The combined internal and external fixation surgery is effective and safe in treating posterior lateral tibial plateau fractures: An observational study.

To investigate the treatment outcomes of combined internal and external fixation surgery for patients with posterior lateral tibial plateau fractures and explore its safety. The study was conducted from February 2020 to February 2023 and included a total of 77 patients with Schatzker IV and Schatzker V type posterior lateral tibial plateau fractures. Patients were divided into control group and treatment group according to different treatment methods: the control group with 38 cases received treatment with dual-support plates, and the study group with 39 cases received treatment with internal fixation using medial plates combined with lateral locking plates. Clinical indicators during treatment, immediate postoperative and 12-month postoperative radiographic indicators, Rasmussen knee joint function scores before and 3 months after surgery, knee joint function recovery, quality of life, and postoperative complications were recorded and compared between the 2 groups. The inter-group comparisons were made for intraoperative blood loss, surgical duration, and the time to start weight-bearing postoperatively (P > .05). The study group had shorter postoperative hospital stays and fracture healing times compared to the control group (P < .05). Immediately postoperatively, the medial tilt angle and posterior tilt angle in both groups were compared (P > .05). At 12 months postoperatively, the medial tilt angle decreased and the posterior tilt angle increased in both groups compared to immediately postoperative values (P < .05), with no significant difference between the groups (P > .05). However, at 3 months postoperatively, the scores for various dimensions in both groups increased compared to preoperative values, and the study group had higher scores than the control group (P < .05). However, at 3 months postoperatively, the quality of life scores were higher than preoperative values in both groups, with the study group having higher scores (P < .05). The occurrence of complications during the treatment period was compared between the 2 groups (P > .05). The medial and lateral combined plate fixation has a good clinical effect in the treatment of posterolateral tibial plateau fractures, which can shorten the fracture healing time, help the recovery of knee joint function and improve the quality of life of patients after operation, and has high safety in the treatment process.

ATP-P2X7R-mediated microglia senescence aggravates retinal ganglion cell injury in chronic ocular hypertension.

BACKGROUND: Dysfunction of microglia during aging affects normal neuronal function and results in the occurrence of neurodegenerative diseases. Retinal microglial senescence attributes to retinal ganglion cell (RGC) death in glaucoma. This study aims to examine the role of ATP-P2X7R in the mediation of microglia senescence and glaucoma progression. METHODS: Forty-eight participants were enrolled, including 24 patients with primary open-angle glaucoma (POAG) and age-related cataract (ARC) and 24 patients with ARC only. We used ARC as the inclusion criteria because of the availability of aqueous humor (AH) before phacoemulsification. AH was collected and the adenosine triphosphate (ATP) concentration was measured by ATP Assay Kit. The chronic ocular hypertension (COH) mouse model was established by microbead occlusion. Microglia were ablated by feeding PLX5622 orally. Mouse bone marrow cells (BMCs) were prepared and infused into mice through the tail vein for the restoration of microglia function. Western blotting, qPCR and ELISA were performed to analyze protein and mRNA expression in the ocular tissue, respectively. Microglial phenotype and RGC survival were assessed by immunofluorescence. The mitochondrial membrane potential was measured using a JC-1 assay kit by flow cytometry. RESULTS: ATP concentrations in the AH were increased in older adults and patients with POAG. The expression of P2X7R was upregulated in the retinal tissues of mice with glaucoma, and functional enrichment analysis showed that P2X7R was closely related to cell aging. Through in vivo and in vitro approaches, we showed that pathological activation of ATP-P2X7R induced accelerated microglial senescence through impairing PTEN-induced kinase 1 (PINK1)-mediated mitophagy, which led to RGC damage. Additionally, we found that replacement of senescent microglia in COH model of old mice with BMCs from young mice reversed RGC damage. CONCLUSION: ATP-P2X7R induces microglia senescence by inhibiting PINK1-mediated mitophagy pathway. Specific inhibition of ATP-P2X7R may be a fundamental approach for targeted therapy of RGC injury in microglial aging-related glaucoma.

Algorithm for optimized mRNA design improves stability and immunogenicity.

Messenger RNA (mRNA) vaccines are being used to combat the spread of COVID-19 (refs. 1-3), but they still exhibit critical limitations caused by mRNA instability and degradation, which are major obstacles for the storage, distribution and efficacy of the vaccine products4. Increasing secondary structure lengthens mRNA half-life, which, together with optimal codons, improves protein expression5. Therefore, a principled mRNA design algorithm must optimize both structural stability and codon usage. However, owing to synonymous codons, the mRNA design space is prohibitively large-for example, there are around 2.4 × 10632 candidate mRNA sequences for the SARS-CoV-2 spike protein. This poses insurmountable computational challenges. Here we provide a simple and unexpected solution using the classical concept of lattice parsing in computational linguistics, where finding the optimal mRNA sequence is analogous to identifying the most likely sentence among similar-sounding alternatives6. Our algorithm LinearDesign finds an optimal mRNA design for the spike protein in just 11 minutes, and can concurrently optimize stability and codon usage. LinearDesign substantially improves mRNA half-life and protein expression, and profoundly increases antibody titre by up to 128 times in mice compared to the codon-optimization benchmark on mRNA vaccines for COVID-19 and varicella-zoster virus. This result reveals the great potential of principled mRNA design and enables the exploration of previously unreachable but highly stable and efficient designs. Our work is a timely tool for vaccines and other mRNA-based medicines encoding therapeutic proteins such as monoclonal antibodies and anti-cancer drugs7,8.

Does Intraoperative Multi-Drug Wound Infiltration Relieve Postoperative Pain Following Single-Level TLIF Surgery? A Randomized Controlled Trial.

BACKGROUND: How to minimize postoperative pain following spinal surgery has been a great challenge for both surgeons and patients. We hypothesized that intraoperative multi-drug wound infiltration could relieve postoperative pain following single-level transforaminal lumbar interbody fusion (TLIF) surgery. OBJECTIVES: To evaluate the effect of intraoperative multi-drug wound infiltration for postoperative pain following single-level TLIF surgery. STUDY DESIGN: A randomized, double-blinded controlled trial (RCT). SETTING: Department of Orthopaedic Surgery, Qilu Hospital of Shandong University. METHODS: The RCT enrolled 50 patients with 25 cases in 2 groups. The study group received intraoperative wound infiltration of mixed solution with lidocaine, ropivacaine, and epinephrine before wound closure. The control group was infiltrated with an equal amount of normal saline. The primary outcome measure was the visual analog scale (VAS) of postoperative incision pain. The secondary outcome measures were the postoperative opioids dosage, the time of first analgesic demand, and the Oswestry Disability Index (ODI). RESULTS: The VAS of postoperative pain in the study group was significantly lower than the control group within postoperative 24 hours. The opioid dosage was significantly less and the time of first analgesic demand of patient-controlled analgesia (PCA) in the study group was significantly longer than the control group. None of the patients in the study group required analgesic supplementation. The side effects of opioids were significantly less in the study group. There was no significant difference in ODI, operation time, intraoperative blood loss, postoperative drainage, and postoperative incision complications between the 2 groups. LIMITATIONS: Single-center study for single-level TLIF surgery. CONCLUSIONS: Intraoperative multi-drug wound infiltration before closure could significantly relieve postoperative pain following single-level TLIF surgery.

Forensic Pathological Analysis of Death Due to Pulmonary Thromboembolism: A Retrospective Study Based on 145 Cases.

ABSTRACT: Pulmonary thromboembolism (PTE) is a common cause of sudden unexpected death in forensic and clinical practice. Although the prevention of thrombosis has been paid more attention in clinical practice in recent years, the number of deaths due to PTE remains extensive. In the present study, 145 cases of fatal PTE were collected and retrospectively analyzed from 2001 to 2020 at the School of Forensic Medicine, China Medical University in Liaoning Province, northeast of China. The demographic characteristics, risk factors of PTE, origins of thrombi, and time interval from the occurrence of main risk factors to PTE were retrospectively analyzed. The 40 to 59 age group accounted for the 51.0% of the total cases. Immobilization, trauma (especially fracture of the pelvis, femur, tibia, or fibula), surgery, cesarean section, and mental disorders were the top 5 high-risk factors. Among the involved cases, 92.9% of the PTE (130/140) occurred within 60 days and peak at 8 to 15 days after the exposure of main risk factors. According to the autopsy findings, 87.6% of the thrombi blocked the bilateral pulmonary arteries at pulmonary hilus, with a maximum diameter of 1.6 cm and a maximum length of 21.9 cm, which were mainly derived from lower limb (65.5%) or pelvic veins (10.3%). Although the embolus limited the pulmonary circulation, there is no difference on the ratio of lung-to-heart weight between PTE and the disease-free accident victims. Overall, our present retrospective study provides important information for the forensic analysis on the cause of death and potential guidance on clinical prevention of PTE.

Efficacy and safety of combination chemotherapy regimens containing taxanes for first-line treatment in advanced gastric cancer.

Gastric cancer is a very common gastrointestinal malignancy. Since the disease is often asymptomatic in its early stage, it is often diagnosed in its late stage. In this study, our objective was to evaluate the efficacy and safety of combination chemotherapy regimens containing taxanes in the first-line treatment of advanced gastric cancer (AGC). We searched published randomized controlled trials (RCTs) to compare the effect of taxanes combined with basic chemotherapy and chemotherapy without taxanes on AGC. The extracted data are the number of people who achieved the objective response rate (ORR) and disease control rate (DCR), as well as the hazard ratio (HR) of progression-free survival (PFS) and overall survival (OS) including their 95% confidence intervals (95% CI). Six RCTs involving 2263 patients were included. Compared with chemotherapy without taxanes, patients receiving taxanes combined with basic chemotherapy had significantly longer PFS (HR 0.73, 95% CI 0.61-0.88, p = 0.001) and significantly longer OS (HR 0.80, 95% CI 0.69-0.93, p = 0.003); significantly better ORR (RR 1.34, 95% CI 1.15-1.57, p = 0.0001) and significantly better DCR (RR 1.20, 95% CI 1.08-1.33, p = 0.001). However, in patients treated with taxanes combined with basic chemotherapy, diarrhea, leukopenia and neutropenia were significantly increased (p < 0.05). In summary, taxanes combined with basic chemotherapy are superior to chemotherapy without taxanes in first-line treatment of AGC patients.

Application of multimodal identification technology in the innovative management operation department.

Background: The optimization of surgical procedures and the management of surgical quality and safety have become the focus of attention of hospital managers. The application of multimodal identification technology in the innovative management mode of hospital operating department has made remarkable progress. Methods: To investigate the effect of the upgraded multimodal identification technology on the innovative management of the operating department, 2,280 cases of laparoscopic surgery using traditional surgical management procedures from January to December 2019 before the management upgrade were set as the control group, and 2,350 laparoscopic surgeries with the upgraded multimodal identification management process from January to December 2020 were selected as the experimental group. The operating efficiency, material management efficiency, and patient experience and satisfaction of the two groups were investigated and compared. Results: Compared with traditional procedures, the upgraded multimodal surgical management system significantly improves the efficiency of laparoscopic surgery and reduces surgical consumption and costs. In addition, the multimodal surgical information identification system significantly improves the surgical experience for patients undergoing laparoscopic surgery. Conclusion: Application of multimodal identification technology improves the innovative management of operation department compared with traditional surgery management procedure.

Dioscin potentiates the antitumor effect of suicide gene therapy in melanoma by gap junction intercellular communication-mediated antigen cross-presentation.

Dioscin (Dio), steroid saponin, exists in several medicinal herbs with potent anticancer efficacy. This study aimed to explore the effect of Dio on the immune-related modulation and synergistic therapeutic effects of the herpes simplex virus thymidine kinase/ganciclovir (HSV-Tk/GCV) suicide gene therapy system in murine melanoma, thereby providing a research basis to improve the potential immunomodulatory mechanism underlying combination therapy. Using both in vitro and in vivo experiments, we confirmed the immunocidal effect of Dio-potentiated suicide gene therapy on melanoma. The results showed that Dio upregulated connexin 43 (Cx43) expression and improved gap junction intercellular communication (GJIC) in B16 cells while increasing the cross-presentation of antigens by dendritic cells (DCs), eventually promoting the activation and antitumor immune killing effects of CD8+ T lymphocytes. In contrast, inhibition or blockade of the GJIC function (overexpression of mutant Cx43 tumor cells/Gap26) partially reversed the potentiating effect. The significant synergistic effect of Dio on HSV-Tk/GCV suicide gene therapy was further investigated in a B16 xenograft mouse model. The increased number and activation ratio of CD8+ T lymphocytes and the levels of Gzms-B, IFN-γ, and TNF-α in mice reconfirmed the potential modulatory effects of Dio on the immune system. Taken together, Dio targets Cx43 to enhance GJIC function, improve the antigens cross-presentation of DCs, and activate the antitumor immune effect of CD8+ T lymphocytes, thereby providing insights into the potential immunomodulatory mechanism underlying combination therapy.

Relationship between different body composition and bone mineral density in Qinhuangdao city

SUMMARY OBJECTIVE: This study aimed to explore the correlation between different body components and bone mineral density in healthy adults. METHODS: A total of 306 non-manual subjects, 161 males and 145 females, were selected from the physical examination center of our hospital from June to September 2019. They were divided into control group, overweight group, and obese group according to body mass index. The muscle mass and fat mass, body fat content, trunk fat mass, upper limb and thigh fat mass, bone density of femoral neck and lumbar vertebra, and bone mineral salt content of the whole body were measured by dual-energy X-ray absorptiometry. RESULTS: Body mass index, systolic blood pressure, diastolic blood pressure, femoral neck bone mineral density, bone mineral salt content, fat mass, muscle mass, upper limb fat mass, thigh fat mass, and trunk fat mass in the overweight group and obese group were all higher than those in the control group (P<0.05). The fat mass, muscle mass, upper limb fat mass, and trunk fat mass were positively correlated with the femoral neck bone mineral density, total lumbar vertebra bone mineral density, and bone mineral salt content (P<0.05). In addition, thigh fat mass was positively correlated with femoral neck bone mineral density and total lumbar spine bone mineral density, whereas body fat content was negatively correlated with bone mineral salt content. CONCLUSION: Body composition was related to bone mineral density and bone mineral salt content, and the correlation between different body composition indexes, and bone mineral density, and bone mineral salt content was different.

Microglia-derived TNF-α mediates Müller cell activation by activating the TNFR1-NF-κB pathway.

Microglia and its interaction with Müller cells are responsible to retinal surveillance during retinal neurodegeneration, however, the role and mechanism of microglia-derived tumor necrosis factor (TNF)-α in the activation of retinal Müller cells have not been fully elucidated. In the present study, primary microglia and Müller cells were isolated from newborn Sprague-Dawley (SD) rats with purities of 88.2 ± 6.2% and 92.2 ± 2.2%, respectively. By performing immunofluorescence and Western blot analysis, we found that TNF receptor (TNFR)-1 and TNFR2 were expressed in Müller cells. After co-cultured with microglia-conditioned medium (MCM), the elevated mRNA levels of glial fibrillary acidic protein (GFAP), proinflammatory factors (TNF-α, IL-1ß, CXCL-1, CSF-1, NOS2, COX2) and decreased CNTF mRNA levels were found in Müller cells. However, pretreatment with R-7050 (a TNF-α receptor inhibitor) or anti-TNFR1 significantly abrogated the changes. Simultaneously, pretreatment with anti-TNFR2 slightly inhibited the expression of GFAP in MCM-incubated Müller cells. Meanwhile, anti-TNFR1 treatment reversed the increased expression of CSF-1 and IL-1ß induced by TNF-α. Compared to the control groups, the phosphorylation of NF-κB P65, MAPK P38 and ERK1/2 in TNF-α-treated Müller cells was significantly increased. Nevertheless, pretreatment with anti-TNFR1 inhibited the phosphorylation of NF-κB P65 and MAPK p38, especially NF-κB P65. Additionally, pretreatment with Bay117082 (an NF-κB inhibitor) also significantly inhibited NF-κB P65 phosphorylation and GFAP expression. Moreover, anti-TNFR1 and Bay117082 treatment reduced NF-κB P65 phosphorylation of Müller cells induced by MCM. These results suggested that microglia-derived TNF-α served as a vital role in regulating Müller cells activation during retinal neurodegeneration.

Associations between health indicators and sleep duration of American adults: NHANES 2011-16.

BACKGROUND: This study aimed to investigate associations between health indicators and sleep duration in the general population. METHODS: This cross-sectional data from the National Health and Nutrition Examination Survey. Self-reported sleep duration was classified into short sleep (<7 h/day), regular sleep (7-8 h/day) and long sleep duration (>8 h/day). Health indicators included lifestyle indicators (smoking, alcohol use and physical inactivity), general health indicators (waist circumference and self-reported health condition) and chronic conditions [overweight/obesity, hypertension, diabetes, high cholesterol, chronic low back pain (CLBP) and oral health problems]. A series of multinomial logistic regression analysis were performed, controlling for confounders (age, sex, marital status, ethnic background, education level and poverty-to-income ratio). RESULTS: Data of 12 835 participants were analyzed. The mean (SD) age of participants was 50.0 (±17.4) years, and 50.6% were women. After adjusting for all health indicators, current smoking (OR: 1.37; 95% CI: 1.17-1.61), a poor (OR: 1.52; 95% CI: 1.23-1.88) health condition, CLBP (OR: 1.40; 95% CI: 1.16-1.69) and oral health problems (OR: 1.28; 95% CI: 1.10-1.49) were associated with short sleep duration. No independent association with long sleep duration was observed in this study. CONCLUSIONS: The results confirm that lifestyle indicators (current smoking and physical inactivity), general health indicators (self-reported health condition) and presence of some chronic conditions (CLBP and oral health problems) are associated with short sleep duration. The results did not confirm that any health indicator was associated with long sleep duration.

ANGPTL3 Overexpression Suppresses the Development of Oncogenic Properties in Renal Cell Carcinoma via the Wnt/ß-Catenin Signaling Pathway and Predicts Good Prognosis.

Angiopoietin-like 3 (ANGPTL3), which is involved in new blood vessel growth, has been reported to exhibit an abnroaml expression in many different cancers. However, the expressing pattern and functions of ANGPTL3 renal cell carcinoma (RCC) were rarely reported. In this study, we observed that ANGPTL3 expression was distinctly downregulated in both RCC specimens from TCGA datasets and cell lines. Survival assays also revealed that patients with low ANGPTL3 expression exhibited a shorter overall survival and disease-free survival than those with high ANGPTL3 expression. Cell counting kit-8 (CCK-8) assay, Colony formation assay, and flow cytometry showed that overexpression of ANGPTL3 distinctly suppressed the proliferation of RCC cells, and promoted apoptosis. Transwell assays and Wound healing assays revealed that ANGPTL3 upregulation suppressed the migration and invasion of RCC cells. Then, we explored whether ANGPTL3 dysregulation influenced the alteration of Wnt/ß-catenin signaling using TOP/FOP flash reporter assays and western blot. The results showed that overexpression of ANGPTL3 distinctly suppressed the activity of Wnt/ß-catenin signaling. Overall, our results confirmed that overexpression of ANGPTL3 was related to the malignancy and good prognosis of RCC patients, and ANGPTL3 upregulation inhibited the tumor proliferation and metastasis via the Wnt/ß-catenin pathway. ANGPTL3 may be a novel therapeutic target and a prognostic biomarker for RCC patients.

Transmuscular quadratus lumborum block versus oblique subcostal transversus abdominis plane block for analgesia in laparoscopic hysterectomy: a randomised single-blind trial.

OBJECTIVE: The transmuscular quadratus lumborum (TQL) block and the oblique subcostal transversus abdominis plane (OSTAP) block both contribute to multimodal analgesia after laparoscopic surgery. The objective of this study was to compare the analgesic effects of the TQL block versus OSTAP block after laparoscopic hysterectomy. DESIGN: Prospective single-centre randomised single-blind trial. SETTING: University-affiliated hospital. PARTICIPANTS: Patients aged between 18 and 65 years scheduled for laparoscopic hysterectomy. INTERVENTIONS: Patients were randomised into two groups (1:1 ratio) and received bilateral TQL block or bilateral OSTAP block with 0.375% ropivacaine 20 mL on each side before surgery. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the cumulative morphine dose in the first 24 hours. The secondary outcome measures were the morphine consumption at each time interval after surgery, the time from the end of surgery to the first need for morphine, the Numerical Rating Scale (NRS) scores for visceral and incisional pain intensity, and the incidence of adverse events. RESULTS: The cumulative morphine dose was significantly lower in the TQL group than in the OSTAP group (17.2 (12.5) vs 26.1 (13.3) mg, p=0.010). Compared with the OSTAP group, the morphine doses from 6 to 12, 12 to 18, and 18 to 24 hours were significantly lower, the time of first need for morphine was significantly longer and the NRS scores for visceral pain intensity were significantly lower in the TQL group. CONCLUSION: Compared with the OSTAP block, the TQL block reduced morphine consumption and provided better visceral pain relief with a longer duration of effect after laparoscopic hysterectomy. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR1800017995); pre-results.

Immune checkpoint inhibitor (ICI) combination therapy compared to monotherapy in advanced solid cancer: A systematic review.

Aim: To evaluate the efficacy and safety of immune checkpoint inhibitor (ICI) two-drug combination therapy in patients with advanced malignancy. Methods: We searched PubMed, PMC, EMBASE, EBSCO, Cochrane Central Register of Controlled Trials (CENTRAL), American Society of Clinical Oncology (ASCO and the European Society of Medical Oncology (ESMO) to identify primary research reporting the survival outcomes and safety of ICI combination therapy in patients with advanced malignancy. We performed a meta-analysis that evaluated the risk ratio (RR) and its 95% confidence interval (CI) for objective response rates (ORR) and disease control rates (DCR), hazard ratio (HR) and 95% CI for progression-free survival (PFS) and overall survival time (OS), and RR and 95% CI for adverse events (AEs). Results: The final 10 studies (15 cohorts) and 2410 patients were included in the meta-analysis. The ICI combination therapy resulted in improved ORR (RR 1.82, 95% CI 1.31-2.54, p = 0.0004), DCR (RR 1.41, 95% CI 1.29-1.55, p < 0.0001), PFS (HR 0.83, 95% CI 0.74-0.94, p = 0.003) and OS (HR 0.90, 95% CI 0.82-0.98, p = 0.02) in patients with advanced malignant tumors. The incidence of some high grade (≥3) AEs increased, such as fatigue, nausea, diarrhea, colitis, rash, pruritus, elevated transaminase and lipase. Conclusion: Our study showed that ICI combination therapy can improve ORR, DCR, PFS and OS in patients with advanced malignancy. Compared with ICI monotherapy, ICI combination therapy was more likely to induce severe AEs.

Blood biomarkers of bone metastasis in digestive tract malignant tumors.

Aim: To evaluate the role of clinical features and blood markers in patients with malignant digestive tract tumors bone metastasis. Materials & methods: A total of 267 patients were included in this trial. Age, gender, primary tumor site, metastatic sites, T/N stage, high-density lipoprotein, low-density lipoprotein, total cholesterol, triglycerides, alkaline phosphatase, LDH, Ca levels, platelet, neutrophils to absolute value of lymphocytes (NLR), ratio of platelets to absolute values of lymphocytes (PLR) were analyzed. Results: T stage, lymph node metastasis, N stage and liver and lung metastasis were independent risk factors. LDH + alkaline phosphatase + NLR + PLR and LDH + NLR, respectively have higher predictive value for bone metastasis compared with patients with early-stage malignant digestive tract tumor and patients with advanced malignant digestive tract tumor without bone metastasis. Conclusion: Some clinical features or blood markers have the potential to detect bone metastasis early to avoid skeletal complications.

Predictive value of tumor mutation burden (TMB) with targeted next-generation sequencing in immunocheckpoint inhibitors for non-small cell lung cancer (NSCLC).

Background: To evaluate the clinical predictive value of tumor mutation burden (TMB) for immune checkpoint inhibitor (ICI) therapy in patients with non-small cell lung cancer (NSCLC). Method: As of 15 February 2020, PubMed, PMC and EMBASE databases as well as the American society of clinical oncology (ASCO) and European society of medical oncology (ESMO) databases were searched. The Mantel-Haenszel or inverse variance weighted fixed-effects model (I2 ≤ 50%) or random-effects model (I2 > 50%) were used to evaluate OR and its 95% CI of objective response rate (ORR) and disease control rate (DCR) , as well as HR and its 95% CI of progression-free survival (PFS) and overall survival (OS). In addition, we did publication bias, heterogeneity analysis, sensitivity analysis and subgroup analysis. And quality of the studies included and the level of evidence for outcome measures were evaluated. Results: 14 studies involving 2872 patients were included. The ORR (OR 3.52, 95%CI 2.32-5.35, p < 0.00001), DCR (OR 3.26, 95%CI 1.91-5.55, p < 0.0001), PFS (HR 0.81, 95%CI 0.74-0.89, p < 0.00001) and OS (HR 0.83, 95%CI 0.74-0.94, p = 0.002) of ICI therapy in the high TMB group were all superior to those in the low TMB group. Conclusions: TMB is a promising biomarker, which can predict the efficacy of ICI therapy in advanced NSCLC patients, included ORR, DCR, PFS and OS.

TSG101 Promotes the Proliferation, Migration, and Invasion of Human Glioma Cells by Regulating the AKT/GSK3ß/ß-Catenin and RhoC/Cofilin Pathways.

The tumor susceptibility gene 101 (TSG101) has been reported to play important roles in the development and progression of several human cancers, such as pancreatic cancer, prostate cancer, and hepatocellular carcinoma. However, its potential roles and underlined mechanisms in human glioma are still needed to be further clarified. This study was designed to assess the expression of TSG101 in glioma patients and its effects on glioma cell proliferation, migration, and invasion. Publicly available data revealed that TSG101 mRNA was significantly upregulated in glioma tissues, and high levels of TSG101 were associated with poor prognosis in glioma patients. Western blot and immunohistochemistry experiments further showed that the expression level of TSG101 protein was significantly upregulated in glioma patients, especially in the patients with high-grade glioma. The functional studies showed that knockdown of TSG101 suppressed the proliferation, migration, and invasion of glioma cells, while overexpression of TSG101 facilitated them. Mechanistic studies indicated that the proliferation, migration, and invasion induced by TSG101 in human glioma were related to AKT/GSK3ß/ß-catenin and RhoC/Cofilin signaling pathways. In conclusion, the above results suggest that the expression of TSG101 is elevated in glioma patients, which accelerates the proliferation, migration, and invasion of glioma cells by regulating the AKT/GSK3ß/ß-catenin and RhoC/Cofilin pathways.

Efficacy and safety of immune checkpoint inhibitors (ICIs) in extensive-stage small cell lung cancer (SCLC).

BACKGROUND: To evaluate the efficacy and safety of an immune checkpoint inhibitor (ICI) combined with chemotherapy in patients with advanced SCLC. METHODS: We searched published randomized-controlled trials (RCTs) to compare the effect of ICIs combined with chemotherapy and chemotherapy alone on SCLC. The extracted data included the number of people who achieved an objective response rate (ORR), the disease control rate (DCR), the hazard ratio (HR) of progression-free survival (PFS), and the overall survival (OS) with 95% confidence intervals (95% CI). RESULTS: Six RCTs involving 2477 patients were included. Compared with chemotherapy alone, patients receiving an ICI combined with chemotherapy had a significantly longer PFS (HR, 0.91; 95% CI 0.88-0.95, p < 0.00001) and OS (HR 0.92; 95% CI 0.89-0.96, p = 0.0001). The ORR increased, but the difference was not statistically significant (RR 1.05; 95% CI 0.99-1.12, p = 0.13). There was no significant difference in the DCR between the two treatment regimens; however, in patients treated with an ICI, fatigue, rashes, diarrhea, and elevated aminotransferase enzymes were significantly increased (p < 0.05). CONCLUSION: ICI combined with chemotherapy is superior to chemotherapy alone with respect to PFS and OS in patients with advanced SCLC.

Retinal dehydrogenase 5 (RHD5) attenuates metastasis via regulating HIPPO/YAP signaling pathway in Hepatocellular Carcinoma.

Retinal dehydrogenase 5 (RDH5) is an important enzyme in the visual cycle. Several studies have reported that the RDH family may play crucial roles in tumor prognosis. However, the role of RDH5 in tumor prognosis is still unclear. We examined the mRNA level of RDH5 by using q-PCR in hepatocellular carcinoma (HCC) and adjacent non-cancerous tissues. The proliferation rate of HCC cells was detected by MTS assay, and the invasive ability was examined by transwell and scratch wound assays. The YAP protein localization and expression were visualized by immunofluorescence in two different cell lines. CpG islands in the promoter region were predicted by using the methprimer database. Clinical characteristics of a patient cohort data came from The Cancer Genome Atlas database. RDH5 was significantly downregulated in hepatocellular carcinoma tissues, and low RDH5 expression was associated with metastasis and poor patient prognosis. Functional assays revealed that the RDH5 promoter is methylated in HCC cell lines. Moreover, overexpressing RDH5 can suppress metastasis by reversing the epithelial-mesenchymal transition (EMT) process, and RDH5 also inhibits cell proliferation in HCC cell lines. Furthermore, suppressing RDH5 can activate the Hippo/YAP signaling pathway and promote the nuclear translocation of YAP. Clinical data demonstrated that RDH5 is an independent prognostic factor in HCC. In our study, we provided the first evidence that RDH5 plays a crucial role in suppressing proliferation and metastasis, and the RDH5 promoter is methylated in hepatocellular carcinoma. And as an important regulator, RDH5 can suppress the Hippo/YAP signaling pathway. Taken together, it revealed that RDH5 might be a potential therapeutic target in HCC patients.