阑尾源性腹膜假黏液瘤单中心诊疗经验

目的:总结细胞减灭术加腹腔热灌注化疗(cytoreductive surgery&hyperthermic intraperitoneal chemotherapy,CRS+HIPEC)治疗阑尾源性腹膜假黏液瘤(pseudomyxoma peritonei,PMP)的单中心诊疗经验。方法:回顾性分析2012年1月至2018年12月于航天中心医院收治,病理证实为阑尾源性PMP并经CRS+HIPEC治疗604例患者的临床数据,进行统计学分析。结果:604例患者经历621次CRS+HIPEC治疗,平均年龄56.7岁,其中女性364例(60.3%),男性240例(39.7%),平均腹膜癌指数(peritoneal cancer index,PCI)为25.7。28.5%(172/604)的患者完全减瘤(CCR 0/1)。3～4级不良事件发生率为21.7%(131/604),围手术期死亡率为0.7%(4/604),术后5年生存率为53.6%。高级别病理类型、不完全减瘤(CCR 2/3)、PCI>20、3～4级不良事件是PMP患者预后不良的独立危险因素。结论:阑尾源性PMP临床罕见,...     

Epidemiology and risk factors of colorectal cancer in China

In China, colorectal cancer(CRC) ranked fourth and fifth in the highest incidence and mortality rates of all malignancies in 2018, respectively. Although these rates are below the world average, China placed first worldwide in the number of new CRC cases and CRC-related deaths because of its comparatively large population. This disease represents a threat to the health of population and incurs a heavy economic burden on the society and individuals. CRC has various risk factors, including age, se...     

透壁穿刺与经乳头引流对胰管断裂综合征的远期疗效观察

目的　探讨3种内镜治疗方式（透壁穿刺引流、经乳头胰管支架引流及联合引流）对胰管断裂综合征复发的影响。方法　收集2018年1月至2022年12月北京协和医院消化内科收治的确诊为胰管断裂综合征并行内镜下治疗的患者22例。通过回顾患者病历资料以及对患者进行电话随访,记录患者的临床特征、影像学特征、引流方式、并发症、治疗效果等。结果　22例患者共有27例次内镜治疗事件,根据操作方式分为3组：囊肿透壁穿刺引流组11例次,经乳头胰管支架引流组8例次,联合引流组8例次。联合引流组引流成功率100.0%（8/8）,明显高于经乳头胰管支架引流组的50.0%（4/8）（P=0.012）,但与透壁穿刺引流组的90.9%（10/11）相比,差异无统计学意义（P=0.621）。联合引流组的1年复发率0.0%（0/8）,显著低于单纯透壁穿刺引流组的55.6%（5/9）（P=0.018）,而且低于经乳头胰管支架引流组的42.9%（3/7）,但差异无统计学意义（P=0.085）。3组的临床症状缓解率分别为45.5%（5/11）、75.0%（6/8）和87.5%（7/8）,差异无统计学意义（H=3.890,P=0.143）,操作并发症发生率分别为54.5%（6/11）、75.0%（6/8）和25.0%（2/8）,差异无统计学意义（H=3.909,P=0.142）。结论　囊肿透壁穿刺引流联合胰管支架置入可在短期内获得满意的囊液引流效果,并显著减少1年复发。     

Mini-dCas13X–mediated RNA editing restores dystrophin expression in a humanized mouse model of Duchenne muscular dystrophy

Approximately 10% of monogenic diseases are caused by nonsense point mutations that generate premature termination codons (PTCs), resulting in a truncated protein and nonsense-mediated decay of the mutant mRNAs. Here, we demonstrate a mini-dCas13X–mediated RNA adenine base editing (mxABE) strategy to treat nonsense mutation–related monogenic diseases via A-to-G editing in a genetically humanized mouse model of Duchenne muscular dystrophy (DMD). Initially, we identified a nonsense point mutation (c.4174C>T, p.Gln1392*) in the DMD gene of a patient and validated its pathogenicity in humanized mice. In this model, mxABE packaged in a single adeno-associated virus (AAV) reached A-to-G editing rates up to 84% in vivo, at least 20-fold greater than rates reported in previous studies using other RNA editing modalities. Furthermore, mxABE restored robust expression of dystrophin protein to over 50% of WT levels by enabling PTC read-through in multiple muscle tissues. Importantly, systemic delivery of mxABE by AAV also rescued dystrophin expression to averages of 37%, 6%, and 54% of WT levels in the diaphragm, tibialis anterior, and heart muscle, respectively, as well as rescued muscle function. Our data strongly suggest that mxABE-based strategies may be a viable new treatment modality for DMD and other monogenic diseases.     

99Tcm-3PRGD2 SPECT/CT显像在不摄碘进展性放射性碘难治性分化型甲状腺癌中的诊断价值

目的 评价99Tcm-甲苯磺酸钠烟酰胺腙聚乙二醇双环精氨酸-甘氨酸-天冬氨酸肽（简称99Tcm-3PRGD2） SPECT/CT显像对不摄碘进展性放射性碘难治性分化型甲状腺癌（RAIR-DTC）的诊断效能。 方法 前瞻性选择2019年10月至2022年5月在福建省立医院行99Tcm-3PRGD2 SPECT/CT检查的59例RAIR-DTC患者,其中男性17例、女性42例,中位年龄为51（28,80）岁。所有患者均行99Tcm-3PRGD2 SPECT/CT显像,其中22例接受酪氨酸激酶抑制剂（TKI）治疗,37例接受促甲状腺激素（TSH）抑制治疗（13例在2周内接受了18F-FDG PET/CT显像）。取每例患者最大病灶的最大标准化摄取值（SUVmax）进行分析。采用ROC曲线评估99Tcm-3PRGD2 SPECT/CT显像的诊断效能并计算99Tcm-3PRGD2 SPECT/CT显像检出RAIR-DTC病灶的SUVmax临界值;采用Pearson相关分析法分析病灶长径（TL）、刺激性甲状腺球蛋白（sTg）水平与SUVmax的相关性;采用配对t检验比较分析RAIR-DTC患者TKI治疗前后sTg水平、SUVmax、TL间的关系;采用Spearman分析法分析99Tcm-3PRGD2 SPECT/CT显像与18F-FDG PET/CT显像在检出阳性病灶的SUVmax之间的关系。 结果 59例RAIR-DTC患者的276个病灶被纳入分析,其中TKI治疗前后对比病灶59个。99Tcm-3PRGD2 SPECT/CT显像对RAIR-DTC病灶诊断的灵敏度和特异度分别为94.9% （95%CI：90.7%~97.3%）和88.7%（95%CI：77.5%~95.0%）。ROC曲线结果显示,99Tcm-3PRGD2 SPECT/CT显像检出RAIR-DTC病灶的SUVmax临界值为2.70。Pearson相关分析结果显示,靶病灶的SUVmax与sTg水平、TL均呈正相关（r=0.811、0.635,均P=0.001）。22例患者经TKI治疗后,RAIR-DTC病灶的SUVmax显著降低（t=11.027,P=0.001）。Spearman相关分析结果显示,99Tcm-3PRGD2 SPECT/CT显像与18F-FDG PET/CT显像在检出阳性病灶的SUVmax间呈正相关（r=0.560,P=0.001）,且ROC曲线分析结果显示,99Tcm-3PRGD2 SPECT/CT显像对RAIR-DTC病灶的诊断效能与18F-FDG PET/CT显像的差异无统计学意义（Z=0.312,P=0.753）。 结论 99Tcm-3PRGD2 SPECT/CT显像对不摄碘进展性RAIR-DTC的诊断具有较高的灵敏度和特异度,与18F-FDG PET/CT显像相似。     

134例老年急性髓系白血病的临床特点及预后分析

  目的  分析老年急性髓系白血病（acute myeloid leukemia,AML）（非早幼粒细胞白血病）的临床特点,治疗方式以及疗效和预后特点。  方法  收集2015年1月至2023年2月北京大学国际医院收治的134例老年AML患者资料,回顾性分析患者初诊时的白细胞计数、骨髓原始细胞计数、细胞遗传学及分子学特点、ELN危险分层,根据不同治疗方案将患者分为高强度化疗组和低剂量治疗组,观察在治疗过程中强化疗是否能给患者带来生存获益以及影响老年患者生存的因素。  结果  高强度化疗患者36例,22例完全缓解（complete response,CR）（61.1%）,低剂量治疗90例中46例获得CR（51.1%）,其中19例阿扎胞苷（AZA）联合维奈克拉（VEN）治疗换着中14例获得CR（73.7%）;高强度化疗与低剂量治疗的总生存期（overall survival,OS）分别为15个月和14.5个月（P=0.226）。欧洲白血病网（ELN）危险分层低、中、高危组患者OS分别为18、14、9个月（P=0.009）,低危组高强度化疗和低剂量治疗的OS分别为22个月和15个月（P=0.745）,中危组分别为9个月和15个月（P=0.783）,高危组分别为9个月和8个月（P=0.739）。强化疗（36例）与阿扎胞苷+维奈克拉治疗（19例）相比OS分别为15个月和17个月（P=0.689）。TP53基因突变者6例,预后明显差于无突变者,中位生存期分别为2个月和14个月（P=0.004）。低、中、高危患者的1年生存率为79%、53%和44%,3年生存率分别为41%、20%和3%。多因素分析显示外周血高白细胞计数（P=0.034）、ELN危险分层（P=0.002）、合并症（P=0.017）与OS相关,而治疗强度、年龄、性别、骨髓原始细胞计数与OS 无明显相关性。  结论  高强度化疗在老年AML中没有显示明显的生存获益,但这一结果在低危患者中有待于进一步观察。TP53突变者预后较差。多因素分析预测老年AML的生存期时,基线的分子学特征、白细胞计数、合并症比治疗强度更重要。     

CircSMAD2 accelerates endometrial cancer cell proliferation and metastasis by regulating the miR-1277-5p/MFGE8 axis

ObjectiveEndometrial cancer (EC) is a common gynecological malignant tumor. CircRNAs play crucial roles in cancer progression and metastasis. However, the biological functions of circRNAs in EC remain largely unknown.MethodsCircSMAD2, miR-1277-5p, MFGE8 and relative maker protein expression in EC tissues or cell lines were analyzed by quantitative real-time polymerase chain reaction and Western blot. In vitro and in vivo functional assays, including EDU, CCK8, colony formation, transwell, tube formation and tumor xenograft assays, were conduct to explore the effects of circSMAD2 on EC. Mechanism assays were conducted to confirm the binding between miR-1277-5p and circSMAD2 or MFGE8 expression.ResultsUpregulation of circSMAD2 was uncovered in both EC tissues and cell lines. Functionally, silencing of circSMAD2 apparently inhibited the proliferation, migration, invasion and angiogenesis of EC cell lines in vitro. Mechanistically, circSMAD2 sponged miR-1277-5p to upregulate MFGE8 expression. The decrease of miR-1277-5p and increase of MFGE8 were observed both in EC tissues and cell lines. Then MFGE8 knockdown or miR-1277-5p upregulation suppressed EC cell oncogenic biological behavior. Rescue experiments showed that miR-1277-5p mimics countervailed the anticancer effects of circSMAD2 silencing on EC. Besides that, MFGE8 overexpression also attenuated the inhibitory action of miR-1277-5p mimic in EC. Moreover, knockdown of circSMAD2 inhibited EC growth in vivo.ConclusionCircSMAD2 functions as an oncogene in promoting the progression of EC through miR-1277-5p/MFGE8 axis.     

Respiratory syncytial virus disease burden in adults aged 60 years and older in high‐income countries: A systematic literature review and meta‐analysis

BackgroundRespiratory syncytial virus (RSV)‐associated acute respiratory infection (ARI) is an underrecognized cause of illness in older adults. We conducted a systematic literature review and meta‐analysis to estimate the RSV disease burden in adults ≥60 years in high‐income countries.MethodsData on RSV‐ARI and hospitalization attack rates and in‐hospital case fatality rates (hCFR) in adults ≥60 years from the United States, Canada, European countries, Japan, and South Korea were collected based on a systematic literature search (January 1, 2000–November 3, 2021) or via other methods (citation search, unpublished studies cited by a previous meta‐analysis, gray literature, and an RSV‐specific abstract booklet). A random effects meta‐analysis was performed on estimates from the included studies.ResultsTwenty‐one studies were included in the meta‐analysis. The pooled estimates were 1.62% (95% confidence interval [CI]: 0.84–3.08) for RSV‐ARI attack rate, 0.15% (95% CI: 0.09–0.22) for hospitalization attack rate, and 7.13% (95% CI: 5.40–9.36) for hCFR. In 2019, this would translate into approximately 5.2 million cases, 470,000 hospitalizations, and 33,000 in‐hospital deaths in ≥60‐year‐old adults in high‐income countries.ConclusionsRSV disease burden in adults aged ≥60 years in high‐income countries is higher than previously estimated, highlighting the need for RSV prophylaxis in this age group.     

Influence of Cold Atmospheric Plasma on Surface Characteristics and Bond Strength of a Resin Nanoceramic

The purpose of this study was to investigate the effect of cold atmospheric plasma (CAP) treatment on resin nanoceramic (RNC) surface state and its bond strength with resin cement. RNC with different surface treatments were prepared: control, sandblasting treatment (SB), hydrofluoric acid etching (HF) and plasma treatment of helium gas (CAP-He) and argon gas (CAP-Ar). The prepared samples were measured by SEM, Ra, Rz, contact angle goniometer, and XPS for surface characteristics. The shear bond test of RNC was examined in nine groups: SB + saline coupling agent (SL), HF + SL, CAP-He/Ar, CAP-He/Ar + SL, SB + CAP-He/Ar + SL, and control. The bond strength between RNC and resin cement was compared using shear bond strength test, before and after thermocycling. After CAP irradiation, the surface topography maintained, while the surface water contact angle was significantly reduced to 10.18° ± 1.36° (CAP-He) and 7.58° ± 1.79° (CAP-Ar). The removal of carbon contamination and inducing of oxygen radicals was detected after CAP treatment. The bond strength was improved by CAP treatment, but varied on CAP gas species and combination methods. CAP of Ar gas had better SBS than He gas. After thermocycling, CAP-Ar + SL showed the maximized shear bond strength (32.38 ± 1.42 MPa), even higher than SB + SL group (30.08 ± 2.80 MPa, p < 0.05). In conclusion, CAP treatment of helium and argon can improve the bonding properties of RNC by improving surface wettability, and CAP of argon gas combined with silane coupling agent shows the highest bond strength.