Autophagy inhibits the mesenchymal stem cell aging induced by D-galactose through ROS/JNK/p38 signalling

Autophagy and cellular senescence are two critical responses of mammalian cells to stress and may have a direct relationship given that they respond to the same set of stimuli, including oxidative stress, DNA damage, and telomere shortening. Mesenchymal stem cells (MSCs) have emerged as reliable cell sources for stem cell transplantation and are currently being tested in numerous clinical trials. However, the effects of autophagy on MSC senescence and corresponding mechanisms have not been fully evaluated. Several studies demonstrated that autophagy level increases in aging MSCs and the downregulation of autophagy can delay MSC senescence, which is inconsistent with most studies that showed autophagy could play a protective role in stem cell senescence. To further study the relationship between autophagy and MSC senescence and explore the effects and mechanisms of premodulated autophagy on MSC senescence, we induced the up- or down-regulation of autophagy by using rapamycin (Rapa) or 3-methyladenine, respectively, before MSC senescence induced by D-galactose (D-gal). Results showed that pretreatment with Rapa for 24 hours remarkably alleviated MSC aging induced by D-gal and inhibited ROS generation. p-Jun N-terminal kinases (JNK) and p-38 expression were also clearly decreased in the Rapa group. Moreover, the protective effect of Rapa on MSC senescence can be abolished by enhancing the level of ROS, and p38 inhibitor can reverse the promoting effect of H₂O₂ on MSC senescence. In summary, the present study indicates that autophagy plays a protective role in MSC senescence induced by D-gal, and ROS/JNK/p38 signalling plays an important mediating role in autophagy-delaying MSC senescence.     

超声引导下经皮微波消融与冷冻消融治疗高风险部位肝癌的对照研究

目的：比较超声引导下经皮微波消融与冷冻消融治疗高风险部位肝癌的临床结局及术后并发症,并分析影响预后和术后复发的因素。 方法：选取2014年4月至2018年3月广州复大肿瘤医院收治的120例高风险部位肝癌患者,其中64例接受微波消融治疗（微波组）,56例接受冷冻消融治疗（冷冻组）。比较两组的治疗结局,主要包括生存、复发及术后并发症。用Cox回归模型分析预后和术后复发的影响因素。 结果：微波消融组1、3、5年总生存率分别为85.8%、63.5%、63.5%,冷冻消融组为92.0%、87.4%、74.9%,两组差异无统计学意义（P=0.141）。微波消融组1、3、5年无复发生存率分别为77.8%、49.0%、49.0%,冷冻消融组分别为81.4%、58.5%、46.8%,两组差异无统计学意义（P=0.469）。微波消融组的3、6、9、12个月的局部进展率分别为3.1%、6.3%、9.4%、15.9%,高于冷冻消融组（分别为0%、0%、3.7%、19.0%）,差异有统计学意义（P=0.003）。微波组的主要和次要并发症发生率（分别为6.3%、82.8%）均高于冷冻组（分别为0%、32.1%）,差异有统计学意义。年龄≥65岁,直径3~5 cm及Child-Pugh分级B级是肝癌术后预后较差的危险因素;直径3~5 cm、多个肿瘤以及多次消融是消融术后复发的危险因素。 结论：冷冻消融治疗高风险部位的肝癌具有与微波消融接近的生存结局,但具有更好的局部肿瘤控制率及更少的并发症,适合在临床中推广应用。     

负压封闭引流治疗深度烧伤创面及对炎性因子、致痛因子的影响

目的研究负压封闭引流(VSD)治疗深度烧伤创面(DBW)及对血清炎性因子、致痛因子的影响。方法 2015年1月—2017年12月内江市第一人民医院治疗DBW患者106例,其中男性69例,女性37例;年龄25～59岁,平均44. 5岁;受伤至入院时间0. 5～13d,平均5. 65d。致伤原因:火烧伤75例,热液烧伤31例。按照治疗方法分为VSD组(n=53)和对照组(n=53),VSD组行VSD+游离植皮治疗,对照组行常规清创换药+游离植皮治疗。治疗7d后观察两组创面愈合率及视觉模拟疼痛评分(VAS)、创面完全愈合时间、住院时间、住院费用,治疗前及治疗后7d血清超敏C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白介素-8(IL-8)、补体C3a等炎性因子及血清5-羟色胺(5-HT)、脑内神经肽(NPY)、前列腺素E2(PGE2)等致痛因子水平。结果治疗后7d VSD组创面愈合率大于对照组[(80. 86±9. 12)%vs.(69. 58±7. 30)%],疼痛评分、创面完全愈合时间、住院时间及住院费用均少于对照组[(2. 78±0. 29)分vs.(5. 79±0. 62)分,(19. 26±2. 04) d vs.(25. 74±2. 65) d,(23. 63±2. 44) d vs.(30. 51±3. 19) d,(3. 29±0. 35)万元vs.(3. 92±0. 41)万元](P <0. 05)]。治疗后7d,VSD组血清CRP、TNF-α、IL-8、补体C3a及5-HT、NPY、PGE2水平均低于对照组[(8. 92±9. 93) mg/L vs.(18. 87±1. 96) mg/L,(35. 74±3. 61)μg/L vs.(67. 94±6. 88)μg/L,(32. 92±4. 37)μg/L vs.(60. 76±6. 19)μg/L,(13. 52±1. 50)μg/L vs.(16. 77±1. 72)μg/L,(109. 92±10. 16) ng/L vs.(143. 97±15. 22) ng/L,(112. 86±11. 41)μg/L vs.(154. 37±16. 03)μg/L,(121. 33±12. 42) pg/m L vs.(186. 93±18. 72) pg/m L,P <0. 05)]。结论 VSD可促进DBW愈合,降低炎性因子及致痛因子水平,患者康复快。     

Synthesis and preliminary evaluation of a 99mTc‐labeled folate‐PAMAM dendrimer for FR imaging

Folate receptor is an ideal target for tumor‐specific diagnostic and therapeutic. The aim of this study was to synthesize ^99mTc‐labeled folate‐polyamidoamine dendrimer modified with 2‐hydrazinonicotinic acid (^99mTc‐HP ₃FA ) for FR imaging. The ^99mTc‐HP ₃FA conjugate was prepared using N‐tris‐(hydroxymethyl)‐methylglycine and trisodium triphenylphosphine‐3,3′,3″‐trisulfonate as coligands. Physicochemical properties, in vitro cell uptake study, and in vivo micro‐single‐photon emission computed tomography/CT imaging were performed. The radiolabeled ^99mTc‐HP ₃FA conjugate was prepared with high radiolabeling yield, good stability, and water solubility (logP  = ?1.70 ± 0.21). In cell uptake study, the radiolabeled conjugate showed high uptakes in the FR ‐abundant KB cells and could be blocked significantly by excess folic acid. The 7721 cells which served as control group substantially had no uptakes. The results of micro‐single‐photon emission computed tomography/CT imaging exhibited that high accumulation of activity was found in FR ‐overexpressed KB tumor, and the tumor‐to‐muscle ratio was approximately 25.78, while, using free FA as inhibitor, the uptakes of ^99mTc‐HP ₃FA in KB tumor and kidney were obviously inhibited. In summary, a new radiocompound was synthesized successfully with specific FR targeting ability. The feasibility of ^99mTc‐HP ₃FA for early diagnosis of FR ‐positive tumors with non‐invasive single‐photon emission computed tomography imaging was demonstrated and the possibility of imaging‐guided drug delivery based on multifunctional polyamidoamine will be studied in the future.     

基于UPLC-MS/MS联用微透析技术的三七总皂苷在帕金森病小鼠模型中的药动学和药效学研究

目的探究1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)模型小鼠以三七总皂苷干预后,脑微透析液中三七皂苷R1(R1)、人参皂苷Rg1(Rg1)和氨基酸神经递质的含量变化。方法给小鼠ip MPTP造成PD小鼠模型,经iv三七总皂苷(PNS)溶液后,采用微透析技术采集脑微透析液。将样品分为2部分,一部分采用UPLC-MS/MS对R1和Rg1进行药动学研究,另一部分采用氨基酸柱前衍生化和HPLC-FLD进行药效学研究。结果小鼠iv PNS后,脑微透析液中R1的峰浓度(Cmax)为(35.48±24.4)ng/mL,Rg1的Cmax为(75.61±41.35)ng/m L。R1和Rg1的达峰时间(tmax)均为1.75 h。R1和Rg1的药时曲线下面积(AUC)分别为(100.12±84.29)ng·h/m L和(218.84±144.73)ng·h/m L。且给予PNS后的PD模型小鼠体内天冬氨酸和谷氨酸浓度降低,甘氨酸、牛磺酸和γ-氨基丁酸浓度增加。结论 PNS能一定程度透过血脑屏障(BBB)进入脑内,调节PD模型小鼠体内氨基酸水平的失衡,进而发挥神经保护作用。     

浙江省中学生焦虑抑郁症状共病状况分析

目的 对浙江省中学生焦虑抑郁症状共病的流行特征进行分析,为制定防治策略及评估干预效果提供依据。方法 采用多阶段分层整群抽样和自我管理式问卷调查方法,于2022年4-6月对浙江省30个市（县、区）376所学校的28 043名初中、普通高中和非普通高中的学生采用统一的问卷进行匿名调查。焦虑症状判定采用广泛性焦虑量表,抑郁症状判定采用患者健康问卷抑郁量表,最终纳入分析27 004名。结果 中学生焦虑抑郁症状共病率为11.54%（95%CI：10.90%~12.19%）,女生（15.42%,95%CI：14.47%~16.38%）高于男生（8.05%,95%CI：7.43%~8.67%）（P<0.001）;农村（12.35%,95%CI：11.49%~13.22%）高于城市（10.06%,95%CI：9.27%~10.86%）（P<0.001）;初中、普通高中和非普通高中学生共病率分别为11.73%（95%CI：10.82%~12.64%）、12.49%（95%CI：11.20%~13.79%）和9.98%（95%CI：8.68%~11.27%）（P=0.025）;离异/丧偶/分居家庭的学生共病率（16.64%,95%CI：14.86%~18.43%）高于在婚家庭（10.82%,95%CI：10.14%~11.50%）（P<0.001）;家庭经济状况越好,共病率越低（P<0.001）;过去30 d吸烟者共病率（21.70%,95%CI：18.24%~25.16%）高于未吸烟者（11.13%,95%CI：10.51%~11.76%）;过去30 d饮酒者共病率（19.36%,95%CI：17.58%~21.14%）高于未饮酒者（10.05%,95%CI：9.43%~10.68%）;共病率随每周体育活动天数增加而降低（P<0.001）;自报学习成绩越差的学生,共病率越高（P<0.001）;过去12个月参与过打架者共病率（18.42%,95%CI：16.75%~20.09%）高于未参与过者（10.45%,95%CI：9.81%~11.10%）。结论 浙江省中学生焦虑抑郁症状共病率较高,应关注中学生心理健康。     

小儿化脓性脑膜炎脑脊液中HBP和VE-cadherin的水平变化及其对预后的预测价值

目的 探讨小儿化脓性脑膜炎脑脊液肝素结合蛋白(Heparin-binding protein,HBP)和血管内皮细胞钙黏蛋白(Vascular endothelial-cadherin,VE-cadherin)的水平变化及其对预后的预测价值。方法 选取2019年2月-2021年本院收治的化脓性脑膜炎患儿106例[(Purulent meningitis,PM)组]和病毒性脑炎患儿75例[(Vascular endothelial,VE)组],同时选取60例在本院就诊的非感染性疾病患儿作为对照组; 比较3组患儿脑脊液HBP,VE-cadherin水平变化; 将PM组患儿依据出院时格拉斯哥预后评分(Glasgow outcome scale,GOS)标准分为预后良好组和预后不良组,对比预后良好组和预后不良组患儿脑脊液HBP,VE-cadherin水平以及其他可能的影响因素; 采用Logistic回归分析法明确影响化脓性脑膜炎患儿预后不良的危险因素; 绘制受试者工作特征(ROC)曲线,分析脑脊液HBP,VE-cadherin水平对化脓性脑膜炎患儿预后不良的预测价值。结果 入院第1 d PM组、VE组患儿脑脊液HBP,VE-cadherin水平均高于对照组(P<0.05); PM组患儿脑脊液HBP,VE-cadherin水平均高于VE组(P<0.05)。治疗后PM组与VE组患儿脑脊液HBP,VE-cadherin水平均低于入院第1 d(P<0.05),但2组治疗7 d后比较无明显差异(P>0.05)。单因素分析显示,预后不良组休克、意识障碍、脑脊液细菌培养阳性的占比、脑脊液白细胞计数(White blood cell,WBC)、C-反应蛋白(C-reactive protein,CRP)、降钙素原(Procalcitonin,PCT)、HBP(入院第1 d与治疗7 d后)、VE-cadherin(入院第1 d与治疗7 d后)水平高于预后良好组(P<0.05)。经Logistic回归分析显示,休克、意识障碍、HBP(入院第1 d与治疗7 d后)、VE-cadherin(入院第1 d与治疗7 d后)水平均是化脓性脑膜炎患儿预后不良的危险因素(P<0.05)。受试者工作特征(Receiver operating characteristic,ROC)曲线分析显示,入院第1 d脑脊液HBP联合VE-cadherin水平预测化脓性脑膜炎患儿预后不良的灵敏度、准确度、曲线下面积(Areaunder the curve,AUC)分别为93.57%、92.16%、0.915,均高于脑脊液HBP,VE-cadherin单独预测; 治疗7 d后脑脊液HBP联合VE-cadherin水平预测化脓性脑膜炎患儿预后不良的灵敏度、准确度、曲线下面积(AUC)分别为96.89%、95.71%、0.931,均高于脑脊液HBP,VE-cadherin单独预测。结论 在化脓性脑膜炎患儿中脑脊液HBP,VE-cadherin水平异常升高,且是导致化脓性脑膜炎患儿预后不良的危险因素,对小儿化脓性脑膜炎的预后具有较高的预测价值。