Background: The traditional anti-inflammation disease-modifying anti-rheumatic drugs (DMARDs) have limited therapeutic effects in rheumatoid arthritis (RA) patients. We previously reported the safety and efficacy of umbilical cord mesenchymal stem cell (UC-MSC) treatment in RA patients that were observed for up to 8 months after UC-MSC infusion. The aim of this study is to assess the long-term efficacy and safety of UC-MSC along with DMARDs for the treatment of RA. Methods: 64 RA patients aged 18-64 years were recruited in the study. During the treatment, patients were treated with 40 mL UC-MSC suspension product (2 × 10 7 cells/ 20 mL) via intravenous injection immediately after the infusion of 100 mL saline. The serological markers tests were used to assess safety and the 28-joint disease activity score (DAS28) and the Health Assessment Questionnaire (HAQ) to assess efficacy. Results: 1 year and 3 years after UC-MSC cells treatment, the blood routine, liver and kidney function and immunoglobulin examination showed no abnormalities, which were all in the normal range. The ESR, CRP, RF of 1 year and 3 years after treatment and anti-CCP of 3 years after treatment were detected to be lower than that of pretreatment, which showed significant change (P < 0.05). Health index (HAQ) and joint function index (DAS28) decreased 1 year and 3 years after treatment than before treatment (P < 0.05). Conclusion: UC-MSC cells plus DMARDs therapy can be a safe, effective and feasible therapeutic option for RA patients.

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Little is known about noncoding tumor suppressor genes. An effective way to identify these genes is by analyzing somatic copy number variation (CNV)-related noncoding genes. By integrated bioinformatics analyses of differentially expressed long noncoding RNAs (lncRNAs) and arm-level CNVs in lung adenocarcinoma (LUAD), we identified a potential antitumor gene, MIR99AHG, encoding lncRNA MIR99AHG as well as a miR-99a/let-7c/miR-125b2 cluster on chromosome 21q. All four of these transcripts were downregulated in LUAD tissues partly due to the copy number deletion of the MIR99AHG gene. Both MIR99AHG and miR-99a expression was positively correlated with the survival of LUAD patients. MIR99AHG suppressed proliferation and metastasis and promoted autophagy both in vitro and in vivo. Mechanistically, the interaction between MIR99AHG and ANXA2 could accelerate the ANXA2-induced ATG16L+ vesicle biogenesis, thus promoting phagophore assembly. Additionally, miR-99a targeted a well-known autophagy suppressor, mammalian target of rapamycin (mTOR), thereby synergistically promoting autophagy and postponing LUAD progression with MIR99AHG. In summary, MIR99AHG emerges as a noncoding tumor suppressor gene in LUAD, providing a new strategy for antitumor therapy.

Abstract. Inflammation and immunity are important in the pathogenesis of cerebral ischemia. Toll-like receptor 4 (TLR4) is involved in the inflammatory responses of injured brain tissues. Emerging studies have focused on the effect of isoflurane (ISO) pretreatment on cerebral ischemia, however, the association between ISO pretreatment and TLR4 during cerebral ischemia remains to be elucidated. In the present study, the protective role of ISO pretreatment in rats with focal cerebral ischemia reperfusion was investigated and the molecular mechanism was discussed. Using a middle cerebral artery occlusion (MCAO) model, triphenyltetrazolium chloride staining was utilized to measure the infarct volume and brain edema and immunofluorescence staining was used to detect the MCAO-induced TLR4 expression and localization. Western blot analyses were conducted to quantify the protein expression levels of TLR4, myeloid differentiation primary response 88 (MyD88) and nuclear factor (NF)-κB in ischemic brain tissue at different time points. The results demonstrated that, following ISO pretreatment, the neurological deficits, brain edema and cerebral infarct size caused by ischemia/reperfusion were attenuated. The astrocyte and microglial activation in the brain tissue was decreased. In addition, the expression levels of TLR4, MyD88 and NF-κB were decreased. The present study indicated that ISO pretreatment may protect the brain from ischemic damage by downregulating the expression levels of TLR4, MyD88 and NF-κB.

Abstract. The current study presents the case of a 68-year-old female patient who received biological intensity-modulated radiotherapy (BIMRT) and neoadjuvant chemotherapy for multiple peritoneal metastases of ovarian cancer. The International Federation of Gynecology and Obstetrics disease stage was Ⅲc. In addition, the patient presented with urination and defecation difficulties. The result of tumor marker detection showed a carcinoembryonic antigen level of 348.2ng/ml, a cancer antigen 125 level of 2,091 U/ml and a cancer antigen 19-9 level of 113 U/ml. Computed tomography (CT) indicated and ovarian cystic or solid package, enlargement of multiple abdominal and retroperitoneal lymph nodes and abdominal cavity effusion. Positron emission tomography/CT indicated multiple internal organ metastases. The center of the ovarian cystic or solid package was considered to be a malignant tumor. A large amount of ascites were detected, as well as abdominal and retroperitoneal lymph node metastasis. The patient was treated with BIMRT at a total dose of 48 Gy, administered as a single 4.0-Gy dose 12 times. In addition, 100 mg cisplatin was administered as a peritoneal perfusion, followed by two cycles of 180 mg Taxol and 100 mg cisplatin. Furthermore, the enlargement of the lymph nodes was reduced and the tumor in the region of the ovary had decreased in size by 90%. The ascites had disappeared and the abdominal pain was greatly improved. At the time of writing this manuscript, the patient was well and without relapse. Therefore, modern radiotherapy techniques, such as BIMRT, may be considered as a beneficial treatment option for ovarian cancer patients with multiple peritoneal metastases in whom surgery is not suitable.