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Yi-Zi Zheng,1,2 Hong-Bin Qin,1 Zi-Zheng Li,1 He-Sheng Jiang,3 Greg Zhang,4 Shi-Wei Yang,5 Xian-Ming Wang,2 Yang-Chun Xu,1 Zhen-Han Deng,6 Guo-Wen Liu2 1Department of Thyroid and Breast Surgery, The People’s Hospital of Hechi, Hechi, Guangxi, People’s Republic of China; 2Department of Thyroid and Breast Surgery, Shenzhen Breast Tumor Research Center for Diagnosis and Treatment, National Standardization Center for Breast Cancer Diagnosis and Treatment, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 3Department of Surgery, Oregon Health & Science University, Portland, OR, USA; 4McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA; 5Teaching Office, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 6Department of Sports Medicine, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Yang-Chun XuDepartment of Thyroid and Breast Surgery, The People’s Hospital of Hechi, Middle 455 Jinchengjiang Road, Hechi, 547000, Guangxi, People’s Republic of ChinaTel/Fax +86-778-2293900Email xuyangchun2010@163.comYi-Zi ZhengDepartment of Thyroid and Breast Surgery, Shenzhen Breast Tumor Research Center for Diagnosis and Treatment, National Standardization Center for Breast Cancer Diagnosis and Treatment, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, 3002 Sungang West Road, Shenzhen, 518035, Guangdong, People’s Republic of ChinaTel/Fax +86-755-83366388Email 14111230029@fudan.edu.cnPurpose: Ductal carcinoma in situ with microinvasion (DCISM) can be challenging to balance the risks of overtreatment versus undertreatment. We aim to identify prognostic factors in patients with DCISM and construct a nomogram to predict breast cancer-specific survival (BCSS).Materials and Methods: A retrospective cohort study of women diagnosed with DCISM from 1988 to 2015 who were identified in the Surveillance, Epidemiology and End Results database. Clinical variables and tumor characteristics were evaluated, and Cox proportional-hazards regression was performed. A nomogram was constructed from the multivariate logistic regression to combine all the prognostic factors to predict the prognosis of DCISM patients at 5 years, 10 years, and 15 years.Results: We identified 5438 total eligible breast cancer patients with a median and max survival time of 78 and 227 months, respectively. Here, patients with poorer survival outcomes were those diagnosed between 1988 and 2001, African-American race, under 40 years of age, higher tumor N stage, progesterone receptor-negative tumor, and received no surgery. The nomogram was constructed by the seven variables and passed the calibration and validation steps. The area under the receiver operating characteristic (ROC) curve (AUC) of both the training set and the validating set (5-year AUC: 0.77 and 0.88, 10-year AUC: 0.75 and 0.73, 15-year AUC: 0.72 and 0.65). Receiving chemotherapy was associated with a better BCSS (hazard ratio, HR=0.45, 95% confidence interval, 95% CI = 0.23– 0.89), especially in patients with estrogen receptor (ER) negative, progesterone receptor (PR) negative (HR = 0.35, 95% CI = 0.13– 0.97) and ER+PR-/ER-PR+ DCISM (HR = 0.07, 95% CI = 0.01– 0.59).Conclusion: Our current study is the first to construct nomograms of patients with DCISM which could help physicians identify breast cancer patients that more likely to benefit from more intensive treatment and follow-up. Chemotherapy might benefit patients with ER-PR- and ER+PR-/ER-PR+ DCISM.Keywords: breast cancer, ductal carcinoma in situ, microinvasion, nomogram, survival

Background: Helicobacter pylori (H. pylori) stands as the predominant infectious agent linked to the onset of gastritis, peptic ulcer diseases, and gastric cancer (GC). Identified as the exclusive bacterial factor associated with the onset of GC, it is classified as a group 1 carcinogen by the World Health Organization. The elimination of H. pylori plays a crucial role in the primary prevention of GC. While the prevalence has declined in recent decades, H. pylori infection is still highly prevalent in China, accounting for a significant part of the disease burden of GC. Therefore, updated prevalence information for H. pylori infection, especially regional and demographic variations in China, is an important basis for the design of targeted strategies that will be effective for the prevention of GC and application of policies for H. pylori control., Aim: To methodically evaluate the occurrence of H. pylori infection throughout China and establish a reference point for subsequent investigations., Methods: A systematic review and meta-analysis was conducted following established guidelines, as detailed in our methodology section., Results: Our review synthesized data from 152 studies, covering a sample of 763827 individuals, 314423 of whom were infected with H. pylori . We evaluated infection rates in mainland China and the combined prevalence of H. pylori was 42.8% (95%CI: 40.7-44.9). Subgroup analysis indicated the highest prevalence in Northwest China at 51.3% (95%CI: 45.6-56.9), and in Qinghai Province, the prevalence reached 60.2% (95%CI: 46.5-73.9). The urea breath test, which recorded the highest infection rate, showed a prevalence of 43.7% (95%CI: 41.4-46.0). No notable differences in infection rates were observed between genders. Notably, the prevalence among the elderly was significantly higher at 44.5% (95%CI: 41.9-47.1), compared to children, who showed a prevalence of 27.5% (95%CI: 19.58-34.7)., Conclusion: Between 2014 and 2023, the prevalence of H. pylori infection in China decreased to 42.8%, down from the previous decade. However, the infection rates vary considerably across different geographical areas, among various populations, and by detection methods employed., Competing Interests: Conflict-of-interest statement: The authors disclose that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Microorganisms typically used to produce food and pharmaceuticals are now being explored as medicines and agricultural supplements. However, maintaining high viability from manufacturing until use remains an important challenge, requiring sophisticated cold chains and packaging. Here we report synthetic extremophiles of industrially relevant gram-negative bacteria (Escherichia coli Nissle 1917, Ensifer meliloti), gram-positive bacteria (Lactobacillus plantarum) and yeast (Saccharomyces boulardii). We develop a high-throughput pipeline to define species-specific materials that enable survival through drying, elevated temperatures, organic solvents and ionizing radiation. Using this pipeline, we enhance the stability of E. coli Nissle 1917 by more than four orders of magnitude over commercial formulations and demonstrate its capacity to remain viable while undergoing tableting and pharmaceutical processing. We further show, in live animals and plants, that synthetic extremophiles remain functional against enteric pathogens and as nitrogen-fixing plant supplements even after exposure to elevated temperatures. This synthetic, material-based stabilization enhances our capacity to apply microorganisms in extreme environments on Earth and potentially during exploratory space travel., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Pills are a cornerstone of medicine but can be challenging to swallow. While liquid formulations are easier to ingest, they lack the capacity to localize therapeutics with excipients nor act as controlled release devices. Here we describe drug formulations based on liquid in situ-forming tough (LIFT) hydrogels that bridge the advantages of solid and liquid dosage forms. LIFT hydrogels form directly in the stomach through sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by a drug-containing polymer solution of alginate and four-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels robustly form in the stomachs of live rats and pigs, and are mechanically tough, biocompatible and safely cleared after 24 h. LIFT hydrogels deliver a total drug dose comparable to unencapsulated drug in a controlled manner, and protect encapsulated therapeutic enzymes and bacteria from gastric acid-mediated deactivation. Overall, LIFT hydrogels may expand access to advanced therapeutics for patients with difficulty swallowing., (© 2024. The Author(s).)

Background: Alexander disease is a rare, progressive leukodystrophy, which predisposes patients to complications under general anesthesia due to clinical manifestations including developmental delay, seizures, dysphagia, vomiting, and sleep apnea. However, study of anesthetic outcomes is limited., Aims: Our aim was to describe patient characteristics, anesthetic techniques, and anesthesia-related complications for Alexander disease patients undergoing magnetic resonance imaging and/or lumbar puncture at a quaternary-care children's hospital., Methods: We performed a retrospective review of anesthetic outcomes in patients with Alexander disease enrolled in a prospective observational study. Included patients had diagnosed Alexander disease and underwent magnetic resonance imaging and/or lumbar puncture at our institution. We excluded anesthetics for other procedures or at outside institutions. Collected data included patient characteristics, anesthetic techniques, medications, and complications under anesthesia and in the subsequent 24 h. We performed descriptive statistics as appropriate., Results: Forty patients undergoing 64 procedures met inclusion criteria. Fifty-six procedures (87.5%) required general anesthesia or monitored anesthesia care (MAC) and eight (12.5%) did not. The general anesthesia/MAC group tended to be younger than nonanesthetized patients (median age 6 years [IQR 3.8; 9] vs. 14.5 years [IQR 12.8; 17.5]). In both groups, dysphagia (78.6% vs. 87.5%, respectively), seizures (62.5% vs. 25%), and recurrent vomiting (17.9% vs. 25%) were frequently reported preprocedure symptoms. Inhalational induction was common (N = 48; 85.7%), and two (3.6%) underwent rapid sequence induction. Serious complications were rare, with no aspiration or seizures. Hypotension resolving with ephedrine occurred in eight cases (14.3%). One patient each (1.8%) experienced postprocedure emergence agitation or vomiting. Fifty-three (94.6%) were ambulatory procedures. No inpatients required escalation in acuity of care., Conclusions: In this single-center study, patients with Alexander disease did not experience frequent or irreversible complications while undergoing general anesthesia/MAC. Co-morbid symptoms were not increased postanesthesia. Some patients may not require anesthesia to complete short procedures., (© 2024 The Author(s). Pediatric Anesthesia published by John Wiley & Sons Ltd.)

The tumor microenvironment (TME) plays a pivotal role in the onset, progression, and treatment response of cancer. Among the various components of the TME, cancer-associated fibroblasts (CAFs) are key regulators of both immune and non-immune cellular functions. Leveraging single-cell RNA sequencing (scRNA) data, we have uncovered previously hidden and promising roles within this specific CAF subgroup, paving the way for its clinical application. However, several critical questions persist, primarily stemming from the heterogeneous nature of CAFs and the use of different fibroblast markers in various sample analyses, causing confusion and hindrance in their clinical implementation. In this groundbreaking study, we have systematically screened multiple databases to identify the most robust marker for distinguishing CAFs in lung cancer, with a particular focus on their potential use in early diagnosis, staging, and treatment response evaluation. Our investigation revealed that COL1A1, COL1A2, FAP, and PDGFRA are effective markers for characterizing CAF subgroups in most lung adenocarcinoma datasets. Through comprehensive analysis of treatment responses, we determined that COL1A1 stands out as the most effective indicator among all CAF markers. COL1A1 not only deciphers the TME signatures related to CAFs but also demonstrates a highly sensitive and specific correlation with treatment responses and multiple survival outcomes. For the first time, we have unveiled the distinct roles played by clusters of CAF markers in differentiating various TME groups. Our findings confirm the sensitive and unique contributions of CAFs to the responses of multiple lung cancer therapies. These insights significantly enhance our understanding of TME functions and drive the translational application of extensive scRNA sequence results. COL1A1 emerges as the most sensitive and specific marker for defining CAF subgroups in scRNA analysis. The CAF ratios represented by COL1A1 can potentially serve as a reliable predictor of treatment responses in clinical practice, thus providing valuable insights into the influential roles of TME components. This research marks a crucial step forward in revolutionizing our approach to cancer diagnosis and treatment., (© 2024. The Author(s).)

Aim: The study was conducted to evaluate the feasibility and safety profile of hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (HAIC-FOLFOX) as an alternative therapeutic choice for patients with advanced hepatocellular carcinoma (HCC) that is refractory to systemic treatment including immune checkpoint blockades or molecular targeting agents., Methods: Two hundred and forty five consecutive patients with advanced HCC who received HAIC-FOLFOX treatment after systemic treatment failure were retrospectively reviewed in six institutions and their survival, tumor response, and tolerance were assessed., Results: The median overall survival (OS) and progression-free survival of the 209 included participants were 10.5 months (95% confidence interval [CI], 8.1-12.9) and 6.0 months (95% CI, 5.1-6.9), respectively. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, the objective response rate was 21.1%, and the disease control rate was 64.6%. Multivariate analysis of risk factors of OS were albumin-bilirubin grade (2 and 3 vs. 1, hazard ratio [HR] 1.57; 95% CI, 1.05-2.34; p = 0.028), tumor number (>3 vs. 1-3, HR 2.18; 95% CI, 1.10-4.34; p = 0.026), extrahepatic spread (present vs. absent, HR 1.61, 95% CI, 1.06-2.45; p = 0.027), synchronous systemic treatment (present vs. absent, HR 0.55, 95% CI, 0.37-0.83; p = 0.004) and treatment response (responder vs. nonresponder, HR 0.30, 95% CI, 0.17-0.53; p < 0.001). Grade 3-4 adverse events (AEs) occurred in 59 (28.2%) HCC patients. All AEs were manageable, and deaths related to hepatic artery infusion chemotherapy treatment were not observed., Conclusions: Our findings support the effectiveness and safety of HAIC-FOLFOX treatment for patients with advanced HCC who have failed systemic treatment., (© 2023 Japan Society of Hepatology.)

Background: Cognitive deficits and behavioral disorders such as anxiety and depression are common manifestations of Alzheimer's disease (AD). Our previous work demonstrated that Trichostatin A (TSA) could alleviate neuroinflammatory plaques and improve cognitive disorders. AD, anxiety, and depression are all associated with microglial inflammation. However, whether TSA could attenuate anxiety- and depression-like behaviors in APP/PS1 mice through anti-inflammatory signaling is still unclearly., Methods: In the present study, all mice were subjected to the open field, elevated plus maze, and forced swim tests to assess anxiety- and depression-related behaviors after TSA administration. To understand the possible mechanisms underlying the behavioral effects observed, CST7 was measured in the hippocampus of mice and LPS-treated BV2 microglia., Results: The results of this study indicated that TSA administration relieved the behaviors of depression and anxiety in APP/PS1 mice, and decreased CST7 levels in the hippocampus of APP/PS1 mice and LPS-induced BV2 cells., Conclusion: Overall, these findings support the idea that TSA might be beneficial for reducing neurobehavioral disorders in AD and this could be due to suppression of CST7 -related microglial inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Su, Ren, Liu, Gao, Zhang, Zhang, Pei and Li.)

Objective: The primary objective of this paper is to investigate the research hotspots and future trends of immune-related adverse events induced by immune checkpoint inhibitors, offering valuable insights for researchers in this field., Methodology: Using the visual analysis software, this study conducted quantitative statistics and visualization research on the relevant literature concerning immune-related adverse events caused by immune checkpoint inhibitors in the Web of Science Core Collection Database. By evaluating the publication trends, countries, institutions, keywords, research status, cited documents, and document co-citations, among several others, the discussion revolved around the hot spots and future development trends in this field and provided references for future research., Findings and Conclusions: A total of 514 English articles were included, and the top three countries in the research field at the time of this study were the United States, Japan, and China. More specifically, the University of Texas MD Anderson Cancer Center, Dana-Farber Cancer Institute, and Massachusetts General Hospital have been the top three research institutes with more than 10 publications. The frequency of keyword use linked to immune-related adverse events caused by immune checkpoint inhibitors in literature research has been steadily growing over the years. Additionally, the research with respect to the disease focuses on melanoma, cell lung cancer, hepatocellular carcinoma, and breast cancer. In the context of drugs, cancer-related research has mainly focused on the combined use of nivolumab, pembrolizumab, ipilimumab, and immune checkpoint inhibitors. Meanwhile, research on adverse events has delved into the immune checkpoint inhibitors causing vitiligo, thyroid dysfunction, pancreatitis, cholangitis, and rheumatism. Related studies cover acute arthritis, myositis, acute kidney injury, as well as the combination therapy of immune checkpoint inhibitors and docetaxel, management of irAEs in cancer immunotherapy, and biomarkers of immune adverse reactions of immune checkpoint inhibitors. Finally, case report studies of immune adverse reactions caused by immune checkpoint inhibitors could serve as research hotspots in the future., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Deoxynivalenol (DON) is a common mycotoxin that is widely found in various foods and feeds, posing a potential threat to human and animal health. This study aimed to investigate the protective effect of the natural polyphenol piceatannol (PIC) against DON-induced damage in porcine intestinal epithelial cells (IPEC-J2 cells) and the underlying mechanism. The results showed that PIC promotes IPEC-J2 cell proliferation in a dose-dependent manner. Moreover, it not only significantly relieved DON-induced decreases in cell viability and proliferation but also reduced intracellular reactive oxygen species (ROS) production. Further studies demonstrated that PIC alleviated DON-induced oxidative stress damage by increasing the protein expression levels of the antioxidant factors NAD(P)H quinone oxidoreductase-1 (NQO1) and glutamate-cysteine ligase modifier subunit (GCLM), and the mRNA expression of catalase ( CAT ), Superoxide Dismutase 1 ( SOD1 ), peroxiredoxin 3 ( PRX3 ), and glutathione S-transferase alpha 4 ( GSTα4 ). In addition, PIC inhibited the activation of the nuclear factor-B (NF-κB) pathway, downregulated the mRNA expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) to attenuate DON-induced inflammatory responses, and further mitigated DON-induced cellular intestinal barrier injury by regulating the protein expression of Occludin. These findings indicated that PIC had a significant protective effect against DON-induced damage. This study provides more understanding to support PIC as a feed additive for pig production.

Objective: To determine the ages at acquisition of developmental milestones, loss of motor function, and clinical symptoms in Alexander disease. Methods: Patients with confirmed cerebral Alexander disease were included. Data abstraction of developmental and disease-specific milestones was performed from medical records, physical exams, and questionnaires. Mixed effects logistic regression was used to determine if key clinical features were associated with milestone achievement, controlling for patient age. Results: 51 patients with cerebral/infantile Alexander disease were evaluated at a mean age of 10.96 years (range 2.29-31.08 years). Developmental milestones in Alexander disease were often achieved but delayed. Ambulation was achieved in 44 subjects (86%); 34 (67%) subjects walked independently (mean age 1.9 years, range 0.91-3.25 years) and an additional 10 (20%) subjects walked with assistance (mean age 3.9 years, range 1.8-8 years) but did not progress to independent ambulation. Developmental delay was the earliest and most prevalent symptom (N = 48 [94%], mean age 0.58 years), compared to an initial seizure (N = 41 [80%], mean age 2.80 years), and macrocephaly (N = 28 [55%], mean age 4.04 years), P  < .0001 between these ages of onset. Loss of independent ambulation occurred in 11 of the 34 (32%) children who had acquired ambulation (range 3.41-15.10 years). Presence of seizures or macrocephaly did not predict the achievement or loss of ambulation. Conclusions: The clinical triad of developmental delay, seizures, and macrocephaly are not universally present in cerebral Alexander disease. Clinicians should have a high index of suspicion for Alexander disease in patients with mild delays and a first seizure., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Roxarsone (3-nitro-4-hydroxyphenylarsonic acid, Rox), a widely used organoarsenical feed additive, can enter soils and be further biotransformed into various arsenic species that pose human health and ecological risks. However, the pathway and molecular mechanism of Rox biotransformation by soil microbes are not well studied. Therefore, in this study, we isolated a Rox-transforming bacterium from manure-fertilized soil and identified it as Pseudomonas chlororaphis through morphological analysis and 16S rRNA gene sequencing. Pseudomonas chlororaphis was able to biotransform Rox to 3-amino-4-hydroxyphenylarsonic acid (3-AHPAA), N-acetyl-4-hydroxy-m-arsanilic acid (N-AHPAA), arsenate [As(V)], arsenite [As(III)], and dimethylarsenate [DMAs(V)]. The complete genome of Pseudomonas chlororaphis was sequenced. PcmdaB, encoding a nitroreductase, and PcnhoA, encoding an acetyltransferase, were identified in the genome of Pseudomonas chlororaphis. Expression of PcmdaB and PcnhoA in E. coli Rosetta was shown to confer Rox(III) and 3-AHPAA(III) resistance through Rox nitroreduction and 3-AHPAA acetylation, respectively. The PcMdaB and PcNhoA enzymes were further purified and functionally characterized in vitro. The kinetic data of both PcMdaB and PcNhoA were well fit to the Michaelis-Menten equation, and nitroreduction catalyzed by PcMdaB is the rate-limiting step for Rox transformation. Our results provide new insights into the environmental risk assessment and bioremediation of Rox(V)-contaminated soils., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To discuss the hotspots and future trends of autophagy in traditional Chinese medicine (TCM) and provide a reference for researchers in this field., Method: Using visual analysis tools, metrological statistics and visual research on the pertinent literature in the area of autophagy use in TCM were undertaken in the core collection database of the Web of Science. By examining the authors, keywords, research circumstances, research hotspots, and trends of linked research, the use of autophagy in TCM was investigated., Results and Conclusions: A total of 916 studies were included, among which Beijing University Chinese Medicine was the largest number of advantageous research institutions, followed by Shanghai University Traditional Chinese Medicine and Guangzhou University Chinese Medicine.The keywords of literature research primarily comprise apoptosis, activation, inhibition, pathway, mechanism, oxidative stress, proliferation, NF-κB, cancer, mtor, etc. At present, the research on autophagy in the field of TCM is increasing on a year-to-year basis. The research has focused on the role played by TCM in malignant tumors, atherosclerosis, Alzheimer's disease through autophagy, and the regulation of autophagy signaling pathways (e.g., PI3K/AKT/mTOR signaling pathway, TLR4 signaling pathway,nrf2 signaling pathway and NF-κB signaling pathway). In the future, the therapeutic effect of TCM on chemotherapy-resistant tumor cells through autophagy pathway, the role of TCM mediating mitophagy and activating autophagy function, and the therapeutic effect of TCM components represented by luteolin on tumors, asthma, myocardial injury and other diseases through autophagy mechanism will be the research hotspots in the future., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Objective: To understand the incidence of HIV infection, high risk behaviors and pre-exposure prophylaxis/post-exposure prophylaxis (PrEP/PEP) utilization in men who have sex with men (MSM) in Beijing. Methods: Sample size was estimated to be 1 227 persons and 207 person year respectively in the survey and the cohort by using Epi Info 7.0 software. Using convenient sampling method, MSM were recruited by using Wechat app. Questionnaire was completed online to collect the information about demographic characteristics, high risk behavior, and utilization of PrEP/PEP of the MSM. MSM collected dry blood spot (DBS) samples by themselves, and mailed the DBS samples to laboratory for HIV nucleic acid testing. Open cohort was established and those with HIV negative nucleic acid testing results were followed up. Non-conditional binary logistic regression method was used to identify the associated factors for high risk anal sex in the last month and having multiple homosexual partners in the last month. Results: A total of 1 147 MSM were recruited, and follow up for 236 person years was conducted in 956 MSM with negative HIV nucleic acid testing results. The detection rate of new HIV infection was 1.3 per 100 person-years (3/236). During the last month, the proportions of consistent condom use in anal sex and oral sex were 50.7% (238/469) and 4.9% (23/469). In the MSM, 5.9% (43/723) had sex with HIV positive partners in the last month. 9.8% (103/1 049) used PrEP, and 8.7% (91/1 049) used PEP. The proportion of consistent condom use in PrEP and PEP were 34.3% (24/70) and 72.2% (39/54) respectively. Logistic regression analysis revealed that compared with those who used no PrEP/PEP, those who used PrEP/PEP were more likely to have unprotected anal sex in the last month (a OR =3.16, 95% CI :1.45-7.18), and more likely to have multiple homosexual partners in the last month (a OR =2.64, 95% CI :1.19-6.30), and compared with those who used no Rush Popper or drugs in the last month, those who used Rush Popper or drugs in the last month were more likely to have unprotected anal sex in the last month (a OR =2.34, 95% CI :1.67-3.30), and more likely to have multiple homosexual partners (a OR =2.42,95% CI :1.76-3.33). Conclusions: It is necessary to strengthen the health education to promote condom use and introduce the harm of drug use in MSM. In PrEP and PEP services, it is still necessary to suggest consistent condom use for MSM.

Objective: To conduct a preliminary study on joint injuries of anterior and calcaneal fibular ligaments of the lateral ankle joint, and to analyze mechanism of action of shaking and poking in treating ankle joint and biomechanical properties of ankle during the recovery of joint injuries., Methods: CT scan was performed on a male volunteer with right ankle sprain. Mimics 10.0, Solidworks 2016, Hypermesh 12.0 and Abaqus 6.13 software were used to establish 3D nonlinear finite element analysis model of foot and ankle, and the validity of model was verified. Combined with clinical study, the finite element simulation analysis was carried out on the toe flexion, dorsiflexion, varus and valgus of ankle joint under different treatment periods by adjusting elastic modulus of ligament to simulate ligament injury., Results: With the treatment of shake and prick and recovery of ligament injury, the maximum stress and area with large stress on tibial pitch and fibular joint surface gradually increased under the four working conditions, and the stress value of the maximum stress ligament gradually increased, and the stress of the anterior and calcaneal fibular ligament dispersed and transferred, and the axial force gradually decreased., Conclusion: The finite element method was used to simulate the mechanical condition of the shaking and stamping technique, and the changes of the forces of the ligament and articular surface before and after treatment of anterior and calcaneal ligament combined injury of ankle talus were intuitively observed. The treatment effect was quantified, and could provid objective and scientific basis for clinical promotion and application of this technique.

The protection of the Yangtze River is an important national strategy in China, but it faces many problems such as difficult water environment protection, unclear pollution sources, and low integration of measures. Aimed at addressing watershed scale multi-source pollution together with facing the bottleneck method, by combining research data analysis, mechanism model, and intelligent algorithm optimization, this study built the framework for accurate pollution apportionment, measures evaluation, and overall measure optimization. Shun'an watershed in Tongling City of Anhui Province was set as an example for the application. The results showed that the new method could accurately quantify the impacts of planting industry, rural life, livestock and poultry breeding, aquaculture, industrial sewage, and domestic sewage in the watershed and evaluate the overall effects of various measures. The multi-objective optimization algorithm provided a cooperative multi-source pollution control scheme with higher cost performance and better environmental benefit by comparing the cost effectiveness of various schemes systematically. The optimization scheme showed that total nitrogen could be reduced by 1274.24 t·a -1 in wet years, 855.24 t·a -1 in normal years, and 381.96 t·a -1 in dry years. Total phosphorus was reduced by 321.42 t·a -1 in wet years, 159.80 t·a -1 in normal years, and 42.93 t·a -1 in dry years, such that the water quality reached the surface class Ⅲ water quality standard. These research results can be extended to other watersheds and provide a method reference for water environment protection under the background of the high-quality development of watersheds.

Acute-on-chronic liver failure (ACLF) is a clinical syndrome of acute decompensation accompanied by organ failure that occurs on the basis of chronic liver disease and has a high short-term mortality rate. Currently, there are still differences in relation to the definition of ACLF; thus, baseline characteristics and dynamic changes are important bases for clinical decision-making in patients with liver transplantation and others. The basic strategies for treating ACLF currently include internal medicine treatment, artificial liver support systems, and liver transplantation. Multidisciplinary active collaborative management throughout the whole course is of great significance for further improving the survival rate in patients with ACLF.

The current study aimed to investigate the sagittal morphology of the spinopelvic complex and the components of the lumbar spine in the normal population. In total, 132 adult volunteers were retrospectively evaluated and divided into four groups according to the Roussouly classification. Statistical analysis of radiological parameters, including lumbar lordosis (LL), thoracic kyphosis (TK), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), PI-LL, LL-TK, lumbar vertebral lordosis from L1 to L5 (L1L-L5L), the intervertebral angle from L1-L2 to L5-S1 (IVA1-2-IVA5-1), segmental lordosis from L1 to L5 (S1L-S5L), the proportion of L1-L5 (L1%-L5%), the proportion of the intervertebral angle from L1-L2 to L5-S1 (IVA1-2%-IVA5-1%), and proportion of segmental lordosis from L1 to L5 (S1L%-S5L%), was performed. Based on the classification, type II (n = 46) was the most common, followed by type I (n = 39), type III (n = 36), and type IV (n = 11). The quantitative values of the sagittal parameters of the four groups were obtained. Results showed a significant difference in terms of LL, PI, SS, and LL-TK. Further, L1%, L2%, L3%, IVA1-2%, IVA2-3%, S1L%, S2L%, and S3L% had an increasing trend. PI was positively correlated with LL, S1L, S2L, S3L, S4L, S1L%, and S2L%, but not with S5L%. In conclusion, pelvic parameters had a significant effect on lumbar curvature and lordosis distribution. Further, the abovementioned results were beneficial for individual surgical decision-making regarding targeted intervertebral angle, screw-insertion dimension, and rod contouring., (© 2023 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Agomelatine is a selective agonist of melatonin receptor 1A/melatonin receptor 1B (MT 1 /MT 2 ) and antagonist of 5-hydroxytryptamine 2C receptors. It is used clinically to treat major depressive episodes in adults. The pro-chronobiological activity of agomelatine reconstructs sleep-wake rhythms and normalizes circadian disturbances via its agonistic effect of melatonin receptor 1A/melatonin receptor 1B, which work simultaneously to counteract depression and anxiety disorder. Moreover, by antagonizing neocortical postsynaptic 5-hydroxytryptamine 2C receptors, agomelatine enhances the release of dopamine and noradrenaline in the prefrontal cortex, increases the activity of dopamine and noradrenaline, and thereby reduces depression and anxiety disorder. The combination of these two effects means that agomelatine exhibits a unique pharmacological role in the treatment of depression, anxiety, and disturbance of the circadian rhythm. Emotion and sleep are closely related to memory and cognitive function. Memory disorder is defined as any forms of memory abnormality, which is typically evident in a broad range of neurodegenerative diseases, including Alzheimer's disease. Memory impairment and cognitive impairment are common symptoms of neurodegenerative and psychiatric diseases. Therefore, whether agomelatine can improve memory and cognitive behaviors if used for alleviating depression and circadian-rhythm sleep disorders has become a research "hotspot". This review presents the latest findings on the effects of agomelatine in the treatment of psychologic and circadian-rhythm sleep disorders in clinical trials and animal experiments. Our review evaluates recent studies on treatment of memory impairment and cognitive impairment in neurodegenerative and psychiatric diseases., Competing Interests: None

Endothelial cells play critical roles in circulatory homeostasis and are also the gateway to the major organs of the body. Dysfunction, injury, and gene expression profiles of these cells can cause, or are caused by, prevalent chronic diseases such as diabetes, cardiovascular disease, and cancer. Modulation of gene expression within endothelial cells could therefore be therapeutically strategic in treating longstanding disease challenges. Lipid nanoparticles (LNP) have emerged as potent, scalable, and tunable carrier systems for delivering nucleic acids, making them attractive vehicles for gene delivery to endothelial cells. Here, we discuss the functions of endothelial cells and highlight some receptors that are upregulated during health and disease. Examples and applications of DNA, mRNA, circRNA, saRNA, siRNA, shRNA, miRNA, and ASO delivery to endothelial cells and their targets are reviewed, as well as LNP composition and morphology, formulation strategies, target proteins, and biomechanical factors that modulate endothelial cell targeting. Finally, we discuss FDA-approved LNPs as well as LNPs that have been tested in clinical trials and their challenges, and provide some perspectives as to how to surmount those challenges., (© 2023. The Author(s).)

In this work, a solvent-free ZnO-template method is used to synthesize hierarchical porous carbons (denoted as HPC- X ; X = 1, 1.5, 2, and 4 g of ZnO) via the pyrolysis of petroleum industrial-residual pitch with ZnO. The proposed method allows precise control of the micro/meso/macroporous structure of the HPC by adjusting the amount of ZnO. The results show that the average pore size of HPCs prominently increases from 2.4 to 3.7 nm with the increase in the ZnO/pitch ratio. In addition, it is shown that HPCs have a high surface area between 1141 and 1469 m 2 g -1 , a wide-range pore size distribution (micro-, meso-, and macropores), and a tap density ranging from 0.2 to 0.57 g cm -3 . The capacitive deionization performances of HPCs for sodium and chloride ions are investigated. The results show that HPC-2 exhibits the highest electrosorption capacity of 9.94 mg g -1 within 10.0 min and a maximum electrosorption capacity of 10.62 mg g -1 at 1.2 V in a 5.0 mM NaCl solution. Hence, HPC-2 is a highly promising candidate as an electrode material for rapid deionization., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Objectives: Diabetic kidney disease (DKD) is one of the most common chronic complications in diabetic patients, and there are major limitations in its pathological diagnosis. This study's objectives were to examine the changes in serum insulin-like growth factor-1 (IGF-1) and interleukin-6 (IL-6) levels in DKD patients with various urinary albumin/creatinine ratio (ACR) and to evaluate the utility of these two biological markers in the clinical diagnosis of the condition., Methods: We chose 80 type 2 diabetic patients as the experimental group and 20 healthy normal participants as the control group. The experimental group was split into three groups based on the ACR range: diabetes without nephropathy group (ACR < 30 mg/g), microalbuminuric group (30 < ACR < 300 mg/g), and macroalbuminuric group (ACR > 300 mg/g). The levels of serum IL-6 and IGF-1 were assessed in each trial participant., Results: Serum IGF-1 was higher in the experimental group than in the control group ( P < 0.01), and serum IL-6 levels were also higher than in the control group ( P < 0.001). In DKD patients, serum levels of IL-6 and IGF-1 tended to rise when ACR levels rose. By Pearson correlation analysis, serum IGF-1 and IL-6 were positively correlated with ACR (r = 0.765 and r = 0.651, all P < 0.001) and negatively correlated with eGFR (r = -0.389 and r = -0.364, all P < 0.01). Additionally, the receiver operating characteristic (ROC) characteristic curve showed that the area under the curve (AUC) values for serum IGF-1 and IL-6 were 0.9056 and 0.7850, respectively, while the AUR value for both combined was 0.9367., Conclusion: Serum IGF-1 and IL-6 levels can be used to diagnose DKD, and the combined analysis of these two indicators can improve the sensitivity and specificity of the disease diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Zeng and Li.)

Background: Few studies have focused specifically on prognostic factors and optimal surgical intervention for early-onset triple-negative breast cancer (eTNBC), which is characterized by high malignancy and poor prognosis., Methods: We performed a cohort study with a median follow-up of 31 months using Surveillance, Epidemiology, and End Results (SEER) data of patients diagnosed with stages I-III eTNBC between 2010 and 2016. In addition, we collected cases between 2006 and 2016 from our center as an external validation set. Clinical features, pathologic characteristics and oncologic outcomes were analyzed. Prognostic factors for overall survival (OS) and breast cancer-specific survival (BCSS) were determined by Cox proportional hazards analyses and were incorporated into the prognostic nomogram. Subgroup analysis based on propensity score matching method was conducted to explore the subset of patients that would benefit from breast-conserving therapy (BCT)., Results: Based on SEER dataset, patients with eTNBC were more likely to undergo mastectomy than BCT. On multivariable analysis, patients with better survival outcomes were those not married, uninsured, had higher T and N stage, and had histological type of mixed invasive ductal and lobular carcinoma. The prognostic nomogram based on these variables successfully predicted the 3- and 5-year BCSS (C-index in training cohort, 0.774; in validation cohort from SEER, 0.768; in validation cohort from our center, 0.723). Subgroup analysis illustrated that patients with T1N0M0 or T2-4N+M0 tumors who underwent BCT achieved longer overall survival than those who underwent mastectomy (for T1N0M0, P = 0.022; for T2-4N+M0, P = 0.003); however, the type of surgery did not influence OS among patients with T1N+M0 or T2-4N0M0 tumors (for T1N+M0, P = 0.305; for T2-4N0M0, P = 0.317)., Conclusions: The prognosis of patients with eTNBC is mainly affected by marital status, insurance status, T stage, N stage and histological type. The prognostic nomogram based on these factors is quite reliable. Subgroup analysis suggested that BCT may be a superior option for patients with eTNBC, especially those with T1N0M0 and T2-4N+M0 tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zheng, Liu, Deng, Liu and Xie.)

Objectives: To establish a risk prediction model for in-hospital death in acute stroke patients based on nutritional risk scores., Methods: A retrospective analysis was performed including 268 acute stroke patients. The Nutritional Risk Screening 2002 (NRS2002) and modified Nutritional Risk in the Critically Ill (mNUTRIC) score were used to evaluate the nutritional status of patients with acute stroke after admission to the neurological intensive care unit (NICU), and laboratory parameters and clinical characteristics were collected. Multivariate logistic regression analysis was performed to screen the risk factors for in-hospital death in acute stroke patients, and a nomogram for predicting death based on the nutritional risk score was established., Results: The mortality of acute stroke in the NICU was 25.8%. Multivariate logistic regression analysis showed that the mNUTRIC score, female sex, lymphocyte count, pulmonary infection and mechanical ventilation were independent risk factors for in-hospital mortality in acute stroke patients (P &lt; 0.001 or 0.05). The above indexes were used to establish a prediction model of the in-hospital death risk for acute stroke patients. The area under the ROC curve, sensitivity, and specificity of the prediction model were 0.891 (95% CI = 0.853-0.928), 82.5%, and 81.7%, respectively. The nomogram was established and then internally validated using bootstrap repeat sampling 2000 times, the C-index was 0.880, and the predicted values of the calibration curve were in agreement with the measured values., Conclusion: The mNUTRIC-based nomogram model can be used as a reliable tool to predict the in-hospital mortality risk of acute stroke patients., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Case: A 48-year-old man presented to our facility with debilitating motor and sensory symptoms due to advanced T10-11 thoracic spinal stenosis secondary to diffuse idiopathic skeletal hyperostosis (DISH). The patient's condition was addressed with endoscopic spine surgery through a yet-to-be-reported interlaminar approach, and at the 12-month follow-up, his neurologic function was significantly improved., Conclusion: Select patients with symptomatic thoracic spinal stenosis secondary to DISH can be effectively managed with endoscopic spine surgery through an interlaminar approach by clinicians with extensive endoscopic spine experience., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B806)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Objective: To observe the effects on liver function, portal hemodynamics, plasma nitric oxide (NO), intestinal endotoxin (ETM) and interferon γ (IFN-γ) treated with acupoint-penetrating needling technique of acupuncture and enema with tuihuang mixture in the patients with refractory ascites of cirrhosis., Methods: A total of 120 patients with refractory ascites of cirrhosis were divided randomly into an observation group and a control group, 60 cases in each one. In the control group, the routine western medicine treatment was applied in combination with enema with tuihuang mixture. In the observation group, on the base of the treatment as the control group, acupoint-penetrating needling technique of acupuncture was added, Zhongwan (CV12) penetrated toward Shuifen (CV9), CV9 toward Qihai (CV6), CV6 toward Guanyuan (CV4) and CV4 toward Zhongji (CV3) respectively. The duration of treatment was 60 days in both groups. The clinical therapeutic effect was analyzed in the patients of both groups. Before and after treatment, the changes in body mass, abdominal circumference, 24 h urine output/week, maximum depth of dark area of ascites, liver function indicators, portal vein hemodynamics, plasma NO, ETM and IFN-γ were observed in the patients of the two groups., Results: The total effective rate was 81.03% (47/58) in the observation group, higher than 63.16% (36/57) in the control group ( P <0.05). After treatment, in the self-comparison of each group, the levels of body mass, abdominal circumference, the maximum depth of the dark area of ascites, the main portal vein diameter (Dpv), maximum blood flow velocity (Vmax) and venous blood flow (Q) were all lower than those before treatment ( P <0.05), 24 h urine output/week was higher than that before treatment ( P <0.05), and every indicator of liver function was improved ( P <0.05). After treatment, the values of body mass, abdominal circumference, the maximum depth of the dark area of ascites, Dpv, Vmax and Q in the observation group were all lower than those in the control group ( P <0.05), 24 h urine output/week was higher than that in the control group ( P <0.05), and the improvement in every indicator of liver function was larger than that in the control group ( P <0.05). The levels of plasma NO and ETM after treatment were all lower than those before treatment in both two groups ( P <0.05), and the level of IFN-γ was higher than that before treatment ( P <0.05). After treatment, the levels of NO and ETM in the observation group were lower than those of the control group and the level of IFN-γ was higher than that in the control group ( P <0.05)., Conclusion: The combined therapy of acupoint-penetrating needling technique of acupuncture and enema with tuihuang mixture effectively improves the effective rate on refractory ascites of cirrhosis, which is related to the decrease of endotoxin and the improvements of portal hemodynamics and cellular immune function.

An increasing global population and a sharply upward trajectory of per capita energy consumption continue to drive the demand for fossil fuels, which remain integral to energy grids and the global transportation infrastructure. The oil and gas industry is increasingly reliant on unconventional deposits such as heavy crude oil and bitumen for reasons of accessibility, scale, and geopolitics. Unconventional deposits such as the Canadian Oil Sands in Northern Alberta contain more than one-third of the world's viscous oil reserves and are vital linchpins to meet the energy needs of rapidly industrializing populations. Heavy oil is typically recovered from subsurface deposits using thermal recovery approaches such as steam-assisted gravity drainage (SAGD). In this perspective article, we discuss several aspects of materials science challenges in the utilization of heavy crude oil with an emphasis on the needs of the Canadian Oil Sands. In particular, we discuss surface modification and materials' design approaches essential to operations under extreme environments of high temperatures and pressures and the presence of corrosive species. The demanding conditions for materials and surfaces are directly traceable to the high viscosity, low surface tension, and substantial sulfur content of heavy crude oil, which necessitates extensive energy-intensive thermal processes, warrants dilution/emulsification to ease the flow of rheologically challenging fluids, and engenders the need to protect corrodible components. Geopolitical reasons have further led to a considerable geographic separation between extraction sites and advanced refineries capable of processing heavy oils to a diverse slate of products, thus necessitating a massive midstream infrastructure for transportation of these rheologically challenging fluids. Innovations in fluid handling, bitumen processing, and midstream transportation are critical to the economic viability of heavy oil. Here, we discuss foundational principles, recent technological advancements, and unmet needs emphasizing candidate solutions for thermal insulation, membrane-assisted separations, corrosion protection, and midstream bitumen transportation. This perspective seeks to highlight illustrative materials' technology developments spanning the range from nanocomposite coatings and cement sheaths for thermal insulation to the utilization of orthogonal wettability to engender separation of water-oil emulsions stabilized by endogenous surfactants extracted during SAGD, size-exclusion membranes for fractionation of bitumen, omniphobic coatings for drag reduction in pipelines and to ease oil handling in containers, solid prills obtained from partial bitumen solidification to enable solid-state transport with reduced risk of damage from spills, and nanocomposite coatings incorporating multiple modes of corrosion inhibition. Future outlooks for onsite partial upgradation are also described, which could potentially bypass the use of refineries for some fractions, enable access to a broader cross-section of refineries, and enable a new distributed chemical manufacturing paradigm., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: Optical coherence tomography (OCT) is capable of quantifying retinal damage. Defining the extent of anterior visual pathway injury is important in multiple sclerosis (MS) as a way to document evidence of prior disease, including subclinical injury, and setting a baseline for patients early in the course of disease. Retinal nerve fiber layer (RNFL) thickness is typically classified as low if values fall outside of a predefined range for a healthy population. In adults, an interocular difference (IOD) in RNFL thickness greater than 5 μm identified a history of unilateral optic neuritis (ON). Through our PERCEPTION (PEdiatric Research Collaboration ExPloring Tests in Ocular Neuroimmunology) study, we explored whether RNFL IOD informs on remote ON in a multicenter pediatric-onset MS (POMS) cohort., Methods: POMS (defined using consensus criteria and first attack <18 years) patients were recruited from 4 academic centers. A clinical history of ON (>6 months prior to an OCT scan) was confirmed by medical record review. RNFL thickness was measured on Spectralis machines (Heidelberg, Germany). Using a cohort of healthy controls from our centers tested on the same machines, RNFL thickness <86 μm (<2 SDs below the mean) was defined as abnormal. Based on previously published findings in adults, an RNFL IOD >5 μm was defined as abnormal. The proportions of POMS participants with RNFL thinning (<86 μm) and abnormal IOD (>5 μm) were calculated. Logistic regression was used to determine whether IOD was associated with remote ON., Results: A total of 157 participants with POMS (mean age 15.2 years, SD 3.2; 67 [43%] with remote ON) were enrolled. RNFL thinning occurred in 45 of 90 (50%) ON eyes and 24 of 224 (11%) non-ON eyes. An IOD >5 μm was associated with a history of remote ON (P < 0.001). An IOD >5 μm occurred in 62 participants, 40 (65%) with remote ON. Among 33 participants with remote ON but normal RNFL values (≥86 μm in both eyes), 14 (42%) were confirmed to have ON by IOD criteria (>5 μm)., Conclusions: In POMS, the diagnostic yield of OCT in confirming remote ON is enhanced by considering RNFL IOD, especially for those patients with RNFL thickness for each eye in the normal range. An IOD >5 μm in patients with previous visual symptoms suggests a history of remote ON., Competing Interests: A. T. Waldman has received research support from the NIH (NINDS K23NS069806, PI); she has received research support from the NIH (R01NS071463, site investigator; U54NS115052, project PI), Biogen Idec (PI), IONIS Pharmaceuticals (PI), United Leukodystrophy Foundation, and the Children's Hospital of Philadelphia (Foerderer Award, PI), royalties from UpToDate, and served as a consultant to Optum. L. Benson does not have disclosures directly related to the content of this article; Biogen sponsored clinical trial; paid consultant for the national vaccine injury compensation program. G. W. Liu discloses her spouse's royalties for Liu, Volpe, Galetta: Neuro-Ophthalmology, Diagnosis and Management. 2010, Elsevier. A. J. Green does not have disclosures directly related to the content of this article; he has received research support from NINDS, NMSS, NINDS SBIR, Adelson Medical Research Foundation, Hilton Foundation, Hellman Family Foundation/That Many May See, and Inception Sciences (Prior); he has received fees or other compensation from Bionure, Pipeline Therapeutics, Inception Sciences and Mylan Pharma; he is an Associate Editor at JAMA Neurology and has previously served on an endpoint adjudication committee for Medimmune/Viela Bio and has intellectual property and patents related to the UCSF Small Molecule Remyelination Program. E. Waubant is the site principal investigator for ongoing trials with Genentech and Biogen; she has research funding from NIH, PCORI, NMSS, and Race to Erase MS. She has received honoraria for lectures from Medscape, The Corpus, and AAN and for consulting work from Jazz Pharmaceuticals, Emerald, and DBV; she is the cochief editor for MSARD. G. Heidary has no disclosures relevant to the content of the article; she has grant support from the Children's Tumor Foundation and NIH. J. Graves does not have disclosures directly related to the content of this article; she has received honoraria from Genzyme for nonpromotional trainee education events; she has received personal fees from Novartis and Celgene; she has received recent grant and clinical trial support from the National MS Society, Race to Erase MS, Biogen, Genentech, and Octave. B. Greenberg has received grant support from the NIH, NMSS, Transverse Myelitis Association, PCORI, Guthy Jackson Charitable Foundation, Chugai, Medimmune, Medday, and Genentech. He has received consulting fees from Alexion, Novartis, EMD Serono, Genentech, and Celgene; he is an unpaid board member of the Transverse Myelitis Association. The other authors report no conflicts of interest., (Copyright © 2020 by North American Neuro-Ophthalmology Society.)

A primary mode of failure of thin-film coatings is the mismatch in thermal expansion coefficients of the substrate and the coating, which results in accumulation of interfacial stresses and ultimately in film delamination. While much attention has been devoted to modulation of interfacial bonding to mitigate delamination, current strategies are constrained in their generalizability and have had limited success in imbuing resistance to prolonged thermal cycling. We demonstrate here the incorporation of rigid thermal expansion compensators within polymeric films as a generalizable strategy for minimizing thermal mismatch with the substrate. Nanostructures of the isotropic negative thermal expansion (NTE) material HfV 2 O 7 have been prepared based on the reaction of nanoparticulate precursors. The NTE behavior, derived from transverse oxygen displacement within the cubic structure, has been examined using temperature-variant powder X-ray diffraction, Raman spectroscopy, electron microscopy, and selected-area electron diffraction measurements. HfV 2 O 7 initially crystallizes in a 3 × 3 × 3 superlattice but undergoes phase transformations to stabilize a cubic structure that exhibits strong and isotropic NTE with a coefficient of thermal expansion (CTE) = -6.7 × 10 -6 °C -1 across an extended temperature range of 130-700 °C. Incorporation of HfV 2 O 7 in a high-temperature thermoset polybenzimidazole enables the reduction of compressive stress by 67.3% for a relatively small loading of 26.6 vol % HfV 2 O 7 . Based on a composite model, we demonstrate that HfV 2 O 7 can reduce the thermal expansion coefficient of polymer nanocomposite films, even at low volume fractions, as a result of its substantially higher elastic modulus compared to the continuous polymer matrix. By changing the volume fraction of HfV 2 O 7 , the overall coefficients of thermal expansion of the film can be tuned to match a range of substrates, thereby mitigating thermal stresses and resolving a fundamental challenge for high-temperature composites and nanocomposite coatings.

In recent years, the substantial burden of medical comorbidities in autism spectrum disorder (ASD) populations has been described. We report a retrospective observational case series of pediatric patients with suspected idiopathic intracranial hypertension (IIH) and concurrent ASD. Pediatric subjects with suspected IIH aged 2-18 years were identified by review of a pediatric neuro-ophthalmologist's database spanning from July 1993 to April 2013. ASD diagnoses were identified within this cohort by an ICD-9 diagnosis code search and database review. Three subjects had concurrent ASD diagnoses; all were non-obese males. Since the retrospective observational case series was performed in April 2013, we identified three additional IIH cases in boys with ASD. Our experience suggests that IIH may be a comorbidity of ASD, particularly in non-obese boys.

Non-occupational post-exposure prophylaxis (nPEP), a biological means to block the transmission of HIV, is recommended by European countries, USA and WHO to use in HIV high-risk groups, but its utilization rate is still very low. The information-motivation-behavioral skills model (IMB) can accurately explain the prevalence and change of health behaviors. Based on this model, this paper summarizes the progress in research of the influencing factors for nPEP use to provide a basis for further research to promote the use of nPEP.

Background: Postmenopausal osteoporosis is characterized by an imbalance of bone resorption exceeding bone formation, resulting in a net loss of bone mass. Whether a menopause-related excess of iron contributes to the development of postmenopausal osteoporosis has remained unresolved due to a lack of an appropriate animal model. This study aimed to explore the effects of iron accumulation in bone mass in estrogen-deficient rats., Methods: In the present study, ovariectomy (OVX) was performed in female rats and the changes of iron metabolism and some related modulated genes were detected. Ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. Moreover, micro-CT was performed to assess the bone microarchitecture in sham group, OVX, and FAC groups. Histological detection of iron in liver was assessed by Perl's staining. The expressions of β-CTX and osteocalcin were assessed by ELISA., Results: It was found that serum iron decreased after OVX. It was found that the expressions of Hepcidin in liver and Fpn, DMT-1 in duodenum significantly decreased at transcriptional level in OVX group than sham group. However, no difference existed in the expression of DMT-1. Then, ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. The FAC group manifested significant iron accumulation by increased serum iron and hepatic iron content. In addition, FAC treatment accelerated bone loss and decreased BMD and biomechanics in OVX rats. Moreover, bone biomarker β-CTX rather than osteocalcin increased significantly in FAC groups than OVX group., Conclusions: In conclusion, no iron accumulation occurred in OVX rats. Furthermore, iron accumulation could further deteriorate osteopenia through enhanced bone resorption., (© 2021. The Author(s).)

Ethnopharmacological Relevance: Scutellaria barbata D.Don (SB) and Oldenlandia diffusa (Willd.) Roxb are commonly known as Ban Zhi Lian and Bai Hua She Cao in Chinese herbal medicines, respectively. As a pair of herbs, they have traditionally been used as ethnomedicines for clearing away heat and toxins, removing blood stasis, and promoting blood circulation, diuresis, and detumescence., Aim of the Study: The aim of the present study was to determine the active ingredients in SB and OD extracts and to investigate whether these extracts can inhibit the growth of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) cell lines (HepG2.2.15 and Hep3B) in vitro and in vivo, as well as to explore their mechanisms of action., Materials and Methods: We determined the levels of total flavonoids, luteolin, and apigenin in SB and OD extracts via ultraviolet-visible spectrophotometry and high-performance liquid chromatography. The effects of SB and OD extracts on HBV-associated HCC cell growth were assessed by HepG2.2.15 and Hep3B cells phenotype and RNA sequencing of Hep3B cells in vitro, and xenograft models in vivo., Results: The extracts of SB and OD contained total flavonoids. There were active ingredients of luteolin and apigenin in SB, but not in OD. The extracts of SB and OD significantly inhibited HCC growth, migration, invasion, and HBV activity in vitro and in vivo, as well as altered circRNA expression in Hep3B cells. Moreover, we constructed a circRNA-miRNA-mRNA co-expression network., Conclusions: The extracts of SB and OD may inhibit HCC cell growth and HBV activity in vitro and in vivo through altering circRNA-miRNA-gene expression and that the efficacies of these extracts may be related to the presence of luteolin and apigenin., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Nuciferine (NF) has received extensive attention due to its medicinal value in the treatment of metabolic diseases, such as obesity; however, to date, the effects of NF on obesity-related intestinal permeability, autophagy and the gut microbiota have not been investigated. Herein, C57BL/6J mice were fed either a chow or a high-fat diet (HFD) with or without NF for 8 weeks. The results showed that NF supplement reduced weight gain, fat accumulation and intestinal permeability in the HFD mice accompanied by improved autophagy. Subsequently, an in vitro experiment was performed using Caco-2 and HT-29 cells, which showed that NF supplement not only promoted the formation of autophagosomes and autophagolysosomes, but also alleviated LPS-increased intestinal permeability. Importantly, NF supplement protected from LPS-induced paracellular permeability impairment after the administration of autophagy-related gene (Atg) 5 small-interfering RNA (siRNA). These results demonstrate that NF exerts beneficial effects on the intestinal permeability by improving autophagy. Furthermore, we also found that NF supplement lowered the abundance of Butyricimonas and increased the abundance of Akkermansia, an anti-obesity bacterium. Thus, overall, we demonstrated that NF supplement confers reduced intestinal permeability by improving autophagy and alters the composition of the gut microbiota in HFD-fed mice, thereby producing an anti-obesity effect.

Objective: To quantitatively study the biomechanical parameters of Bachuorounian manipulation in the treatment of humeral epicondylitis, and discuss the effects of individual characteristics on the biomechanical parameters were discussed., Methods: From July 2019 to February 2020, 40 patients with external humeral epicondylitis were selected, including 18 males and 22 females, ranging in age from 20 to 50 years old, with an average of (34.37±8.41) years old;and the course of disease ranged from 1 to 11 months, with a mean of (6.05±2.71) months. The biomechanical parameters of the elbow joint of the affected side were measured by using the biomechanical sensor. At thesame time, the individual characteristic parameters of patients were collected to analyze the influence of different individual characteristics of patients on biomechanical parameters., Results: The results of mechanical analysis in each stage of the bachuorounian manipulation were as follows:the rolling back rotation force was (31.17±2.99) N;the buckling bending drawing force was (44.99±2.38) N;the rolling pre rotation force was (31.03±2.75) N;and stretching drawing force was (48.75±2.09) N. The correlation analysis between the parameters showed that there was a significant positive correlation between the buckling bending drawing force and the stretching drawing force parameters, and a significant positive correlation between the rolling force back-rotation force and the rolling pre-rotation force parameters. The multivariate linear regression analysis on the parameters of influencing factors and manipulative biomechanics showed that there was a significant correlation between body weight and rolling back-rotation force, significant correlation between elbow tenderness and the buckling bending drawing force, and significant correlation between disease duration and the stretching drawing force., Conclusion: The bachuorounian manipulation of humeral epicondylitis has a certain range of operating force. Manipulation of each stage has a correlation and systematic. The patient's weight, elbow tenderness and disease course are important factors affecting the bachuorounian manipulation.

Objective: To explore the mechanisms of ursolic acid for treating colon cancer based on network pharmacology., Method: In this study, the potential targets of ursolic acid against colon cancer were predicted and screened through the TCMSP, SYMMAP, Drug Bank, UNI-PROT, and DISGENET databases. The protein interaction (PPI) network was constructed based on the STRING database, and graphs were drawn with the help of Cytoscape software. GO and KEGG enrichment analyses were performed on the targets by using the DAVID database for biological information annotation., Results: Ursolic acid has 113 targets in the treatment of colon cancer. The core targets included interleukin-6 (IL-6), mitogen-activated protein kinase 3 (MAPK3), vascular endothelial growth factor receptor (VEGFA), prostaglandin endoperoxide synthase 2 (PTGS2), caspase-3 (CASP3), mitogen-activated protein kinase 8 (MAPK8), tumor necrosis factor (TNF), cyclin D1 (CCND1), JUN, signal transducer and transcriptional activator 3 (STAT3), and other targets. The first 10 pathways related to colon cancer were screened out. The main signaling pathways included the TNF signaling pathway and the AGE-RAGE signaling pathway in diabetic complications and human colon cancer infections., Conclusion: This study revealed that ursolic acid played a multitarget and multichannel antitumor role by inhibiting the proliferation of tumor cells, inducing apoptosis, and enhancing antiangiogenesis., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Jun Zhao et al.)

Objective: To study mechanism of improvement of stress concentration on patellofemoral joint by stiletto needle releasing lateral patellar retinaculum guided by the theory of Jinshugu() and based on the finite element model of knee joint. and to elucidate the biomechanical mechanism of stiletto needle releasing changing patellar trajectory and reducing patellofemoral joint pressure., Methods: CT data of knee joint from a normal male (aged 29, heighted 171 cm, weighted 58 kg) was selected. Starting with construction of three-dimensional model of knee joint by using finite element software, the finite element model of knee joint with complete tendonand bone structures were established through several steps, such as geometric reconstruction, reverse engineering, meshing, material assignment and loading analysis. The loading condition was set as 500 N load on knee joint, and the average tensile stress of quadriceps femoris tendon was about 200 N. To simulate the release of lateral patellar retinaculum by stiletto needle at 30 and 90 position of knee flexion in finite element model separately, and to compare the improvement of stress concentration of patellofemoral joint by stiletto needle intervention under different knee flexion conditions., Results: The peak stress of patellofemoral joint and tibiofemoral joint decreased after stiletto needle releasing of patellofemoral lateral retinaculum compared with before intervention, which was(1) knee flexion at 30 degrees:patellar cartilage decreased by 0.498 MPa (decreased 9.06%), femoral trochlea decreased by 0.886 MPa(decreased 16.27%);(2) knee flexion at 90 degrees:patellar cartilage decreased by 0.558 MPa (decreased 8.6%), femoral trochlea decreasedby 0.607 MPa (decreased 9.94%)., Conclusion: Releasing lateral patellofemoral retinaculum with stiletto needle could effectively alleviate the stress concentration of patellofemoral joint and reduce local stress peak value, which it is helpful to improve patellar trajectory and make stress distribution more uniform.

Background: Colorectal cancer is harmful to the patient's life. The treatment of patients is determined by accurate preoperative staging. Magnetic resonance imaging (MRI) played an important role in the preoperative examination of patients with rectal cancer, and artificial intelligence (AI) in the learning of images made significant achievements in recent years. Introducing AI into MRI recognition, a stable platform for image recognition and judgment can be established in a short period. This study aimed to establish an automatic diagnostic platform for predicting preoperative T staging of rectal cancer through a deep neural network., Methods: A total of 183 rectal cancer patients' data were collected retrospectively as research objects. Faster region-based convolutional neural networks (Faster R-CNN) were used to build the platform. And the platform was evaluated according to the receiver operating characteristic (ROC) curve., Results: An automatic diagnosis platform for T staging of rectal cancer was established through the study of MRI. The areas under the ROC curve (AUC) were 0.99 in the horizontal plane, 0.97 in the sagittal plane, and 0.98 in the coronal plane. In the horizontal plane, the AUC of T1 stage was 1, AUC of T2 stage was 1, AUC of T3 stage was 1, AUC of T4 stage was 1. In the coronal plane, AUC of T1 stage was 0.96, AUC of T2 stage was 0.97, AUC of T3 stage was 0.97, AUC of T4 stage was 0.97. In the sagittal plane, AUC of T1 stage was 0.95, AUC of T2 stage was 0.99, AUC of T3 stage was 0.96, and AUC of T4 stage was 1.00., Conclusion: Faster R-CNN AI might be an effective and objective method to build the platform for predicting rectal cancer T-staging., Trial Registration: chictr.org.cn: ChiCTR1900023575; http://www.chictr.org.cn/showproj.aspx?proj=39665., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background It was uncertain if direct endovascular thrombectomy (ET) was superior to bridging thrombolysis (BT) for patients with acute ischemic stroke caused by large-vessel occlusions. We aimed to examine real-world clinical outcomes of ET using nationwide registry data in China and to compare the efficacy and safety between BT and direct ET. Methods and Results Patients treated with ET from a nationwide registry study in China were included. Rapid neurological improvement, intracranial hemorrhage, and in-hospital mortality were compared between the 2 groups using multivariate logistic models and propensity-score matching analyses. A total of 7674 patients from 592 stroke centers were included. The median onset-to-puncture time, onset-to-door time, and door to puncture time were 290, 170, and 99 minutes, respectively. A total of 2069 (27.0%) patients received BT treatment. Patients in the BT group had a significantly shorter onset-to-puncture time (235 versus 323 minutes; P <0.001) and onset-to-door time (90 versus 222 minutes; P <0.001) compared with the direct ET group. The prior use of intravenous thrombolysis was associated with a higher rate of rapid neurological improvement (adjusted odds ratio [OR], 0.83; 95% CI, 0.71-0.96) and higher risk of intracranial hemorrhage (adjusted OR, 1.46; 95% CI, 1.18-1.80) in multivariate analyses and propensity-score matching analyses. Conclusions This study reflects the current application of ET in China. More patients received direct ET than BT. Our results suggested that favorable short-term outcomes could be achieved with BT compared with direct ET. Higher risk of intracranial hemorrhage was observed in the BT group.

Background: The clinical relevance of the highest mediastinal lymph node (HMLL) metastasis in patients with pathological N2 non-small cell lung cancer (NSCLC) is still controversial. Our study aimed to reassess the effect of HMLL metastasis on survival., Methods: Patients with stage pT1-4N2M0 NSCLC who underwent major lung resection and systemic lymphadenectomy at Peking University People's Hospital from 2004 to 2015 were identified. Patients in the HMLL-positive group were matched to patients in the HMLL-negative group using 1:1 propensity score matching analysis. Overall survival was estimated by Kaplan-Meier method and compared using log-rank test, and multivariable Cox proportional hazard regression was constructed to identify risk factors associated with overall survival. The cumulative incidence of cancer specific mortality was evaluated through a competing risk analysis., Results: A total of 266 NSCLC patients with stage pT1-4N2M0 NSCLC were enrolled. Of those, 128 cases were HMLL positive and 138 cases were HMLL negative. A higher proportion of patients in the HMLL-positive group were female (P = .034) and had a higher rate of adenocarcinoma (P = .003). Compared with the HMLL-negative, the HMLL-positive group was not associated with worse survival in unmatched cohorts (adjusted hazard ratio = 1.21; 95% confidence interval, 0.87-1.68). After propensity score matching, 109 pairs were selected. No survival difference remained in matched cohorts (adjusted hazard ratio = 1.00; 95% confidence interval, 0.70-1.42)., Conclusions: Highest mediastinal lymph node metastasis does not exhibit worse survival in patients with stage pT1-4N2M0 NSCLC. The clinical relevance of HMLL metastasis needs further examination., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background/purpose: One effective way to deal with dentin hypersensitivity is to develop materials to seal the tubules. The porous bio-calcium carbonate-silica (BCCS) contained well-dispersed CaCO 3 would form calcium phosphates to seal the dentinal tubules when mixed with an acidic solution. The acidic hydrothermal treatment and calcination to isolate the BCCS from the agricultural waste like equisetum grass was used, which would be more environmentally friendly than chemically synthesized mesoporous biomaterials. The aim of this study was to develop mesoporous materials from natural resources to occlude the dentinal tubules which could be more environmentally-friendly., Methods: Dentin disc samples were prepared and treated with different methods as follows: (1) BCCS mixed with H 3 PO 4 ; (2) BCCS mixed with KH 2 PO 4 ; (3) Seal & Protect® was used as a comparison group. Sealing efficacy was evaluated by measuring the depths and percentages of precipitate occlusion in dentinal tubules with SEM., Results: The N 2 adsorption-desorption isotherm of the BCCS demonstrated a pore size of around 15.0 nm and a surface area of 61 m 2 g-1. From the results of occlusion percentage and depth, the BCCS treated with H 3 PO 4 or KH 2 PO 4 demonstrated promising sealing efficacy than the commercial product., Conclusion: This synthetic process used the agricultural waste equisetum grass to produce bio-calcium carbonate-silica would be environmentally friendly, which has great potential in treating exposed dentin related diseases., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020. Published by Elsevier B.V.)

Objective: Peripheral nerve invasion (PNI) is associated with local recurrence and poor prognosis in patients with advanced gastric cancer. A risk-assessment model based on preoperative indicators for predicting PNI of gastric cancer may help to formulate a more reasonable and accurate individualized diagnosis and treatment plan. Methods: Inclusion criteria: (1) electronic gastroscopy and enhanced CT examination of the upper abdomen were performed before surgery; (2) radical gastric cancer surgery (D2 lymph node dissection, R0 resection) was performed; (3) no distant metastasis was confirmed before and during operation; (4) postoperative pathology showed an advanced gastric cancer (T2-4aN0-3M0), and the clinical data was complete. Those who had other malignant tumors at the same time or in the past, and received neoadjuvant radiochemotherapy or immunotherapy before surgery were excluded. In this retrospective case-control study, 550 patients with advanced gastric cancer who underwent curative gastrectomy between September 2017 and June 2019 were selected from the Affiliated Hospital of Qingdao University for modeling and internal verification, including 262 (47.6%) PNI positive and 288 (52.4%) PNI negative patients. According to the same standard, clinical data of 50 patients with advanced gastric cancer who underwent radical surgery from July to November 2019 in Qingdao Municipal Hospital were selected for external verification of the model. There were no statistically significant differences between the clinical data of internal verification and external verification (all P >0.05). Univariate analysis and multivariate logistic regression analysis were used to determine the independent risk factors for PNI in advanced gastric cancer, and the clinical indicators with statistically significant difference were used to establish a preoperative nomogram model through R software. The Bootstrap method was applied as internal verification to show the robustness of the model. The discrimination of the nomogram was determined by calculating the average consistency index (C-index). The calibration curve was used to evaluate the consistency of the predicted results with the actual results. The Hosmer-Lemeshow test was used to examine the goodness of fit of the discriminant model. During external verification, the corresponding C-index index was also calculated. The area under ROC curve (AUC) was used to evaluate the predictive ability of the nomogram in the internal verification and external verification groups. Results: A total of 550 patients were identified in this study, 262 (47.6%) of which had PNI. Multivariate logistic regression analysis revealed that carcinoembryonic antigen level ≥ 5 μg/L (OR=5.870, 95% CI: 3.281-10.502, P <0.001), tumor length ≥5 cm (OR=5.539,95% CI: 3.165-9.694, P <0.001), mixed Lauren classification (OR=2.611, 95%CI: 1.272-5.360, P =0.009), cT3 stage (OR=13.053, 95% CI: 5.612-30.361, P <0.001) and the presence of lymph node metastasis (OR=4.826, 95% CI: 2.729-8.533, P <0.001) were significant independent risk factors of PNI in advanced gastric cancer (all P <0.05). Based on these results, diffused Lauren classification and cT4 stage were included to establish a predictive nomogram model. CEA ≥ 5 μg/L was for 68 points, tumor length ≥ 5 cm was for 67 points, mixed Lauren classification was for 21 points, diffused Lauren classification was for 38 points, cT3 stage was for 75 points, cT4 stage was for 100 points, and lymph node metastasis was for 62 points. Adding the scores of all risk factors was total score, and the probability corresponding to the total score was the probability that the model predicted PNI in advanced gastric cancer before surgery. The internal verification result revealed that the AUC of nomogram was 0.935, which was superior than that of any single variable, such as CEA, Lauren classification, cT stage, tumor length and lymph node metastasis (AUC: 0.731, 0.595, 0.838, 0.757 and 0.802, respectively). The external verification result revealed the AUC of nomogram was 0.828. The C-ndex was 0.931 after internal verification. External verification showed a C-index of 0.828 from the model. The calibration curve showed that the predictive results were good in accordance with the actual results ( P =0.415). Conclusion: A nomogram model constructed by CEA, tumor length, Lauren classification (mixed, diffuse), cT stage, and lymph node metastasis can predict the PNI of advanced gastric cancer before surgery.

Loss and dysfunction of glomerular podocytes result in increased macromolecule permeability through the glomerular filtration barrier and nephrotic syndrome. Current therapies can induce and maintain disease remission, but cause serious and chronic complications. Nanoparticle drug carriers could mitigate these side effects by delivering drugs to the kidneys more efficiently than free drug through tailoring of carrier properties. An important extrinsic factor of nanoparticle biodistribution is local pathophysiology, which may drive greater nanoparticle deposition in certain tissues. Here, we hypothesized that a "leakier" filtration barrier during glomerular kidney disease would increase nanoparticle distribution into the kidneys. We examined the effect of nanoparticle size and disease state on kidney accumulation in male BALB/c mice. The effect of size was tested using a panel of fluorescent polystyrene nanoparticles of size 20-200 nm, due to the relevance of this size range for drug delivery applications.Experimental focal segmental glomerulosclerosis was induced using an anti-podocyte antibody that causes abrupt podocyte depletion. Nanoparticles were modified with carboxymethyl-terminated poly(ethylene glycol) for stability and biocompatibility. After intravenous injection, fluorescence from nanoparticles of size 20 and 100 nm, but not 200 nm, was observed in kidney glomeruli and peritubular capillaries. During conditions of experimental focal segmental glomerulosclerosis, the number of fluorescent nanoparticle punctae in kidney glomeruli increased by 1.9-fold for 20 and 100 nm nanoparticles compared to normal conditions. These findings underscore the importance of understanding and leveraging kidney pathophysiology in engineering new, targeted drug carriers that accumulate more in diseased glomeruli to treat glomerular kidney disease., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objective: To explore the feasibility of using faster regional convolutional neural network (Faster R-CNN) to evaluate the status of circumferential resection margin (CRM) of rectal cancer in the magnetic resonance imaging (MRI). Methods: This study was registered in the Chinese Clinical Trial Registry (ChiCTR-1800017410). Case inclusion criteria: (1) the positive area of CRM was located between the plane of the levator ani, anal canal and peritoneal reflection; (2) rectal malignancy was confirmed by electronic colonoscopy and histopathological examination; (3) positive CRM was confirmed by postoperative pathology or preoperative high-resolution MRI. Exclusion criteria: patients after neoadjuvant therapy, recurrent cancer after surgery, poor quality images, giant tumor with extensive necrosis and tissue degeneration, and rectal tissue construction changes in previous pelvic surgery. According to the above criteria, MRI plain scan images of 350 patients with rectal cancer and positive CRM in The Affiliated Hospital of Qingdao University from July 2016 to June 2019 were collected. The patients were classified by gender and tumor position, and randomly assigned to the training group (300 cases) and the validation group (50 cases) at a ratio of 6:1 by computer random number method. The CRM positive region was identified on the T2WI image using the LabelImg software. The identified training group images were used to iteratively train and optimize parameters of the Faster R-CNN model until the network converged to obtain the best deep learning model. The test set data were used to evaluate the recognition performance of the artificial intelligence platform. The selected indicators included accuracy, sensitivity, positive predictive value, receiver operating characteristic (ROC) curves, areas under the ROC curves (AUC), and the time taken to identify a single image. Results: The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the CRM status determined by the trained Faster R-CNN artificial intelligence approach were 0.884, 0.857, 0.898, 0.807, and 0.926, respectively; the AUC was 0.934 (95% CI: 91.3% to 95.4%). The Faster R-CNN model's automatic recognition time for a single image was 0.2 s. Conclusion: The artificial intelligence model based on Faster R-CNN for the identification and segmentation of CRM-positive MRI images of rectal cancer is established, which can complete the risk assessment of CRM-positive areas caused by in-situ tumor invasion and has the application value of preliminary screening.

Medical artificial intelligence is a deeply integrated field of production-university-research. The collaborative innovation system of "industry, education and research" has broken down the barriers between various disciplines and has shown great impetus in scientific and technological innovation and achievement transformation. The Affiliated Hospital of Qingdao University where the authors work, relying on Shandong Key Laboratory of Digital Medicine and Computer-Assisted Surgery and Institute of Digital Medicine and Computer-Assisted Surgery of Qingdao University, has jointly established a close "industry-university-research" cooperation mechanism with the State Key Laboratory of Virtual Reality Technology and Systems of Beijing University of Aeronautics and Astronautics and Qingdao Hisense Medical Equipment Co., Ltd., which lasted for 10 years and carried out a series of useful explorations in scientific and technological innovation and achievement transformation in the field of gastrointestinal surgery of artificial intelligence with fruitful results. It mainly comprises of the following: (1) The research and development (R&D) of Hisense computer-assisted surgery (CAS) system has important clinical significance for laparoscopic gastrointestinal surgery guided by surrounding blood vessels that grasps globally the movement and variation of blood vessels in order to accurately select surgical strategies. (2) R&D of an automatic identification system for gastrointestinal diseases (namely image-assisted diagnosis system of artificial intelligence) initially applies deep neural network of artificial intelligence to the identification of lymph node metastases in rectal cancer, which has achieved accurate clinical diagnosis. (3) The virtual endoscopy platform for the gastrointestinal tract developed can successfully provide a new virtual endoscopy view of the intestinal wall eversion and realize the one-way navigation of the intestinal wall. (4) A localized platform of laparoscopic surgery simulation training is established with completely independent intellectual property rights. We realize that clinical requirement is the source of research and development, clinical practice is the source of innovation, and clinicians are practitioners of transformation of achievements. The establishment of artificial intelligence models often requires the support of massive and high-quality clinical data. Therefore, the effectiveness of its promotion and application can only be ensured by adopting a multi-center research approach. In the whole process of scientific and technological innovation and achievement transformation, the issues of medical ethics and intellectual property rights cannot be ignored.

Objectives: To understand the prevalence of HIV nucleic acid using internet-based dry blood spots HIV testing strategy in men who had sex with men (MSM) and to probe the factors associated with HIV infection. Methods: Using convenient sampling method, 1 375 MSM were recruited and their dry blood spots samples were collected before being mailed to the laboratories for HIV nucleic acid testing. Results were showed to these MSM on a specific website by inputting their codes to it. Non-conditional binary logistic regression method was used to identify the associated factors on HIV infection. Results: The overall proportions of HIV nucleic acid positives appeared as 9.7 % (131/1 349) and HIV antibody positives as 8.3 % (112/1 349). Fresh infections accounted for 14.5 % (19/131) among the newly-identified HIV nucleic acid positives, and the interval was ranging from 6 to 120 days, between the laboratory testings and the closest date that experiencing high risk behavior. Risk factors that related to HIV infection would include: 30 to 39 years of age (comparing to those under the age of 30, OR =1.88, 95 %CI : 1.07-3.29), ≥8 000 Yuan of monthly income (comparing to those without income, OR =0.42, 95 %CI : 0.19-0.96), inconsistent condom use during anal sexual contacts in the last six months (compared with those who had not anal sex or used condoms consistently in anal sex in the past six months, OR =2.22, 95 %CI : 1.45-3.40), ever use of Rush Poppers (compared with those who never used Rush Poppers, OR =2.33, 95 %CI : 1.49-3.64), addictive drug abuse (compared with those who never abused addictive drugs, OR =5.43, 95 %CI : 2.32-12.69), and not having regular sexual partners (compared with having regular sexual partners, OR =1.74, 95 %CI : 1.13-2.68) etc .. Conclusions: Dry blood spots HIV nucleic acid testing could help to identify the fresh HIV infections at an early stage, so as to prevent further transmission in the MSM population, among which fresh HIV infections accounted for a fairly large proportion. It is necessary to set up programs in reducing the abuse of drugs or Rush Poppers, and to promote condom use and advocate on stable sexual partnership etc ., among the MSM population.

Background: High-contrast visual acuity (HCVA) changes with age, yet little is known about pediatric-specific age- and sex-normative values for low-contrast letter acuity (LCLA). We define maturational changes in monocular and binocular HCVA and LCLA in childhood and adolescence., Methods: Normally sighted youth (ages 5-20 years, without neurologic or ophthalmologic disease and best-corrected HCVA of 20/25 or better in each eye) were recruited. Mean monocular and binocular scores using Early Treatment Diabetic Retinopathy Study (for HCVA) and 2.5% and 1.25% Sloan (for LCLA) charts and the magnitude of binocular summation were calculated using 2-year bins. Relationships between scores and age were explored using scatterplots with Locally Weighted Scatterplot Smoothing (LOWESS) and analysis of variance that accounts for intereye correlation, followed by test of linear trend for age effect., Results: Among 101 (202 eyes) healthy participants (mean age 13 years, 42% males), monocular and binocular scores varied by age, with highest mean scores achieved in the 13 to 14-year age group for both HCVA and LCLA. Between the ages of 5 and 14.9 years, monocular scores increased linearly with age (0.76 letter/year for HCVA, 1.11 letters/year for 2.5% LCLA, and 0.97 letter/year for 1.25% LCLA; all P < 0.0001). Binocular HCVA scores also increased with age between 5 and 14.9 years (0.71 letters/year, P < 0.0001). The magnitude of binocular summation for HCVA or LCLA did not change with age., Conclusions: HCVA and LCLA abilities mature into adolescence, peak between 13 and 14.9 years of age, and then plateau into adulthood. Evaluation of patients with visual deficits should consider age-expected normal visual acuity.

Objective: To construct a dynamic knee joint finite element model based on CT image data and verify the validity of the model. To provide a simulation model and basic data for biomechanical research of the knee joint by further finite element analysis., Methods: The CT data of a healthy male knee joint was selected. With the help of Mimics 19.0 and Hypermesh 12.0 software, a high simulation finite element model of knee joint was established following steps, including geometric reconstruction, reverse engineering, meshing and material characterization. The dynamic knee flexion model was generated by determining the boundary conditions and torque loading, and the validity of themodel was confirmed. The biomechanical changes of the tibiofemoral and patellofemoral joints under different knee flexion angles were analyzed by applying the loads (500 N) to the finite element model during knee flexion., Results: A finite element model of knee joint was established based on CT images and anatomical characteristics. The model included three-dimensional elements such as bone, ligament, cartilage, meniscus and patellar retinaculum. The different finite element models of knee flexion states were produced by applying different torques after establishing boundary conditions. According to equivalent conditions (knee flexion 30 degrees, quadriceps tendon under 200 N stretch), the peak stress value of patella was 2.209 MPa and the average Mises stress was 1.132 MPa; the peak stress value of femoral trochlear was 1.405 MPa and the average Mises stress was 0.936 MPa. The validity of the model was proved by the difference between the model and previous studies of 1% to 13.5%. Dynamic model loading showed that the Mises stressof tibiofemoral joint decreased with the increase of knee flexion angle, while the Mises stress of patellofemoral joint was positively correlated with knee flexion angle. The Mises stress of cartilage stress planes at different knee flexion angles was significantly different( P <0.05)., Conclusion: The finite element model established in this study is more comprehensive and can effectively simulate the biomechanical characteristics of dynamic knee joint, which provides support for further simulation mechanics researches of the knee joint.

Objective: To examine the value and clinical application of convolutional neural network in pathological diagnosis of metastatic lymph nodes of gastric cancer. Methods: Totally 124 patients with advanced gastric cancer who underwent radical gastrectomy plus D2 lymphadenectomy at Affiliated Hospital of Qingdao University from July 2016 to December 2018 were selected in the study. According to the chronological order, the first 80 cases were served as learning group. The remaining 44 cases were served as verification group. There were 45 males and 35 females in the study group, with average age of 57.6 years. There were 29 males and 15 females in the validation group, with average age of 9.2 years. The pre-training convolutional neural network architecture Resnet50 was trained and fine-tuned by 21 352 patches with cancer areas and 14 997 patches without cancer areas in the training group. A total of 78 whole-slide image served as a test dataset including positive ( n= 38) and negative ( n= 40) lymph nodes. The convolutional neural network computer-aided detection (CNN-CAD) system was used to analyze the ability of convolutional neural network system to screen metastatic lymph nodes at the level of slice by setting threshold, and evaluate the system's classification accuracy by calculating its sensitivity, specificity, positive predictive value, negative predictive value and area under the receiver operating characteristic curve (AUC). Results: The classification accuracy of CNN-CAD system at slice level was 100%.The AUC for the CNN-CAD system was 0.89. The sensitivity was 0.778, specificity was 0.995, overall accuracy was 0.989. Positive and negative predictive values were 0.822 and 0.994, respectively. The CNN-CAD system achieved the same classification results as pathologists. Conclusions: The CNN-CAD system has been constructed to distinguished benign and malignant lymph node slides with high accuracy and specificity. It could achieve the similar classification results as pathologists.