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简介：AbstractEbola virus (EBOV) is one of the most pathogenic viruses in humans which can cause a lethal hemorrhagic fever. Understanding the cellular entry mechanisms of EBOV can promote the development of new therapeutic strategies to control virus replication and spread. It has been known that EBOV virions bind to factors expressed at the host cell surface. Subsequently, the virions are internalized by a macropinocytosis-like process, followed by being trafficked through early and late endosomes. Recent researches indicate that the entry of EBOV into cells requires integrated and functional lipid rafts. Whilst lipid rafts have been hypothesized to play a role in virus entry, there is a current lack of supporting data. One major technical hurdle is the lack of effective approaches for observing viral entry. To provide evidence on the involvement of lipid rafts in the entry process of EBOV, we generated the fluorescently labeled Ebola virus like particles (VLPs), and utilized single-particle tracking (SPT) to visualize the entry of fluorescent Ebola VLPs in live cells and the interaction of Ebola VLPs with lipid rafts. In this study, we demonstrate the compartmentalization of Ebola VLPs in lipid rafts during entry process, and inform the essential function of lipid rafts for the entry of Ebola virus. As such, our study provides evidence to show that the raft integrity is critical for Ebola virus pathogenesis and that lipid rafts can serve as potential targets for the development of novel therapeutic strategies.

简介：AbstractPrenatal micronutrients in pregnant women’s diets, including supplements, have an essential role in fetal brain development and may reduce the risk of mental disorders in offspring. Folic acid, vitamin D, omega-3 fatty acids, and choline have been investigated for this purpose. Folic acid supplementation throughout pregnancy has well-established positive effects. Vitamin D, administered to the mother before birth or to the newborn, has also been shown to reduce the risk of neurodevelopmental disorders. Omega-3 fatty acids during pregnancy have a more uncertain role, with recent trials questioning a beneficial effect on cognition and attention deficit disorder, despite positive effects on prematurity and neonatal wheezing prevention. Choline supplementation is associated with positive effects on cognition and behavior, including early behaviors associated with the development of autism and schizophrenia. There is no experience yet with COVID-19, but adverse effects on fetal brain development of most common coronaviruses are mitigated by higher choline levels. Maternal dietary supplementation of nutrients is a benign and inexpensive intervention in pregnancy to prevent life-long disability from mental illness. Use of dietary supplements in poorer, rural areas of China is below recommendations. Physicians, midwives, and public health officials in China can promote prenatal nutrient supplementation to reduce the future burden of mental illnesses that might be prevented before birth.

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简介：摘要目的探讨应用Flow-through背阔肌肌皮瓣修复儿童四肢创面的手术方法及临床疗效。方法2017年1月至2019年9月,应用Flow-through的背阔肌肌皮瓣修复儿童四肢创面9例,其中上肢3例,下肢6例；年龄5～12岁,平均9.4岁；I期行创面清创,负压海绵封闭创面,5～8 d后II期应用Flow-through游离背阔肌肌皮瓣修复创面,6例患者结合植皮修复创面。术中受区动脉两端均修整为管腔向下的斜面,受区血管近端和肩胛下动脉吻合,远端和旋肩胛动脉吻合,胸背静脉和受区静脉吻合。8例患者有1条胸背静脉,1例患者有2条胸背静脉。术后常规抗感染、抗凝血和抗血管痉挛治疗,并定期随访。结果本组中8例皮瓣完全成活,1例远端部分表皮坏死,后痂下愈合。植皮成活良好。术后9例均获得随访,随访时间3~28（平均13）个月,术后门诊随访7例,微信随访2例。所有患者术后1个月CDU检查提示血流通畅,3例术后1年随访CDU检查提示血流通畅。皮瓣血运良好,质地柔软,3例后期行皮瓣整形手术。结论应用Flow-through背阔肌肌皮瓣修复儿童四肢创面,皮瓣成活良好,受区主干血管血流通畅,对肢体远端血供无明显影响。

简介：摘要目的探讨Flow-through嵌合股前外侧穿支皮瓣（ALTP）急诊一期修复四肢Gustillo III C型损伤的临床疗效。方法2010年1月至2017年12月,采用Flow-through嵌合ALTP急诊修复四肢Gustillo III C型损伤患者17例。其中男16例,女1例；年龄19~55岁,平均32.4岁。创面范围16 cm×8 cm~45 cm×30 cm。旋股外侧动脉降支Flow-through吻合受区动脉以重建肢体血供,股外侧肌瓣填塞深部死腔,皮瓣和筋膜瓣覆盖浅表创面。供区皮肤直接闭合6例,腹部取皮植皮11例。结果术后采用门诊结合微信、电话随访,时间5~60个月,平均21.8个月。皮瓣成活15例,2例失败并截肢。6例采用皮瓣和筋膜瓣修复,11例采用皮瓣、筋膜瓣和肌瓣修复。术后4例皮瓣一期愈合；11例患者皮瓣边缘出现坏死,其中1例换药后瘢痕愈合,其余10例患者二期植皮愈合。所有患者供区未出现并发症。结论急诊Flow-through嵌合ALTP在重建肢体血供的同时实现创面三维立体修复,是修复四肢Gustillo III C型损伤的有效方法之一。

简介：AbstractPurpose:To assess the clinical efficacy of converting partial articular supraspinatus tendon avulsion (PASTA) lesions to full-thickness tears through a small local incision of the bursal-side supraspinatus tendon followed by repair.Methods:We retrospectively analyzed 41 patients with Ellman grade 3 PASTA lesions and an average age of (54.7 ± 11.4) years from March 2013 to July 2017. Patients without regular conservative treatment and concomitant with other shoulder pathologies or previous shoulder surgery were excluded from the study. The tears were confirmed via arthroscopy, and a polydioxanone suture was placed to indicate the position of each tear. A small incision of approximately 6 mm was made using a plasma scalpel on the bursal-side supraspinatus tendon around the positioned suture to convert the partial tear into a full-thickness tear. The torn rotator cuff was sutured through the full thickness using a suture passer after inserting a 4.5-mm double-loaded suture anchor. Data were analyzed using a paired Student’s t-test with statistical significance defined as p <0.05.Results:At the final follow-up of 2 years, the pain-free shoulder joint range of motion and visual analog scale score were significantly improved compared to those before surgery (p < 0.001). The postoperative American Shoulder and Elbow Surgeons shoulder score was (90.6 ± 6.2), which was significantly higher than the preoperative score of (47.9 ± 8.3) (p < 0.001). The University of California at Los Angeles shoulder rating scale score increased from (14.7 ± 4.1) prior to surgery to (32.6 ± 3.4) points after surgery (p < 0.001). No patient had joint stiffness.Conclusion:This modified tear completion repair, by conversion to full-thickness tears through a small incision, has less damage to the supraspinatus tendon on the side of the bursa compared to traditional tear completion repair in the treatment of PASTA lesions. This surgical method is a simple and effective treatment that can effectively alleviate pain and improve shoulder joint function.

简介：AbstractObjective:Paclitaxel (PAC) is a chemotherapy drug and has an active role in the treatment of lung, breast, and ovarian cancers; however, its use causes increased levels of free radicals, leading to severe and irreversible organ damage. Thymus vulgaris is a species of flowering plant that contains various antioxidant chemical compounds. This study aimed to investigate the effect of T. vulgaris on PAC-induced oxidative damage in mice testis and sperm parameters.Methods:In this study, 40 BALB/c mice were divided into five groups: normal control (NC); positive control (20 mg/kg of PAC); and three treatment groups (4.5, 9, and 18 mg/kg doses of T. vulgaris extract + 20 mg/kg PAC). Treatments were administered intraperitoneally daily for 50 days. Finally, the levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were measured using immunoassay method. Testicular stereological features and sperm parameters were also calculated. Antioxidant parameters were measured using nitrite oxide (NO) and perioxidation levels and ferric-reducing ability of plasma assay. The expressions of p53, caspase-3, Bax, and Bcl-2 were measured through real-time quantitative polymerase chain reaction.Results:T. vulgaris + PAC treatments at all doses significantly increased all parameters in NC and three treatment groups compared with the positive control group (20 mg/kg of PAC) (P < 0.05), except the LH, FSH, and NO levels, which were decreased. Further, significantly downregulated levels of p53, caspase-3, and Bax genes and upregulated levels of Bcl-2 gene expression were noted in NC and three treatment groups in comparison with the positive control group (P < 0.05).Conclusions:T. vulgaris administration attenuates the toxic effects of PAC on male reproductive parameters.

简介：AbstractObjective:SOX4, a transcription factor, has been found to contribute to tumorigenesis in several cancers. This study was performed to determine whether SOX4 mediates BRAF inhibitor resistance in melanoma.Methods:Melanoma cell lines with acquired resistance to BRAF inhibitor (SK-MEL-5R, SK-MEL-28R, and A375R) were generated by adding escalating concentrations of PLX4032 into parental SK-MEL-5, SK-MEL-28, and A375 cells for >6 months. The expression of SOX4 and insulin-like growth factor 1 receptor (IGF-1R) was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The downstream signaling of IGF-1R was detected by Western blotting. SOX4 and IGF-1R overexpression or knockdown was conducted by lentivirus transfection. Cell viability and apoptosis were demonstrated by MTT and flow cytometry, respectively. The binding ability of SOX4 to IGF-1R promoter was determined by chromatin immunoprecipitation quantitative PCR assay.Results:SOX4 was upregulated in BRAF inhibitor-resistant melanoma cells as compared with parental cells (SK-MEL-5 group, 1.02 vs. 6.33; SK-MEL-28 group, 1.03 vs. 3.22; A375 group, 1.00 vs. 1.86; t=°7.069, 29.26, and 5.291, respectively; all P < 0.01), and PLX4032 treatment could not alter the expression of SOX4 in resistant cells. SOX4 overexpression attenuated the response of parental cells to PLX4032 (for cell viability, SK-MEL-5 group: 77.76% vs. 104.28%, F= 91.50; SK-MEL-28 group: 60.59% vs. 93.13%, F= 171.8; A375 group: 62.50% vs. 80.87%, F= 47.15. For apoptosis rates, SK-MEL-5 group: 34.90% vs. 14.31%, F= 4.781; SK-MEL-28 group, 40.8% vs. 29.4%, F= 13.32, P= 0.063; A375 group: 40.20% vs. 17.09%, F= 11.39; all P < 0.05, otherwise indicated). While SOX4 knockdown enhanced the response of resistant cells to PLX4032 (for cell viability, SK-MEL-5R group: 93.75% vs. 69.53%, F= 94.45, SK-MEL-28R group: 95.60% vs. 66.79%, F= 30.41, A375R group: 95.51% vs. 59.98%, F= 111.6; for apoptosis rates, SK-MEL-5R group: 16.2% vs. 44.4%, F= 25.67, SK-MEL-28R group: 26.59% vs. 44.20%, F= 158.0, A375R group: 5.98% vs. 31.51 %, F= 14.35, and all P < 0.01). Chromatin immunoprecipitation quantitative PCR assay demonstrated that SOX4 binded to the promoter of IGF-1R (1.04 vs. 1.94 [-1044 to -920 bp] and 0.110 vs. 0.139 [GAPDH], F= 534.5, P < 0.01). In addition, SOX4 overexpression increased IGF-1R and its downstream phosphorylated ERK, phosphorylated AKT, and phosphorylated STAT3 expression, while SOX4 knockdown exerted the opposite effects. Moreover, IGF-1R knockdown overcame SOX4 overexpression-induced PLX4032 resistance (cell viability: 35.85% vs. 52.79% vs. 37.84% [A375 group, negative control group vs. SOX4 overexpressing group vs. SOX4 overexpressing + sh-IGF-1R group]; apoptosis rates: 25.30% vs. 9.56% vs. 22.26 [A375 group, negative control group vs. SOX4 overexpressing group vs. SOX4 overexpressing+ sh-IGF-1R group]; F= 13.01 and 41.87, respectively; all P < 0.01), while IGF-1R overexpression abrogated SOX4 knockdown-induced response enhancement to PLX4032 for comparison of negative control group, sh-SOX4 group and sh-SOX4 + IGF-1R overexpressing group (cell viability: 96.62% vs. 86.86% vs. 97.26% (A375R), 98.15% vs. 81.63% vs. 98.49% [SK-MEL-5R]; apoptosis rates: 13.81% vs. 32.00% vs. 12.16 [A375R], 29.70% vs. 41.40% vs. 26.10% [SK-MEL-5R]; F= 13.56, 12.86, 38.81, and 39.85, respectively; all P < 0.01).Conclusion:SOX4 mediates BRAF inhibitor resistance in melanoma through regulation of IGF-1R signaling. SOX4 might serve as a potential target for the treatment of BRAF inhibitor-resistant melanoma.

简介：摘要目的探讨Flow-through股前外侧穿支皮瓣（ALTP）在断肢再植创面修复中的临床应用及效果。方法2016年8月至2018年8月,利用Flow-through ALTP修复断肢再植后遗留创面共9例,急诊修复3例,择期修复6例。其中前臂离断创面2例,肘部离断创面1例,踝部离断创面3例,小腿离断创面3例,创面内均有肌腱与骨质外露。软组织缺损大小13.0 cm×7.0 cm～25.0 cm×12.0 cm,血管缺损长度6.0~10.0 cm。术后观察再植肢体及皮瓣成活情况,对皮瓣外形及感觉、桥接血管通畅性、再植肢体功能及供区外形功能恢复情况定期随访。结果本组9例再植肢体及皮瓣全部成活。术后随访6～24个月,平均12个月,再植肢体及皮瓣血运良好,CDU探查桥接血管血流通畅。皮瓣质地良好,2例外形稍臃肿,7例外形满意；3例无感觉恢复,6例恢复保护性感觉。供区遗留线形瘢痕,下肢功能正常。根据陈中伟断肢再植评定标准,良5例,可3例,差1例。结论利用Flow-through ALTP修复断肢再植后的遗留创面,保留肢体完整性,恢复肢体外形,同时供区损伤小,是一种理想修复方法。

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简介：AbstractBackground:Topoisomerase II alpha (TOP2A) has been reported to play a crucial role in the tumorigenesis of various cancer types. However, the biological role of TOP2A in gallbladder cancer (GBC) remains unknown. The current study aimed to explore the function and potential mechanism of TOP2A in GBC.Methods:Based on Gene Expression Profiling Interactive Analysis data, we found TOP2A was significantly up-regulated in GBC tissues and resulting in shorter overall survival. Quantitative real-time polymerase chain reaction and immunohistochemistry were conducted to detect the expression of TOP2A in 45 pairs of GBC tissues and adjacent non-tumor tissues. In vitro, cell proliferation, migration, and invasion ability were examined by cell counting kit-8 and transwell assay, respectively. Epithelial-mesenchymal transition (EMT) related and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway-related markers were measured by Western blotting. Xenograft model assay was performed to evaluate the effect of TOP2A in vivo.Results:TOP2A was found up-regulated in GBC (tumor vs. normal, 12.62 vs. 0.34) and correlated with the late tumor node metastasis stage (P = 0.0032), present of lymph node metastasis (P = 0.0273), and poor prognosis in GBC patients (log-rank P = 0.028). In vitro and in vivo assays showed that knockdown of TOP2A notably inhibited cell proliferation, migration, invasion, EMT process, and tumor growth in GBC. In addition, TOP2A down-regulation significantly decreased the protein levels of phosphor (p)-PI3K, p-Akt, and p-mTOR.Conclusion:Our study demonstrates that TOP2A was overexpressed in GBC and associated with poor prognosis in GBC patients. TOP2A promotes GBC cell proliferation, migration, invasion, EMT process, and tumor growth through activating PI3K/Akt/mTOR signaling pathway, and may serve as a novel prognostic biomarker and therapeutic target for GBC.

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简介：摘要目的探讨flow-through游离尺动脉腕上支皮瓣治疗手指掌侧皮肤软组织缺损合并节段性指血管缺损的临床疗效。方法回顾性分析2015年1月至2019年3月我科应用flow-through游离尺动脉腕上支皮瓣治疗手指掌侧皮肤软组织缺损合并节段性指固有动脉缺损的16例患者，其中手指双侧指固有动脉节段性缺损12例，单侧缺损4例，血管缺损长度为1.0～2.5 cm。急诊一期皮瓣修复12例，亚急诊皮瓣修复4例。术后定期进行随访，末次随访时采用手指关节总主动活动度(total active motion，TAM)法评定手功能。结果术后16例16指皮瓣全部存活，未发生指端或皮瓣坏死。所有患者均获得随访，时间为6～24个月，平均15个月。末次随访时患指外观满意，皮瓣弹性、血运良好。手功能采用手指关节TAM法评定：优9例，良4例，可3例。供区无并发症。结论Flow-through游离尺动脉腕上支皮瓣治疗手指掌侧皮肤软组织缺损合并节段性指固有动脉缺损，术后手指外形及功能恢复良好，是治疗此类损伤的一种有效方法。

简介：AbstractBackground:Pancreatic cancer (PC) is a highly deadly malignancy with few effective therapies. We aimed to unmask the role that long non-coding RNA small nucleolar RNA host gene 6 (SNHG6) plays in PC cells by targeting far upstream element binding protein 1 (FUBP1) via microRNA-26a-5p (miR-26a-5p).Methods:SNHG6 expression was predicted by bioinformatics, followed by verification via reverse transcription quantitative polymerase chain reaction. Then, the interactions among SNHG6, miR-26a-5p, and FUBP1 were detected through online software analysis, dual luciferase reporter assay and RNA pull-down. After that, cells were treated with different small interfering RNAs and/or mimic to determine the interactions among SNHG6, miR-26a-5p, and FUBP1 and their roles in PC cells. Finally, the role of SNHG6 in tumor growth in vivo was evaluated by measuring the growth and weight of transplanted tumors in nude mice. A t-test, one-way and two-way analysis of variance were used for data analysis.Results:Compared with that in normal tissues, SNHG6 was highly expressed in PC tissues (1.00 ± 0.05 vs. 1.56 ± 0.06, t= 16.03, P < 0.001). Compared with that in human pancreatic duct epithelial cells (HPDE6-C7), SNHG6 showed the highest expression in PANC-1 cells (1.00 ± 0.06 vs. 3.87 ± 0.13, t= 34.72, P < 0.001) and the lowest expression in human pancreatic cancer cells (MIAPaCa-2) (1.00 ± 0.06 vs. 1.41 ± 0.07, t= 7.70, P= 0.0015). Compared with the levels in the si-negative control group, SNHG6 (0.97 ± 0.05 vs. 0.21 ± 0.06, t = 16.85, P < 0.001), N-cadherin (0.74 ± 0.05 vs. 0.41 ± 0.04, t= 8.93, P < 0.001), Vimentin (0.55 ± 0.04 vs. 0.25 ± 0.03, t= 10.39, P < 0.001), and β-catenin (0.62 ± 0.05 vs . 0.32 ± 0.03, t= 8.91, P < 0.001) were decreased, while E-cadherin (0.65 ± 0.06 vs. 1.36 ± 0.07, t= 13.34, P < 0.001) was increased after SNHG6 knockdown or miR-26a-5p overexpression, accompanied by inhibited cell proliferation, migration, and invasion. SNHG6 overexpression exerted the opposite effects. SNHG6 upregulated FUBP1 expression by sponging miR-26a-5p. Silencing SNHG6 blocked the growth of PC in vivo.Conclusion:Silencing SNHG6 might ameliorate PC through inhibition of FUBP1 by sponging miR-26a-5p, thus providing further supporting evidence for its use in PC treatment.

简介：AbstractBackground:Developing effective spinal cord repair strategies for spinal cord injury (SCI) is of great importance. Emerging evidence suggests that microRNAs (miRNAs) are closely linked to SCI recovery. This study aimed to investigate the function of miR-34c in the neuronal recovery in rats with SCI.Methods:A rat model with SCI was established. Differentially expressed miRNAs were identified by a microarray analysis. MiR-34c expression in rats was measured by reverse transcription quantitative polymerase chain reaction. Altered expression of miR-34c or C-X-C motif ligand 14 (CXCL14) was introduced in SCI rats to measure their roles in neuronal recovery. Western blot analysis was performed to determine the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription-3 (STAT3). Neuronal apoptosis in rat spinal cord tissues was detected. The concentrations of SCI recovery-related proteins thyrotropin releasing hormone (TRH), prostacyclin (PGI2), and ganglioside (GM) were evaluated by enzyme-linked immunosorbent assay. Data were analyzed using a t-test with a one-way or two-way analysis of variance.Results:Rats with SCI presented decreased grip strength (112.03 ± 10.64 vs. 17.32 ± 1.49 g, P < 0.01), decreased miR-34c expression (7 days: 3.78 ± 0.44 vs. 0.95 ± 0.10, P < 0.05), and increased CXCL14 expression (7 days: 0.61 ± 0.06 vs. 2.91 ± 0.27, P < 0.01). MiR-34c was found to directly bind to CXCL14. Overexpression of miR-34c increased grip strength (11.23 ± 1.08 vs. 31.26 ± 2.99 g, P < 0.01) and reduced neuronal apoptosis in spinal cord tissues (53.61% ± 6.07% vs. 24.59% ± 3.32%, P < 0.01), and silencing of CXCL14 also increased the grip strength (12.76 ± 1.13 vs. 29.77 ± 2.75 g, P < 0.01) and reduced apoptosis in spinal cord tissues (55.74% ± 6.24% vs. 26.75% ± 2.84%, P < 0.01). In addition, miR-34c upregulation or CXCL14 downregulation increased the concentrations of TRH, PGI2, and GM, and reduced phosphorylation of JAK2 and STAT3 in rats with SCI (all P < 0.01).Conclusion:The study provided evidence that miR-34c could promote neuronal recovery in rats with SCI through inhibiting CXCL14 expression and inactivating the JAK2/STAT3 pathway. This study may offer new insights into SCI treatment.