Osteosarcoma is a highly aggressive malignant bone tumor whose immuno evasion mechanisms play a pivotal role in tumor progression and therapeutic resistance. Recent studies have identified mitochondrial transfer as a novel mode of intercellular communication that significantly influences metabolic reprogramming and immune evasion in osteosarcoma cells. This mechanism operates through three principal pathways: (1) enhancing energy metabolic efficiency in tumor cells; (2) mitigating intracellular oxidative stress; and (3) modulating immune checkpoint molecule expression. Collectively, these alterations impair host immune surveillance while promoting tumor proliferation, invasion, and distant metastasis through metabolic remodeling, immune tolerance induction, and tumor microenvironment reconstruction. This review systematically elucidates the molecular mechanisms by which mitochondrial transfer regulates immune evasion in osteosarcoma and its dynamic impact on the tumor microenvironment. Furthermore, we discuss the translational potential of targeting this pathway for precision therapy and outline future research directions in this emerging field.

Objective To investigate the regulatory mechanism of Notch signaling pathway by YAP in non-alcoholic steatohep-atitis(NASH)liver fibrosis,and assess the intervention effect of Cigu Xiaozhi prescription in detoxification and phlegm treatment.Methods C57BL/6J mice were randomly divided into different groups,including a normal group,NASH liver fibrosis model group,verteporfin(VP)intervention group,VP+Chinese medicine(Cigu Xiaozhi prescription)low-dose group,VP+Chinese medicine high-dose group,and dimethyl sulfoxide control group.The methionine/choline-deficient diet combined with low-dose CCl4 was used to construct the NASH liver fibrosis model.The degree of liver fibrosis was evaluated using hematoxylin and eosin(HE)and Masson staining.Four protein factors associated with liver fibrosis were detected using enzyme-linked immunosorbent assay,and hydroxyproline levels in the mouse liver was determined using the alkaline water method.The localization of α-SMA,ColⅠ,YAP,and Notch1 proteins in the liver was determined using immunohistochemistry.Additionally,the mRNA and protein expression levels of the Notch signaling pathway molecules,namely Notch1/2,J agged1,and DLL4,were assessed using real-time quantitative PCR and Western blotting analyses,respectively.Results The HE and Masson staining results revealed that the liver cells of NASH liver fibrosis mice were swollen and the cytoplasm was transparent.Additionally,evident fibrosis was observed in the hepatic lobule,portal area,and sinus;it was accompanied by heightened levels of inflam-matory cell infiltration,a large number of fat droplets,and instances of local hepatocyte necrosis,dissolution,and cirrhosis.The four factors associated with liver fibrosis showed a substantial increase(P<0.01).α-SMA,ColⅠ,YAP,and Notch1 were localized in the cytoplasm of hepatocytes.YAP,Notch1/2,and Jagged1 were highly expressed in the liver(P<0.01)but were downregulated after intervention with VP and VP+high and low doses of Cigu Xiaozhi prescription(P<0.05).Meanwhile,DLL4 factor was upregulated in the VP+high-dose of Cigu Xiaozhi prescription group(P<0.05).Conclusion YAP may inhibit activation of the Notch pathway by downregulating Notch1/2 and Jagged1 and upregulating DLL4,thereby interfering with the occurrence of liver fibrosis in NASH.Treatment with Cigu Xiaozhi pre-scription may inhibit Notch signaling pathway activation by downregulating YAP,Notch1/2,and Jagged1 and upregulating DLL4 through its multi-components and multi-targets properties,ultimately slow the progression of liver fibrosis in NASH.

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies

The facultative anaerobic and strict anaerobic microorganisms enriched and acclimated during the anaerobic digestion process are crucial for the efficiency of the anaerobic digestion system. Most of the problems encountered during running anaerobic digestion processes could be effectively improved via stimulation of microbial metabolic activity. Benefited from the rapid development of microbiome techniques, deeper insights into the microbial diversity in anaerobic digestion systems, e.g. the microbe-microbe interactions and microbe-environment interactions, have been gained. A complex and intricate metabolic network exists in the anaerobic digestion system of solid organic wastes. However, little is known about these interactions and the underlying mechanisms. This review briefly summarized the representative interactions between microbial communities during anaerobic digestion process discovered to date. In addition, typical issues encountered during the anaerobic digestion of solid organic wastes and how microbes can tackle and alleviate these issues were discussed. Finally, future priorities on microbiome research were proposed based on present contribution of microbiome analysis in anaerobic digestion system.
Anaerobiosis ; Bioreactors ; Methane ; Microbial Interactions ; Microbiota ; Solid Waste

Objective Toevaluatetheclinicalvalueofmagneticresonanceenterography (MRE)indiagnosingCrohn’sdisease (CD).Methods ThearticlesconcerningthediagnosisofCD byusing MRE weresystematicallysearchedindatabasesincluding PubMed,EMbase,CochraneLibrary,WebofScience,CNKI,CBM,WanFangandVIPdata.Tworeviewersindependentlyscreenedliterature, extracteddata,andassessedbiasriskofincludedstudiesbyusingtheQUADAS-2.Then,thisMeta-analysiswasperformedbyusing Stata12.0software.Thepooledweightedsensitivity,specificity,positivelikelihoodratio(PLR),negativelikelihoodratio (NLR)and diagnosticoddsratio(DOR)werecalculated,thesummaryreceiveroperatingcharacteristiccurve(sROC)wasdrawnandtheAUC wascalculated.Results Atotalof16studieswereincluded,involving1276patientsand919bowelsegments.TheresultsofMeta-analysisshowed that,thepooledsensitivity,specificity,PLR,NLR,DORandAUCofMREdiagnosingCDwere0.87(95%CI:0.79,0.92),0.92(95%CI:0.89, 0.94),10.6(95%CI:7.4,15.2),0.15(95%CI:0.09,0.24),72.69(95%CI:32.7,161.51),0.95(95%CI:0.93,0.97),respectively.Theresultsof subgroupanalysissuggestedthat,thestudytype,MRT-field,pathogenicsiteanddiagnosticcriteriaplayedlittleeffectonthevalueof MREdiagnosingCD (P>0.05).Conclusion MREhadhigheraccuracyfordiagnosingCDand mayservedasanefficientimaging methodfordiagnosingCD.

Objective: To investigate the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) on patients with lung adenosquamous carcinoma, and to analyze relative factors. Methods: From August 2007 to July 2017, 40 patients who were pathologically diagnosed as lung adenosquamous carcinoma in our hospital and received EGFR TKIs treatment were retrospectively analyzed. All patients underwent EGFR mutation detection, resulted in 11 wild type, 13 19Del, 13 21L858R mutations, and 3 uncommon EGFR mutations in 20 exon and 19/21 complex mutation. A higher frequency of EGFR mutation was found in non-smokers and patients with adenocarcinoma components over 50.0%. Results: Twenty-six (65.0%) patients had disease progression after EGFR TKIs treatment, with a median progression-free survival (PFS) of 5.5 months (95% CI 0.52-10.49 months). A total of 20 (50.0%) patients died with an median overall survival (OS) of 15 months (95% CI 11.03-18.97 months). Multivariate analysis showed that gender, age, smoking, histopathological subtypes, EGFR mutations, and brain metastasis had no influence on PFS (all P>0.05). Gender, age, smoking, histopathological subtypes, and the presence of brain metastasis during TKI treatment had no influence on OS (P>0.05), while EGFR mutation is the only influencing factor of OS (P<0.05) in the current study. Conclusions EGFR TKIs had modest efficacy in lung adenosquamous carcinoma, especially in patients with EGFR mutation. Based on the pathological features, EGFR mutation and EGFR TKIs treatment should be introduced into the routine clinical practice to improve the survival of patients with lung adenosquamous carcinoma.

Objective To evaluate whether an early change in 18F-fluorodeoxyglucose (18F-FDG) uptake can predict tumor response to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and prognosis in patients with non-small cell lung cancer (NSCLC). Methods From August 2009 to April 2015, 22 patients with NSCLC who were eligible to EGFR-TKI treatment were enrolled. PET-CT scan was performed before (baseline) and 1 month after EGFR-TKI administration. Up to 5 hottest single tumor lesions (no more than 2 per organ) were considered to be target lesions. Maximum standardized uptake values (SUVmax) were measured, and post-treatment percentage changes in SUVmax (ΔSUV%) were calculated. PET responses were classified using PET response criteria in solid tumors (PERCIST). Then conventional CT scan was performed every 2 months for follow-up. Kappa statistic was used to compare agreement between the RERCIST recommendations-based therapeutic response evaluation and those based on RECIST1.1 criteria. Fisher exact test was used to compare the probability of disease progression in the early metabolic response and non-response groups. Predictive accuracy of ΔSUV% with respect to response or non-progression at CT scan was evaluated by ROC analysis. Progression-free survival (PFS) was determined by Kaplan-Meier survival analysis, and between-group comparison was performed by log-rank test. Results After 1 month of EGFR-TKI treatment, 12 patients (55%) showed partial metabolic response (PMR), 6 (27%) had stable metabolic disease (SMD), and 4 (18%) had progressive metabolic disease (PMD). There was a moderate agreement(Kappa=0.506,P<0.05) between PET response at 1 month based on PERCIST recommendations and CT response at 3 months according to RECIST 1.1. Non-progression was significantly more frequent in patients with an early PMR (χ2=11.941, P=0.005). Progression had been confirmed later during therapy in all patients with PMD . By using ROC analysis, the area under the curve for prediction of response was 0.906 (95% CI, 0.766—1.000; P=0.002), corresponding to a sensitivity of 88.9% and specificity of 84.6% at a cut-off of 40.36% in ΔSUV%. Using a cut-off value of 25.84% in ΔSUV%, highΔSUV% group (ΔSUV% ≥ 25.84%) had significantly longer PFS than low ΔSUV% group (ΔSUV%<25.84%). Conclusion Early assessment of PET-CT at 1 month of EGFR-TKI treatment could be useful to predict tumor response and clinical outcome in patients with NSCLC.

BACKGROUND:When the intervertebral disc is under stress, the hydraulic pressure generated inside the nucleus pulposus makes the annulus fibrosus extend outward and expand, and the annulus colagen fibers are stretched so that the extracelular matrix of annulus fibrosus cels is also under the pressure. In the intervertebral disc, aggrecan is the main component of proteoglycans, matrix metaloproteinase-2 is a major enzyme for extracelular matrix degradation, and tissue inhibitor of metaloproteinase is a multifunctional specific inhibition factor for matrix metaloproteinase activity. There is a mutual regulation between the latter two to keep the homeostasis between them.
OBJECTIVE: To investigate the mechanism of cyclic tensile strain in the metabolism of intervertebral disc annulus matrix.
METHODS:Rat anulus fibrosus cels were subjected to 2% or 10% cyclic tensile strain at 1.0 Hz for 2 and 12 hours using Flexcel4000 tension system. Then cels were colected and cultured in conditioned medium for gene and protein detection. Real-time quantitative PCR was used to detect mRNA expression of aggrecan, matrix metaloproteinases-2 and tissue inhibitor of metaloproteinase-2. Gelatin zymography was used to detect matrix metaloproteinases-2 activity.
RESULTS AND CONCLUSION:The use of 2% cyclic tensile strain had no obvious effect on the stress fiber of actin cytoskeleton, whereas actin cytoskeleton was depolymerized in response to 10% cyclic tensile strain. The 2% cyclic tensile strain raised the expression of Aggrecan at 12 hours; whereas raised the matrix metaloproteinases-2 and tissue inhibitor of metaloproteinase-2 at 2 hours, both of which were in homeostasis; matrix metaloproteinases-2 activity had no significant changes. 10% cyclic tensile strain had no effect on the mRNA expression of Aggrecan. No matter stretching 2 or 12 hours, the matrix metaloproteinases-2 was up-regulated, and the tissue inhibitor of metaloproteinase-2 was down-regulated, both of which were not in balance. Moreover, the matrix metaloproteinases-2 activity was not significantly changed. These findings indicate that the mRNA expressions of Aggrecan, matrix metaloproteinases-2 and tissue inhibitor of metaloproteinase-2 alter in response to cyclic tensile strain in rat anulus fibrosus cels, and the tensile strain induces different mechano-responses in the actin cytoskeleton.

Objective To observe the safety and short?term efficacy of sigle drug albumin?bound paclitaxel (ABP) in the treatment of elderly patients with advanced non?small cell lung cancer (NSCLC). Methods A total of 23 elderly patients with advanced NSCLC who received weekly ABP regimen (130 mg/m2/week) in our hospital from October 2011 to March 2014 were retrospectively evaluated. The short?term efficacy, progression?free survival ( PFS) , and overall survival ( OS) were analyzed. Results The median treatment period was 4 cycles (2?10 cycles). Partial response, stable disease, progressive disease, overall response rate, and disease control rate were 26.1%, 43.5%, 30.4%, 26.1% and 69.6%, respectively. The median PFS was 5.33 months (95% CI:2.95?7.70 months), while the median OS was 40.33 months (95% CI:29.82?50.83 months). Major adverse events included leucopenia (82.6%), neutropenia (78.3%), nausea or vomiting (56.5%), fatigue (52.2%), peripheral neuropathy (26.1%), myalgia/arthralgia (30.4%), thrombocytopenia ( 13. 0%) and arrhythmia ( 4. 3%) . The patients accompanied with chronic diseases had significantly higher incidence rate of peripheral neuropathy and myalgia/arthralgia compared with the patients without accompanied chronic diseases ( 50. 0% vs. 9. 1% and 66. 7% vs. 9. 1%, P<0. 05 for both ) . Conclusion The weekly single drug ABP regimen is effective and well?tolerated in elderly patients with advanced NSCLC.

Objective To observe the safety and short?term efficacy of sigle drug albumin?bound paclitaxel (ABP) in the treatment of elderly patients with advanced non?small cell lung cancer (NSCLC). Methods A total of 23 elderly patients with advanced NSCLC who received weekly ABP regimen (130 mg/m2/week) in our hospital from October 2011 to March 2014 were retrospectively evaluated. The short?term efficacy, progression?free survival ( PFS) , and overall survival ( OS) were analyzed. Results The median treatment period was 4 cycles (2?10 cycles). Partial response, stable disease, progressive disease, overall response rate, and disease control rate were 26.1%, 43.5%, 30.4%, 26.1% and 69.6%, respectively. The median PFS was 5.33 months (95% CI:2.95?7.70 months), while the median OS was 40.33 months (95% CI:29.82?50.83 months). Major adverse events included leucopenia (82.6%), neutropenia (78.3%), nausea or vomiting (56.5%), fatigue (52.2%), peripheral neuropathy (26.1%), myalgia/arthralgia (30.4%), thrombocytopenia ( 13. 0%) and arrhythmia ( 4. 3%) . The patients accompanied with chronic diseases had significantly higher incidence rate of peripheral neuropathy and myalgia/arthralgia compared with the patients without accompanied chronic diseases ( 50. 0% vs. 9. 1% and 66. 7% vs. 9. 1%, P<0. 05 for both ) . Conclusion The weekly single drug ABP regimen is effective and well?tolerated in elderly patients with advanced NSCLC.