Pamrevlumab for Idiopathic Pulmonary Fibrosis: The ZEPHYRUS-1 Randomized Clinical Trial.

Importance: Current treatments for idiopathic pulmonary fibrosis slow the rate of lung function decline, but may be associated with adverse events that affect medication adherence. In phase 2 trials, pamrevlumab (a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity) attenuated the progression of idiopathic pulmonary fibrosis without substantial adverse events. Objective: To assess the efficacy and safety of pamrevlumab for patients with idiopathic pulmonary fibrosis. Design, Setting, and Participants: Phase 3 randomized clinical trial including 356 patients aged 40 to 85 years with idiopathic pulmonary fibrosis who were not receiving antifibrotic treatment with nintedanib or pirfenidone at enrollment. Patients were recruited from 117 sites in 9 countries between July 18, 2019, and July 29, 2022; the last follow-up encounter occurred on August 28, 2023. Interventions: Pamrevlumab (30 mg/kg administered intravenously every 3 weeks; n = 181) or placebo (n = 175) for 48 weeks. Main Outcomes and Measures: The primary outcome was absolute change in forced vital capacity (FVC) from baseline to week 48. There were 5 secondary outcomes (including time to disease progression, which was defined as a decline of ≥10% in predicted FVC or death). The exploratory outcomes included patient-reported symptoms. Adverse events were reported. Results: Among 356 patients (mean age, 70.5 years; 258 [72.5%] were men; 221 [62.1%] were White), 277 (77.8%) completed the trial. There was no significant between-group difference for absolute change in FVC from baseline to week 48 (least-squares mean, -260 mL [95% CI, -350 to -170 mL] in the pamrevlumab group vs -330 mL [95% CI, -430 to -230 mL] in the placebo group; mean between-group difference, 70 mL [95% CI, -60 to 190 mL], P = .29). There were no significant between-group differences in any of the secondary outcomes or in the patient-reported outcomes. In the pamrevlumab group, there were 160 patients (88.4%) with treatment-related adverse events and 51 patients (28.2%) with serious adverse events vs 151 (86.3%) and 60 (34.3%), respectively, in the placebo group. During the study, 23 patients died in each group (12.7% in the pamrevlumab group vs 13.1% in the placebo group). Conclusions and Relevance: Among patients with idiopathic pulmonary fibrosis treated with pamrevlumab or placebo, there was no statistically significant between-group difference for the primary outcome of absolute change in FVC from baseline to week 48. Trial Registration: ClinicalTrials.gov Identifier: NCT03955146.

A Novel Punch Technique for Facial Pigmented Melanocytic Nevus.

The punch tool is a swift and practical instrument in the facial pigmented melanocytic nevus. However, few studies have evaluated the efficacy of the method for facial pigmented nevus. The aim of this study was to evaluate the practicability and effectiveness of removing facial pigmented nevus by punch biopsy technique. This was an observational study of patients with facial pigmented nevus in the Hospital of Plastic Surgery, Weifang Medical University. The ages of patients ranged from 15 to 36 years (average, 25 y). The outcome evaluations included Vancouver Scar Scale (VSS) score, esthetic appearance, and patient satisfaction. Following standard procedures, preoperative surgical excision was performed with safety margins. Anatomopathologic analysis of the surgical specimen was used as the gold standard to evaluate the accuracy of diagnosis by punch biopsy. From January 2019 to January 2020, this punch technique was carried out on 96 patients (151 pigmented nevus) with 35 melanocytic nevus on the forehead, 39 on the cheek, 21 on the eyelid, and 45 on the nose, whereas 11 were on nasolabial folds. The diameters of pigmented nevus are 0.5 to 10 mm on the face. All patients were evaluated at a follow-up visit ranging from 6 to 20 months (average, 11±1.5 mo) and healed with no complication. The histopathological examinations of the skin lesions showed benign outcomes. The mean Vancouver Scar Scale were 1.1±0.4. Ideal cosmetic and functional outcomes were achieved in 94 patients (97.9%). All patients achieved complete satisfaction except 2 patients with partial satisfaction. No recurrences and complications were recorded. This study demonstrated that the punch technique is an effective method to remove facial pigmented melanocytic nevus with acceptable functional and esthetic outcomes without relapse.

Development, application and practical experience of clinical research integration platform of a third-class hospital in Beijing / 中华医学科研管理杂志

Objective:To explore the development, application and practical experience of investigator-initiated integrated clinical research information platform.Methods:The process of developing and constructing an integrated clinical research platform in a tertiary hospital in Beijing was introduced, the functions and advantages of the platform were described and displayed, and the main problems and risk points in the development and construction process were analyzed.Results:The integrated clinical research platform meets the management requirements of clinical research initiated by investigators, and the standardized management of the whole life cycle of the project can be realized through the platform, and the key issues of data security, information capture, sharing and interoperability need to be further explored in terms of platform docking.Conclusions:The integrated clinical research platform effectively improves the standardization, management quality and efficiency of investigator-initiated clinical research.

Comparative analysis of multiple models of electronic informed consent in clinical research / 中华医学科研管理杂志

Objective:To provide decision-making support for electronic informed consent selection and promotion in clinical research, and lay a possible theoretical foundation for better protection of subjects′ rights and interests, as well as promotion of clinical research quality and efficiency.Methods:This paper summarized the relevant laws and regulations of electronic informed consent, analyzed the advantages and challenges of the application of electronic informed consent in clinical research, sorted out several common electronic informed consent modes in domestic clinical research, explored their operational processes and applications, and discussed their advantages and limitations.Results:At present, three electronic informed consent modes were mainly used in domestic clinical studies. Each had their own advantages and limitations in terms of convenience of operation, data security, privacy protection of subjects, cost input, popularization degree and so on.Conclusions:Electronic informed consent needs continuing improvement of relevant laws and regulations and the joint efforts of all stakeholders engaged in clinical research. The sponsor and the researcher should take full consideration of the cost, safety, security, feasibility, and ofters, and make the selection according to the actual needs of the research.

Reflection and Practice on Exemption from Ethical Review / 中国医学伦理学

According to the Ethical Review Measures for Life Sciences and Medical Research Involving Humans jointly issued by the National Health Commission, the Ministry of Education, the Ministry of Science and Technology and the State Administration of Traditional Chinese Medicine in 2023, to optimize the ethical review process and reduce the burden on clinical researchers, it is proposed that some eligible situations can be "exempted from ethical review". This is a breakthrough progress in China’s ethical review management measures that firstly aimed at "exemption from ethical review". This paper reviewed and sorted out the relevant situations about exemption from review at home and abroad, focused on analyzing and exploring the four situations of exemption from review, especially discussed and analyzed the understanding of anonymization and personal sensitive information in exemption from review, and proposed practical suggestions for the four situations. Based on the actual situation of ethical review work, this paper also explored the establishment of practical standards and processes for exemption from review, providing reference for other medical institutions to implement the exemption from ethical review process.

Explosive strength training under lower limbs in soccer / Treinamento de força explosiva sob membros inferiores no futebol / Entrenamiento de fuerza explosiva en los miembros inferiores en el fútbol

ABSTRACT Introduction: Technical movements that mainly include running and jumping are soccer's main sport selection processes. These technical movements demand high requirements of lower limb endurance and explosive strength by athletes. Objective: Study the methods of strength and explosive force training in the lower limbs of soccer players. Methods: The experiment with 40 volunteers lasted 12 weeks and was conducted as a control experiment. The experimental group performed extensive lower limb strength training represented by weight resistance strength training on Monday and Wednesday. In contrast, the control group performed traditional modes of strength training such as half squats and deep squats. Diet was controlled, targeting to minimize the interference of unrelated variables. Results: The scores of the experimental group and the control group were improved and statistically more favorable in the experimental group. Conclusion: The strength training system with weight bearing on the lower limbs used in this study may promote better muscular development of the athletes, improve the explosive power of their lower limbs, and allow better performance on the field, and may be replicated. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: Os movimentos técnicos que incluem principalmente a corrida e o salto são os principais processos de seleção esportiva no futebol. Estes movimentos técnicos exigem altos requisitos de resistência dos membros inferiores e força explosiva pelos atletas. Objetivo: Estudar os métodos de treinamento da força e da força explosiva nos membros inferiores dos jogadores de futebol. Métodos: O experimento com 40 voluntários durou 12 semanas, sendo conduzido na forma de um experimento de controle. O grupo experimental realizou um amplo treinamento da força nos membros inferiores representado pelo treinamento da força de resistência ao peso na segunda e quarta-feira, enquanto o grupo de controle realizou os modos tradicionais de treinamento da força, como meio agachamento e agachamento profundo. A dieta foi controlada visando minimizar a interferência de variáveis não relacionadas. Resultados: As pontuações do grupo experimental e do grupo de controle foram aprimoradas, estatisticamente mais favorável no grupo experimental. Conclusão: O sistema de treinamento de força com sustentação de peso nos membros inferiores utilizado neste trabalho pode promover melhor o desenvolvimento muscular dos atletas, melhorar o poder explosivo de seus membros inferiores e permitir um melhor desempenho no campo, podendo ser replicado. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: Los movimientos técnicos que incluyen principalmente la carrera y el salto son los principales procesos de selección deportiva en el fútbol. Estos movimientos técnicos exigen grandes requisitos de resistencia de los miembros inferiores y fuerza explosiva por parte de los atletas. Objetivo: Estudiar los métodos de entrenamiento de la fuerza y la fuerza explosiva en las extremidades inferiores de los futbolistas. Métodos: El experimento con 40 voluntarios duró 12 semanas, realizándose en forma de experimento de control. El grupo experimental realizó un extenso entrenamiento de fuerza de las extremidades inferiores representado por el entrenamiento de fuerza de resistencia con pesas los lunes y miércoles, mientras que el grupo de control realizó modos tradicionales de entrenamiento de fuerza como la media sentadilla y la sentadilla profunda. La dieta se controló con el objetivo de minimizar la interferencia de variables no relacionadas. Resultados: Las puntuaciones del grupo experimental y del grupo de control mejoraron, siendo estadísticamente más favorables en el grupo experimental. Conclusión: El sistema de entrenamiento de fuerza con carga de peso en los miembros inferiores utilizado en este estudio puede promover un mejor desarrollo muscular de los atletas, mejorar la potencia explosiva de sus miembros inferiores y permitir un mejor rendimiento en el campo, y puede ser replicado. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Misdiagnosis of pancreatic metastasis from renal cell carcinoma: A case report.

BACKGROUND: Pancreatic metastases account for only a small proportion of all pancreatic malignancies. Isolated pancreatic metastasis from renal cell cancer (isPM-RCC) is extremely rare and may be difficult to differentiate from more common primary neoplasms. A history of nephrectomy is crucial for the diagnosis. CASE SUMMARY: We report the case of a 64-year-old Asian man who was diagnosed with a mass in the pancreatic head using computed tomography. He had no related symptoms, and his medical history was unremarkable, except for unilateral nephrectomy performed to remove a "benign" tumor 19 years ago. All preoperative imaging findings suggested a diagnosis of pancreatic neuroendocrine tumor. However, ultrasound-guided biopsy revealed features of clear cell renal cell carcinoma (ccRCC). Re-examination of the specimen resected 19 years ago confirmed that he had a ccRCC. The pancreatic mass was resected and pathological examination confirmed isPM-RCC. CONCLUSION: Misdiagnosis of isPM-RCC is common because of its rarity and the long interval from resection of the primary tumor and manifestation of the metastasis. The history of the previous surgery may be the only clue.

Diagnostic value of elevated serum carbohydrate antigen 125 level in sarcoidosis.

BACKGROUND: Sarcoidosis is a multisystem disorder with unknown etiology, and it predominantly affects the lungs and intrathoracic lymph nodes. For patients with atypical clinical manifestations, the diagnosis of sarcoidosis is difficult and specific biomarkers may play an important role in assisting diagnosis. Previous research has demonstrated a correlation between sarcoidosis and increased carbohydrate antigen 125 (CA125), but remains a lack of large cohort studies to validate this observation. AIM: To compare serum CA125 levels in sarcoidosis patients and healthy controls, and explore whether CA125 can be used as a biomarker for the diagnosis of sarcoidosis. METHODS: In this study, the serum CA125 levels were measured by enzyme-linked immunosorbent assay in 108 consecutive sarcoidosis patients between June 2016 and December 2020 (31 males, 77 females; age at diagnosis 49.69 ± 9.10 years) and 112 healthy subjects. Data on the C-reactive protein, erythrocyte sedimentation rate, and angiotensin-converting enzyme were also collected. The association of serum CA125 levels with clinical, radiological, and respiratory functional characteristics was analyzed between patient groups with CA125 ≤ 35 U/mL or CA125 > 35 U/mL. RESULTS: We found that serum CA125 levels were higher in sarcoidosis patients compared to healthy controls (median: 44.78 vs 19.11 U/mL, P < 0.001). The area under the receiver operator characteristic was 0.9833 (95%CI: 0.9717-0.9949), and the best cutoff point was 32.33 U/mL. The elevated serum CA125 was notably associated with the percentage of predicted forced vital capacity (FVC%) and neutrophil-to-lymphocyte ratio (P = 0.043 and P = 0.038, respectively) in sarcoidosis patients. Multivariate analysis revealed that FVC% was a statistically notable predictor of elevated serum CA125 (P = 0.029). Also, our research revealed that compared to patients with Stage I of radiology classification, patients with Stage II and III showed a higher concentration of serum CA125 (46.16 ± 8.32 vs 41.00 ± 6.04 U/mL, P = 0.005, and 47.92 ± 10.10 vs 41.00 ± 6.04 U/mL, P = 0.002, respectively). CONCLUSION: Serum CA125 was highly increased in sarcoidosis patients and showed high efficiency for noninvasive diagnosis of the disease. In addition, abnormally elevated serum CA125 was correlated with pulmonary function and radiological Scadding's classification of sarcoidosis.

Feasibility of Transabdominal Real-time CDFI and HDFI Techniques for Fetal Pulmonary Vein Display in the First Trimester.

OBJECTIVE: This study aimed to assess the feasibility and usefulness of transabdominal color Doppler flow imaging (CDFI) technology and the high-definition flow imaging (HDFI) technique in detecting fetal pulmonary veins (PVs) in the first trimester (11-13+6 weeks). METHODS: From December 2018 to October 2019, 328 pregnant women with 328 normal singleton fetuses (crown-rump length: 45-84 mm) who had undergone CDFI and HDFI scans for fetal heart and vessel examination were enrolled in this study. The cases were divided into three groups according to the gestational age: group A, 11+0 -11+6 weeks; group B, 12+0 -12+6 weeks; and group C, 13+0 -13+6 weeks. Baseline sonograms and CDFI and HDFI images were analyzed by two senior radiologists independently and blindly. The abilities of CDFI and HDFI to display PVs were compared. RESULTS: Successful PV display rates via CDFI and HDFI were 2.3% and 68.2% (P<0.01), 22.4% and 82.4% (P<0.01), 41.5% and 91.2% (P<0.01) for group A, group B, and group C, respectively. The total successful display rates for the two methods were 28.9% (CDFI) and 84.8% (HDFI) (P<0.01). CONCLUSIONS: The HDFI technique is more valuable than CDFI for detecting PVs in early pregnancy (11-13+6 weeks). HDFI can detect at least one PV in all cases and may be used to detect pulmonary venous anomalies early.

Ethical Issues and Ethical Review of Human Genetic Resource Management in Real-world Studies / 中国医学伦理学

Human genetic resources are an important strategic resource for the development of science and technology in China. In order to fully utilize and effectively protect human genetic resources in real-world studies, through analyzing the status and characteristics of real-world studies, this study found that the number of real-world studies was increasing year by year, and with some characteristics, such as many uncontrollable factors, strict requirements for evidence formation, and easy information acquisition and disclosure. Combined with the characteristics of real-world studies, the ethical issues of human genetic resource management in real-world studies were summarized into three aspects, including scientific and value of research development, informed consent and privacy protection of subjects, and fairness and justice in benefit sharing. Accordingly, the key points of ethical review were proposed as scientific rationality, fully informed consent and privacy, as well as data security and stakeholders. In addition, it is necessary to give full play to the role of ethical review in research access and process supervision responsibilities, guide researchers to make full use of human genetic resources by strengthening training and process management, and further promote the standardization of real-world studies.

Exploration of Investigator-Initiated Clinical Trials human genetic resource administration in a large hospital / 中华医学科研管理杂志

Objective:The management system of Investigator Initiated Clinical Trials (IIT) using human genetic resources in large hospitals is still not optimal. The purpose of this study is to sort out the existing problems of human genetic resources management in IIT of large hospitals, analyze the management practices, and provide reference for the standardized management of human genetic resources in IIT.Methods:The existing problems of human genetic resources management in IIT of large hospitals were sorted out by literature analysis, and the management practices since the establishment of human genetic resources management office were analyzed, and suggestions were put forward.Results:The problems of human genetic resources management in IIT of large hospitals mainly focused on the lack of awareness and attention of investigators and managers, the lack of process supervision, and the imbalance between input and output of genetic resources. A large hospital has implemented personnel and system construction, strengthened node management and control, and developed a training system. The approval rate of administrative approval and archival projects of human genetic resources of the Ministry of Science and Technology in 2021 increased by 52.69% compared with the previous year.Conclusions:Large hospitals should proceed from the actual situation, establish the human genetic resource management system jointly through multi-department linkage, improve management process, strengthen quality control, increase training efforts, improve the professional capacity and quality of researchers and managers, promote the high-quality, high-level and well development of IIT.

Survey on status qua of community practice bases for general practice residency training in Wuhan city / 中华全科医师杂志

Objective:To survey the status quo of community practice bases for general practice residency training in Wuhan city.Methods:A questionnaire survey was conducted in 12 community general practice training bases affiliated to 11 tertiary hospitals in Wuhan city from March to June 2021. A total of 123 general practice residents and 41 instructors participated in the survey using the different questionnaires. The contents of questionnaires included the basic conditions of the training base and the current status of training at community base, as well as their satisfaction on the program and related problems. The statistical analysis was performed with SPSS software.Results:The conditions of the 12 primary practice bases met the requirements of the Standard for Standardized Training Bases for General Practice Residents (2019 Revision) in terms of size of community hospitals, qualification of the person in charge and faculty team. The survey showed that only 3 bases had psychiatric department; 7 bases had literature retrieval system; all 12 bases had a teaching secretary, but only 1 had a full-time teaching secretary; all 12 bases had established formal assistant relationship with higher-level hospitals, but the frequency of communication was low in some bases. Survey also showed that 68.3% (28/41) instructors were aged 40-50 years; 90.2% (37/41) of instructors participated in epidemic prevention and control; 36.6% (15/41) thought that instructing work was related to professional promotion; 87.8% (36/41) of instructors were generally satisfied with the work performance. Most of trainees (92.7%, 114/123) were satisfied with the training at the primary base, and there was a difference in satisfaction degree between trainees with different enrollment sources (χ 2=6.92, P=0.032). The proportion of trainees with confidence for future career increased from 39.8% (49/123) before training in community bases to 60.2% (74/123) after training. Conclusions:The survey shows that primary practice bases for general practice residency training in Wuhan have met the basic requirements; however, the evaluation and motivation of teachers need to be improved, the opportunities for trainees to practice in general outpatient clinics should be increased, research and teaching need to be emphasized, and the management of trainees needs to be strengthened.

Incident Heart Failure in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.

Background: The contemporary incidence of heart failure (HF) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains unclear. This prospective cohort study was designed to study the incidence and predictors of new-onset HF in CAD patients after PCI (ChiCTR1900023033). Methods: From January 2014 to December 2018, 3,910 CAD patients without HF history undergoing PCI were prospectively enrolled. Demographics, medical history, cardiovascular risk factors, cardiac parameters, and medication data were collected at baseline. Multivariable adjusted competing-risk regression analysis was performed to examine the predictors of incident HF. Results: After a median follow-up of 63 months, 497 patients (12.7%) reached the primary endpoint of new-onset HF, of which 179, 110, and 208 patients (36.0, 22.1, and 41.9%) were diagnosed as having HF with reduced ejection fraction (EF) (HFrEF), HF with mid-range EF (HFmrEF), and HF with preserved EF (HFpEF), respectively. Higher B-type natriuretic peptide (BNP) or E/e' level, lower estimated glomerular filtration rate (eGFR) level, and atrial fibrillation were the independent risk factors of new-onset HF. Gender (male) and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) prescription were the negative predictors of new-onset HF. Moreover, it was indicated that long-term ACEI/ARB therapy, instead of beta-blocker use, was linked to lower risks of development of all three HF subtypes (HFrEF, HFmrEF and HFpEF). Conclusions: This prospective longitudinal cohort study shows that the predominant subtype of HF after PCI is HFpEF and ACEI/ARB therapy is accompanied with reduced risks of incident HF across three subtypes.

First report of Pythium aphanidermatum causing root rot of head lettuce in China.

Head lettuce (Lactuca sativa L.) is an important crop for fresh consumption in China. In Shandong Province, head lettuce is planted in spring and in autumn each year. Because of the on-and-off rain for three weeks, head lettuce plants planted directly into the field in Jiyang City, in July 2017, 20% of the plants rapidly showed symptoms of rotting, water-soaked lesions on roots and stem bases, and then death. The diseased plants first appeared in low-lying areas prone to water accumulation. One-millimeter pieces were excised from water-soaked roots and stem bases, dipped in a 0.2% calcium hypochlorite solution for 10 min, then placed on V8 medium, and incubated in the dark at 28°C for 5 d. Two Pythium-like strains were isolated from the roots and stems. The isolates transferred to CMA and grown for 7 d, and the morphological characteristics of the two isolates on corn meal agar (CMA) were white with dense, cottony, aerial and well-branched mycelia. The two isolates produced sporangia, oogonia, antheridia and oospores. Most of the sporangia were lobate. The oogonia were smooth, nearly globose and terminal. Oospores were globose, smooth and aplerotic. The average dimensions of 50 oogonia and oospores respectively ranged from 19.5 to 25.2 (av. 23.1) µm and 17.8 to 22.3 (av. 19.9) µm. The antheridia were broadly sac-shaped. The isolates morphological characteristics were consistent with P. aphanidermatum (van der Plaats-Niterink, 1981). The COI gene and ITS region of the rDNA were amplified and sequenced using primers FM55/FM52R (Long et al. 2012) and ITS1/ITS4 (White et al. 1990), respectively. The two aligned COI sequences were identical for both isolates, as were the two ITS sequences. BLASTn analysis of the 1,133-bp COI sequence (accession no. MT952703) resulted in a 100% identity with accession number AY129164 from Lactuca sativa, which belongs to P. aphanidermatum, and the 808-bp ITS sequence (accession no. MT921597) showed a 99% identity with Genbank accession number HQ643442 belonging to P. aphanidermatum. Koch's postulates were conducted by first soaking corn kernels for 24 h in water, and then autoclaving for 2 h at 121˚C. Isolate SDHL-1 was grown on CMA for 10 days, after which agar plugs were transferred to the sterilized corn kernels and incubated at 28℃ for approximately 15 d, until the corn kernels were covered in white hyphae. Ten healthy head lettuce plants were transplanted into a sterilized loam potting soil artificially infested with the corn inoculum (3 g inoculum per 100 g loam mixture). Inoculated plants and noninoculated controls were maintained in a greenhouse at 28°C and 100% relative humidity with a 12-h photoperiod; the experiment was repeated once. All twenty inoculated plants exhibited symptoms within one week similar to those observed. Pythium aphanidermatum was recovered only from the water-soaked roots and stem bases of inoculated plants and the re-isolated cultures again identified based on morphological characteristics and sequencing of the ITS and COI genes. No symptoms were observed on the control plants. Sclerotinia sclerotiorum is reported to cause stem base rot of L. sativa in China (Zhou et al. 2011). To our knowledge, however, this is the first report of root rot of head lettuce caused by Pythium aphanidermatum. Identification of the pathogen will assist in devising strategies to reduce yield loss.

STAT1-induced regulation of lncRNA ZFPM2-AS1 predicts poor prognosis and contributes to hepatocellular carcinoma progression via the miR-653/GOLM1 axis.

Long noncoding RNAs (lncRNAs) have drawn growing attention owing to their important effects in various tumors, including hepatocellular carcinoma (HCC). Recently, a newly identified lncRNA, ZFPM2 antisense RNA 1 (ZFPM2-AS1), was reported to serve as an oncogene in gastric cancer. However, its function in tumors remains largely unknown. In this study, we identified ZFPM2-AS1 as a novel HCC-related lncRNA, which was observed to be distinctly upregulated in HCC tissues and associated with shorter overall survival. Luciferase reporter and chromatin immunoprecipitation assays suggested that overexpression of ZFPM2-AS1 was induced by STAT1. Functional investigations suggested that the inhibition of ZFPM2-AS1 suppressed cell proliferation, metastasis, cell cycle progression while accelerated cell apoptosis. Mechanistic studies showed that there were two binding sites of miR-653 within the sequence of ZFPM2-AS1 and the levels of ZFPM2-AS1 were negatively correlated with miR-653. In addition, ZFPM2-AS1 could reverse the suppressor effects of miR-653 on the proliferation and metastasis of HCC cells by the modulation of GOLM1, a target gene of miR-653. To conclude, we provided a better understanding of the interaction mechanism between ZFPM2-AS-miR-653-GOLM1 axis, which may help develop prognostic biomarkers and therapeutic target for HCC.

Distinctive Clinical Characteristics and Outcome of ILD-Onset Rheumatoid Arthritis and ACPA-Positive ILD: a Longitudinal Cohort of 282 Cases.

The aim of this study is to investigate the clinical features and outcome of interstitial lung disease (ILD)-onset rheumatoid arthritis (RA) and anti-citrullinated protein antibody (ACPA)-positive ILD-only patients. Arthritis-onset and ILD-onset RA-ILD and ACPA-positive ILD-only patients consecutively admitted to Peking Union Medical College Hospital from January 2008 to December 2017 were enrolled and followed-up. Their demographic, clinical, and laboratory features as well as outcome were collected and analyzed. Compared with arthritis-onset RA-ILD (n = 166, median arthritis-to-ILD interval: 60 months), the ILD-onset RA-ILD (n = 75, median ILD-to-arthritis interval: 2 months) had less rheumatoid nodules and higher titer of ACPA, and manifested more stable ILD (median estimated progression-free survival: 120 vs. 100 months, p = 0.019). Elder age (≥ 65 years) at ILD diagnosis and UIP pattern were associated with ILD progression by both univariate and Cox hazards modeling analysis (p < 0.05). In ACPA-positive ILD-only patients (n = 41), arthritis developed in 7 (17.1%) female patients after a median interval of 24 months. ACPA-positive ILD who subsequently developed arthritis exhibited higher frequency of rheumatoid factor (RF), higher titer of ACPA, and higher levels of ESR and CRP (p < 0.05). Multivariate regression analysis showed that positive RF (OR 12.55, 95% CI 1.31 to 120.48) was the independent risk factor for arthritis development in ACPA-positive ILD-only patients. ILD-onset RA-ILD had more stable ILD compared with arthritis-onset RA-ILD. ACPA-positive ILD patients with positive RF are at increased risk of developing RA.

Balloon Deflation Strategy during Primary Percutaneous Coronary Intervention in Acute ST-Segment Elevation Myocardial Infarction: A Randomized Controlled Clinical Trial and Numerical Simulation-Based Analysis.

BACKGROUND: Primary percutaneous coronary intervention (PCI) is the best available reperfusion strategy in patients with acute ST-segment elevation myocardial infarction (STEMI). However, PCI is associated with a serious problem known as no-reflow phenomenon, resulting in poor clinical and functional outcomes. This study aimed to compare the influences of different balloon deflation velocity on coronary flow and cardiovascular events during primary PCI in STEM as well as transient hemodynamic changes in in vitro experiments. Method and Results. 211 STEMI patients were randomly assigned to either a rapid or a slow balloon deflation group during stent deployment. The primary end point was coronary flow at the end of PCI procedure, and secondary end points included myocardial infarct size. Transient hemodynamic changes were evaluated through an in vitro experimental apparatus and a computer model. In clinical practice, the level of corrected TIMI frame count (cTFC) in slow balloon deflation after primary PCI was significantly lower than that of rapid balloon deflation, which was associated with smaller infarct size. Numerical simulations revealed that the rapid deflation led to a sharp acceleration of flow in the balloon-vessel gap and a concomitant abnormal rise in wall shear stress (WSS). CONCLUSION: This randomized study demonstrated that the slow balloon deflation during stent implantation improved coronary flow and reduced infarct size in reperfused STEMI. The change of flow in the balloon-vessel gap and WSS resulted from different balloon deflation velocity might be partly accounted for this results.

First Report of Root and Crown Rot of American Ginseng Caused by Pythium spinosum in China.

American ginseng (Panax quinquefolius) is a perennial herb whose dried roots are used for health care products, medicine, and food in China (Yuan et al. 2010). Shandong Province is the main area growing American ginseng and contributes more than 50% of the production in China. Wendeng city, located in the east of Shandong Peninsula, is the primary production area of American ginseng in Shandong Province since it has four distinct seasons, sufficient light, loose soil (pH 5.5～7.0), and with thus a similar geographical environment and climate conditions to the American ginseng production area of the United States and Canada. In March 2016, 2-year old American ginseng plants that were planted directly into the ground in the greenhouses in Wendeng city, contained up to 6-10% stunted plants. Water-soaked lesions were observed on the crowns and the tips of fine roots. The leaves of the infected plants became scalded, dark green starting at the top of the plants and gradually move downward. Moreover, the leaves and petioles gradually curled withered and drooped, and the whole plant collapsed. Tissue samples, 10 mm in size, were excised from the water-soaked roots and crowns of diseased plants, rinsed under running water for 24 hours, dipped in a 0.2% calcium hypochlorite solution for 10 minutes, placed on sterile filter paper to dry and then placed on V8 medium (200 mL V8 Campbell Soup, 15 g agar, 0.2 g CaCO3, and 1 L distilled water) and incubated in the dark at 28 °C for 5 days. Five Pythium-like isolates which were arachnoid-cottony on cornmeal agar were isolated and they all produced hyphal swellings, oogonia, antheridia and oospores. Oospores were globose, smooth and plerotic, with some being aplerotic. The dimensions of hyphal swellings, oogonia and oospores respectively ranged from 9.0 to 21.3 (average 14.1) µm, 12.9 to 22.5 (average 18.2) µm, and 12.5 to 20.5 (average 16.7) µm. Finger-like projections were uniformly distributed on the walls of the oogonia and the antheridia were curved rods. The five Pythium-like isolates were identified as P. spinosum based on morphological characteristics (van der Plaats-Niterink, 1981). Genomic DNA was extracted from the isolates of the Pythium sp. using a DNA extraction kit (OMEGA, U.S.A.). The cytochrome c oxidase subunit I (COI) gene and internal transcribed spacer (ITS) region rDNA were amplified and sequenced using primers FM55/FM52R (Long et al. 2012) and ITS1/ITS4, respectively (White et al.1990). The five COI sequences were aligned and were identical for all five isolates, as well as the five ITS sequences. BLASTn analysis of the 538-bp COI sequence (accession no. MT822775) resulted in a 99% identity with that of the P. spinosum strain CBS122663 (accession no. HQ708832.1), and the 916-bp ITS sequence (accession no. MN847595) showed 100% identity with Genbank accession number AB217665 belonging to P. spinosum. Koch's postulates were confirmed. Corn kernels that had been soaked in water for 24 hours in water, autoclaved for 2 hours at 121˚C and allowed to cool were inoculated with agar plugs of P. spinosum grown on corn meal agar medium (CMA) for 10 days. The inoculated corn kernels were incubated at 28 ℃ for 13～15 days, until the corn kernels were covered with white hypha of P. spinosum. Ten healthy approximately 2-years old American ginseng plants growing in Wengdeng greenhouses were transplanted into a sterilized potting soil that was artificially infested with the corn inoculum (3 g inoculum per 100 g loam mixture). Inoculated and non-inoculated control plants were maintained in a greenhouse with a roof covered with sunshade net at 28 °C and 100% relative humidity. The experiment was repeated once. Four days after inoculation (DAI), the crown of inoculated plants developed water-soaked symptoms similar to those observed in field. No symptoms developed on the control plants. By 7 DAI, the inoculated fine roots and crowns showed water-soaked lesions identical to those observed in field, whereas control plants remained symptomless. The re-isolated isolate of P. spinosum was identical morphologically and by DNA sequence analysis to the original isolate. To our knowledge, this is the first report of root rot on American ginseng caused by P. spinosum in China and worldwide. Identification of the pathogen will assist in devising strategies to protect this important medicine plant from the pathogen, and to prevent yield losses.

Herpes Simplex Virus 1 UL2 Inhibits the TNF-α-Mediated NF-κB Activity by Interacting With p65/p50.

Herpes simplex virus 1 (HSV-1) is a large double-stranded DNA virus that encodes at least 80 viral proteins, many of which are involved in the virus-host interaction and are beneficial to the viral survival and reproduction. However, the biological functions of some HSV-1-encoded proteins are not fully understood. Nuclear factor κB (NF-κB) activation is the major antiviral innate response, which can be triggered by various signals induced by cellular receptors from different pathways. Here, we demonstrated that HSV-1 UL2 protein could antagonize the tumor necrosis factor α (TNF-α)-mediated NF-κB activation. Co-immunoprecipitation assays showed that UL2 could interact with the NF-κB subunits p65 and p50, which also revealed the region of amino acids 9 to 17 of UL2 could suppress the NF-κB activation and interact with p65 and p50, and UL2 bound to the immunoglobulin-like plexin transcription factor functional domain of p65. However, UL2 did not affect the formation of p65/p50 dimerization and their nuclear localizations. Yet, UL2 was demonstrated to inhibit the NF-κB activity by attenuating TNF-α-induced p65 phosphorylation at Ser536 and therefore decreasing the expression of downstream inflammatory chemokine interleukin 8. Taken together, the attenuation of NF-κB activation by UL2 may contribute to the escape of host's antiviral innate immunity for HSV-1 during its infection.