Improved Prognostication for the Updated AJCC Breast Cancer Pathological Prognostic Staging Varied in Higher-Stage Groups

BackgroundIn addition to TNM-based anatomical staging (AS), a novel pathological prognostic staging (PPS) has been proposed by the American Joint Committee on Cancer (AJCC). PPS demonstrated better prognostication, but its superiority in breast cancer subtypes and related to staging discrepancies between AS and PPS are not clear.MethodsA cohort of 1729 patients with breast cancer was staged into AS and PPS according to the latest AJCC staging. Patient characteristic and restaging outcomes were compared.ResultsCompared with AS, 799 and 135 cases were upstaged and downstaged respectively in PPS, mostly involved stage I cases. For the overall cohort, PPS demonstrated superior prognostic power over AS in both disease-free survival (DFS) and breast cancer–specific survival. However, such superiority was found mainly in estrogen receptor (ER)/progesterone receptor (PR)+ but not ER−PR− cancers. Comparing the restaged cases within the same PPS, PPS 1A cases showed similar survival irrespective of the original AS. Interestingly, in other PPS groups (PPS 1B and higher), there was a difference in outcome among patients with same PPS but different AS. Within PPS 1B patients, downstaged cases from higher AS showed worse DFS (3A>1B vs. 2A>1B: χ² = 4.732, P = .030).ConclusionsPPS may provide a more accurate prognostication, mostly among ER/PR+ cancers and with PPS 1A patients. Patients restaged to higher PPS stages showed significant differential survival even within the same PPS. Also, only limited improvement was observed for ER–PR– cancers. Caution needs to be exercised in using PPS for patient prognostication, as in some cases the outcome can be variable with the same PPS.     

尤昭玲教授辨证治疗子宫切口假腔三步法

尤昭玲教授认为瘀热、邪毒、气虚是子宫切口假腔形成之根本，临床运用中医辨证治疗主要分三步：非经期以“清宫”为主，经前期以“逼宫”为主，经后期以“缩宫”为主。分别使用自拟内炎方加减，妇科外敷包和假腔方加减。该“三步法”在临床应用中疗效显著。     

Hypertensive Crisis during Microwave Ablation of Adrenal Neoplasms: A Retrospective Analysis of Predictive Factors

PurposeTo identify risk factors for hypertensive crisis (HC) during ultrasound-guided percutaneous microwave (MW) ablation of adrenal neoplasms.Materials and MethodsPatients who underwent MW ablation for adrenal tumors between April 2006 and November 2017 were retrospectively identified for this study (51 consecutive patients; 35 males, 16 females; mean age, 55 years; range, 15–85 years). A total of 77 MW ablation treatments were performed for 67 tumors (24 primary [9 pheochromocytomas, 8 adenomas, and 7 cortical carcinomas]; and 43 metastases [22 hepatocellular carcinoma, 8 renal cell carcinoma, 5 non-small cell lung cancer, 4 colorectal cancer, 3 liposarcoma, and 1 malignant fibrous histiocytoma]). The mean diameter of the adrenal tumors was 4.6 cm (range, 1.2–16.2 cm). Information about patient demographics, imaging studies, pathology and laboratory results, procedure records, and clinical outcomes was retrieved and analyzed. Statistical analysis was then performed to determine potential risk factors for HC.ResultsOf the 77 MW ablation procedures, HC occurred in 13 (16.9%). A significantly higher risk of HC was observed in patients with pheochromocytoma (odds ratio [OR], 9.037; 95% confidence interval [CI], 1.731–47.172; P = .009), body mass index <24 kg/m² (OR, 5.167; 95% CI, 1.060–25.194; P = .042), dominant tumor size ≤4.5 cm (OR, 4.023; 95% CI, 1.011–16.005; P = .048), and pre-procedural systolic blood pressure ≥130 mmHg (OR, 0.242; 95% CI, 0.068–0.861; P = .029).ConclusionHC can occur during MW ablation in patients with either primary or metastatic adrenal tumors. Pheochromocytoma, body mass index, tumor size, and pre-procedural systolic blood pressure appear to be significant risk factors for the occurrence of HC.     

Social Determinants of Breastfeeding in the United States

Despite overall improvement in breastfeeding in the past 3 decades in the United States, significant and alarming social disparities persist. Adverse social determinants of health are increasingly recognized as root causes of social disparities in health outcomes, including breastfeeding initiation and continuation. We provide an overview of the evidence and mechanisms by which social determinants of health, including education, employment, food, neighborhood, and housing contribute to ongoing social disparities in breastfeeding in the United States, including current research gaps. We also review the intersection of social determinants of health with income, racism, and theory of planned behavior, a commonly used decision-making framework for breastfeeding promotion. Future interventions to address social determinants of breastfeeding should occur at the policy, community, organization, and individual levels.     

Health Care Providers' Advice on Lifestyle Modification for Older Adults

ObjectivesTo describe the pattern of health care providers' advice on lifestyle modification to older adults, and identify correlates of receiving such advice.DesignCross-sectional survey.Setting and participantsData from the National Health and Nutrition Examination Survey study from 2007-2016 on adults ≥65 years (n = 3758) were analyzed.MethodsWe estimated the weighted prevalence and correlates of receiving advice on the following lifestyle modifications: (1) increase physical activity, (2) reduce fat/calories, (3) control/lose weight, and (4) a combination of control/lose weight and physical activity. Data were analyzed according to level of comorbidity (number of chronic conditions including high blood pressure, high blood cholesterol, type 2 diabetes mellitus, coronary heart disease, and arthritis) and body mass index (BMI).ResultsPhysical activity was the most widely prescribed lifestyle modification, reported by 15.7% of older adults free of chronic conditions and 28.9%, 35.4%, and 52.6% of older adults with 1, 2, and ≥3 comorbidities. Advice on reducing fat/calories was reported by 9.2%, 18.5%, 26.3%, and 40.9% of older adults with 0, 1, 2, and ≥3 comorbidities, respectively, and advice on weight loss/control was reported by 6.5%, 19.1%, 20.8%, and 37.5%, respectively. The combination of advice on weight loss/control and physical activity was least commonly reported: 5.1%, 13.5%, 16.6%, and 32.0%, respectively. Overall, lifestyle modifications were more frequently advised to older adults who were overweight, obese, or Hispanic.Conclusions and implicationsIn the United States, lifestyle modifications are not routinely recommended to older adults, particularly those free of chronic conditions, presenting a missed opportunity for chronic disease prevention and management. Among those advised to lose or manage weight, concurrent advice to increase physical activity is not consistently provided.     

腹腔镜下腹壁疝腹膜外补片修补术与腹腔内补片修补术比较的多中心回顾性研究

背景与目的 腹壁疝修补术是最常见的外科手术之一,全球每年有200万例左右的腹壁疝患者接受手术治疗。与开放手术相比,腹腔镜下腹壁疝修补术优势明显。然而腹腔镜下腹腔内补片修补术（IPOM）与腹腔镜下腹膜外补片修补术（ESR）这两种腔镜术式的优缺点及疗效如何,尚无大样本的临床研究证实。因此,本研究通过比较ESR与IPOM两种手术方式治疗腹壁疝的近远期疗效,为临床提供循证参考。方法 回顾性分析2017年1月1日—2022年12月31日湖南省11家医疗机构收治的157例行腹腔镜腹壁疝修补术患者的临床资料,其中124例行ESR（ESR组）,33例行IPOM（IPOM组）,对比分析两组病例的临床特点、手术方式和术后近远期效果。结果 全组无中转开腹病例或围术期死亡病例。两组病例的年龄、性别、BMI、类型差异均无统计学意义（均P>0.05）。两组病例疝环横径、手术时间、术中出血量、疝环闭合概率差异均无统计学意义（均P>0.05）。网片固定方式ESR组以自固定和缝线固定为主（91.1%）,而IPOM组以钉枪固定为主（69.7%）,差异有统计学意义（P<0.05）。ESR组的术后疼痛评分明显低于IPOM组（2.4±0.8 vs. 2.8±1.0,P<0.05）,住院费用明显低于IPOM组（21 001元vs. 38 437元,P<0.05）。两组的术后住院时间和近期并发症发生率差异无统计学意义（均P>0.05）。中位随访10.3个月,ESR组无复发病例,IPOM组2例复发（6.1%）,差异有统计学意义（P<0.05）。结论 ESR是湖南地区腹腔镜下腹壁疝修补的主流术式之一。由于固定方式和网片选择的不同,ESR较之IPOM而言,术后疼痛更轻微、费用更低、复发率更低,且并不明显增加手术时间和术后近期并发症。     

MR T2 mapping成像评估止痛健骨方治疗膝骨性关节炎关节软骨损伤疗效的实验研究

目的探讨MR T2mapping成像评价止痛健骨方治疗骨性关节炎软骨损伤疗效的价值。方法采用木瓜蛋白酶关节腔注射法制作新西兰大白兔膝骨关节炎模型,根据治疗方法不同将48只新西兰大白兔随机分为正常对照组、模型对照组、盐酸氨基葡萄糖治疗组、止痛健骨方治疗组。各组治疗4周后行膝关节MR T2mapping成像并对关节软骨基质金属蛋白酶1(MMP-1)含量进行免疫组化分析。比较各组间关节软骨T2值及关节软骨MMP-1含量的差异,并分析不同干预方法、关节软骨MMP-1含量与关节软骨T2值的相关性。结果模型对照组关节软骨T2值高于其他3组(P均0.01),其他3组间关节软骨T2值差异无统计学意义。盐酸氨基葡萄糖治疗模型组、止痛健骨方治疗模型组间关节软骨MMP-1含量差异无统计学意义,但2组关节软骨的MMP-1含量低于模型对照组(P均0.05)、高于正常对照组(P均0.05)。关节软骨MMP-1含量与T2值间为非线性关系,随着前者的升高,后者先缓慢上升再快速上升(P0.05)。结论 MR T2mapping成像有助于评价止痛健骨方治疗模型兔骨关节炎软骨损伤的疗效,关节软骨MMP-1含量与T2值间可能为非线性关系。     

Synergistic effects of autophagy/mitophagy inhibitors and magnolol promote apoptosis and antitumor efficacy

Mitochondria as a signaling platform play crucial roles in deciding cell fate. Many classic anticancer agents are known to trigger cell death through induction of mitochondrial damage. Mitophagy, one selective autophagy, is the key mitochondrial quality control that effectively removes damaged mitochondria. However, the precise roles of mitophagy in tumorigenesis and anticancer agent treatment remain largely unclear. Here, we examined the functional implication of mitophagy in the anticancer properties of magnolol, a natural product isolated from herbal Magnolia officinalis. First, we found that magnolol induces mitochondrial depolarization, causes excessive mitochondrial fragmentation, and increases mitochondrial reactive oxygen species (mtROS). Second, magnolol induces PTEN-induced putative kinase protein 1 (PINK1)‒Parkin-mediated mitophagy through regulating two positive feedforward amplification loops. Third, magnolol triggers cancer cell death and inhibits neuroblastoma tumor growth via the intrinsic apoptosis pathway. Moreover, magnolol prolongs the survival time of tumor-bearing mice. Finally, inhibition of mitophagy by PINK1/Parkin knockdown or using inhibitors targeting different autophagy/mitophagy stages significantly promotes magnolol-induced cell death and enhances magnolol's anticancer efficacy, both in vitro and in vivo. Altogether, our study demonstrates that magnolol can induce autophagy/mitophagy and apoptosis, whereas blockage of autophagy/mitophagy remarkably enhances the anticancer efficacy of magnolol, suggesting that targeting mitophagy may be a promising strategy to overcome chemoresistance and improve anticancer therapy.     

伊班膦酸钠对大鼠膝骨关节炎关节软骨及软骨下骨的影响

目的观察伊班膦酸钠对大鼠膝骨关节炎关节软骨及软骨下骨的影响,并从MAPKs信号通路探讨其作用机制。方法将30只3月龄SD雄性大鼠随机分成3组(每组10只)。假手术组、前交叉韧带切断术组(ACLT组)、前交叉韧带切断术+伊班膦酸钠治疗组(治疗组)。其中ACLT组及治疗组均行ACLT术(膝关节前交叉韧带切断术)处理。术后1w,治疗组予以腹腔注射伊班膦酸钠10μg/kg,1 w 1次,共12 w;ACLT组腹腔注射生理盐水,剂量参照伊班膦酸钠,1w 1次,共12 w。12 w后处死动物,对关节软骨行Mankin评分、软骨下骨显微CT及骨组织定量分析、以及对MAPKs信号通路和MMP-13 mRNA表达水平进行分析。结果 1ACLT组的骨体积分数(BV/TV)、骨小梁数量(Tb.N)显著低于假手术组(P0.05、P0.05),骨小梁厚度(Tb.Th)两组之间差异无明显统计学意义、而骨小梁间隔(Tb.Sp)显著高于假手术组(P0.01);治疗组骨体积分数(BV/TV)、骨小梁数量(Tb.N)明显高于ACLT组(P0.05、P0.05),骨小梁厚度(Tb.Th)两组之间差异无明显统计学意义,而骨小梁间隔(Tb.Sp)显著低于ACLT组(P0.05)。2ACLT组的Mankin评分明显高于假手术组(P0.01);治疗组的Mankin评分明显低于ACLT组(P0.05)。3ACLT组中MAPKs信号通路(C-JUN、ERK1及P38)和MMP-13水平明显高于假手术组(P0.01、P0.01、P0.01、P0.01);治疗组的MAPKs信号通路(C-JUN、ERK1及P38)和MMP-13水平明显低于ACLT组(P0.01、P0.01、P0.01、P0.01)。结论伊班膦酸钠可能通过调控MAPKs信号通路的机制缓解大鼠膝骨关节炎关节软骨退变,并且抑制软骨下骨的骨质疏松。     

古汉养生精对肾阳虚哮喘大鼠表达P62、TGF-β1的影响

目的探讨古汉养生精对肾阳虚哮喘大鼠P62、转化生长因子-β1(TGF-β1)表达的影响。方法将30只健康雄性Wistar大鼠随机分成正常组、哮喘组、肾阳虚哮喘组、古汉养生精低、中、高剂量组,每组5只。以氢化可的松制备肾阳虚模型,卵蛋白与氢氧化铝致敏激发制备哮喘模型,造模成功后 通过灌胃方式,各剂量组予以相应剂量古汉养生精,在最后一次激发24 h后,于大鼠左肺切取部分组织,用于行苏木精-伊红(HE)染色,应用图像分析技术测定支气管基底膜周径(Pbm)、支气管管壁面积(Wat)、支气管内壁面积(Wai)、支气管管壁平滑肌面积(Wam),所得数据采用Pbm进行标化,得到Wat/Pbm、Wai/Pbm、Wam/Pbm等重塑指标;取右肺组织使用qRT-PCR检测TGF-β1 mRNA的表达,采用Western blot检测肺组织P62蛋白的表达。结果肾阳虚哮喘组大鼠病理改变较哮喘组大鼠明显,各剂量组较肾阳虚哮喘组大鼠病理改变明显减轻(P＜0.05)。肾阳虚哮喘组Wat/Pbm、Wai/Pbm、Wam/Pbm较哮喘组升高,各剂量组较肾阳虚哮喘组降低(P＜0.05)。肾阳虚哮喘组肺组织中TGF-β1 mRNA表达量较正常组明显上升(P＜0.05),各剂量组TGF-β1 mRNA表达量较肾阳虚哮喘组降低(P＜0.05)。肾阳虚哮喘组P62表达较哮喘组降低,而各剂量组P62表达较肾阳虚哮喘组升高(P＜0.05)。结论古汉养生精对肾阳虚哮喘大鼠的气道重塑有抑制作用,可能机制与调控P62、TGF-β1的表达相关。