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Abstract Background Renal fibrosis is considered an irreversible pathological process and the ultimate common pathway for the development of all types of chronic kidney diseases and renal failure. Diosmin is a natural flavonoid glycoside that has antioxidant, anti-inflammatory, and antifibrotic activities. However, whether Diosmin protects kidneys by inhibiting renal fibrosis is unknown. We aimed to investigate the role of Diosmin in renal interstitial fibrosis and to explore the underlying mechanisms. Methods The UUO mouse model was established and gavaged with Diosmin (50 mg/kg·d and 100 mg/kg·d) for 14 days. HE staining, Masson staining, immunohistochemistry, western blotting and PCR were used to assess renal tissue injury and fibrosis. Elisa kits were used to detect the expression levels of IL-1β, IL-6, and TNF-α and the activity of SIRT3 in renal tissues. In addition, enrichment maps of RNA sequencing analyzed changes in signaling pathways. In vitro, human renal tubular epithelial cells (HK-2) were stimulated with TGF-β1 and then treated with diosmin (75 μM). The protein and mRNA expression levels of SIRT3 were detected in the cells. In addition, 3-TYP (selective inhibitor of SIRT3) and SIRT3 small interfering RNA (siRNA) were used to reduce SIRT3 levels in HK-2. Results Diosmin attenuated UUO-induced renal fibrosis and TGF-β1-induced HK-2 fibrosis. In addition, Diosmin reduced IL-1β, IL-6, and TNF-α levels in kidney tissues and supernatants of HK-2 medium. Interestingly, Diosmin administration increased the enzymatic activity of SIRT3 in UUO kidneys. In addition, Diosmin significantly increased mRNA and protein expression of SIRT3 in vitro and in vivo. Inhibition of SIRT3 expression using 3-TYP or SIRT3 siRNA abolished the anti-inflammatory effects of diosmin in HK-2 cells. Enrichment map analysis by RNA sequencing indicates that the nuclear factor-kappa B (NF-κB) signaling pathway was inhibited in the Diosmin intervention group. Furthermore, we found that TGF-β1 increased the nuclear expression of nuclear NF-κB p65 but had little significant effect on the total intracellular expression of NF-κB p65. Additionally, Diosmin reduced TGF-β1-caused NF-κB p65 nuclear translocation. Knockdown of SIRT3 expression by SIRT3 siRNA increased the nuclear expression of NF-κB p65 and abolished the inhibition effect of Diosmin in NF-κB p65 expression. Conclusions Diosmin reduces renal inflammation and fibrosis, which is contributed by inhibiting nuclear translocation of NF-κB P65 through activating SIRT3.

Objective To summarize the diagnosis and treatment of refractory brain metastases and leptomeningeal metastases from small cell lung cancer (SCLC). Methods and Results An extensive stage SCLC male patient (44⁃year⁃old) with diffuse parenchymal meningeal metastases and large volume brain metastasis was treated with muti⁃disciplinary team (MDT), namely precise helical tomotherapy with concurrent temozolomide chemotherapy, combined with intrathecal chemotherapy and systemic therapy. After intracranial recurrent, intrathecal chemotherapy and radiotherapy were used to release the symptoms. At last, this patient died of extracranial disease and the survival time after the diagnosis of brain metastases was 16 months. Conclusions For treatment of brain or leptomeningeal metastases, comprehensive and individualized treatment are needed, and MDT treatment discussion is highly recommended. DOI：10.3969/j.issn.1672⁃6731.2019.11.011

OBJECTIVE:To evaluate concurrent chemotherapy for T4 classification nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT). METHODS:From July 2004 to June 2011, 180 non-metastatic T4 classification NPC patients were retrospectively analyzed. Of these patients, 117 patients were treated by concurrent chemoradiotherapy (CCRT) using IMRT and 63 cases were treated by IMRT alone. RESULTS:The median follow-up time was 58.97 months (range, 2.79-114.92) months. For all the patients, the 1, 3 and 5-year local failure-free survival (LFFS) rates were 97.7%, 89.2% and 85.9%, regional failure free survival (RFFS) rates were 98.9%, 94.4% and 94.4%, distant failure-free survival (DFFS) rates were 89.7%, 79.9% and 76.2%, and overall survival (OS) rates were 92.7%, 78.9% and 65.3%, respectively. No statistically significant difference was observed in LFFS, RFFS, DFFS and OS between the CCRT group and the IMRT alone group. No statistically significant difference was observed in acute toxicity except leukopenia (p = 0.000) during IMRT between the CCRT group and the IMRT alone group. CONCLUSION:IMRT alone for T4 classification NPC achieved similar treatment outcomes in terms of disease local control and overall survival as compared to concurrent chemotherapy plus IMRT. However, this is a retrospective study with a limited number of patients, such results need further investigation in a prospective randomized clinical trial.

BACKGROUND:Vitamin D deficiency is common in pregnant women, but an optimal serum vitamin D level during pregnancy has not been determined and remains an area of active research. Vitamin D data from large populations of pregnant Chinese women are still limited. OBJECTIVE:To evaluate the vitamin D status of women in Eastern China during the second trimester of pregnancy. METHODS:A hospital-based, cross-sectional, observational study. Serum 25-hydroxyvitamin D [25(OH)D] concentration was measured in samples from 5823 pregnant women in Wuxi City, China (latitude: 31.5o N), from January 2011 to June 2012. RESULTS:The median serum 25(OH)D concentration was 34.0 nmol/L [2.5 nmol/L 25(OH)D = 1 ng/mL 25(OH)D]. Vitamin D deficiency [defined as 25(OH)D < 30 nmol/L according to the Institute of Medicine (National Academy of Sciences, Washington, D.C., USA)] or inadequacy [25(OH)D of 30-49.9 nmol/L] was identified in 40.7% and 38.0% of the women, respectively. Only 0.9% had a 25(OH)D level ≥ 80.0 nmol/L, which is the concentration recommended as adequate by the Endocrine Society (Washington, D.C., USA). Compared with older women, younger women were more likely to be deficient in vitamin D. There were significant differences in the 25(OH)D levels according to season. The 25(OH)D levels reached peak values in September and were correlated with (r = 0.337, P < 0.001), and fluctuated with, average monthly air temperatures. CONCLUSIONS:There is a high prevalence of Vitamin D deficiency among pregnant Chinese women, and 25(OH)D levels varied according to season and air temperature. The results of this study also suggest that currently there is a big gap between the levels of Vitamin D detected in pregnant Chinese women and the levels recommended by the Endocrine Society.

Preimplantation genetic screening (PGS) is widely used to select in vitro-fertilized embryos free of chromosomal abnormalities and to improve the clinical outcome of in vitro fertilization (IVF). A disadvantage of PGS is that it requires biopsy of the preimplantation human embryo, which can limit the clinical applicability of PGS due to the invasiveness and complexity of the process. Here, we present and validate a noninvasive chromosome screening (NICS) method based on sequencing the genomic DNA secreted into the culture medium from the human blastocyst. By using multiple annealing and looping-based amplification cycles (MALBAC) forwhole-genome amplification (WGA), we performed next-generation sequencing (NGS) on the spent culture medium used to culture human blastocysts (n = 42) and obtained the ploidy information of all 24 chromosomes. We validated these results by comparing each with their corresponding whole donated embryo and obtained a high correlation for identification of chromosomal abnormalities (sensitivity, 0.882, and specificity, 0.840).With this validated NICS method, we performed chromosome screening on IVF embryos from seven couples with balanced translocation, azoospermia, or recurrent pregnancy loss. Six of them achieved successful clinical pregnancies, and five have already achieved healthy live births thus far. The NICS method avoids the need for embryo biopsy and therefore substantially increases the safety of its use. The method has the potential of much wider chromosome screening applicability in clinical IVF, due to its high accuracy and noninvasiveness. [ABSTRACT FROM AUTHOR]

Background: Although parotid-sparing IMRT decreased the dose distribution of parotid, parotid region recurrence has been reported. Prophylactic irradiation in parotid area would be necessary in patients with high risk of parotid lymph node metastasis (PLNM). This study was to detect the high-risk factors of PLNM in nasopharyngeal carcinoma.Methods: This was a 1:2 case-control study. All patients in this study were newly diagnosed NPC with N2-3 classification from January 2005 to December 2012. Cases were 22 sides with ipsilateral PLNM. Controls were 44 patients who were randomly selected from N2-3 disease in database.Results: 20/1096 (1.82 %) NPC patients were found PLNM. Sum of the longest diameter for multiple lymph nodes (SLD) in level II was larger in case group than that in control group (6.0 cm vs. 3.6 cm, p = 0.003). Level II lymph node necrosis, level Va/b involvement, and rare neck areas involvement were more common in case group (p = 0.016, p = 0.034, and p < 0.001, respectively). RPN, level III, and level IV metastases showed no significant difference between the two groups. Multivariate analysis in logistic regression showed that only SLD ≥5 cm in II area (OR = 4.11, p = 0.030) and rare neck areas involvement (OR = 3.95, p = 0.045) were associated with PLNM in NPC patients.Conclusions: PLNM was an uncommon event in NPC patients. SLD ≥5 cm in level II and involvement in rare-neck areas may be potentially high-risk factors for PLNM. Sparing parotid in IMRT was not recommended for NPC patients with high risks of PLNM. [ABSTRACT FROM AUTHOR]

Objective: To explore the outcome and prognostic factors of recursive partitioning analysis (RPA) Class III brain metastatic patients treated with stereotactic radiotherapy (SRT).Materials and Methods: Fifty-six consecutive patients with metastatic brain tumors and Karnofsky performance scale (KPS) scores <70 treated with SRT from January 2008 to October 2013 were involved in the analysis. Twenty-five patients (44.6%) were with symptomatic extracranial lesions (SELs), and the other 31 patients (55.4%) were without SELs. The detailed follow-up data of KPS scores were available in 44 patients. The KPS score drop time (KDT) was calculated as the time between SRT and 10 points drop of KPS scores compared to the baseline. Kaplan-Meier and Cox proportional hazards regression analyses were performed for univariate and multivariate analyses.Results: The median overall survival time was 5.0 months (95% confidence interval [CI] 3.42-6.59) for the whole group. In multivariate analysis, the presence of SELs (P = 0.007, relative risk = 4.44, 95% CI 1.036-20.818) was the independent prognosis factor for survival. Median survival time was 3 months for the patients with SELs, 8 months for the patients without SELs. The median KDT of the 44 patients was 3.0 months (95% CI, 1.927-4.073 months). Again only the presence of SELs (P = 0.001, OR = 6.622, 95% CI, 2.108-20.801) was significantly related to KDT in multivariate analysis. The median KDT of the patients with SELs was 1.5 months, which was 5 months for the patients without SELs.Conclusion: The presence of SELs was a negative prognosis factor for the survival of RPA Class III brain metastatic patients. If RPA Class III brain metastatic patients were without SELs, SRT may be a reasonable treatment option, but if they had SELs, SRT may not be a reasonable treatment due to the short overall survival time and KDT. [ABSTRACT FROM AUTHOR]

Background: To evaluate the efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) in patients with residual nasopharyngeal carcinoma (NPC). Methods: From January 2000 to December 2009, 136 NPC patients with residual lesions after primary radiotherapy (RT) were treated by FSRT. The total dose of primary RT was 68.0-78.0 Gy (median, 70.0 Gy). The median time from the primary RT to FSRT was 24.5 days. Tumor volumes for FSRT ranged from 0.60 to 77.13 cm3 (median, 13.45 cm3). The total FSRT doses were 8.0-32.0Gy (median, 19.5 Gy) with 2.0-10.0 Gy per fraction. Results: Five-year local failure-free survival (LFFS), freedom from distant metastasis (FFDM), overall survival (OS), and disease free survival (DFS) rates for all patients were 92.5%, 77.0%, 76.2%, and 73.6%, respectively. No statistical significant differences were found in LFFS, DFS and OS in patients with stage I/II versus stage III/ IV diseases. Nineteen patients exhibited late toxicity. T stage at diagnosis was a significant prognostic factor for OS and DFS. Age was a prognostic factor for OS. Conclusion: FSRT after external beam radiotherapy provides excellent local control for patients with residual NPC. The incidence of severe late toxicity is low and acceptable. Further investigation of optimal fractionation regimens will facilitate reduction of long-term complications. [ABSTRACT FROM AUTHOR]

Reports on the cloning, expression and purification of the thermostable nonhomodimeric restriction enzyme, BslI, from Bacillus in Escherichia coli. Formation of heterodimers, heterotetramers and possibly oligomers in solution by BslI; Presence of two putative zinc fingers in the alpha subunit of BslI endonuclease.