in mice with nephritis. In addition, LP-HFY15 inhibited the positive rate of double-stranded deoxyribonucleic acid (dsDNA) antibodies in mice with nephritis. The observation of H&E sections showed that LP-HFY15 alleviated the glomerulus morphological incompleteness and inflammatory infiltration caused by nephritis. Further results showed that LP-HFY15 downregulated the mRNA expression of TGF-ß1, vascular endothelial growth factor (VEGF), and nuclear factor kappa-B (NF-κB) in the kidneys of lupus nephritis mice, and the expression of inhibitor of NF-κB (IκB-α), copper/zinc superoxide dismutase (Cu/Zn-SOD), and manganese superoxide dismutase (Mn-SOD) was also upregulated. Conclusion: These results indicated that LP-HFY15 plays a significant role in experimental intervention for lupus nephritis. The effect of LP-HFY15 was positively correlated with its concentration, and the effect was similar to that of prednisone at 109 CFU/kg.

Laparoscopic Radical Hysterectomy Combined with Neoadjuvant Chemotherapy for Cervical Cancer Patients Effectively Improves Immune Function.

Objective: To evaluate the clinical efficacy of neoadjuvant chemotherapy plus laparoscopic radical hysterectomy for cervical cancer and the effect on the immune function of patients. Methods: Between January 2021 and December 2021, 42 patients with cervical cancer diagnosed and treated at our hospital were recruited and randomly assigned at a 1 : 1 ratio to receive neoadjuvant chemotherapy plus open radical hysterectomy (control group) or neoadjuvant chemotherapy plus laparoscopic radical hysterectomy (treatment group) (study group). Outcome measures included surgical indices, clinical outcomes, and immunological function. Results: There were no significant differences in the operative time between the two groups (P > 0.05). Patients receiving laparoscopic surgery had significantly less intraoperative bleeding and shorter time lapse before postoperative anal exhaustion, time lapse before out-of-bed activities, and hospital stay versus patients receiving open surgery (P < 0.05). Laparoscopic surgery resulted in a significantly higher efficacy (90.48%) versus open surgery (57.14%) (P < 0.05). After treatment, patients in the study group showed lower levels of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), and cancer antigen (CA125) than those in the control group (P < 0.05). After treatment, patients given laparoscopic surgery showed significantly lower CD3+, CD4+, and CD8+ levels and higher CD4+/CD8+ levels versus those with open surgery (P < 0.05). The postoperative conditions of the two groups, including recatheterization, postoperative blood transfusion, and secondary anti-inflammation were not significantly different (P > 0.05). The study group showed a significantly lower incidence of complications (19.05%) than the control group (71.43%) (P < 0.05). Patients in the study group had a lower reoperation rate and a higher survival rate (0.00%, 95.24%) than those in the control group (19.05%, 66.67%) (P < 0.05). Conclusion: Neoadjuvant chemotherapy plus laparoscopic radical hysterectomy effectively improves clinical efficacy, lowers cancer marker levels, improves patients' immune function, reduces the risk of adverse events, and improves patients' prognosis with less intraoperative bleeding, less trauma, faster postoperative recovery, and shorter hospital stay for cervical cancer patients.

Hedgehog signaling regulates the development and treatment of glioblastoma.

Glioblastoma (GBM) is the most common and fatal malignant tumor type of the central nervous system. GBM affects public health and it is important to identify biomarkers to improve diagnosis, reduce drug resistance and improve prognosis (e.g., personalized targeted therapies). Hedgehog (HH) signaling has an important role in embryonic development, tissue regeneration and stem cell renewal. A large amount of evidence indicates that both normative and non-normative HH signals have an important role in GBM. The present study reviewed the role of the HH signaling pathway in the occurrence and progression of GBM. Furthermore, the effectiveness of drugs that target different components of the HH pathway was also examined. The HH pathway has an important role in reversing drug resistance after GBM conventional treatment. The present review highlighted the relevance of HH signaling in GBM and outlined that this pathway has a key role in the occurrence, development and treatment of GBM.

The Relationship Between Baseline Cortisol Levels and Surgery Method of Primary Bilateral Macronodular Adrenal Hyperplasia.

Aim was to explore the associations between baseline cortisol levels and surgery method of primary bilateral macronodular adrenal hyperplasia (PBMAH). We retrospectively reviewed the clinical features and management of 30 patients (18 females and 12 males) who were diagnosed with PBMAH in our center between 2005 and 2019. Based on surgery method, we divided the patients into two groups: unilateral adrenalectomy (UA) group; and bilateral adrenalectomy (BA) group. Serum cortisol rhythm and 24-hour urinary free cortisol (UFC/24 h) levels were assayed using chemiluminescence method. Associations between baseline cortisol levels and BA were assessed using logistic regression. The predictive value of baseline cortisol levels for BA was calculated using receiver operating characteristic (ROC) curves. Twenty patients (66.7%) underwent UAs and ten patients (33.3%) underwent BAs. After adjusting for age, sex, BMI, SBP, and adrenal volume, the concentrations of baseline serum cortisol (8 AM, 4 PM, and 0 AM) and UFC/24 h were associated with bilateral adrenalectomy (all p<0.05). The area under the ROC curve based on 8 AM serum cortisol level model was larger than that in models based on 4 PM, 0 AM serum cortisol levels and UFC/24 h, but the differences were non-significant (all p>0.05). According to maximum Youden index criteria, the optimal cutoffs of 8 AM serum cortisol level and UFC were 26.89 µg/dl and 406.65 µg/24 h, respectively, for BA. The baseline cortisol levels are positively associated with BA. Increased levels of baseline cortisol levels may predict higher possibility of BA, which should be confirmed by prospective studies.

Application of 3D-printed prosthesis in revision surgery with large inflammatory pseudotumour and extensive bone defect: A case report.

BACKGROUND: Hip revision surgery is the final treatment option for the failure of artificial hip joints, but it is more difficult than the initial operation. For patients with hip joint loosening around the prosthesis combined with large inflammatory pseudotumours and large segment bone defects, hip revision is even more difficult, and clinical reports are rare. CASE SUMMARY: Male, 59 years old. The patient underwent left hip replacement 35 years ago and was now admitted to hospital due to massive masses in the left thigh, shortening of the left lower extremity, and pain and lameness of the left hip joint. X-ray, computed tomography and magnetic resonance imaging revealed prosthesis loosening, left acetabular bone defect (Parprosky IIIB type), and a bone defect of the left proximal femur (Parprosky IIIA type). Inflammatory pseudotumours were seen in the left hip and left thigh. Hip revision surgery was performed using a 3D-printed custom acetabular prosthesis was used for hip revision surgery, which was produced by Arcam Electron Beam Melting system with Electron Beam Melting technology. The operation was successful, and the patient was followed up regularly after the operation. The custom-made acetabular prosthesis was well matched, the inflammatory pseudotumour was completely removed, the postoperative hip prosthesis was stable, and the old greater trochanter fracture was well reduced and fixed. The patient was partially weight-bearing with crutches 3 mo after the operation and walked with full weight-bearing after 6 mo. The hip prosthesis was stable, and there was no recurrence of inflammatory pseudotumours at the last follow-up. The Visual Analogue Scale was 3, and the Harris hip score was 90. CONCLUSION: The use of 3D-printed personalized custom prostheses for complex hip revision surgery has satisfactory surgical results and has great clinical application value.

ANKRD22 Drives Rapid Proliferation of Lgr5+ Cells and Acts as a Promising Therapeutic Target in Gastric Mucosal Injury.

BACKGROUND & AIMS: Rapid gastric epithelial progenitor cell (EPC) proliferation and inflammatory response inhibition play key roles in promoting the repair of gastric mucosal damage. However, specific targets inducing these effects are unknown. In this study, we explored the effects of a potential target, Ankyrin repeat domain 22 (ANKRD22). METHODS: An acute gastric mucosal injury model was established with Ankrd22-/- and Ankrd22+/+ mice by intragastric administration of acidified ethanol. Organoid culture and flow cytometry were performed to evaluate the effects of ANKRD22 on leucine-rich repeat-containing G-protein-coupled receptor 5-positive (Lgr5+) gastric EPC proliferation. The mechanisms by which ANKRD22 affects gastric EPC proliferation and inflammatory responses were explored by mitochondrial Ca2+ influx and immunoblotting. Candidate ANKRD22 inhibitors then were screened virtually and validated in vitro and in vivo. RESULTS: After acute gastric mucosal injury, the number of Lgr5+ gastric EPCs was increased significantly in Ankrd22-/- mice compared with that in Ankrd22+/+ mice. Moreover, Ankrd22 knockout attenuated inflammatory cell infiltration into damaged gastric tissues. ANKRD22 deletion also reduced mitochondrial Ca2+ influx and cytoplasmic nuclear factor of activated T cells in gastric epithelial cells and macrophages, which further induced Lgr5+ gastric EPC proliferation and decreased macrophage release of tumor necrosis factor-α and interleukin 1α. In addition, a small molecule, AV023, was found to show similar effects to those produced by ANKRD22 deletion in vitro. Intraperitoneal injection of AV023 into the mouse model promoted the repair of gastric mucosal damage, with increased proliferation of Lgr5+ gastric EPCs and visible relief of inflammation. CONCLUSIONS: ANKRD22 inhibition is a potential target-based therapeutic approach for promoting the repair of gastric mucosal damage.

Resveratrol ameliorated endothelial injury of thoracic aorta in diabetic mice and Gly-LDL-induced HUVECs through inhibiting TLR4/HIF-1α.

To explore the effects of resveratrol on the levels of inflammatory cytokines and Toll-like receptor-4/ hypoxia-inducible transcription factors-1α (TLR4/HIF-1α) signalling pathway in diabetes mellitus. C57BL/6 mice received intraperitoneal injection of streptozocin for constructing diabetic mice models. Human umbilical vein endothelial cells (HUVECs) were treated with 50 µg/mL Gly-LDL for inducing injury models. 10, 100 and 1000 mmol/L resveratrol were obtained and added into each group. Haematoxylin-eosin (H&E) staining was used for histological evaluation. CCK8 assay was performed for determination of cell viability, and Transwell assay was implemented for detecting cell migration ability. Cell apoptosis was analysed using flow cytometry. The content of inflammatory factors including interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), vascular adhesion molecule-1 (VCAM-1) and vascular endothelial growth factor (VEGF) were measured by ELISA. GST pull-down assay was employed for determining interactions between TLR4 and HIF-1α. The protein expression of TLR4 and HIF-1α was detected using Western blotting and immunohistochemistry, while relative mRNA expression was measured by RT-qRCR. Resveratrol could reduce bodyweight and ameliorate endothelial injury of thoracic aorta in diabetic mice. Both in vivo and in vitro results revealed that the level of IL-6, TNF-α, VCAM-1 and VEGF was significantly down-regulated after being treated with resveratrol. Resveratrol inhibited the increase of MDA and ROS and increased the level of SOD in diabetic mice. Western blotting, IHC and RT-qPCR results showed that the levels of TLR4 and HIF-1α were significantly down-regulated in resveratrol group. Overexpression of TLR4 or HIF-1α could reverse the effect of resveratrol. GST pull-down elucidated that there might be a close interaction between TLR4 and HIF-1α. Resveratrol ameliorated endothelial injury of thoracic aorta in diabetic mice and Gly-LDL-induced HUVECs through inhibiting TLR4/HIF-1α signalling pathway.

Resveratrol improves Gly-LDL-induced vascular endothelial cell apoptosis, inflammatory factor secretion and oxidative stress by regulating miR-142-3p and regulating SPRED2-mediated autophagy.

BACKGROUND: Resveratrol improves cell apoptosis and tissue damage induced by high glucose, but the specific mechanism is unknown. METHODS: This is a basic research. We performed cell transfection, real-time fluorescence quantitative PCR (qPCR), flow cytometry, immunofluorescence, western blot, enzyme linked immunosorbent assay (ELISA) and cell viability assay to analyze cell viability, cell cycle, cellular oxidative stress, intracellular inflammatory factors and autophagy activities in vitro. Meanwhile, dual luciferase reporter assay was conducted to explore the influence of miR-142-3p and sprouty-related EVH1 domain 2 (SPRED 2) on human glycated low-density lipoprotein (Gly-LDL)-induced vascular endothelial cell apoptosis, inflammatory factor secretion and oxidative stress. RESULTS: Resveratrol inhibited the expression of miR-142-3p in human umbilical vein endothelial cells (HUVECs) induced by Gly-LDL in a dose-dependent manner, and the overexpression of miR-142-3p reverses the effect of resveratrol on the proliferation, apoptosis, secretion of inflammatory factors, oxidative stress, and autophagy. The dual-luciferase report analysis found a negative regulatory relationship between miR-142-3p and SPRED2. Inhibition of SPRED2 reversed the effects of resveratrol on Gly-LDL-induced HUVECs proliferation, apoptosis, inflammatory factor secretion and oxidative stress, and reversed the effects of resveratrol on Gly-LDL-induced HUVECs autophagy. CONCLUSION: miR-142-3p promotes the development of diabetes by inhibiting SPRED2-mediated autophagy, including inducing cell apoptosis, aggravating cellular oxidative stress and secretion of inflammatory factors, and resveratrol improves this effect.

Traumatic Obturator Dislocation of the Hip Joint Associated with Greater Trochanter Fracture: A Case Report.

BACKGROUND: Traumatic obturator dislocation of the hip joint associated with greater trochanter fracture is a rare injury. We used the lateral approach through the rectus abdominis to remove the femoral head dislocated into the obturator, and the posterolateral approach was used for reduction and internal fixation of the femoral greater trochanteric fracture and total hip replacement (THR). Good follow-up results were achieved. To the best of our knowledge, this is the first report on this particular type of injury and on this approach to treating this type of injury. CASE REPORT: The patient was hospitalized due to a traffic accident that resulted in the patient experiencing swelling and deformity accompanied by limited mobility of the left hip and left knee. X-ray examination and CT confirmed that the patient suffered from left hip obturator dislocation, greater trochanter fracture, pelvic fracture (Tile B), left acetabular fracture, right open tibiofibular comminuted fracture (Gustilo III), and posterior urethral injury. The femoral head was removed from the pelvic cavity through a pararectus approach under general anesthesia. A posterolateral approach was used for open reduction, and cable internal fixation for the left intertrochanteric fracture and uncemented THR were performed. RESULTS: The ability to work was restored 6 months after the operation. The Harris hip score, reflecting joint function, was 86 points after 2 years of follow-up observation. CONCLUSION: A lateral approach of rectus abdominis to remove the dislocated femoral head in the pelvis from the obturator should be selected, along with the posterolateral approach for reduction and internal fixation of the intertrochanteric fracture and THR. This case also provides a new reference for the treatment of this type of hip fracture dislocation.

Circular RNA circ_PVT1 induces epithelial-mesenchymal transition to promote metastasis of cervical cancer.

Cervical cancer is one of the most common gynecological malignant tumors. At present, it has been confirmed that the occurrence and development of cervical cancer is related to human papillomavirus infection. As a new regulatory molecule and research hotspot, circRNA is abnormally expressed in tumors and other diseases, and is expected to become a new biomarker for diagnosis and prediction of tumor occurrence and development. In this research, bioinformatics analysis and RT-PCR analysis showed that hsa_circ_0009143 (circRNA_PVT1) was up-regulated in cervical cancer. Knockdown of circRNA_PVT1 inhibits the migration and invasion of cervical cancer cells and would prevent pulmonary metastasis. Overexpression of circRNA_PVT1 induced migration and invasion of cervical cancer cells, which would result in the promotion of pulmonary metastasis. Finally, we found that circRNA_PVT1 can induce EMT of cervical cancer cells via targeting miR-1286 by exosome pathway, which can be a novel mechanism of cervical cancer progression.