阳和汤联合唑来膦酸治疗肺癌骨转移癌痛的疗效及对血清NTX、ALP的影响

目的 探讨阳和汤联合唑来膦酸治疗肺癌骨转移瘤癌痛的疗效及对血清NTX、ALP的影响。方法 采用完全随机法将84例患者随机分为对照组和观察组,各42例。对照组予以唑来膦酸治疗,观察组在对照组的基础上加用阳和汤。通过对比治疗前后癌痛的疗效、疼痛VAS评分、血清NTX及ALP水平、卡氏功能（KPS）评分、不良反应等,比较两组治疗方法的疗效差异。结果 治疗后两组癌痛治疗有效率比较,观察组为78.5%,对照组为54.7%,差异有统计学意义（P<0.05）,治疗后两组患者疼痛VAS评分均较治疗前下降,且观察组低于对照组,差异有统计学意义（P<0.05）。治疗后观察组血清骨代谢标志物NTX、ALP水平较对照组明显下降,差异有统计学意义（P<0.05）,治疗后两组患者KPS评分比较,观察组有效率为88.09%,对照组有效率为80.95%,差异无统计学意义（P>0.05）。两组患者不良反应比较,差异无统计学意义（P>0.05）。结论 阳和汤联合唑来膦酸能够有效缓解肺癌骨转移癌痛,并降低血清NTX、ALP水平。     

Evaluating the population measles susceptibility in Tianjin,China

BackgroundMeasles is a highly infectious illness requiring herd immunity of 95% to interrupt transmission. China has not reached elimination goals despite high vaccination coverage. We estimated the population susceptibility against measles in Tianjin, China and to tailor awareness raising activities in the measles elimination plan.MethodsAge-specific measles seroprevalence was evaluated by Enzyme-Linked Immunosorbent Assay (ELISA) on 12,164 individual aged 0–44 years in 2009–2018. Measles IgG avidity testing was performed to confirm the relationship of the waning immunity after vaccination and secondary vaccination failures (SVF) on 324 confirmed measles cases in 2013–2018.Results11,108 samples (91.32%) tested positive for measles IgG, 239 (1.96%) tested as equivocal and 817 (6.72%) were negative. The age distribution of measles cases in Tianjin followed a U-shaped curve and was highest for those at <8 months and again at 20–39 years which correlated closely with the age distribution of measles susceptibility based on measles IgG antibody status (r = 0.72, P < 0.001). The seropositivity rate and antibody geometric mean concentration (GMC) for the 2018 study population were significantly lower (χ² = 7.45, P = 0.006 and t = 12.01, P < 0.001) compared to 2009. The multivariate stepwise logistic regression analysis showed that age and region were the risk factors for both measles seropositivity rate and GMC after vaccination. The proportion of high avidity cases increased with age, being significantly higher in 75.31% of cases in patients aged 30–34 years (χ² = 18.04, P = 0.003).ConclusionsHigh immunization coverage in children alone will not be adequate to realizing sufficient levels of population herd immunity, particularly given that the potential susceptibility window in adult. Implementation of supplemental immunization activity (SIA) targeted to appropriate group aged 30–34 years is recommended.     

青光安对抗青光眼术后滤过道瘢痕化中胶原纤维、α-SMA及FN的影响

目的：观察青光安4种有效组份对抗兔眼青光眼术后滤过道胶原纤维、α-平滑肌肌动蛋白(α-SMA)和纤维连接蛋白(FN)的影响。

方法：将青光安4种有效组份与青光安中药混悬液应用于滤过手术后D组(有效组份1组)、E组(有效组份2组)、F组(有效组份3组)、G组(有效组份4组)、H组(青光安混悬液组),通过与A组(空白对照组)、B组(模型组)和C组(丝裂霉素C组)进行比较,观察青光安4种有效组份与青光安中药混悬液对青光眼术后滤过道瘢痕组织中胶原纤维、α-SMA及FN的影响。

结果：C组、E组、F组、H组胶原纤维面积比值、α-SMA的表达、FN的表达与B组比较均有差异(P<0.05)。

结论：青光安有效组份2、青光安有效组份3、丝裂霉素C以及青光安混悬液通过抑制胶原纤维、α-SMA及FN的表达,表现出明显的抗青光眼术后滤过道瘢痕化的作用。     

Pathological features and survival analysis of gastric cancer patients with positive surgical margins: A large multicenter cohort study

ObjectiveTo investigate the factors related to positive surgical margins of gastric cancer and their correlation with the prognosis of these patients.MethodsThe clinicopathological data of gastric cancer patients undergoing gastrectomy were collected, and the relationship between surgical margins status and patient outcome was analyzed.ResultsA total of 10080 patients were included, among which 311 (3.1%) had positive surgical margins. pT3-4, pN+ and M1 were independent risk factors for positive margins, and a tumor in the middle of the stomach was a protective factor (p < 0.05). The 5-year overall survival (OS) rates of the patients with positive and negative margins after propensity score matching (PSM) were 24.2% and 36.8%, respectively (p < 0.001). For M0 patients, the 5-year OS of the margin-positive patients was lower than that of the margin-negative patients, and was higher than that of patients with M1. For the M1 patients, no statistically significant difference in 5-year OS was noted between patients with positive and negative margins. Age, positive margins, tumor location, pN+, and M1 were independent prognostic factors for OS in patients undergoing gastrectomy, and pN2-3 and M1 stages were independent prognostic factors for patients with positive surgical margins. Postoperative chemotherapy could improve the 5-year OS in pN2-3 and M1 margin-positive patients (p < 0.05).ConclusionThe prognosis of M0 gastric cancer patients with positive surgical margins is poor, and it is recommended that these patients should undergo routine intraoperative frozen-section pathological examination to reduce the risk of positive surgical margins.     

Safety,Clinical Activity,and Pharmacokinetics of Alflutinib (AST2818) in Patients With Advanced NSCLC With EGFR T790M Mutation

IntroductionAlflutinib (AST2818) is a newly developed third-generation EGFR tyrosine kinase inhibitor selective for EGFR-sensitizing and T790M-resistant mutations. We assessed the safety, efficacy, and pharmacokinetics of alflutinib in patients with advanced NSCLC with confirmed EGFR T790M mutation, whose status progressed after the first- or second-generation EGFR tyrosine kinase inhibitor therapy.MethodsIn the dose-escalation (NCT02973763) and dose-expansion (NCT03127449) studies, patients received alflutinib orally until disease progression, unacceptable toxicity, or subject withdrawal. The primary end points were safety, tolerability, and pharmacokinetics for the dose-escalation study and the objective response rate (assessed by an independent radiological review committee) for the dose-expansion study.ResultsBetween November 30, 2016, and July 24, 2018, a total of 130 patients (14 in dose escalation, 116 in dose expansion) received alflutinib treatment (20 mg, 40 mg, 80 mg, 160 mg, or 240 mg once daily). On October 30, 2018, 79 patients (61%) remained on the treatment. No dose-limiting toxicities were observed in the dose-escalation study. In the dose-expansion study (40–240 mg), the overall objective response rate was 76.7% (89 of 116), and it was 70.6% in patients with central nervous system metastases (12 of 17). A total of 79% of all patients had possibly treatment-related adverse events (AEs) (103 of 130); 8% had treatment-related grade 3 or higher AEs (11 of 130). Serious AEs were reported in 15% of patients (20 of 130), and two serious AEs were related to treatment. No clear dose-response (antitumor activity and AEs) relationships were observed. Exposures to alflutinib and its active metabolite (AST5902) were comparable at steady state.ConclusionsAlflutinib was clinically effective with an acceptable toxicity profile in patients with advanced NSCLC (including those with central nervous system metastases) with EGFR T790M mutation. Further investigation is ongoing.     

Real-world treatment patterns and outcomes of pyrotinib-based therapy in patients with HER2-positive advanced breast cancer (PRETTY): A nationwide,prospective, observational study

Pyrotinib, an irreversible pan-ErbB inhibitor, has been approved for treating HER2-positive advanced breast cancer in China. We conducted a nationwide, prospective observational study to examine the real-world data of pyrotinib-based therapy in this population. Patients from 61 sites across China were included. Pyrotinib-based regimens were prescribed at local physician's discretion. Demographics, treatment patterns, prognosis and safety were evaluated. The primary outcome was real-world progression-free survival (rwPFS). Of 1129 patients, pyrotinib-based therapy was prescribed as first-, second- and third- or later-line treatment in 437 (38.7%), 476 (42.2%) and 216 (19.1%) patients, respectively. Median rwPFS (mrwPFS) was 14.3 (95% CI, 13.3-15.2) months in the total population, with the longest mrwPFS of 17.8 (95% CI, 15.2-24.9) months in the first-line setting, followed by 14.4 (95% CI, 12.9-15.3) months in the second-line setting. Patients with third- or later-line treatment also achieved a mrwPFS of 9.3 (95% CI, 8.4-11.8) months. Patients with trastuzumab- or trastuzumab-pertuzumab-treated disease achieved a mrwPFS of 14.3 and 13.6 months, respectively. Dual HER2 blockade with pyrotinib plus trastuzumab showed a mrwPFS of 16.2 months in the total population, with data not mature in the first-line setting. For patients with baseline brain metastases, the mrwPFS was 11.7 months. The most common adverse event was diarrhea (any grade, 73.5%; grade ≥ 3, 15.3%). In real world, pyrotinib-based therapy shows promising effectiveness in the first-, as well as second- and later-line treatment, with acceptable tolerability. Further investigations regarding front-line use or novel combinations of pyrotinib might facilitate to maximize its anti-tumor potential.     

The mitochondrial seryl-tRNA synthetase SARS2 modifies onset in spastic paraplegia type 4

PurposeHereditary spastic paraplegia type 4 is extremely variable in age at onset; the same variant can cause onset at birth or in the eighth decade. We recently discovered that missense variants in SPAST, which influences microtubule dynamics, are associated with earlier onset and more severe disease than truncating variants, but even within the early and late-onset groups there remained significant differences in onset. Given the rarity of the condition, we adapted an extreme phenotype approach to identify genetic modifiers of onset.MethodsWe performed a genome-wide association study on 134 patients bearing truncating pathogenic variants in SPAST, divided into early- and late-onset groups (aged ≤15 and ≥45 years, respectively). A replication cohort of 419 included patients carrying either truncating or missense variants. Finally, age at onset was analyzed in the merged cohort (N = 553).ResultsWe found 1 signal associated with earlier age at onset (rs10775533, P = 8.73E-6) in 2 independent cohorts and in the merged cohort (N = 553, Mantel–Cox test, P < .0001). Western blotting in lymphocytes of 20 patients showed that this locus tends to upregulate SARS2 expression in earlier-onset patients.ConclusionSARS2 overexpression lowers the age of onset in hereditary spastic paraplegia type 4. Lowering SARS2 or improving mitochondrial function could thus present viable approaches to therapy.     

Initial evaluation and management of wide-complex tachycardia: A simplified and practical approach

The evaluation and treatment of wide QRS-complex tachycardia remains a challenge, and mismanagement is quite common. Diagnostic aids such as wide-complex tachycardia algorithms perform poorly in the real-life setting. The purpose of this review is to offer a simple clinical-electrocardiographic approach for the initial evaluation and management of the adult patient with stable wide-complex tachycardia that does not require recollection of complex guidelines or algorithms.     

微型腹腔镜治疗学龄前小儿腹股沟疝：附212例报告

目的探讨腹腔镜手术在小儿腹股沟疝治疗的临床效果。方法在全麻下用微型腹腔镜对212例0.5~6岁,平均5.3岁的小儿腹股沟疝进行治疗,对有肠管嵌顿者于肠管还纳,并检查肠管有无缺血、坏死、溃破,行内环口高位结扎。结果212例小儿腹股沟疝均在微型(直径0.3 cm)腹腔镜下完成疝囊高位结扎,无需行肠切除者。212例患儿随访0.5~2年,平均1.2年,无复发病例。结论微型腹腔镜手术治疗小儿腹股沟疝安全可行,创伤小,恢复快。