Traumatic fractures place a substantial burden on health-care systems worldwide. Although detailed information about incidence, distribution, and risk factors for traumatic fractures is vital for ...planning and prevention, in China, national data are unavailable. We aimed to do an up-to-date national survey on the population-weighted incidence of traumatic fractures in China.
The China National Fracture Study (CNFS) was a retrospective epidemiological study that recruited a nationally representative sample from eight provinces, 24 urban cities, and 24 rural counties in China using stratified random sampling and the probability proportional to size method. All eligible household members who had lived in their current residence for 6 months or longer were personally interviewed by trained research teams about traumatic fractures of the trunk, arms, or legs (not including the skull, sternum, and ribs) that had occurred in 2014. Telephone surveys were used for participants who were non-contactable after repeated visits. Fracture cases were verified by clinical records, medical history, and radiographs by orthopaedic surgeons and radiologists. We estimated incidence rates for traumatic fractures for the overall population and for subgroups by age and sex, as well as by demographic factors such as ethnic origin, occupation, geographical region, and residency category. We also studied potential associations between fractures and various factors of interest, such as age, ethnic origin, education, smoking, alcohol drinking, sleep time per day, and history of previous fracture. Data were weighted during statistical analysis to ascertain the national incidence rate. This study is registered with the Chinese Clinical Trial Registry, number ChiCTR-EPR-15005878.
Between Jan 19, 2015, and May 16, 2015, 535 836 individuals were selected and invited to participate in the study. Questionnaires from 23 649 (4%) individuals were excluded due to missing items, insufficient responses, or logical errors. Following exclusions, 512 187 (96%) individuals participated in the CNFS, consisting of 259 649 (51%) boys and men and 252 538 (49%) girls and women. Of these individuals, 1763 individuals had experienced traumatic fractures during 2014 (n=1833). The population-weighted incidence rate of traumatic fractures of the trunk, arms, or legs was 3·21 (95% CI 2·83–3·59) per 1000 population in 2014 (3·65, 3·12–4·18 in men and 2·75, 2·46–3·04 in women). For all ages, sleeping less than 7 h per day was identified as a risk factor for traumatic fractures. We identified previous fracture history as a risk factor for adults aged 15 years and older. Alcohol consumption incurred a risk effect for men aged 15 years and older and women aged 15–64 years.
Our results provide detailed information about fracture incidence, distribution, and risk factors, which can now be used as an up-to-date clinical evidence base for national health-care planning and preventive efforts in China and elsewhere. Specific public health policies that focus on decreasing alcohol consumption, prohibiting drunk driving, promoting smoking cessation, and encouraging individuals to obtain sufficient sleep and maintain a healthy bodyweight should be urgently implemented to help reduce the risk of traumatic fractures.
The Hebei Province Medical Science Special Major Projects Research Fund.
Curcumin is a major yellow pigment and active component of turmeric widely used as dietary spice and herbal medicine. This compound has been reported to be a promising antitumor agent, although the ...underlying molecular mechanisms are not fully understood yet. In this study, we reported that curcumin inhibited growth of lung adenocarcinoma cells, but had no cytotoxic activity to IMR-90 normal lung fibroblast cells. Curcumin induced autophagy in the A549 human lung adenocarcinoma cell line, evidenced by LC3 immunofluorescence analysis and immunoblotting assays on LC3 and SQSTM1. Moreover, the autophagy inhibitor 3-MA partly blocked the inhibitory effect of curcumin on the growth of A549 cells. Curcumin markedly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetylCoA carboxylase in A549 cells. At last, pharmacological blockade of the AMPK signaling pathway by compound C and genetic disruption of the AMPK signaling pathway with siRNA-mediated AMPKα1 knockdown impaired the autophagy-inducing effect of curcumin. Collectively, our data suggests that curcumin induces autophagy via activating the AMPK signaling pathway and the autophagy is important for the inhibiting effect of curcumin in lung adenocarcinoma cells.
Despite advances in technology, the bronchoscopic diagnosis of parenchymal pulmonary lesions (PPLs) remains difficult to achieve. Transbronchial lung cryobiopsy (TLCB) offers the potential for larger ...samples with improved diagnostic yield; however, a paucity of data exists describing its safety and usefulness for the diagnosis of PPL.
What is the safety profile of TLCB for PPL?
An observational, retrospective, multicenter cohort study enrolled patients without endobronchial disease undergoing TLCB of PPL from 2015 through 2019. All procedures were performed using both rigid and flexible bronchoscopy with a flexible cryoprobe. Complication rates, including bleeding and pneumothorax rates, were collected. Bleeding was graded on a scale from 0 (trace) to 4 (requiring surgical intervention) with a grade of ≥ 3 considered clinically significant. Pneumothorax, tube thoracostomy placement, diagnostic yield, and need for subsequent interventions were recorded.
One thousand twenty-four patients underwent TLCB. One hundred eighty-eight patients (18%) experienced bleeding; in 36 patients (3.5%), the bleeding was clinically significant. Sixty-eight patients (6.6%) demonstrated a pneumothorax and 64 patients (6.3%) required drainage with tube thoracostomy. All chest drains were removed within 4 days, and no cases of prolonged air leak occurred. A definitive diagnosis was achieved in 932 patients (91%). Adenocarcinoma (46%) and metastatic disease (21%) were the most common diagnoses.
TLCB showed an acceptable safety profile and diagnostic yield for the evaluation of PPL in this large retrospective cohort. Prospective clinical trials are underway to validate these findings further.
The study protocol was approved by the institutional ethics committee of Shanghai Chest Hospital (No. According to the assumptions, 24 procedures are required to verify p0 and 20 to verify p1. The ...results of the analysis showed that the only two factors associated with the diagnostic performance of the ION™ procedure were the r-EBUS view before the first sampling attempt and achievement of a concentric r-EBUS view before and/or during samplings (χ2 = 10.952, P = 0.022 and P = 0.021 Fisher's exact test). ...the graph crossed the lower decision boundary at case 9 during the study period Figure 1D, indicating that proficiency was obtained.
Lessons Learned
The findings of this prospective, single‐arm, phase II study showed that neoadjuvant erlotinib was well tolerated and might improve the radical resection rate in patients with stage ...IIIA‐N2 epidermal growth factor receptor mutation‐positive non‐small cell lung cancer (NSCLC).
Erlotinib shows promise as a neoadjuvant therapy option in this patient population.
Next‐generation sequencing may be useful for predicting outcomes with preoperative tyrosine kinase inhibitors (TKIs) in patients with NSCLC.
Large‐scale randomized controlled trials investigating the role of TKIs in perioperative therapy, combining neoadjuvant and adjuvant treatments to enhance personalized therapy for patients in this precision medicine era, are warranted.
Background
Information on epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as neoadjuvant therapy in non‐small cell lung cancer (NSCLC) is scarce. We evaluated whether neoadjuvant erlotinib improves operability and survival in patients with stage IIIA‐N2 EGFR mutation‐positive NSCLC.
Methods
We conducted a prospective, single‐arm, phase II study. Patients received erlotinib 150 mg per day for 56 days in the neoadjuvant period. The primary endpoint was the radical resection rate.
Results
Nineteen patients were included in the final analysis. After erlotinib treatment, 14 patients underwent surgery. The radical resection rate was 68.4% (13/19) with a 21.1% (4/19) rate of pathological downstaging. The objective response rate was 42.1%; 89.5% (17/19) of patients achieved disease control, with a 10.3‐month median disease‐free survival among patients who underwent surgery. Among all 19 patients who received neoadjuvant therapy, median progression‐free survival (PFS) and overall survival were 11.2 and 51.6 months, respectively. Adverse events (AEs) occurred in 36.8% (7/19) of patients, with the most common AE being rash (26.3%); 15.8% experienced grade 3/4 AEs. Quality of life (QoL) improvements were observed after treatment with erlotinib for almost all QoL assessments. Effects of TP53 mutation on prognosis were evaluated in eight patients with adequate tissue samples. Next‐generation sequencing revealed that most patients had a TP53 gene mutation (7/8) in addition to an EGFR mutation. No TP53 mutation, or very low abundance, was associated with longer PFS (36 and 38 months, respectively), whereas high abundance was associated with short PFS (8 months).
Conclusion
Neoadjuvant erlotinib was well tolerated and may improve the radical resection rate in this patient population. Next‐generation sequencing may predict outcomes with preoperative TKIs.
经验获取
• 本次前瞻性单组 II 期研究结果显示，埃罗替尼新辅助治疗在 IIIA‐N2 期表皮生长因子受体突变阳性非小细胞肺癌 (NSCLC) 患者中的耐受性良好，可以提高根治性切除率。
• 在此患者群体中，埃罗替尼显示出了作为新辅助治疗选择的希望。
• 对于预测 NSCLC 患者的手术前酪氨酸激酶抑制剂 (TKI) 结果而言，下一代测序可能十分有用。
• 为了在这个精准医疗的时代提高患者的个性化治疗水平，开展旨在调查 TKI 在围术期治疗(新辅助治疗与辅助治疗相结合)中作用的大规模随机对照试验很有必要。
摘要
背景。关于表皮生长因子受体 (EGFR) 酪氨酸激酶抑制剂 (TKI) 作为非小细胞肺癌 (NSCLC) 的新辅助治疗的信息十分匮乏。我们对埃罗替尼新辅助治疗能否改进 IIIA‐N2 期 EGFR 突变阳性 NSCLC 患者的可手术性和生存期进行了评估。
方法。我们进行了一项前瞻性单组 II 期研究。在新辅助治疗期间，患者每天服用埃罗替尼 150 mg，连续给药 56 天。主要终点是根治性切除率。
结果。最终分析中包含 19 名患者。在埃罗替尼治疗之后，14 名患者接受手术。根治性切除率为 68.4% (13/19)，病理性降级率为 21.1% (4/19)。客观反应率为 42.1%；89.5% (17/19) 的患者病情得到控制，在接受手术的患者中，中位无病生存期为 10.3 个月。在所有接受新辅助治疗的 19 名患者中，中位无进展生存期 (PFS) 和总体生存期分别为 11.2 个月和 51.6 个月。36.8% (7/19) 的患者出现不良反应 (AE)，最常见的 AE 为皮疹 (26.3%)；15.8% 的患者出现 3/4 级 AE。对于几乎所有的生存质量 (QoL) 评估，在治疗后均观察到了 QoL 改善。我们针对 8 名具有适当组织样本的患者评估了 TP53 突变对预后的影响。下一代测序显示，除 EGFR 突变之外，大多数患者均有 TP53 基因突变 (7/8)。无 TP53 突变或极低丰度与较长的 PFS(分别为 36 个月和 38 个月)相关，而高丰度与短 PFS(8 个月)相关。
结论。埃罗替尼新辅助治疗在此患者群体中的耐受性良好，可以提高根治性切除率。下一代测序可以预测手术前 TKI 的结果。
We report a biocompatible nanomedicine (GFCT) that possesses both H2O2 self-supply and GSH-elimination properties for achieving highly synergistic enhanced CDT and chemotherapy effects by integrating ...iron-doped calcium phosphate nanoparticles with hypoxia-sensitive prodrug (tirapazamine). Such a biocompatible and biodegradable nanomedicine provides a promising nanotheranostics for efficient tumor microenvironment-specific synergistic therapies.
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•A biocompatible iron-doped calcium phosphate-based nanomedicine is proposed for synergistic chemotherapy/chemodynamic therapy.•The engineered GFCT presents H2O2 self-supply and GSH-elimination properties for enhanced CDT efficacy.•This work provides an effective strategy via the integration of TME regulation with TPZ-induced chemotherapy.
Chemodynamic therapy (CDT) has been exploited as an emerging therapeutic modality for cancer treatment. However, insufficient intracellular H2O2 levels and ultrahigh glutathione (GSH) in the tumor microenvironment (TME) severely restrict CDT efficacy. To address these concerns, in this work, a self-reinforcing biodegradable nanotherapeutic was developed to modulate the TME to amplify CDT. The nanotherapeutic (GOD-FeCaP@TPZ, abbreviated GFCT) was fabricated through a mild one-step biomineralization process using the enzyme catalyst glucose oxidase (GOD) as a template to form biodegradable iron-doped calcium phosphate nanoparticles, followed by the loading of the prodrug tirapazamine (TPZ). When GFCT decomposes and releases Fe3+ in the acidic TME, the delivered GOD can effectively catalyze the oxidization of glucose to enhance the subsequent Fenton-like reaction by promoting intracellular acidity (via the production of gluconic acid) and improving the generation of H2O2. Moreover, the released iron constantly depletes GSH by self-cyclic valence alterations in Fe(III) and Fe(II) and then triggers H2O2 to produce •OH through an Fe(II)-mediated Fenton-like reaction. Moreover, the elevated level of hypoxia induced by GOD-mediated glucose oxidization can activate the prodrug TPZ for effective chemotherapy, thus achieving remarkable synergistic therapeutic outcomes. This work provides another paradigm to augment antitumor efficacy via modulation of the TME.
Recently, Professor Chunxue Bai and colleagues have proposed a definition of the Metaverse in Medicine as the medical Internet of Things (MIoT) facilitated using AR and/or VR glasses.
A ...multi-disciplinary panel of doctors and IT experts from Asia, the United States, and Europe analyzed published articles regarding expert consensus on the Medical Internet of Things, with reference to study results in the field of metaverse technology.
It is feasible to implement the three basic functions of the MIoT, namely, comprehensive perception, reliable transmission, and intelligent processing, by applying a metaverse platform, which is composed of AR and VR glasses and the MIoT system, and integrated with the technologies of holographic construction, holographic emulation, virtuality-reality integration, and virtuality-reality interconnection. In other words, through interactions between virtual and real cloud experts and terminal doctors, we will be able to carry out medical education, science popularization, consultation, graded diagnosis and treatment, clinical research, and even comprehensive healthcare in the metaverse. The interaction between virtual and real cloud experts and terminal users (including terminal doctors, patients, and even their family members) could also facilitate different medical services, such as disease prevention, healthcare, physical examination, diagnosis and treatment of diseases, rehabilitation, management of chronic diseases, in-home care, first aid, outpatient attendance, consultation, etc. In addition, it is noteworthy that security is a prerequisite for the Metaverse in Medicine, and a reliable security system is the foundation to ensure the normal operation of such a platform.
The application of a Cloud Plus Terminal platform could enable interaction between virtual and real cloud experts and terminal doctors, in order to realize medical education, science popularization, consultation, graded diagnosis and treatment, clinical research, and even comprehensive healthcare in the metaverse.
Activation of STING signaling in DCs promotes antitumor immunity. Aerobic glycolysis is a metabolic hallmark of activated DCs, but how the glycolytic pathway intersects with STING signaling in ...tumor-infiltrating DCs remains elusive. Here, we show that glycolysis drives STING signaling to facilitate DC-mediated antitumor immune responses. Tumor-infiltrating DCs exhibited elevated glycolysis, and blockade of glycolysis by DC-specific Ldha/Ldhb double deletion resulted in defective antitumor immunity. Mechanistically, glycolysis augmented ATP production to boost STING activation and STING-dependent DC antitumor functions. Moreover, DC-intrinsic STING activation accelerated HIF-1α-mediated glycolysis and established a positive feedback loop. Importantly, glycolysis facilitated STING-dependent DC activity in tissue samples from patients with non-small cell lung cancer. Our results provide mechanistic insight into how the crosstalk of glycolytic metabolism and STING signaling enhances DC antitumor activity and can be harnessed to improve cancer therapies.
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure that has enabled mediastinal and hilar lymph node assessment with a high sensitivity, ...but its role in the diagnosis of intrathoracic tuberculosis (TB) has not been established.
We prospectively studied 59 patients suspected of having TB with thoracic lymph node lesions or intrapulmonary lesions accessible by EBUS-TBNA at a clinical center for thoracic medicine from January 2010 to December 2011. Bronchoscopic findings, EBUS-TBNA procedures, pathologic findings, and microbiologic results were recorded.
Of 59 eligible patients, 41 patients had TB, 5 had lung cancer, 7 had inflammation, and 6 had sarcoidosis. Sensitivity was 85%, specificity was 100%, positive and negative predictive values were 100% and 75%, respectively, and accuracy was 90% by EBUS-TBNA for TB. Pathologic findings were consistent with TB in 80% of patients (33 of 41), and in 27% (11 of 41) the smear was positive. A total of 37 patients with TB had cultures, of whom 17 (46%) were positive. There were 80 mediastinal and hilar lymph nodes and 5 intrapulmonary lesions that were biopsied in the 41 patients with TB. Multivariate logistic regression revealed that short-axis diameter was an independent risk factor associated with positive pathology, smear, and culture (p < 0.05). Additionally, pathology showing necrosis was an independent risk factor associated with a positive culture.
Endobronchial ultrasound-guided transbronchial needle aspiration has a high diagnostic yield in the investigation of suspected intrathoracic TB by means of aspiration of intrathoracic lymph nodes and tracheobronchial wall-adjacent lung lesions.
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