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Although dementia and atrial fibrillation (AF) are common in older adults, risk factors for dementia have not been sufficiently characterized in patients with AF. We studied 621,773 patients with AF without dementia at the time of AF diagnosis who were enrolled in the MarketScan Commercial and Medicare Supplemental databases from 2007 to 2015. Dementia incidence and presence of predictors at the time of AF diagnosis (cardiometabolic conditions, mental and neurologic disorders, and other chronic conditions) were based on International Classification of Diseases, Ninth Revision, Clinical Modification codes in outpatient and inpatient claims, whereas medication usage was based on outpatient pharmacy claims. A frailty score was calculated using a previously established algorithm. The associations between the predictors of interest and dementia were assessed with multivariable Cox models. Patients had a mean age of 68 years (SD 14 years) and 41% were women. During a mean follow-up of 2.0 years, there were 16,073 cases of dementia. The strongest predictors of dementia were frailty (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.40 to 1.45, per 1-SD increase in the score), cognitive impairment (HR 1.50, 95% CI 1.36 to 1.65), mood disorders (HR 1.49, 95% CI 1.32 to 1.70), schizophrenia (HR 1.86, 95% CI 1.75 to 1.98), and substance abuse (HR 1.58, 95% CI 1.39 to 1.80). Among cardiometabolic conditions, only stroke (HR 1.17, 95% CI 1.13 to 1.22) and diabetes mellitus (HR 1.14, 95% CI 1.11 to 1.18) were associated with small increases in dementia risk after adjusting for demographics, frailty, co-morbidities, and medications. We have identified several risk factors for dementia in patients with AF.

A 5-year-old girl came to the Tianjin Medical University Eye Hospital in May 2021 because of her poor eyesight after birth. The physical examination showed that she had high myopia, esotropia, horizontal tremor, and high myopia retinopathy of both eyes. After inquiring about her medical history, we found that the baby's occipital cystic mass swelled after birth, and CT examination showed that the occipital skull plate defect with meningocele, but without treatment, at present, the occipital mass had subsided by itself. Considering the eye manifestations and skull changes of the child, it may be conformed to Knobloch syndrome, after the detection of V4 by full exon gene, it was found that the child had the compound heterozygous variation of pathogenic gene COL18A1, and Knobloch syndrome was definite, Knobloch syndrome is a rare autosomal recessive hereditary disease with typical features of high myopia, retinal detachment and occipital encephalocele. At present, there is no clear treatment plan, and gene therapy may be an effective treatment for Knobloch syndrome in the future.5岁女童因出生后发现双眼视力差于2021年5月就诊于天津医科大学眼科医院，体检提示：双眼高度近视、双眼内斜视、水平震颤、双眼底高度近视改变，追问病史后发现，患儿出生后头颅枕部囊性肿物膨出，查头颅CT提示：枕部颅板缺损伴脑膜膨出，未作治疗，目前枕部肿物已自行消退。考虑患儿的眼部表现及颅骨改变，可能符合Knobloch综合征，后经全外显子基因检测V4发现，患儿为致病基因COL18A1的复合杂合变异，Knobloch综合征明确，该综合征是一种罕见的常染色体隐性遗传性疾病，典型特征是高度近视、视网膜脱离和枕部脑膨出，目前尚无明确的治疗方案，基因治疗可能是未来应对Knobloch综合征的有效治疗手段。.

To examine the effects ofPregnant mice were injected intraperitoneally withOn day 9.5 of pregnancy, the mouse abortion rate was significantly higher in the infected group than that in the control group (83.02% vs. 3.51%

目的 回顾性分析原发中枢神经系统淋巴瘤中弥漫大B细胞淋巴瘤（PCNSL-DLBCL）患者的临床特征及不同治疗方案对患者生存及预后的影响。 方法 回顾性分析天津医科大学总医院自2014年7月至2020年12月收治的49例PCNSL-DLBCL患者的临床资料，根据治疗方案分为MTX组、R-CDOP组、BTKi-R-MTX组和RLZT组，计算各组中位总生存（OS）与无进展生存（PFS）时间，并进行单因素、多因素预后分析，比较各组患者的生存预后。 结果 MTX组、R-CDOP组、BTKi-R-MTX组和RLZT组的中位OS时间分别为16.5个月、4.5个月、42个月和未达到（P

A questionnaire was used to investigate the emergency training needs of novel coronavirus pneumonia of disease prevention and control institutions in provinces, deputy provincial level regions and cities specifically designated in the state plan, and the effect evaluation of emergency training activities conducted by Chinese Center for Disease Control and Prevention (China CDC). The results showed that 67.4% of 47 disease prevention and control institutions (31/46) believed that the emergency training at the initial stage of the epidemic should be conducted as soon as possible, and the form of network training should be given priority. The training should focus on the urgently needed technologies such as epidemiological investigation, formulation and response of prevention and control strategies, laboratory testing, etc. The teaching materials should highlight pertinence and practicability and be presented in the form of electronic video. The average satisfaction score of the video training conducted by China CDC was (8.81±1.125) and the score of audio-video courseware was (8.97±0.893). The needs analysis and evaluation of novel coronavirus pneumonia prevention and control in disease prevention and control institutions could provide reference for the follow-up training and improve the emergency training management.采用问卷调查省级、副省级及计划单列市疾病预防控制机构对新型冠状病毒肺炎的应急培训需求，以及对中国疾病预防控制中心所开展的应急培训活动的效果评价情况，结果显示47家疾病预防控制机构中，有67.4%（31/46）的被调查单位认为疫情初期的应急培训应尽早尽快，优先采用网络培训形式，重点针对基层人员培训流行病学调查、防控策略制定与应对、实验室检测等亟需技术，教材应突出针对性和实用性并以电子视频形式呈现；被调查单位对中国疾病预防控制中心开展的视频培训的满意度评分为（8.81±1.125）分、音视频课件的评分为（8.97±0.893）分。开展疾病预防控制机构新冠肺炎疫情防控应急培训需求分析与效果评价，可为后续开展大培训提供参考，为完善应急培训管理提供借鉴。.

Diabetic retinopathy is one of the three major microvascular complications of diabetes. Proliferative diabetic retinopathy (PDR) is an important ocular complication that affects the vision and quality of life of patients. Vitrectomy is the most effective treatment option. The characteristic of fibrovascular membranes in PDR varies at different stages of the disease, which requires specific treatment strategy and techniques. In order to improve the clinical diagnosis and treatment of PDR, this article proposes that different treatment methods should be correctly adopted for different types of proliferative membranes on the basis of fully understanding the tissue morphology of these membranes, and more attention should be paid to the treatment of the vitreous body to achieve more effective therapeutic effects.糖尿病视网膜病变是糖尿病三大微血管并发症之一，其中增生型糖尿病视网膜病变（PDR）是影响患者视力和生活质量的重要糖尿病眼部并发症，玻璃体切除手术是目前最为有效的治疗方法。PDR的纤维血管增生膜因病程不同而具有不同特点，处理策略和方法应具有针对性。为了指导临床实践，提高临床PDR的诊疗水平，本文提出应在充分认识增生膜组织形态的基础上，对不同类型增生膜采用不同治疗方法区别对待，并应在治疗中充分重视对玻璃体的处理，以便取得更为有效的治疗效果。

Background Circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF) has become a promising surrogate for genomic profiling of central nervous system tumors. However, suboptimal ctDNA detection rates from CSF limit its clinical utility. Thus precise screening of suitable patients is needed to maximize the clinical benefit. Patients and methods Between February 2017 and December 2020, 66 newly diagnosed non-small-cell lung cancer (NSCLC) patients with brain parenchymal metastases were prospectively enrolled as a training cohort and 30 additional patients were enrolled as an external validation cohort. CSF samples and matched primary tumor tissues were collected before treatment and subjected to next-generation sequencing (NGS). The imageological characteristics of patients’ brain tumors were evaluated by radiologists using enhanced magnetic resonance imaging images. The clinical and imageological characteristics were evaluated by complete subsets regression, Akaike information criteria, and Bayesian information criteria methods to establish the prediction model. A nomogram was then built for CSF ctDNA detection prediction. Results The somatic mutation detection rate of genes covered by our targeted NGS panel was significantly lower in CSF ctDNA (59.09%) than tumor tissue (91.84%). The Tsize (diameter of the largest intracranial lesion) and LVDmin (minimum lesion–ventricle distance for all intracranial lesions) were significantly associated with positive CSF ctDNA detection, and thus, were selected to establish the prediction model, which achieved an area under the ROC curve (AUC) of 0.819 and an accuracy of 0.800. The model’s predictive ability was further validated in the independent external cohort (AUC of 0.772, accuracy of 0.767) and by internal cross-validation. The CSF ctDNA detection rate was significantly improved from 58.18% (32/55) to 81.81% (27/33) in patients after model selection (P = 0.022). Conclusions This study developed a regression model to predict the probability of detecting CSF ctDNA using the phenotypic characteristics of metastatic brain lesions in NSCLC patients, thus, maximizing the benefits of CSF liquid biopsies., Graphical abstract, Highlights • Intracranial tumor size and distance to nearest ventricle were significantly correlated with positive CSF ctDNA detection. • A prediction model incorporating Tsize and LVDmin was developed and validated to evaluate the odds of CSF ctDNA positivity. • The CSF ctDNA detection rate was significantly improved in patients after model selection.

Under the background that the national health has become the national priority development strategy, it is essential to speed up public health ability among talents. Based on the consulting project of the Chinese Academy of Engineering, "Research on the training strategy of medical and health personnel in China", this paper analyzes the current situation and existing problems of public health personnel training in disease control and prevention institutions. Based on three stages of public health education, this paper puts forward that the public health personnel training should first solve the problem of public health personnel team construction and create programs on college education-post graduate education-continuing education. Through the personnel training system, different training modes are designed for other groups of people to improve the ability of public health personnel in an all-around way.在全民健康上升为国家优先发展战略地位背景下，加快公共卫生人才能力建设显得尤为重要。本文立足中国工程院咨询项目“我国医药卫生人才培养战略研究”，从公共卫生3个阶段教育基础上，分析了疾病预防控制机构公共卫生人才培养的现状、存在的问题，提出了公共卫生人才培养首先要解决公共卫生人员队伍建设问题，要构建院校教育-毕业后教育-继续教育贯通的人才培养体系，针对不同人群，设计不同的培养模式，全方位提高公共卫生人员能力。.

The case of oral hydrochloric acid poisoning is rare in clinic, and it is easy to be misdiagnosed when the poison is not clear. The clinical data of 1 case of oral hydrochloric acid poisoning successfully treated was retrospectively analyzed to provide reference for diagnosis and treatment of similar clinical cases.口服盐酸中毒的病例临床少见，在毒物不明确的情况下容易误诊。本文对成功救治的1例口服盐酸中毒患者的临床资料进行回顾性分析，为临床类似病例提供诊治参考。.

OBJECTIVE: To explore the stress distribution characteristics of the graft after anterior cruciate ligament (ACL) reconstruction, so as to provide theoretical reference for the surgical plan of ACL reconstruction. METHODS: Based on 3D MRI and CT images, finite element models of the uninjured knee joint and knee joint after ACL reconstruction were established in this study. The uninjured knee model included femur, tibia, fibula, medial collateral ligament, lateral collateral ligament, ACL and posterior cruciate ligament. The ACL reconstruction knee model included femur, tibia, fibula, medial collateral ligament, lateral collateral ligament, ACL graft and posterior cruciate ligament. Linear elastic material properties were used for both the uninjured and ACL reconstruction models. The elastic modulus of bone tissue was set as 17 GPa and Poisson' s ratio was 0.36. The material properties of ligament tissue and graft were set as elastic modulus 390 MPa and Poisson's ratio 0.4. The femur was fixed as the boundary condition, and the tibia anterior tension of 134 N was applied as the loading condition. The stress states of the ACL of the intact joint and the ACL graft after reconstruction were solved and analyzed, including tension, pressure, shear force and von Mises stress. RESULTS: The maximum compressive stress (6.34 MPa), von Mises stress (5.9 MPa) and shear stress (1.83 MPa) of the reconstructed ACL graft were all at the anterior femoral end. It was consistent with the position of maximum compressive stress (8.77 MPa), von Mises stress (8.88 MPa) and shear stress (3.44 MPa) in the ACL of the intact knee joint. The maximum tensile stress of the graft also appeared at the femoral end, but at the posterior side, which was consistent with the position of the maximum tensile stress of ACL of the uninjured knee joint. More-over, the maximum tensile stress of the graft was only 0.88 MPa, which was less than 2.56 MPa of ACL of the uninjured knee joint. CONCLUSION: The maximum compressive stress, von Mises stress and shear stress of the ACL graft are located in the anterior femoral end, and the maximum tensile stress is located in the posterior femoral end, which is consistent with the position of the maximum tensile stress of the ACL of the uninjured knee joint. The anterior part of ACL and the graft bore higher stresses than the posterior part, which is consistent with the biomechanical characteristics of ACL.

We evaluated the non-inferiority of nedaplatin-based and cisplatin-based concurrent chemoradiotherapy in cervical cancer patients.Patients aged 28-82 years with pathologically diagnosed cervical cancer (stage IB-IVA) were randomly chosen for the study. Patients in both the cisplatin and nedaplatin groups received radiotherapy and weekly intravenous nedaplatin 30 mg/mOne hundred and sixty patients who received treatment between 10 May 2018 and 31 August 2020 were included. The 3-year overall survival in the nedaplatin group (median 30.5 months) was not significantly different from that in the cisplatin group (28.5 months; hazard ratio 0.131, 95% confidence interval 0.016-1.068; P = 0.058). No significant differences in hematological toxicity were observed between the two groups. Vomiting (40 versus 61), nausea (44 versus 67), and anorexia (52 versus 71) were more common in the cisplatin group whereas effects on liver function, including total bilirubin (7 versus 3), alanine aminotransferase (7 versus 2), and aspartate aminotransferase (6 versus 2), were more common in the nedaplatin group. Four patients in the cisplatin group had grade I creatinine elevation, whereas none in the nedaplatin group had abnormal creatinine levels. Two patients in the nedaplatin group discontinued concurrent chemotherapy because of infusion, and one patient in the cisplatin group discontinued treatment because of infusion-induced dizziness.Our findings suggest that nedaplatin has a milder gastrointestinal reaction but a more significant effect on liver function than cisplatin. In patients with cervical cancer, nedaplatin-based concurrent chemoradiotherapy could serve as an alternative treatment to cisplatin.

It is known that the expression of the deubiquitinating enzyme BRCA1-BRCA2-containing complex subunit 3 (BRCC3) and cyclin-dependent protein kinase 5 (Cdk5) is increased in Parkinson's disease (both are involved in neuroinflammatory response). However, the regulatory mechanism of Cdk5 on the post-translational modification of BRCC3 remains unclear. Here we studied whether Cdk5 phosphorylates BRCC3. Phosphorylation of BRCC3 by Cdk5 was predicted by GPS 5.0 software. His-BRCC3 plasmid was constructed by cloning the BRCC3 gene into pGEX-6P-1 vector, and then His-BRCC3 fusion protein was induced with isopropyl β-d-1-thiogalactopyranoside and purified using His-Tag affinity chromatography purification agarose. Phosphorylation of BRCC3 fusion protein by Cdk5 in vitro was detected by mass spectrometry and Western blotting. The results showed that multiple phosphorylation sites were predicted by GPS 5.0, and the His-BRCC3 fusion protein was successfully induced and purified. In vitro kinase assay, Western blotting, and mass spectrometry showed that Cdk5 can phosphorylate BRCC3. It has been demonstrated that protein kinase Cdk5 can phosphorylate the deubiquitinating enzyme BRCC3 in vitro, which provides new data for further study on the mechanism of neurodegeneration.

To explore the correlation of the growth differentiation factor-15 (GDF-15) with the severity of chronic heart failure (CHF) in patients with coronary atherosclerosis.300 coronary atherosclerosis patients with CHF treated in our hospital from January 2019 to December 2019 and 300 healthy people (control group) were collected and retrospectively analyzed. The basic clinical information of the patients, such as age, gender, smoking/drinking history, waist-hip ratio, BMI and blood lipid were collected, and GDF-15, cystatin C and c-reactive protein (CRP) were determined. The severity of heart failure was classified.No significant differences in clinical information were found such as age, gender, smoking/drinking history, waist-to-hip ratio, BMI and blood lipid. However, there were significant differences in GDF-15, cystatin C and CRP among patients with different severities of heart failure. The GDF-15 level was 582.6 ± 104.4 pg/ml in patients with grade IV heart failure and 408.4 ± 94.8 pg/ml in patients with grade I heart failure. There was a significance after GDF-15, cystatin C and CRP were adjusted (p = 0.03) and also after the clinical information and GDF-15 were adjusted (p0.001).GDF-15 level is correlated with the CHF severity in patients with coronary atherosclerosis, indicating that it is a potential index to evaluate the CHF severity, providing clues to the biological mechanism and treatment of heart failure.

Arsenic trioxide poisoning can cause damage to the nervous system, heart, liver, kidney and other organs, with a lethal dose of 0.8-2.0 mg/kg. Acute poisoning is now rare. This article analyzes the clinical characteristics of 10 patients with acute poisoning caused by the absorption of arsenic trioxide through the respiratory tract, digestive tract, and skin, in order to improve clinicians' understanding of acute arsenic trioxide poisoning.三氧化二砷中毒后可引起神经系统和心脏、肝脏、肾脏等多脏器受损，致死量0.8~2.0 mg/kg，急性中毒少见。本文分析10例经呼吸道、消化道、皮肤吸收三氧化二砷引起急性中毒患者的临床特征，以提高临床医师对急性三氧化二砷中毒的认识。.

To date, skin substitute that can provide permanent wound closure is still autologous tissue-engineered skin using autologous skin cells as seed cells. The development of cultured epithelial autograft has experienced a long and tortuous process. Autologous tissue-engineered composite skin is closer to autologous split-thickness skin graft in terms of structure, function, and efficacy, which has become a research focus in recent years. Based on the actual status of research on tissue-engineered skin application, this paper reviewed the main research progresses and existing problems, and the prospect of research and development and clinical application of autologous tissue-engineered skin as permanent graft in order to provide a reference for the improvement and application of autologous tissue-engineered skin.迄今，能够永久性封闭创面的皮肤替代物仍是以自体皮肤细胞作为种子细胞的自体组织工程皮肤。培养的自体表皮移植物的发展经历了漫长而曲折的历程；自体组织工程复合皮肤在结构、功能与疗效上更接近自体断层皮片，成为近年来研究的热点。本文从组织工程皮肤应用研究的实际现状出发，就自体组织工程皮肤作为永久性移植物的主要研究进展、存在的主要问题、研究开发与临床应用前景进行综述，以期为自体组织工程皮肤改进及应用提供参考。.

To investigate the regulation of long non-coding RNA plasmacytoma variant translocation 1 (LncRNA PVT1) on proliferation, invasion, and aerobic glycolysis in glioma cells via miR-140-5p.Sixty patients with glioma treated in our hospital were recruited. The expression of PVT1 in tissues and cells was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the effects on the prognosis were observed. Glioma cell lines U87 and T98MG were either stably or transiently transfected with over-expression or inhibition vectors. Cell counting kit-8 (CCK-8), transwell, glucose, and lactate detection were employed to measure cell proliferation, invasion, and aerobic glycolysis after transfection. The correlation between PVT1 and miR-140-5p was determined by Dual-Luciferase reporter assay. RNA pull-down and RNA immunoprecipitation (RIP) test were adopted to indicate the correlation between PVT1 and miR-140-5p.PVT1 was highly expressed and had superior diagnostic value in gliomas, and the high expression of PVT1 resulted in poor prognosis of patients. Over-expressing PVT1 increased cell proliferation, invasion, and aerobic glycolysis, while inhibiting PVT1 yielded opposite outcome. Dual-Luciferase reporter assay confirmed that PVT1 could target miR-140-5p. Functional analysis showed that over-expression of miR-140-5p inhibited proliferation, invasion, and aerobic glycolysis in glioma cells. Rescue experiment found that the inhibitory effect of miR-140-5p could be eliminated by up-regulating PVT1 expression.PVT1 promotes proliferation, invasion, and aerobic glycolysis in glioma cells by regulating miR-140-5p.

From January 2014 to June 2018, 28 patients with different types of deep soft tissue injury or infection were admitted to the Affiliated Jiangyin Hospital of Medical College of Southeast University; 5 patients were admitted to the Zhengzhou First People's Hospital. There were 24 males and 9 females, aged 18-89 (40±20) years. Disposable suction tubes with holes cut on side walls were used as self-made drainage tubes. The authors placed the self-made drainage tubes on different deep soft tissue layers and wound surfaces after debridement. The effective drainage sections of the wound surface drainage tubes were wrapped with silver ion antimicrobial functional active dressings. Bio-permeable membrane was used to close the operative area. The drainage tubes in the deep layer of wound and wound surface were connected in parallel by a tee and connected to wall-hanging medical negative-pressure suction device to conduct negative-pressure wound treatment at -20.0 to -10.6 kPa. The deep drainage tubes were usually removed or changed 4 or 5 days after surgery.The drainage tubes in the wound surface were synchronously replaced when removing or replacing he drainage tubes in the deep layer of wound. On 4 to 15 days after surgery, the deep drainage tubes were removed. On 8 to 25 days after surgery, the wound surface drainage tubes were removed. Then the treatment was changed to a conventional dressing change until the wounds were completely healed or the wound bed was ready for skin grafts or tissue flaps. The indwelling time of deep drainage tubes in this group of patients was (6.2±2.8) days, and the indwelling time of wound surface drainage tubes was (12.0±3.0) days. The wound healing time was (22±5) days, the hospital stay time was (29±7) days, and wound bacteria were reduced from 6 species and 11 strains before treatment to 3 species and 4 strains after treatment. No adverse events such as wound bleeding, irritative pain, and chronic sinus occurred during treatment. Twenty-three patients were followed up for 13 to 28 months, no treatment-related complications were observed.2014年1月—2018年6月，东南大学医学院附属江阴医院收治28例、郑州市第一人民医院收治5例不同类型深部软组织损伤或感染患者，其中男24例、女9例，年龄18～89(40±20)岁。笔者将一次性吸痰管侧壁开孔自制引流管，分别放置于清创后深部不同软组织层面和创面表层，创面表层引流管有效引流段使用银离子抗菌功能性敷料包裹，应用生物透性薄膜封闭术区，将创面深层和浅层所有引流管用三通管并联后接壁式医用负压吸引器，以－20.0～－10.6 kPa行负压伤口疗法。深层引流管一般于术后4 d或5 d拔除或更换，拔除或更换深层引流管时同步更换创面表层引流管。本组患者于术后4～15 d拔除深层引流管，术后8～25 d拔除创面表层引流管，改为常规换药，直至创面完全愈合或创基能接受皮片或组织瓣移植。本组患者创面深层引流管留置时间为(6.2±2.8)d，创面表层引流管留置时间为(12.0±3.0)d，创面愈合时间为(22±5)d，住院时间为(29±7)d，创面培养细菌由治疗前的6种11株减少为治疗后的3种4株，治疗过程中未发生创面出血、刺激性疼痛、慢性窦道形成等不良事件。23例患者随访13～28个月，未观察到与治疗相关的并发症。.

金属人工关节置换术主要的并发症为假体松动，翻修中的假体周围组织由于是非肿瘤性病变，学界对其病理组织形态与临床组织不良反应相关性的关注较少。本文对假体周围组织进行全面且细致的分析，对感染病例探讨术中冷冻及常规石蜡两种方法的诊断价值，分析二者对临床感染诊断的提示意义。对无菌性假体周围组织进行详细的分类描述，包括：滑膜上皮、淋巴细胞、组织细胞及磨损颗粒的分级半定量评估。通过各种无菌性淋巴细胞为主型血管炎评分系统对假体周围组织进行综合评分，从而对人工关节置换术后关节翻修术假体周围组织的评估标准化，为临床人工关节置换术后关节翻修术的评价提供相关的依据。.

Sequential treatment with different generations of anaplastic lymphoma kinase (ALK) inhibitors have been widely applied to ALK-positive lung cancer; however, resistance mutations inevitably developed. Further characterization of ALK resistance mutations may provide key guidance to subsequent therapies. Here we explored the emergence of secondary ALK mutations during sequential ALK tyrosine kinase inhibitor (TKI) treatment in a real-world study of Chinese lung adenocarcinoma (ADC) patients.A clinical-genomic database was queried for lung ADC patients with at least one ALK inhibitor treatment and at least one plasma sample collected following ALK inhibitor treatment. Targeted genome profiling was performed with a 139-gene panel in baseline tumor tissue and serial plasma samples of patients.A total of 116 patients met inclusion criteria. ALK G1202R was more common in patients with echinoderm microtubule-associated protein-like 4 (EML4)-ALK v3 fusion, whereas ALK L1196M was more common in v1. TP53 mutant patients were significantly associated with harboring multiple ALK resistance mutations (P = 0.03) and v3+/TP53 mutant patients had the highest rate of multiple ALK resistance mutations. The sequential use of ALK TKI led to an increased incidence of concurrent ALK mutations along the lines of therapies. Alectinib had a lower rate (9%) harboring ALK resistance mutation as first-line ALK TKI compared with crizotinib (36%). ALK compound mutations identified included ALK D1203N/L1196M, ALK G1202R/L1196M, and ALK G1202R/F1174C, which may be lorlatinib resistant. Using paired pretreatment and post-treatment samples, we identified several ALK-independent resistance-related genetic alterations, including PTPRD and CNKN2A/B loss, MYC, MYCN and KRAS amplification, and EGFRSequential postprogression plasma profiling revealed that increased lines of ALK inhibitors can accelerate the accumulation of ALK resistance mutations and may lead to treatment-refractory compound ALK mutations. The selection for optimal first-line TKI is very important to achieve a more efficacious long-term strategy and prevent the emergence of on-target resistance, which may provide guidance for clinical decision making.

Objective To study the mechanism of rib fracture caused by landing on different parts of the trunk using finite element method, and to provide some new techniques and new ideas for the reconstruction of the whole process of falls from height. Methods The finite element method was used to study the rib fracture of human security model THUMS4.0 caused by landing on different parts of the trunk. Then the model was compared with actual cases and the mechanism of rib fracture caused by falls from height was analyzed from a biomechanical point of view. Results There were some differences in the stress and strain distribution as well as the rib fracture sites when different parts touched the ground. Ribs on both sides of the body were fractured when the front of the trunk touched the ground, and the fractures were mainly located in the junction of the ribs and costal cartilage and the midaxillary line area. When the right anterior part of the trunk touched the ground, rib fracture occurred first on the side that touched the ground, and rib fractures were mainly located in the area from the right midaxillary line to the posterior axillary line, and junction of ribs on both sides and costal cartilage. When the back of the trunk touched the ground, the fracture sites were mainly located on the back of the ribs on both sides. When the right posterior part of the trunk touched the ground, multiple rib fractures were likely to occur in the parts that touched the ground. The plastic strains were mainly concentrated at the fracture sites, while the von Mises stresses were not only concentrated at the fracture sites, but also at other sites. Conclusion There are some differences in rib fracture location sites and injury mechanisms when different parts of the trunk touch the ground.有限元法研究高坠中躯干不同部位着地的肋骨骨折机制.目的 利用有限元法研究躯干不同部位着地的肋骨损伤机制，对重建高坠过程提供新技术与新方法。 方法 采用有限元法观察全人类安全模型THUMS4.0在躯干部不同部位着地时的肋骨损伤情况，并与实际案例进行比较，从生物力学角度分析高坠导致的肋骨骨折形成机制。 结果 不同部位着地所形成的应力、应变分布及肋骨骨折部位存在一定差异。躯干前侧着地时双侧均发生肋骨骨折，骨折主要位于肋骨-肋软骨交界处和腋中线区域；躯干右前侧着地时，着地一侧首先发生肋骨骨折，骨折分布于右侧腋中线至腋后线区域以及双侧肋骨-肋软骨交界处；躯干后侧着地时，骨折主要位于双侧肋骨后侧；躯干右后侧着地时，着地部位易发生多发性肋骨骨折。塑性应变多集中于骨折处，von Mises应力除集中于骨折处，也可位于其他部位。 结论 躯干部不同部位着地时，肋骨骨折部位及损伤机制具有一定差异。.法医病理学；生物力学；有限元法；肋骨骨折；骨折，应力性；高坠伤；损伤机制.

OBJECTIVE: To provide new concepts of anterior cruciate ligament (ACL) reconstruction by anatomical gross observation of ACL tibial insertion and finite element analysis of distribution of ACL mechanical insertion. METHODS: In the anatomical study, ten fresh adult cadaveric knees were dissected, including 6 males and 4 females, all knees were generally observed through standard medial parapatellar approaches, paying attention to the close anatomical relationship of tibial insertion and anterior horn of lateral meniscus, and ACL was exposed and gradually removed from the inside. The shape of tibial insertion of ACL was observed and recorded, and anterior-posterior diameters and left-right diameters of tibial insertion were measured with vernier caliper. For the study of finite element analysis, three-dimensional thin-layer magnetic resonance imaging of normal knee joint was used to establish knee joint model. Three-dimensional reconstruction software MIMICS and finite element analysis software ANSYS were used to establish knee joint model, subsequently, clinical physical examination Lachman test and pivot-shift test were simulated to observe the force distribution of ACL tibial insertion and femoral insertion. RESULTS: The ACL tibial mechanical insertion was rather flat and long similar as an arc shape without a clear separation between anterior medial bundle (AMB) and posterolateral bundle (PLB) in gross observation. The dense fibers lies belonged to the medial intercondylar ridge and ended up anterior with the osseous landmark of anterior ridge. Its average anterior-posterior diameter was (13.8±2.0) mm, the average left-right diameter of midsubstance was (5.3±0.6) mm, and the average left-right diameter of anterior margin was (11.5±1.2) mm. The finite element analysis showed that distribution on the femoral side was oval shape mainly below the residents’ ridge, while the tibial side was rather flat mainly along the medial intercondylar ridge, which was consistent with the anatomical observation. The biomechanical characteristics of ACL attachments were verified theoretically. CONCLUSION: Anatomical study and finite element analysis have confirmed the flat arc shape of ACL tibial insertion. The ideal reconstruction technique of ACL should be based on its biomechanical insertion. Based on anatomical study and biomechanical analysis, we have proposed the idea of ACL biomechanical insertion reconstruction (BIR) and established a surgical model with oval femoral tunnel and rounded-rectangle tibial tunnel.

Hepatocellular carcinoma (HCC) is a malignant cancer with a high fatality rate, and the expression of microRNA-145 (miR-145) is significantly low in HCC tissue. Therefore, the effect of miR-145 on HCC was explored.Primary hepatocellular carcinoma samples and corresponding normal samples, and HepG2 cells were analyzed using flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Real-time quantitative reverse transcription-polymerase chain reaction, Western blotting, and dual-luciferase reporter assay.miR-145 expression was significantly downregulated in HCC tissue and HepG2 cells as compared to normal liver tissue. After HepG2 cells were transfected with miR-145 mimics, miR-145 expression was recovered, accompanied by a significantly lower cell number, inhibition of the G1/S phase transition, and promotion of the apoptosis of HepG2 cells, as well as changes in levels of G1/S-specific cyclin-E1 (CCNE1) and activated caspase-3. Furthermore, the rho-associated protein kinase 1 (ROCK1) levels were opposite the levels of miR-145 expression in vivo and in vitro, and additional experiments with co-transfection of miR-145 mimics and pEGFP-N3-3'UTR provided the direct evidence that the ROCK1 gene is a target of miR-145. Moreover, a significant decrease or increase in the expression of ROCK1 was associated with nuclear factor-kB (NF-κB)(p65) activity, and lipopolysaccharide (LPS) significantly increased NF-κB(p65) activity, accompanied by recovery of the reduction in the number of HepG2 cells for miR-145 mimics. The NF-κB activity and cell number were significantly (p0.05, p0.01) increased in response to the overexpression of the ROCK1 gene in HepG2 cells.We showed that miR-145 can target and downregulate ROCK1 expression, and it controls HCC by inhibiting the cell cycle and activating apoptosis via the ROCK1/NF-κB signaling pathway. Our findings will provide a new perspective for the therapy of HCC.

Postmortem changes on corpses appear immediately after death, and can transform the original structure characteristics of the corpse to different degrees as well as show specific changes on computed tomography （CT） images, sometimes with false positives and false negatives, influencing the identification of injuries or diseases. This paper systematically summarizes the postmortem changes of computed tomography imaging characteristics on corpses, to further expand the application of virtopsy in the practices of forensic pathology identification, and provide reference for the identification of injuries, diseases and changes after normal death.死后尸体CT影像学特征变化研究进展.死后尸体变化于死亡后立即出现，会不同程度地改变尸体原有的结构特征，并在计算机断层扫描（computed tomography，CT）图像上表现出特异性改变，有时易出现假阳性与假阴性，影响损伤或疾病的鉴别。本文系统地综述了死后尸体CT影像学的变化特点，以进一步拓展虚拟解剖技术在法医病理学鉴定实践中的应用，为鉴别损伤、疾病与正常死后变化提供参考。.法医病理学；死后变化；计算机断层扫描；虚拟解剖；综述.

To investigate the influences of metformin on the proliferation and migration of endometrial cancer (EC) Ishikawa cells and its mechanism.After the EC Ishikawa cells were treated with metformin at a concentration of 10 mM for 24 h, the proliferation of cancer cells was detected via XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-car-boxanilide] assay and colony formation assay, and the migration and invasion of cancer cells were detected via wound healing assay and transwell assay. In addition, the expressions of epithelial-mesenchymal transition (EMT)-related proteins, E-cadherin and Vimentin, were detected via Western blotting, and immunofluorescence staining was performed for E-cadherin in cancer cells. Finally, the protein expression level of phosphatidylinositol 3-hydroxy kinase/protein kinase B/murine double minute 2 (PI3K/AKT/MDM2) signaling pathway in cancer cells was detected via Western blotting.Metformin inhibited the proliferation of Ishikawa cells in a concentration-dependent manner (0-10 mM) (p0.05). Moreover, metformin (10 mM) also inhibited the proliferation of Ishikawa cells in a time-dependent manner (0-72 h) (p0.05). The results of colony formation assay revealed that metformin (10 mM) could significantly inhibit the colony formation of Ishikawa cells (p0.05). The results of wound healing assay and transwell assay showed that metformin (10 mM) significantly inhibited the migration and invasion of Ishikawa cells (p0.05). According to further studies, metformin (10 mM) inhibited the EMT process in Ishikawa cells. Western blotting results manifested that the activation of PI3K/AKT/MDM2 signaling pathway was inhibited by metformin (p0.05).Metformin can inhibit the proliferation and migration of EC cells by inhibiting the activation of PI3K/AKT/MDM2 signaling pathway. Therefore, metformin is expected to be a new drug for the clinical treatment of EC.

DIRC1, Disrupted in Renal Cancer 1, was identified as a breakpoint-spanning gene in a chromosomal translocation, which was associated with the onset and progression of some cancers. However, the expression in human gastric cancer (GC) and the role of DIRC1 in human gastric tumorigenesis are unknown. Thereby, the main purpose of this study was to unearth the association of DIRC1 with GC.By analyzing The Cancer Genome Atlas (TCGA) datasets, the expression of DIRC1 in GC and normal gastric tissues were compared. Besides, its association with clinicopathological significance, overall survival (OS) and independent prognosis were analyzed by Pearson's x2 test, Kaplan-Meier method and Cox proportional hazards model, respectively. Functionally, the knockdown of DIRC1 was performed by siRNA method; moreover, its effects on the proliferation and metastasis of GC cells were examined by CCK-8 and transwell assays. Furthermore, the key markers of protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling were tested by Western blot assay.The results showed that high expression of DIRC1 was found in GC tissues compared with normal gastric tissues. High expression of DIRC1 was associated with more cases of severer tumor malignancy and shorter OS; besides, high-level of DIRC1 was suggested to be an independent prognostic factor for GC. Furthermore, the knockdown of DIRC1 inhibited SGC-7901 GC cells proliferation, migration and invasion. Mechanically, the activity of AKT/mTOR signaling was suppressed by the knockdown of DIRC1.These findings offer clinical associations and an in vitro evidence showing that the knockdown of DIRC1 impeded the GC carcinogenicity possibly via suppression of AKT/mTOR signaling. This work might provide a potential therapeutic target for GC treatment.

Objective Quantitative analysis and comparison of the expression of ribonucleic acid （RNA） from frozen organs and formaldehyde-fixed and paraffin-embedded （FFPE） tissues. Methods Frozen specimens of human brain, myocardium and liver tissues as well as FFPE samples at different postmortem intervals were collected and mass concentration of RNA was extracted and detected. Reverse transcription-quantitative polymerase chain reaction （RT-qPCR） technology was used to analyze the amplification efficiency and relative expression of each RNA marker. Results The mass concentration and integrity of RNA extracted from FFPE samples were relatively low compared with frozen specimens. The amplification efficiency of RNA markers was related with RNA species and the length of amplification products. Among them, glyceraldehyde-3-phosphate dehydrogenase （GAPDH） and β-actin （ACTB） with relatively long amplification products failed to achieve optimal amplification efficiency, whereas 5S ribosomal RNA （5S rRNA） achieved ideal amplification efficiency and showed quite stable expression across various tissues, therefore it was chosen as internal reference marker. The expression quantity of GAPDH and ACTB in frozen specimens with longer postmortem intervals and in FFPE samples with relatively long amplification products was decreased. The expressions of tissue-specific microRNAs （miRNAs）, GAPDH and ACTB with relatively short amplification products had consistency in the same tissues and FFPE samples. Conclusion Through standardizing the RT-qPCR experiment, selecting the appropriate RNA marker and designing primers of appropriate product length, RNA expression levels of FFPE samples can be accurately quantified.冻存器官和甲醛固定石蜡包埋组织中RNA的定量表达.目的 定量分析并对比冻存器官和甲醛固定石蜡包埋（formaldehyde-fixed and paraffin-embedded，FFPE）组织中核糖核酸（ribonucleic acid，RNA）的表达情况。 方法 选取不同死亡时间人体脑、心肌和肝组织的冻存及FFPE样本，提取并检测RNA质量浓度，运用实时荧光定量反转录聚合酶链反应（reverse transcription-quantitative polymerase chain reaction，RT-qPCR）技术分析各RNA指标的扩增效率及相对表达量。 结果 与冻存样本相比，FFPE样本中所提取RNA的质量浓度和完整性相对较低。各RNA指标扩增效率与RNA种类及扩增产物长度有关，其中扩增产物较长的甘油醛-3-磷酸脱氢酶（glyceraldehyde-3-phosphate dehydrogenase，GAPDH）及β-肌动蛋白（β-actin，ACTB）扩增效率不理想，而5S核糖体RNA（5S ribosomal RNA，5S rRNA）扩增效率理想且在各组织中表达稳定，故选为内参指标。较长死亡时间的冻存样本及FFPE样本中扩增产物较长的GAPDH及ACTB表达量下降，而组织特异性微小RNA（microRNA，miRNA）以及扩增产物较短的GAPDH和ACTB在同一组织冻存和FFPE样本中表达具有一致性。 结论 通过标准化RT-qPCR实验，选取合适的RNA指标及设计合适产物长度的引物，能够准确定量FFPE样本中RNA的表达水平。.法医病理学；核糖核酸；石蜡包埋；冷冻保存；反转录聚合酶链反应；核糖核酸完整性指数.

Background Identifying pneumonia using diagnosis codes alone may be insufficient for research on clinical decision making. Natural language processing (NLP) may enable the inclusion of cases missed by diagnosis codes. Objectives This article (1) develops a NLP tool that identifies the clinical assertion of pneumonia from physician emergency department (ED) notes, and (2) compares classification methods using diagnosis codes versus NLP against a gold standard of manual chart review to identify patients initially treated for pneumonia. Methods Among a national population of ED visits occurring between 2006 and 2012 across the Veterans Affairs health system, we extracted 811 physician documents containing search terms for pneumonia for training, and 100 random documents for validation. Two reviewers annotated span- and document-level classifications of the clinical assertion of pneumonia. An NLP tool using a support vector machine was trained on the enriched documents. We extracted diagnosis codes assigned in the ED and upon hospital discharge and calculated performance characteristics for diagnosis codes, NLP, and NLP plus diagnosis codes against manual review in training and validation sets. Results Among the training documents, 51% contained clinical assertions of pneumonia; in the validation set, 9% were classified with pneumonia, of which 100% contained pneumonia search terms. After enriching with search terms, the NLP system alone demonstrated a recall/sensitivity of 0.72 (training) and 0.55 (validation), and a precision/positive predictive value (PPV) of 0.89 (training) and 0.71 (validation). ED-assigned diagnostic codes demonstrated lower recall/sensitivity (0.48 and 0.44) but higher precision/PPV (0.95 in training, 1.0 in validation); the NLP system identified more “possible-treated” cases than diagnostic coding. An approach combining NLP and ED-assigned diagnostic coding classification achieved the best performance (sensitivity 0.89 and PPV 0.80). Conclusion System-wide application of NLP to clinical text can increase capture of initial diagnostic hypotheses, an important inclusion when studying diagnosis and clinical decision-making under uncertainty.

MiR-181a plays a critical role in modulating T cell and B cell differentiation, as well as immune response. Its abnormal expression probably participates in the pathogenesis of systemic lupus erythematosus (SLE). MiR-203 is involved in regulating Toll-like receptor and inducing immune tolerance. Abnormal expression or function of miR-203 is related to multiple auto-immune diseases but its role in SLE remains unclear. This study, thus, investigated the serum level of miR-181a and miR-203, to analyze their roles in diagnosing and evaluating SLE.SLE patients were recruited from our hospital, and divided into non-active and active SLE based on disease activity index, along with healthy individuals. qRT-PCR was used to quantify the serum miR-181a and miR-203 expression, and their correlation with clinical features. ROC was used to evaluate the diagnostic value on SLE, while survival curves were compared to show progression-free survival (PFS) between populations with high and low expression.SLE patients had significantly higher serum levels of miR-181a and lower miR-203, both of which were correlated with SLE activity. Expression levels of miR-181a and miR-203 were correlated with erythrocyte sedimentation rate, C reactive protein, anti-dsDNA antibody, complements, and SLEDAI score. Their expression levels had certain values in the differential diagnosis for active SLE (AUC=0.885 and 0.843). PFS in miR-181a high-expression individuals was lower than that in the low-miR-181 group (χ2=7.474, p=0.029). Whilst, miR-203 high-expression SLE patients had higher PFS than low-expression group (χ2=4.367, p=0.037).SLE patients had higher miR-181a and lower miR-203 expression, which thus may have critical implications in disease diagnosis and evaluation.

To reconstruct a vehicle-bicycle-cyclist crash accident and analyse the injuries using 3D laser scanning technology, multi-rigid-body dynamics and optimized genetic algorithm, and to provide biomechanical basis for the forensic identification of death cause.The vehicle was measured by 3D laser scanning technology. The multi-rigid-body models of cyclist, bicycle and vehicle were developed based on the measurements. The value range of optimal variables was set. A multi-objective genetic algorithm and the nondominated sorting genetic algorithm were used to find the optimal solutions, which were compared to the record of the surveillance video around the accident scene.The reconstruction result of laser scanning on vehicle was satisfactory. In the optimal solutions found by optimization method of genetic algorithm, the dynamical behaviours of dummy, bicycle and vehicle corresponded to that recorded by the surveillance video. The injury parameters of dummy were consistent with the situation and position of the real injuries on the cyclist in accident.The motion status before accident, damage process by crash and mechanical analysis on the injury of the victim can be reconstructed using 3D laser scanning technology, multi-rigid-body dynamics and optimized genetic algorithm, which have application value in the identification of injury manner and analysis of death cause in traffic accidents.

Lipoprotein lipase (LPL) is a candidate gene for obesity based on its role in triglyceride hydrolysis and the partitioning of fatty acids towards storage or oxidation. Whether dietary fatty acids modify LPL associated obesity risk is unknown.We examined five single nucleotide polymorphisms (SNPs) (rs320, rs2083637, rs17411031, rs13702, rs2197089) for potential interaction with dietary fatty acids for obesity traits in 1171 participants (333 men and 838 women, aged 45-75 y) of the Boston Puerto Rican Health Study (BPRHS). In women, SNP rs320 interacted with dietary polyunsaturated fatty acids (PUFA) for body mass index (BMI) (P = 0.002) and waist circumference (WC) (P = 0.001) respectively. Higher intake of PUFA was associated with lower BMI and WC in homozygotes of the major allele (TT) (P = 0.01 and 0.005) but not in minor allele carriers (TG and GG). These interactions were replicated in an independent population, African American women of the Atherosclerosis Risk in Communities (ARIC) study (n = 1334).Dietary PUFA modulated the association of LPL rs320 with obesity traits in two independent populations. These interactions may be relevant to the dietary management of obesity, particularly in women.