The Clinical Application of Double Taylor Spatial Frame in Segmental Tibial Fracture.

OBJECTIVES: Multi-planar external fixation has been used for the management of segmental tibial fractures with severe soft tissue injuries. However, fewer specialized studies have been reported. The primary aim of this study was to describe our experience of treating fractures of this type using the Taylor Spatial Frame and Ilizarov external fixation methods. METHODS: We retrospectively analyzed 33 patients with segmental tibial fracture treated at our institution between January 2016 and December 2020. The patients were divided into double Taylor Spatial Frame (D-TSF) and Ilizarov groups based on the external fixation structure. Baseline demographic data included sex, age, injury side and cause, open or closed fracture, time from injury to surgery, complications, and external frame removal and fracture healing time. The hip-knee-ankle angle (HKA) was measured from preoperative, immediate postoperative, and final follow-up full-length X-rays of bilateral lower limbs. We determined the degree of deviation in the HKA by calculating the difference between the measured angle and the ideal value of 180°; the absolute value was used to assess recovery of the lower limb force line. At the final follow-up, Johner-Wruhs tibial fracture outcome criteria (J-W TFOC) were used to classify the postoperative function of the affected limb as excellent, good, moderate, or poor. Count data were analyzed with the chi-square test or Fisher's exact test; the Mann-Whitney U test was used for rank data. RESULTS: No statistically significant differences were observed between the two groups in terms of sex, age, side of injury, cause of injury, closed or open fracture, or time between injury and surgery, which indicates that the groups were comparable (p > 0.05). A statistically significant difference was observed in external frame removal and fracture healing time between the D-TSF and Ilizarov groups (36.24 ± 8.34 vs 45.42 ± 10.21 weeks, p = 0.009; 33.33 ± 8.21 vs 42.00 ± 9.78 weeks, p = 0.011). The Johner-Wruhs criteria were used to assess the function of the affected limb, the D-TSF group performed better in correcting the lower limb force line than the Ilizarov group. A statistically significant difference in terms of excellent ratings was observed between the two groups (18/2/1/0 vs 5/5/1/1, p = 0.010). Postoperative follow-up X-rays demonstrated a significant improvement in the HKA in both groups immediately after surgery and at the final follow-up compared to the angle before surgery. At the final follow-up, a statistically significant difference was observed in the degree of deviation in the HKA between the two groups (1.58° ± 0.84° vs 2.37° ± 1.00°, p = 0.023). CONCLUSION: The D-TSF treatment is associated with minimal secondary damage to soft tissue, a straightforward and minimally invasive procedure, multiplanar stable fracture fixation, and optimization of fracture alignment and lower limb force lines, therefore, it is highly effective therapeutic option for segmental tibial fracture.

[The experience on the construction of the cluster prevention and control system for COVID-19 infection in designated hospitals during the period of "Category B infectious disease treated as Category A"].

The COVID-19 epidemic has spread to the whole world for three years and has had a serious impact on human life, health and economic activities. China's epidemic prevention and control has gone through the following stages: emergency unconventional stage, emergency normalization stage, and the transitional stage from the emergency normalization to the "Category B infectious disease treated as Category B" normalization, and achieved a major and decisive victory. The designated hospitals for prevention and control of COVID-19 epidemic in Tianjin has successfully completed its tasks in all stages of epidemic prevention and control, and has accumulated valuable experience. This article summarizes the experience of constructing a hospital infection prevention and control system during the "Category B infectious disease treated as Category A" period in designated hospital. The experience is summarized as the "Cluster" hospital infection prevention and control system, namely "three rings" outside, middle and inside, "three districts" of green, orange and red, "three things" before, during and after the event, "two-day pre-purification" and "two-director system", and "one zone" management. In emergency situations, we adopt a simplified version of the cluster hospital infection prevention and control system. In emergency situations, a simplified version of the "Cluster" hospital infection prevention and control system can be adopted. This system has the following characteristics: firstly, the system emphasizes the characteristics of "cluster" and the overall management of key measures to avoid any shortcomings. The second, it emphasizes the transformation of infection control concepts to maximize the safety of medical services through infection control. The third, it emphasizes the optimization of the process. The prevention and control measures should be comprehensive and focused, while also preventing excessive use. The measures emphasize the use of the least resources to achieve the best infection control effect. The fourth, it emphasizes the quality control work of infection control, pays attention to the importance of the process, and advocates the concept of "system slimming, process fattening". Fifthly, it emphasizes that the future development depends on artificial intelligence, in order to improve the quality and efficiency of prevention and control to the greatest extent. Sixth, hospitals need to strengthen continuous training and retraining. We utilize diverse training methods, including artificial intelligence, to ensure that infection control policies and procedures are simple. We have established an evaluation and feedback mechanism to ensure that medical personnel are in an emergency state at all times.

Mesenchymal Stem Cells-Involved Strategies for Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the joints and bone destruction. Because of systemic administration and poor targeting, traditional anti-rheumatic drugs have unsatisfactory treatment efficacy and strong side effects, including myelosuppression, liver or kidney function damage, and malignant tumors. Consequently, mesenchymal stem cells (MSCs)-involved therapy is proposed for RA therapy as a benefit of their immunosuppressive and tissue-repairing effects. This review summarizes the progress of MSCs-involved RA therapy through suppressing inflammation and promoting tissue regeneration and predicts their potential clinical application.

Immune checkpoint inhibitor plus chemotherapy as first-line treatment for non-small cell lung cancer with malignant pleural effusion: a retrospective multicenter study.

BACKGROUND: Immune checkpoint inhibitors (ICI) combined with chemotherapy are efficacious for treating advanced non-small cell lung cancer (NSCLC); however, the effectiveness of this approach in the malignant pleural effusion (MPE) population is unclear. This study evaluated ICI plus chemotherapy in NSCLC patients with MPE. METHODS: Patients from 3 centers in China with NSCLC and MPE who received ICI plus chemotherapy (ICI Plus Chemo) or chemotherapy alone (Chemo) between December 2014 and June 2023 were enrolled. Clinical outcomes and adverse events (AEs) were compared. RESULTS: Of 155 eligible patients, the median age was 61.0 years old. Males and never-smokers accounted for 73.5% and 39.4%, respectively. Fifty-seven and 98 patients received ICI Plus Chemo or Chemo, respectively. With a median study follow-up of 10.8 months, progression-free survival (PFS) was significantly longer with ICI Plus Chemo than with Chemo (median PFS: 7.4 versus 5.7 months; HR = 0.594 [95% CI: 0.403-0.874], P = 0.008). Median overall survival (OS) did not differ between groups (ICI Plus Chemo: 34.2 versus Chemo: 28.3 months; HR = 0.746 [95% CI: 0.420-1.325], P = 0.317). The most common grade 3 or worse AEs included decreased neutrophil count (3 [5.3%] patients in the ICI Plus Chemo group vs. 5 [5.1%] patients in the Chemo group) and decreased hemoglobin (3 [5.3%] versus 10 [10.2%]). CONCLUSIONS: In patients with untreated NSCLC with MPE, ICI plus chemotherapy resulted in significantly longer PFS than chemotherapy and had a manageable tolerability profile, but the effect on OS may be limited.

An evidence-based guideline on treating lumbar disc herniation with traditional Chinese medicine.

BACKGROUND: Lumbar disc herniation (LDH), as one of the most common causes of lower back pain, imposes a heavy economic burden on patients and society. Conservative management is the first-line choice for the majority of LDH patients. Traditional Chinese medicine (TCM) is an important part of conservative treatment and has attracted more and more international attention. STUDY DESIGN: Evidence-based guideline. METHODS: We formed a guideline panel of multidisciplinary experts. The clinical questions were identified on the basis of a systematic literature search and a consensus meeting. We searched the literature for direct evidence on the management of LDH and assessed its certainty-generated recommendations using the grading of recommendations, assessment, development, and evaluation (GRADE) approach. RESULTS: The guideline panel made 20 recommendations, which covered the use of Shentong Zhuyu decoction, Shenzhuo decoction, Simiao San decoction, Duhuo Jisheng decoction, Yaobitong capsule, Yaotongning capsule, Osteoking, manual therapy, needle knife, manual acupuncture, electroacupuncture, Chinese exercise techniques (Tai Chi, Baduanjin, or Yijinjing), and integrative medicine, such as combined non-steroidal anti-inflammatory drugs, neural nutrition, and traction. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. CONCLUSION: This is the first LDH treatment guideline for TCM and integrative medicine with a systematic search, synthesis of evidence, and using the GRADE method to rate the quality of evidence. We hope these recommendations can help support healthcare workers caring for LDH patients.

Myosteatosis is an independent risk factor for overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunting.

OBJECTIVE: The relationship between skeletal muscle and adipose tissue compositions and risk of overt hepatic encephalopathy (OHE) following transjugular intrahepatic portosystemic shunt (TIPS) treatment needs to be investigated. METHODS: A total of 282 patients were collected from two medical centres. The median time of follow-up was 48.23 + 1.36 months and the first-year results of all patients after TIPS therapy were collected. The muscle and adipose tissue indices were quantified at the third lumbar vertebra level. Sarcopenia and myosteatosis were defined according to previous researches. Receiver operating characteristic curves, chi-square test, univariate and multivariate logistic regression analyses were employed to investigate the potential association between muscle and adipose indices, sarcopenia, myosteatosis and the risk of developing post-TIPS OHE. RESULTS: All skeletal muscle indices, adipose tissue indices and sarcopenia had limited associations with post-TIPS OHE. Myosteatosis (148 cases, 52.5%, 55 with OHE, 37.2%) was identified as an independent risk factor for post-TIPS OHE. with P  < 0.001 in Chi-square test, P  < 0.001, odds ratio (OR): 2.854, 95% confidence interval (CI): 1.632-4.993 in univariate logistic regression analyses, and P  = 0.007, OR: 2.372, 95% CI: 1.268-4.438 in multivariate logistic regression analyses, respectively. CONCLUSION: Our results showed that myosteatosis was proven as an independent risk factor for the development of post-TIPS OHE.

Defect engineering improves CO2/N2 and CH4/N2 separation performance of MOF-801.

A defect engineering modification method is reported to improve the CO2/N2 and CH4/N2 separation performance of MOF-801, owing to skeleton shrinkage caused by defect modification, Zr-FA0.5 shows excellent gas separation performance compared with the prototype MOF.

Anti-Toxoplasma gondii antibodies as a risk factor for the prevalence and severity of systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by the presence of numerous autoantibodies. The interaction of infectious agents (viruses, bacteria and parasites) and a genetically susceptible host may be a key mechanism for SLE. Toxoplasma gondii is a widespread intracellular parasite that has been implicated in the pathogenesis of autoimmune diseases. However, the relationship between T. gondii infection and the increased risk of SLE in Chinese populations remains unclear. METHODS: The seroprevalence of T. gondii infection was assessed in 1771 serum samples collected from Chinese individuals (908 healthy controls and 863 SLE patients) from different regions of China using an enzyme-linked immunosorbent assay. Serum autoantibodies and clinical information were obtained and analysed. RESULTS: Our observations revealed a higher prevalence of anti-T. gondii antibodies (ATxA) immunoglobulin G (IgG) in serum samples from SLE patients (144/863, 16.7%) than in those from the healthy controls (53/917, 5.8%; P < 0.0001), indicating a 2.48-fold increased risk of SLE in the ATxA-IgG+ population, after adjustment for age and sex (95% confidence interval [CI] 1.70-3.62, P < 0.0001). ATxA-IgG+ SLE patients also showed a 1.75-fold higher risk of developing moderate and severe lupus symptoms (95% CI 1.14-2.70, P = 0.011) compared to ATxA-IgG- patients. Relative to ATxA-IgG- patients, ATxA-IgG+ patients were more likely to develop specific clinical symptoms, including discoid rash, oral ulcer, myalgia and alopecia. Seven antibodies, namely anti-ribosomal RNA protein (rRNP), anti-double stranded DNA (dsDNA), anti-cell membrane DNA (cmDNA), anti-scleroderma-70 (Scl-70), anti-cardiolipin (CL), anti-beta2-glycoprotein-I (B2GPI) and rheumatoid factor (RF), occurred more frequently in ATxA-IgG+ patients. When combined with anti-dsDNA and RF/anti-rRNP/anti-cmDNA/ESR, ATxA-IgG significantly increased the risk for severe lupus. CONCLUSIONS: Our results suggest that ATxA-IgG may be a significant risk factor for SLE prevalence and severity in Chinese populations.

Endovenous Microwave Ablation Versus Radiofrequency Ablation for the Treatment of Lower Limb Varicose Veins.

BACKGROUND: This study aimed to retrospectively compare the clinical outcomes of endovenous microwave versus radiofrequency ablation combined with foam sclerotherapy in patients with lower limb varicose veins. METHODS: We identified patients with lower limb varicose veins treated with endovenous microwave ablation or radiofrequency ablation with foam sclerotherapy between January 2018 and June 2021 at our institution. Patients were followed-up for 12 months. Clinical results, including the pre-post-Aberdeen Varicose Vein Questionnaire and post-Aberdeen Varicose Vein Questionnaire and Venous Clinical Severity Score, were compared. Complications were documented and treated accordingly. RESULTS: We included 287 cases (295 limbs total; endovenous microwave ablation + foam sclerosing agent: n = 142, 146 limbs; radiofrequency ablation + foam sclerosing agent: n = 145, 149 limbs). The operative time was shorter for endovenous microwave ablation than radiofrequency ablation (42.58 ± 15.62 min vs. 65.46 ± 24.38 min, P < 0.05); however, other procedural parameters did not differ. Furthermore, hospitalization costs for endovenous microwave ablation were lower than those for radiofrequency ablation (21,063.74 ± 850.47 yuan vs. 23,312.40 ± 1,035.86 yuan, P < 0.05). At the 12-month follow-up, the great saphenous vein closure rate was similar in both groups (endovenous microwave ablation, 97% [142/146] vs. radiofrequency ablation, 98% [146/149]; P > 0.05). Additionally, the satisfaction or incidence rates of complications were not different among the groups. In both groups, the Aberdeen Varicose Vein Questionnaire and Venous Clinical Severity Score values were significantly lower 12 months postsurgery than before surgery; however, the postoperative values did not differ. CONCLUSIONS: Endovenous microwave ablation effectively treated lower limb varicose veins, with similar short-term effects as radiofrequency ablation. Moreover, it had a shorter operative time and was less expensive than endovenous radiofrequency ablation.

Therapeutic properties of isoliquiritigenin with molecular modeling studies: investigation of anti-pancreatic acinar cell tumor and HMG-CoA reductase inhibitor activity for treatment of hypercholesterolemia.

Introduction: Isoliquiritigenin, one of the components in the root of Glycyrrhiza glabra L., is a member of the flavonoids, which are known to have anti-tumor activity in vitro and in vivo. HMG-CoA reductase inhibitors, called statins, are used to reduce the risk of heart disease by lowering blood cholesterol levels. Material and methods: HMG-CoA reductase activity was determined according to the method described by Takahashi et al. The structure of human HMG-COA reductase in the resolution of 2.22 Å with the X-ray diffraction method (PDB ID: 1HWK) was obtained from the PDB database. Results: In our study, the inhibitory activity of isoliquiritigenin towards HMG-CoA reductase showed a lower value of IC50 = 193.77 ±14.85 µg/ml. For a better understanding of biological activities and interactions, the molecular docking study was performed. The results of molecular docking revealed that isoliquiritigenin with a docking score of -6.740 has a strong binding affinity to HMG-COA reductase. Therefore, this compound could be considered as a potential inhibitor for the enzyme. Also, the activity of isoliquiritigenin against common human pancreatic acinar cell tumor cell lines, i.e. 266-6, TGP49, and TGP47, was evaluated. Conclusions: The cells treated with isoliquiritigenin were assessed by MTT assay for 48 h as regards the cytotoxicity and anti-human pancreatic acinar cell tumor properties in normal (HUVEC) and human pancreatic acinar cell tumor cell lines, i.e. 266-6, TGP49, and TGP47. The IC50 values of isoliquiritigenin were 262, 389, and 211 µg/ml against 266-6, TGP49, and TGP47 cell lines, respectively. The viability of the human pancreatic acinar cell tumor cell line decreased dose-dependently in the presence of isoliquiritigenin. After clinical study, isoliquiritigenin can be utilized as an efficient drug in the treatment of human pancreatic acinar cell tumor in humans.

Obstructive sleep apnea promotes the progression of lung cancer by modulating cancer cell invasion and cancer-associated fibroblast activation via TGFß signaling.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with severity of pneumonia; however, the mechanism by which OSA promotes lung cancer progression is unclear. METHODS: Twenty-five lung cancer patients were recruited to investigate the relationship between OSA and cancer-associated fibroblast (CAFs) activation. Lung cancer cells (A549) and WI38 fibroblast cells were used to explore the hypoxia-induced TGFß expression using qPCR, Western blot, and ELISA. Wound healing and transwell assays were performed to evaluate cancer cell migration and invasion. A549 or A549-Luc + WI38 xenograft mouse models were established to detect the intermittent hypoxia (IH) associated with lung tumor growth and epithelial-mesenchymal transition (EMT) in vivo. RESULTS: OSA promotes CAF activation and enrichment in lung cancer patients. Hypoxia (OSA-like treatment) activated TGFß signaling in both lung cancer cells and fibroblasts, which promoted cancer cell migration and invasion, and enriched CAFs. IH promoted the progression and EMT process of lung cancer xenograft tumor. Co-inoculation of lung cancer cells and fibroblast cells could further promote lung cancer progression. CONCLUSIONS: IH promotes lung cancer progression by upregulating TGFß signaling, promoting lung cancer cell migration, and increasing the CAF activation and proportion of lung tumors.

A systematic review of endovenous ablation for the treatment of small saphenous varicose veins.

Insufficiency of the small saphenous vein causes 15% of varicose veins in the lower extremities. Endovenous ablation for the treatment of small saphenous vein varices has become a trend, and an increasing number of studies have reported the effects of different types of endovenous ablation in patients with small saphenous varicose veins. The purpose of this systematic review is to summarize the results of existing studies on endovenous ablation for the treatment of small saphenous varicose veins, compare its role and efficacy, and provide insights into the future development of endovenous ablation for treating small saphenous varicose veins. A systematic review of literature published from January 1, 2002 to January 1, 2022 was conducted from PubMed, Embase, and China Academic Journals full-text databases. The pre-determined inclusion criteria were clinical literature of endovenous ablation for treating small saphenous varicose veins. Keywords included "ablation", "small saphenous vein", "lesser saphenous vein", "short saphenous vein", "xiaoyinjingmai" and "xiaorong". Of the 506 articles screened, 33 articles were included in this review: 19 articles were related to endovenous laser ablation, five were related to mechanochemical ablation, seven were related to radiofrequency ablation, and two were related to both endovenous laser ablation and radiofrequency ablation. The anatomical success rate of endovenous laser ablation, radiofrequency ablation, and mechanochemical ablation were 94.3%, 96.0%, and 88.1%, respectively, and the heterogeneities were all moderate. Most of the current studies are of a low-quality level of research. Hence, long-term follow-up studies and large-scale randomized controlled trials are required to obtain high-quality evidence. Although the gold standard for the treatment of small saphenous vein insufficiency remains unclear, endovenous ablation is still the recommended method.

Mn2+ /Ir3+ -Doped and CaCO3 -Covered Prussian Blue Nanoparticles with Indocyanine Green Encapsulation for Tumor Microenvironment Modulation and Image-Guided Synergistic Cancer Therapy.

The development of smart theranostic nanoplatforms has gained great interest in effective cancer treatment against the complex tumor microenvironment (TME), including weak acidity, hypoxia, and glutathione (GSH) overexpression. Herein, a TME-responsive nanoplatform named PMICApt /ICG, based on PB:Mn&Ir@CaCO3 Aptamer /ICG, is designed for the competent synergistic photothermal therapy and photodynamic therapy (PDT) under the guidance of photothermal and magnetic resonance imaging. The nanoplatform's aptamer modification targeting the transferrin receptor and the epithelial cell adhesion molecule on breast cancer cells, and the acid degradable CaCO3 shell allow for effective tumor accumulation and TME-responsive payload release in situ. The nanoplatform also exhibits excellent PDT properties due to its ability to generate O2 and consume antioxidant GSH in tumors. Additionally, the synergistic therapy is achieved by a single wavelength of near-infrared laser. RNA sequencing is performed to identify differentially expressed genes, which show that the expressions of proliferation and migration-associated genes are inhibited, while the apoptosis and immune response gene expressions are upregulated after the synergistic treatments. This multifunctional nanoplatform that responds to the TME to realize the on-demand payload release and enhance PDT induced by TME modulation holds great promise for clinical applications in tumor therapy.

PPARδ dysregulation of CCL20/CCR6 axis promotes gastric adenocarcinoma carcinogenesis by remodeling gastric tumor microenvironment.

BACKGROUND: Peroxisome proliferator-activated receptor delta (PPARδ) promotes inflammation and carcinogenesis in many organs, but the underlying mechanisms remains elusive. In stomachs, PPARδ significantly increases chemokine Ccl20 expression in gastric epithelial cells while inducing gastric adenocarcinoma (GAC). CCR6 is the sole receptor of CCL20. Here, we examine the role of PPARδ-mediated Ccl20/Ccr6 signaling in GAC carcinogenesis and investigate the underlying mechanisms. METHODS: The effects of PPARδ inhibition by its specific antagonist GSK3787 on GAC were examined in the mice with villin-promoter-driven PPARδ overexpression (PpardTG). RNAscope Duplex Assays were used to measure Ccl20 and Ccr6 levels in stomachs and spleens. Subsets of stomach-infiltrating immune cells were measured via flow cytometry or immunostaining in PpardTG mice fed GSK3787 or control diet. A panel of 13 optimized proinflammatory chemokines in mouse sera were quantified by an enzyme-linked immunosorbent assay. RESULTS: GSK3787 significantly suppressed GAC carcinogenesis in PpardTG mice. PPARδ increased Ccl20 level to chemoattract Ccr6+ immunosuppressive cells, including tumor-associated macrophages, myeloid-derived suppressor cells and T regulatory cells, but decreased CD8+ T cells in gastric tissues. GSK3787 suppressed PPARδ-induced gastric immunosuppression by inhibiting Ccl20/Ccr6 axis. Furthermore, Ccl20 protein levels increased in sera of PpardTG mice starting at the age preceding gastric tumor development and further increased with GAC progression as the mice aged. GSK3787 decreased the PPARδ-upregulated Ccl20 levels in sera of the mice. CONCLUSIONS: PPARδ dysregulation of Ccl20/Ccr6 axis promotes GAC carcinogenesis by remodeling gastric tumor microenvironment. CCL20 might be a potential biomarker for the early detection and progression of GAC.

Functional biomaterials for comprehensive periodontitis therapy.

Periodontitis is an inflammatory disease caused by bacterial infection directly, and the dysregulation of host immune-inflammatory response finally destroys periodontal tissues. Current treatment strategies for periodontitis mainly involve mechanical scaling/root planing (SRP), surgical procedures, and systemic or localized delivery of antimicrobial agents. However, SRP or surgical treatment alone has unsatisfactory long-term effects and is easy to relapse. In addition, the existing drugs for local periodontal therapy do not stay in the periodontal pocket long enough and have difficulties in maintaining a steady, effective concentration to obtain a therapeutic effect, and continuous administration always causes drug resistance. Many recent studies have shown that adding bio-functional materials and drug delivery systems upregulates the therapeutic effectiveness of periodontitis. This review focuses on the role of biomaterials in periodontitis treatment and presents an overview of antibacterial therapy, host modulatory therapy, periodontal regeneration, and multifunctional regulation of periodontitis therapy. Biomaterials provide advanced approaches for periodontal therapy, and it is foreseeable that further understanding and applications of biomaterials will promote the development of periodontal therapy.

MNX1 facilitates the malignant progress of lung adenocarcinoma through transcriptionally upregulating CCDC34.

Lung adenocarcinoma (LUAD) represents the most prevalent subtype of lung cancer and typically has high incidence and fatality rates. Motor neuron and pancreas homeobox 1 (MNX1) and coiled-coil domain-containing 34 (CCDC34) serve as oncogenes in multiple types of cancer. However, their role in LUAD remains to be elucidated. In the present study, bioinformatics analysis and LUAD cell lines were adopted to examine the expression of MNX1 and CCDC34. The proliferation, migration and invasion abilities of A549 cells were determined using Cell Counting Kit-8, colony formation, wound-healing and Transwell assay, and flow cytometry was conducted to assess cell cycle distribution and apoptosis. The interaction between MNX1 and CCDC34 was verified by luciferase reporter and chromatin immunoprecipitation assays. In addition, an in vivo animal model of LUAD was established for validation. The results demonstrated that both MNX1 and CCDC34 were upregulated in LUAD cell lines. MNX1 knockdown significantly suppressed cell proliferation, migration and invasion, hindered cell cycle progression and promoted cell apoptosis in vitro and inhibited tumor growth in vivo. However, the antitumor effect of MNX1 knockdown was weakened by simultaneous CCDC34 overexpression in vitro. In terms of mechanism, MNX1 was demonstrated to directly bind to the CCDC34 promoter and transcriptionally activate CCDC34 expression. In conclusion, the present study highlighted a critical role of the MNX1/CCDC34 axis in regulating LUAD progression, providing novel therapeutic targets for LUAD treatment.

Intermittent hypoxia inhibits anti-tumor immune response via regulating PD-L1 expression in lung cancer cells and tumor-associated macrophages.

Accumulating evidence has shown an increased tumor incidence and reduced survival rate in cancer patients with obstructive sleep apnea (OSA). Although intermittent hypoxia is known to play a crucial role, the molecular mechanism by which intermittent hypoxia accelerates lung cancer progression remains to be elucidated.A lung cancer xenograft mouse model was established by subcutaneously injecting LLC cells into C57BL/6 mice. The tumor-bearing mice were exposed to either normoxia or intermittent hypoxia and received either IgG2a, anti-programmed death ligand-1 (PD-L1), PX-478, or anti-PD-L1 + PX-478 treatment.A significant upregulation of tumor associated macrophages (TAMs) papulation and PD-L1 levels was observed in lung adenocarcinoma patients with OSA. We further confirmed that hypoxia-inducible factor-1 alpha (HIF-1α) regulates PD-L1 at transcriptional levels, mainly through binding to the hypoxia response element 4. Using a lung cancer xenograft mouse model, we observed that intermittent hypoxia exposed tumors grew faster and bigger with upregulated HIF-1α and PD-L1 expression, enhanced TAMs and Treg populations, and reduced cytotoxic T cells and cytokine secretion. Finally, we found a combination of PX-478 and anti-PD-L1 exerted an encouraging tumor inhibition effect compared to single treatment. Combination therapies based on HIF-1α and PD-L1 blockade might serve as a promising strategy to treat lung cancer patients with OSA.

Integrated oxidative stress score for predicting prognosis in stage III gastric cancer undergoing surgery.

Objective: This study aimed to develop a novel scoring system, named the integrated oxidative stress score (IOSS), based on oxidative stress indices to predict the prognosis in stage III gastric cancer. Methods: Retrospective analysis of stage III gastric cancer patients who were operated on between January 2014 and December 2016 were enrolled into this research. IOSS is a comprehensive index based on an achievable oxidative stress index, comprising albumin, blood urea nitrogen, and direct bilirubin. The patients were divided according to receiver operating characteristic curve into two groups of low IOSS (IOSS ≤ 2.00) and high IOSS (IOSS > 2.00). The grouping variable was performed by Chi-square test or Fisher's precision probability test. The continuous variables were evaluated by t-test. The disease free survival (DFS) and overall survival (OS) were performed by Kaplan-Meier and Log-Rank tests. Univariate Cox proportional hazards regression models and stepwise multivariate Cox proportional hazards regression analysis were determined to appraise the potential prognostic factors for DFS and OS. A nomogram of the potential prognostic factors by the multivariate analysis for DFS and OS was established with R software. In order to assess the accuracy of the nomogram in forecasting prognosis, the calibration curve and decision curve analysis were produced, contrasting the observed outcomes with the predicted outcomes. Results: The IOSS was significantly correlated with the DFS and OS, and was a potential prognostic factor in patients with stage III gastric cancer. Patients with low IOSS had longer survival (DFS: χ2 = 6.632, p = 0.010; OS: χ2 = 6.519, p = 0.011), and higher survival rates. According to the univariate and multivariate analyses, the IOSS was a potential prognostic factor. The nomograms were conducted on the potential prognostic factors to improve the correctness of survival prediction and evaluate the prognosis in stage III gastric cancer patients. The calibration curve indicated a good agreement in 1-, 3-, 5-year lifetime rates. The decision curve analysis indicated that the nomogram's predictive clinical utility for clinical decision was better than IOSS. Conclusion: IOSS is a nonspecific tumor predictor based on available oxidative stress index, and low IOSS is found to be a vigorous factor of better prognosis in stage III gastric cancer.

Green Synthesis of MOF-801(Zr/Ce/Hf) for CO2/N2 and CO2/CH4 Separation.

The purification of natural gas and the removal of carbon dioxide from flue gases are crucial to economize precious resources and effectively relieve a series of environmental problems caused by global warming. Metal-organic framework (MOF) materials have demonstrated remarkable performance and benefits in the area of gas separation; however, obtaining materials with high gas capacity and selectivity simultaneously remains difficult. In addition, harsh synthesis conditions and solvent toxicity have been restricted in large-scale production and industrial application. Therefore, MOF-801(Zr/Ce/Hf) was created based on the green synthesis of the MOF-801 construction unit by altering the kinds of metal salts, and the impact of three metal nodes on the performance of gas adsorption and separation was demonstrated by contrasting the three MOFs. The results showed that MOF-801(Ce) has the best CO2 adsorption capacity (3.3 mmol/g at 298 K), which also was demonstrated with in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) results, CO2/CH4 (ideal adsorbed solution theory (IAST) = 13.28 at 298 K, 1 bar, CO2/CH4 = 1:1, v/v), and the separation performance of CO2/N2 (IAST = 57.46 at 298 K, 1 bar, CO2/N2 = 1:1, v/v) among the group. Green synthesis of MOF-801(Zr/Ce/Hf) is an ideal candidate for flue gas separation and methane purification because of its high regeneration capacity and strong cyclic stability.