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Jiaqi Tian,1,* Zhengpu Han,1,2,* Dandan Song,1 Yanjie Peng,1 Min Xiong,3 Zhen Chen,2 Shuyin Duan,4 Lin Zhang1,5 1Clinical Medical Research Center for Women and Children Diseases, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, People’s Republic of China; 2School of Public Health, Weifang Medical University, Weifang, People’s Republic of China; 3School of Public Health, North China University of Science and Technology, Tangshan, People’s Republic of China; 4School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 5Key Laboratory of Birth Defect Prevention and Genetic Medicine of Shandong Health Commission, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin Zhang, Clinical Medical Research Center for Women and Children Diseases, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250001, People’s Republic of China, Tel +86-531-68795046, Email zhanglin8901@163.com Shuyin Duan, School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250001, People’s Republic of China, Tel +86-13419581411, Email shuyinduan@126.comAbstract: Exosomes are nano-sized membrane vesicles that transfer bioactive molecules between cells and modulate various biological processes under physiological and pathological conditions. By applying bioengineering technologies, exosomes can be modified to express specific markers or carry therapeutic cargo and emerge as novel platforms for the treatment of cancer, neurological, cardiovascular, immune, and infectious diseases. However, there are many challenges and uncertainties in the clinical translation of exosomes. This review aims to provide an overview of the recent advances and challenges in the translation of engineered exosomes, with a special focus on the methods and strategies for loading drugs into exosomes, the pros and cons of different loading methods, and the optimization of exosome production based on the drugs to be encapsulated. Moreover, we also summarize the current clinical applications and prospects of engineered exosomes, as well as the potential risks and limitations that need to be addressed in exosome engineering, including the standardization of exosome preparation and engineering protocols, the quality and quantity of exosomes, the control of drug release, and the immunogenicity and cytotoxicity of exosomes. Overall, engineered exosomes represent an exciting frontier in nanomedicine, but they still face challenges in large-scale production, the maintenance of storage stability, and clinical translation. With continuous advances in this field, exosome-based drug formulation could offer great promise for the targeted treatment of human diseases.Keywords: engineered exosomes, drug delivery, clinical application, preparation strategy

Honghao Yu,* Yiping Wu,* Boyu Zhang, Mingchen Xiong, Yi Yi, Qi Zhang, Min Wu Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qi Zhang; Min Wu, Tel +86 15951072198 ; +86 13554254796, Email zhangqi06172@163.com; wumin@hust.edu.cnBackground: Skin wound is a widespread health problem and brings extraordinary burdens to patients. Exosomes derived from adipose-derived stem cells (ADSC-Exos) are considered promising strategies for repairing skin wounds. E2F1 is a member of the E2F family of transcription factors involved in cell growth and apoptosis. E2F1 deficiency in mice enhances wound healing by improving collagen deposition and angiogenesis. Additionally, E2F1 can regulate the transcription and paracrine activity of multiple miRNAs, which will inevitably reshape the paracrine expression profile of ADSC-Exos. This study aimed to investigate the impact of transcription factor E2F1 deficiency on the functions of ADSC-Exos in promoting wound healing.Methods: First, we obtained ADSCs from subcutaneous adipose tissues of WT and E2F1–/– C57BL/6 mice and separated their exosomes, denoted as ADSCWT-Exos and ADSCE2F1-/--Exos. The wound healing effects of ADSCWT-Exos and ADSCE2F1-/--Exos in full-thickness skin wound models were investigated by wound images, H&E staining, and immunohistochemical staining. For the in vitro study, the abilities of ADSCWT-Exos and ADSCE2F1-/--Exos to promote cell activities, collagen formation, and angiogenesis were evaluated. The potential mechanism by which ADSCE2F1-/--Exos promote wound healing was determined by miRNA sequencing, ChIP‒qPCR, and dual-luciferase assays.Results: ADSCE2F1-/--Exos accelerated wound healing by promoting collagen formation and angiogenesis. As a result, compared with the lower wound healing rate of 30.5% within 7 days in the control group and 42.3% in the ADSCWT-Exo group, ADSCE2F1-/--Exos significantly increased the wound healing rate to 72.5%. In vitro, ADSCE2F1-/--Exos activated the function of fibroblasts and vascular endothelial cells. The loss of E2F1 promoted miR-130b-5p expression in ADSCE2F1-/--Exos through transcriptional regulation. MiRNA high-throughput sequencing identified 12 differently expressed miRNAs between ADSCE2F1-/- and ADSCWT. ADSCE2F1-/--Exos enhanced fibroblast activities via the miR-130b-5p/TGFBR3 axis and TGF-β activation.Conclusion: Our results indicated that ADSCE2F1-/--Exos effectively promoted wound healing by regulating the miR-130b-5p/TGFBR3 axis, thus providing a novel strategy of gene-engineered stem cell exosomes for accelerating wound healing. Keywords: wound healing, adipose-derived stem cells, exosome, E2F1, miR-130b-5p

Shuai Jiang,1,2 Man Xiong,3 Xinyi Rao,3 Jieting Liang,3 Xinghan Zhu,3 Hang Fu,1,2 Jiangyun Chen,3 Chengzeng Wang1,2 1The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Institute for Hospital Management of Henan Province, Zhengzhou, Henan, People’s Republic of China; 3School of Health Management, Southern Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Chengzeng Wang; Jiangyun Chen, Email chengzengw@163.com; cjy112@i.smu.edu.cnPurpose: This study aims to investigate factors affecting medical personnel behavioral preferences for providing mHealth in China, so as to provide decision-making basis for mHealth providers and managers to encourage more doctors to participate in mHealth service delivery.Methods: Typical case sampling techniques were applied in a hospital setting to conduct a discrete choice experimental questionnaire survey of doctors (n=216) concerning mHealth preferences between July and October 2022. A conditional logit model was used to assess medical personnel preferences for each attribute and level of mHealth services.Results: Length of service, information security, subjects of treatment and financial compensation all have a significant effect on medical staff’s preference for providing mHealth services (p < 0.05). In terms of service duration and financial compensation, medical staff preferred mHealth services that provided shorter service duration and higher financial compensation; in terms of information security, medical staff preferred mHealth services with confidentiality of diagnostic and therapeutic information compared to information disclosure; and in terms of treatment targets, medical staff preferred the general population compared to key populations, such as pregnant women, the elderly, infants and children.Conclusion: The preference of medical professionals to provide mHealth services is affected by a variety of factors. By enhancing the confidentiality of information in mHealth services, providing more options for service recipients, increasing their financial compensation, and shortening the duration of the service or increasing the number of service hours that can be adjusted can guide improvement of mHealth services and promoting of its adoption among medical professionals.Keywords: doctor, mHealth, preferences, discrete choice experiment

Jihong Gu,1,&ast; Shucheng Shen,1,&ast; Mengyuan Xiong,1,2 Jin Zhao,1,2 Hongpan Tian,1 Xiao Xiao,1,3 Yirong Li1– 3 1Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Wuhan Research Center for Infectious Diseases and Tumors of the Chinese Academy of Medical Sciences, Wuhan, People’s Republic of China; 3Hubei Engineering Center for Infectious Disease Prevention, Control and Treatment, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yirong Li, Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430061, People’s Republic of China, Tel +8618602718052, Email liyirong838@163.comBackground: Staphylococcus aureus (S. aureus) was able to rapidly evolve and adapt under the pressure of antibiotics, host immune and environmental change. After Corona Virus Disease 2019 (COVID-19) epidemic in Wuhan, China, a large number of disinfectants were used, which might result in rapid evolution of S. aureus.Methods: A total of 619 S. aureus isolates were collected from Zhongnan Hospital, Wuhan University from 2018 to 2021, including group BEFORE (309 strains collected before COVID-19 pandemic) and group AFTER (310 strains collected after COVID-19 pandemic), for comparing the changes of molecular epidemiology. The molecular characteristics of isolates were analyzed by Multi-locus sequence typing (MLST), spa, chromosomal cassette mec (SCCmec) typing, virulence genes were screened by the PCR, antibiotic susceptibility test was carried out by the VITEK system.Results: Thirty-six sequence types (STs) belonging to 14 clone complexes (CCs) were identified. ST5 was the most prevalent clone in both groups, and ST7, ranking the sixth in group BEFORE, became the second dominant clone in group AFTER (6.5% vs 10.0%), whereas ST239 decreased from the seventh to the fourteenth (5.8% vs 1.9%). ST7 in group AFTER had a higher positive rate of virulence genes, including hlb, fnbB, seb, lukDE, sdrE and the proportion of ST7-t091 MRSA strains increased from 19.1% to 50% compared with group BEFORE. Though no significant difference of MRSA proportion was found between two groups, SCCmec type-III in group AFTER decreased (p< 0.01). Though the rate of multidrug-resistance (MDR) decreased, the virulence genes hlb, hlg, fnbB, seb and pvl carrying rates were significantly elevated in MRSA strains of group AFTER.Conclusion: After COVID-19 pandemic, ST7 becomes one of the predominant S. aureus clones in Wuhan and the carrying rate of SCCmec and virulence genes is on the rise. Therefore, it is essential to strengthen the surveillance of ST7 S. aureus clone.Keywords: Staphylococcus aureus, molecular characterization, antimicrobial resistance, virulence gene, disinfectant

Bin-Yong Liang,1,&ast; Jin Gu,2,&ast; Min Xiong,3 Er-Lei Zhang,1 Zun-Yi Zhang,1 Wan-Yee Lau,4 Shao-Fa Wang,5 Yan Guan,1 Xiao-Ping Chen,1 Zhi-Yong Huang1 1Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Faculty of Medicine, the Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, People’s Republic of China; 5Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Yong Huang, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Da Dao, Wuhan, People’s Republic of China, Tel +86-27-83665392, Fax +86-27-83663432, Email huangzy@tjh.tjmu.edu.cnBackground: Hepatocellular carcinoma (HCC) is frequently associated with cirrhosis. The present study investigated the impact of histological severity of cirrhosis on surgical outcomes for HCC and further developed novel nomograms to predict postoperative recurrence and survival.Methods: A total of 1524 consecutive patients undergoing curative hepatectomy for HCC between 1999 and 2015 were retrospectively studied. Cirrhotic severity was histologically staged according to the Laennec staging system. Short- and long-term outcomes were investigated. Recurrence-free survival (RFS) and overall survival (OS) predictive nomograms were constructed based on the results of multivariate analysis. The predictive accuracy of the nomograms was measured by the concordance index (C-index) and calibration.Results: Patients in the severe cirrhosis group had significantly higher morbidity and mortality rates than patients in the no, mild, and moderate cirrhosis groups. The 5-year RFS and OS rates were 36.8% and 64.5%, respectively, in the no cirrhosis group, compared to 34.8% and 60.4% in the mild cirrhosis group, 17.3% and 43.4% in the moderate cirrhosis group, and 6.1% and 20.1% in the severe cirrhosis group. Long-term survival outcomes were significantly worse as cirrhotic severity was increased. The C-index was 0.727 for the RFS nomogram and 0.746 for the OS nomogram. Calibration curves showed good agreement between actual observations and nomogram predictions. The 2 nomograms had a superior discriminatory ability to predict RFS and OS compared to other staging systems.Conclusion: Histological severity of cirrhosis significantly affected surgical outcomes in HCC patients undergoing curative hepatectomy. The novel nomograms, including histological severity of cirrhosis, showed an accurate prediction of postoperative recurrence and survival.Keywords: hepatocellular carcinoma, Laennec staging system, prognosis, nomogram, hepatectomy

Jing Zhu,1,2,* Zhiling Zhao,3,* Bin Wu,4 Zhihong Shi,5 Qingrong Nie,6 Zhen Fu,7 Zhaofu Zeng,1 Weihua Hu,1 Minglin Dong,1 Mengqing Xiong,1 Ke Hu1 1Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The People’s Hospital of China Three Gorges University, Yichang, Hubei, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Institute of Respiratory Diseases, Department of Respiratory, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 5Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Xian Jiaotong University, Xian, Shanxi, People’s Republic of China; 6Division of Respiratory Disease, Liangxiang Hospital of Yanjing Medical College, Capital Medical University, Beijing, People’s Republic of China; 7Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ke Hu Email huke-rmhospital@163.comObjective: The aim of this study was to explain “obesity paradox” in chronic obstructive pulmonary disease (COPD) by evaluating the effect of body mass index (BMI) on lung function in Chinese patients with COPD.Methods: A total of 1644 patients diagnosed with COPD were recruited from four Chinese tertiary hospitals and were divided into four groups including underweight, normal weight, overweight and obese according to BMI classification standard. The medical data of these patients were collected and used for the multiple linear regression analyses.Results: After adjustment for age, sex, educational level, economic status, smoking status, alcohol consumption, duration of COPD history, events of acute exacerbation in previous year, hypertension, diabetes mellitus, cardiovascular disease, cerebrovascular disease and osteoporosis, BMI had a curvilinear correlation with the forced expiratory volume in the first second (FEV1) in patients with Global Initiative for Obstructive Lung Disease (GOLD) 1– 2 grade (first-order coefficient β, 0.09; 95% CI, 0.03– 0.16; second-order coefficient β, − 0.002; 95% CI, − 0.003–-0.001; P< 0.01). However, BMI had a positive correlation with FEV1 in patients with GOLD 3– 4 grade (β, 0.01; 95% CI, 0.008– 0.017; P< 0.01) when BMI was used as a quantitative variable. When BMI was used as a qualitative variable, only FEV1 in overweight group with GOLD 1– 2 grade was significantly higher than that of normal weight group (P< 0.01). Interestingly, both overweight and obese groups had higher FEV1 in GOLD 3– 4 grade compared with normal weight group (β, 0.06; 95% CI, 0.02– 0.11; β, 0.11; 95% CI, 0.04– 0.18; P< 0.01). The effect of BMI on predicted percentage of FEV1 (FEV1%) was similar to that of FEV1 in different GOLD grades.Conclusion: Obesity only had a protective effect on lung function in COPD patients with GOLD 3– 4 grade rather than GOLD 1– 2 grade.Trial Registry: ClinicalTrials.gov, No.: NCT 03182309, URL: www.clinicaltrials.gov.Keywords: overweight, obesity

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Fogelman O19 DDIT4 gene expression as a prognostic marker in several malignant tumors L. Bravo, W. Fajardo, H. Gomez, C. Castaneda, C. Rolfo, J. A. Pinto O20 Spatial organization of the genome and genomic alterations in human cancers K. C. Akdemir, L. Chin, A. Futreal, ICGC PCAWG Structural Alterations Group O21 Landscape of targeted therapies in solid tumors S. Patterson, C. Statz, S. Mockus O22 Genomic analysis reveals novel drivers and progression pathways in skin basal cell carcinoma S. N. Nikolaev, X. I. Bonilla, L. Parmentier, B. King, F. Bezrukov, G. Kaya, V. Zoete, V. Seplyarskiy, H. Sharpe, T. McKee, A. Letourneau, P. Ribaux, K. Popadin, N. Basset-Seguin, R. Ben Chaabene, F. Santoni, M. Andrianova, M. Guipponi, M. Garieri, C. Verdan, K. Grosdemange, O. Sumara, M. Eilers, I. Aifantis, O. Michielin, F. de Sauvage, S. Antonarakis O23 Identification of differential biomarkers of hepatocellular carcinoma and cholangiocarcinoma via transcriptome microarray meta-analysis S. Likhitrattanapisal O24 Clinical validity and actionability of multigene tests for hereditary cancers in a large multi-center study S. Lincoln, A. Kurian, A. Desmond, S. Yang, Y. Kobayashi, J. Ford, L. Ellisen O25 Correlation with tumor ploidy status is essential for correct determination of genome-wide copy number changes by SNP array T. L. Peters, K. R. Alvarez, E. F. Hollingsworth, D. H. Lopez-Terrada O26 Nanochannel based next-generation mapping for interrogation of clinically relevant structural variation A. Hastie, Z. Dzakula, A. W. Pang, E. T. Lam, T. Anantharaman, M. Saghbini, H. Cao, BioNano Genomics O27 Mutation spectrum in a pulmonary arterial hypertension (PAH) cohort and identification of associated truncating mutations in TBX4 C. Gonzaga-Jauregui, L. Ma, A. King, E. Berman Rosenzweig, U. Krishnan, J. G. Reid, J. D. Overton, F. Dewey, W. K. Chung O28 NORTH CAROLINA macular dystrophy (MCDR1): mutations found affecting PRDM13 K. Small, A. DeLuca, F. Cremers, R. A. Lewis, V. 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Knoppers, Global Alliance for Genomics and Health - Regulatory and Ethics Working Group O33 High throughput screening platform of competent sineups: that can enhance translation activities of therapeutic target H. Takahashi, K. R. Nitta, A. Kozhuharova, A. M. Suzuki, H. Sharma, D. Cotella, C. Santoro, S. Zucchelli, S. Gustincich, P. Carninci O34 The undiagnosed diseases network international (UDNI): clinical and laboratory research to meet patient needs J. J. Mulvihill, G. Baynam, W. Gahl, S. C. Groft, K. Kosaki, P. Lasko, B. Melegh, D. Taruscio O36 Performance of computational algorithms in pathogenicity predictions for activating variants in oncogenes versus loss of function mutations in tumor suppressor genes R. Ghosh, S. Plon O37 Identification and electronic health record incorporation of clinically actionable pharmacogenomic variants using prospective targeted sequencing S. Scherer, X. Qin, R. Sanghvi, K. Walker, T. Chiang, D. Muzny, L. Wang, J. Black, E. Boerwinkle, R. 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Leimgruber O43 Cpipe: a convergent clinical exome pipeline specialised for targeted sequencing S. Sadedin, A. Oshlack, Melbourne Genomics Health Alliance O44 A Bayesian classification of biomedical images using feature extraction from deep neural networks implemented on lung cancer data V. A. A. Antonio, N. Ono, Clark Kendrick C. Go O45 MAV-SEQ: an interactive platform for the Management, Analysis, and Visualization of sequence data Z. Ahmed, M. Bolisetty, S. Zeeshan, E. Anguiano, D. Ucar O47 Allele specific enhancer in EPAS1 intronic regions may contribute to high altitude adaptation of Tibetans C. Zeng, J. Shao O48 Nanochannel based next-generation mapping for structural variation detection and comparison in trios and populations H. Cao, A. Hastie, A. W. Pang, E. T. Lam, T. Liang, K. Pham, M. Saghbini, Z. Dzakula O49 Archaic introgression in indigenous populations of Malaysia revealed by whole genome sequencing Y. Chee-Wei, L. Dongsheng, W. Lai-Ping, D. Lian, R. O. Twee Hee, Y. Yunus, F. Aghakhanian, S. S. Mokhtar, C. V. Lok-Yung, J. Bhak, M. Phipps, X. Shuhua, T. Yik-Ying, V. Kumar, H. Boon-Peng O50 Breast and ovarian cancer prevention: is it time for population-based mutation screening of high risk genes? I. Campbell, M.-A. Young, P. James, Lifepool O53 Comprehensive coverage from low DNA input using novel NGS library preparation methods for WGS and WGBS C. Schumacher, S. Sandhu, T. Harkins, V. Makarov O54 Methods for large scale construction of robust PCR-free libraries for sequencing on Illumina HiSeqX platform H. DoddapaneniR. Glenn, Z. Momin, B. Dilrukshi, H. Chao, Q. Meng, B. Gudenkauf, R. Kshitij, J. Jayaseelan, C. Nessner, S. Lee, K. Blankenberg, L. Lewis, J. Hu, Y. Han, H. Dinh, S. Jireh, K. Walker, E. Boerwinkle, D. Muzny, R. Gibbs O55 Rapid capture methods for clinical sequencing J. Hu, K. Walker, C. Buhay, X. Liu, Q. Wang, R. Sanghvi, H. Doddapaneni, Y. Ding, N. Veeraraghavan, Y. Yang, E. Boerwinkle, A. L. Beaudet, C. M. Eng, D. M. Muzny, R. A. 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Abduljaleel P13 Digital expression profiling of Purkinje neurons and dendrites in different subcellular compartments A. Kratz, P. Beguin, S. Poulain, M. Kaneko, C. Takahiko, A. Matsunaga, S. Kato, A. M. Suzuki, N. Bertin, T. Lassmann, R. Vigot, P. Carninci, C. Plessy, T. Launey P14 The evolution of imperfection and imperfection of evolution: the functional and functionless fractions of the human genome D. Graur P16 Species-independent identification of known and novel recurrent genomic entities in multiple cancer patients J. Friis-Nielsen, J. M. Izarzugaza, S. Brunak P18 Discovery of active gene modules which are densely conserved across multiple cancer types reveal their prognostic power and mutually exclusive mutation patterns B. S. Soibam P19 Whole exome sequencing of dysplastic leukoplakia tissue indicates sequential accumulation of somatic mutations from oral precancer to cancer D. Das, N. Biswas, S. Das, S. Sarkar, A. Maitra, C. Panda, P. Majumder P21 Epigenetic mechanisms of carcinogensis by hereditary breast cancer genes J. J. Gruber, N. Jaeger, M. Snyder P22 RNA direct: a novel RNA enrichment strategy applied to transcripts associated with solid tumors K. Patel, S. Bowman, T. Davis, D. Kraushaar, A. Emerman, S. Russello, N. Henig, C. Hendrickson P23 RNA sequencing identifies gene mutations for neuroblastoma K. Zhang P24 Participation of SFRP1 in the modulation of TMPRSS2-ERG fusion gene in prostate cancer cell lines M. Rodriguez-Dorantes, C. D. Cruz-Hernandez, C. D. P. Garcia-Tobilla, S. Solorzano-Rosales P25 Targeted Methylation Sequencing of Prostate Cancer N. Jäger, J. Chen, R. Haile, M. Hitchins, J. D. Brooks, M. Snyder P26 Mutant TPMT alleles in children with acute lymphoblastic leukemia from México City and Yucatán, Mexico S. Jiménez-Morales, M. Ramírez, J. Nuñez, V. Bekker, Y. Leal, E. Jiménez, A. Medina, A. Hidalgo, J. Mejía P28 Genetic modifiers of Alström syndrome J. Naggert, G. B. Collin, K. DeMauro, R. Hanusek, P. M. Nishina P31 Association of genomic variants with the occurrence of angiotensin-converting-enzyme inhibitor (ACEI)-induced coughing among Filipinos E. M. Cutiongco De La Paz, R. Sy, J. Nevado, P. Reganit, L. Santos, J. D. Magno, F. E. Punzalan , D. Ona , E. Llanes, R. L. Santos-Cortes , R. Tiongco, J. Aherrera, L. Abrahan, P. Pagauitan-Alan; Philippine Cardiogenomics Study Group P32 The use of “humanized” mouse models to validate disease association of a de novo GARS variant and to test a novel gene therapy strategy for Charcot-Marie-Tooth disease type 2D K. H. Morelli, J. S. Domire, N. Pyne, S. Harper, R. Burgess P34 Molecular regulation of chondrogenic human induced pluripotent stem cells M. A. Gari, A. Dallol, H. Alsehli, A. Gari, M. Gari, A. Abuzenadah P35 Molecular profiling of hematologic malignancies: implementation of a variant assessment algorithm for next generation sequencing data analysis and clinical reporting M. Thomas, M. Sukhai, S. Garg, M. Misyura, T. 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Ucar P54 Direct enrichment for the rapid preparation of targeted NGS libraries C. L. Hendrickson, A. Emerman, D. Kraushaar, S. Bowman, N. Henig, T. Davis, S. Russello, K. Patel P56 Performance of the Agilent D5000 and High Sensitivity D5000 ScreenTape assays for the Agilent 4200 Tapestation System R. Nitsche, L. Prieto-Lafuente P57 ClinVar: a multi-source archive for variant interpretation M. Landrum, J. Lee, W. Rubinstein, D. Maglott P59 Association of functional variants and protein physical interactions of human MUTY homolog linked with familial adenomatous polyposis and colorectal cancer syndrome Z. Abduljaleel, W. Khan, F. A. Al-Allaf, M. Athar , M. M. Taher, N. Shahzad P60 Modification of the microbiom constitution in the gut using chicken IgY antibodies resulted in a reduction of acute graft-versus-host disease after experimental bone marrow transplantation A. Bouazzaoui, E. Huber, A. Dan, F. A. Al-Allaf, W. Herr, G. Sprotte, J. Köstler, A. Hiergeist, A. Gessner, R. 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Weihua Hu,1,* Minglin Dong,1,* Mengqing Xiong,1,* Dong Zhao,1 Yang Zhao,1 Mengmei Wang,1 Tao Wang,1 Zhenlian Liu,2 Li Lu,3 Ke Hu1 1Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Fever Clinic, The East Campus, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Department of Respiratory Medicine, The East Campus, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ke HuDepartment of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Zhangzhidong Road No. 99, Wuhan 430060, People’s Republic of ChinaTel +86-18971035988Fax +86-027-88042292Email huke-rmhospital@163.comPurpose: In this study, we investigated the acute exacerbation and outcomes of COPD patients during the outbreak of COVID-19 and evaluated the prevalence and mortality of COPD patients with confirmed COVID-19.Methods: A prospectively recruited cohort of 489 COPD patients was retrospectively followed-up for their conditions during the COVID-19 pandemic from December 2019 to March 2020 in Hubei, China. In addition, the features of 821 discharged patients with confirmed COVID-19 were retrospectively analyzed.Results: Of the 489 followed-up enrolled COPD patients, 2 cases were diagnosed as confirmed COVID-19, and 97 cases had exacerbations, 32 cases of which were hospitalized, and 14 cases died. Compared with the 6-month follow-up results collected 1 year ago, in 307 cases of this cohort, the rates of exacerbations and hospitalization of the 489 COPD patients during the last 4 months decreased, while the mortality rate increased significantly (2.86% vs 0.65%, p=0.023). Of the 821 patients with COVID-19, 37 cases (4.5%) had pre-existing COPD. Of 180 confirmed deaths, 19 cases (10.6%) were combined with COPD. Compared to COVID-19 deaths without COPD, COVID-19 deaths with COPD had higher rates of coronary artery disease and/or cerebrovascular diseases. Old age, low BMI and low parameters of lung function were risk factors of all-cause mortality for COVID-19 patients with pre-existing COPD.Conclusion: Our findings imply that acute exacerbations and hospitalizations of COPD patients were infrequent during the COVID-19 pandemic. However, COVID-19 patients with pre-existing COPD had a higher risk of all-cause mortality.Keywords: chronic obstructive pulmonary disease, COPD, exacerbation, mortality, novel coronavirus pneumonia, COVID-19, novel coronavirus, SARS-CoV-2

Yu Fu, Mengyuan Xiong, Xuehan Li, Junying Zhou, Xiao Xiao, Fang Fang, Xiaohuan Cheng, Yingbang Le, Yirong Li Department of Clinical Laboratory, Zhongnan Hospital, Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Yirong LiDepartment of Clinical Laboratory, Zhongnan Hospital, Wuhan University, Wuhan, People’s Republic of ChinaEmail liyirong838@163.comPurpose: This study aimed to investigate the molecular characteristics, antimicrobial resistance and virulence genes profiles of S. aureus isolates from Wuhan, central China.Materials and Methods: A total of 302 non-duplicate S. aureus isolates were collected successively during January–December 2018 and subjected to multi-locus sequence typing (MLST), staphylococcal protein A (spa) typing and Panton–Valentine leucocidin (PVL) and staphylococcal enterotoxin A, B, C, D, E, G, H and I (sea, seb, sec, sed, see, seg, seh and sei) detection. All methicillin-resistant S. aureus (MRSA) isolates were additionally subjected to staphylococcal chromosomal cassette mec(SCCmec) typing.Results: Of the 302 S. aureus isolates, 131 were categorised as MRSA, yielding a rate 1.4 times the average rate in China during 2018 (43.4% vs 30.9%). Thirty-one sequence types (STs) and 82 spa types were identified. The most prevalent clones were ST5-t2460 (10.9%), ST239-t030 (9.3%), ST188-t189 (7.9%) and ST59-t437 (6.3%). Notably, the continued prevalence of ST239-t030 in Wuhan differs from other areas in China. SCCmec types and subtypes I, II, III, IVa and V were present in 0.8%, 36.6%, 26.0%, 20.6% and 8.4% of MRSA isolates. A comprehensive analysis identified ST5-t2460-SCCmec II (25.2%,), ST239-t030-SCCmec III (19.8%) and ST59-t437-SCCmec IVa (7.6%) as the major clones among MRSA isolates. The genes pvl, sea, seb, sec, sed, see, seg, seh and sei were detected at respective frequencies of 11.9%, 42.1%, 49.7%, 45.0%, 20.9%, 33.8%, 60.5%, 25.8% and 66.9%.Conclusion: ST239-t030 remains one of the most prevalent clones in S. aureus isolates from Wuhan, leading us to conclude that S. aureus isolates from Wuhan possess unique molecular characteristics. The S. aureus isolates also exhibit unique antimicrobial resistance profiles and harbour relatively high numbers of enterotoxin virulence genes, compared with other reports from China.Keywords: Staphylococcus aureus, molecular characteristics, antimicrobial resistance, virulence

Hao Ding, Yuchuan Luo, Ke Hu, Pei Liu, Mengqing XiongDivision of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Ke HuDivision of Respiratory Disease, Renmin Hospital of Wuhan University, Zhangzhidong Road No. 99, Wuhan 430060, People’s Republic of ChinaTel +86 1 897 103 5988Fax +86 0 278 804 2292Email hukejjx@163.comBackground: Recently, numerous studies have demonstrated the emerging role of long non-coding RNAs (lncRNAs) in human cancers. Linc00467 is a newly defined lncRNA and was reported to promote cell survival in neuroblastoma. However, the function of linc00467 in lung cancer is still unclear.Material and methods: We analyzed linc00467 expression and survival data derived from The Cancer Genome Altas lung adenocarcinoma (LUAD) dataset as well as in collected LUAD tissues. Then, we silenced linc00467 expression in two lung cancer cell lines using small interfering RNAs and explored the effect of linc00467 knockdown on cell growth in vitro and in vivo. Moreover, we revealed a novel target gene of linc00467 and elucidated the underlying competitive endogenous RNA regulatory mechanism in lung cancer cells.Results: Our data suggested that linc00467 expression was elevated in LUAD tissues and correlated with overall survival of LUAD patients. Linc00467 knockdown resulted in reduced proliferation rate in lung cancer cells. Furthermore, we elucidated that linc00467 promoted CCND1 expression in lung cancer cells via functioning as a molecular sponge for miR-20b-5p.Conclusion: Linc00467/miR-20b-5p/CCND1 signaling pathway may provide new insights into lung cancer treatment.Keywords: linc00467, lung adenocarcinoma, cell growth, miR-20b-5p, CCND1

Aimei Peng,*,1 Guoshu Li,*,1 Mengting Xiong,*,2 Shuanshuan Xie,1 Changhui Wang11Department of Respiratory Medicine, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072, People’s Republic of China; 2Department of Respiratory Medicine, Pulmonary Hospital, Tongji University, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workPurpose: Currently, systemic chemotherapy combined with thoracic radiation is the standard treatment for patients with small-cell lung cancer (SCLC). However, the treatment of early stage SCLC remains controversial. This study evaluated the survival outcomes of surgical treatments and the effect of adjuvant chemotherapy and radiotherapy on lung cancer-specific survival (LCSS) in patients with early stage SCLC.Methods: Using the Surveillance, Epidemiology, and End Results registry, we identified 2,453 patients with early stage SCLC (1,295 women and 1,158 men) who had complete clinical information between 2004 and 2015. The Kaplan-Meier analysis was used to determine the propensity score based on the characteristics of patients with early stage SCLC. LCSS was compared between patients treated with surgery and non-surgery after adjusting, stratifying, or matching patients with early stage SCLC. In addition, we compared the effects of chemotherapy and radiotherapy on LCSS in patients with early stage SCLC.Results: Overall, 687 (28.0%) and 1,766 (72.0%) patients with early stage SCLC did and did not undergo surgery, respectively. Kaplan-Meier analysis demonstrated a statistically significant difference in survival curves between the surgery and non-surgery groups (log-rank p

Wen Yuan,1,2,* Songping Xie,3,* Meng Wang,2 Shan Pan,2 Xiaoxing Huang,2 Meng Xiong,2 Rui-jing Xiao,2 Jie Xiong,2 Qiu-ping Zhang,2 Liang Shao1 1Department of Internal Medicine, Zhongnan Hospital of Wuhan University, 2Department of Immunology, Basic School, Wuhan University, 3Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China *These authors contributed equally to this work Background: ZWINT is a crucial component of the mitotic checkpoint. However, its possible role in lung cancer is unclear. In this study, we determined its correlation with lung cancer.Methods: Real-time PCR and immunohistochemistry (IHC) were used to determine 40 collected clinical lung cancer samples. Chi-square test was used to examine possible correlations between ZWINT expression and clinicopathological factors. The prognostic significance of mRNA expression of ZWINT in lung cancer was evaluated using the Kaplan–Meier plotter. Univariate and multivariate Cox proportional hazards regression analysis were performed to determine whether ZWINT is an independent risk factor for overall survival (OS) and disease-free survival (DFS) of lung cancer patients. Additionally, STRING database was used to analyze protein-protein interactions.Results: In this study, we screened 13 GSE datasets and detected that ZWINT is highly expressed in multiple carcinomas including lung, melanoma, prostate, nasopharyngeal, gastric, pancreatic, colon, esophageal, ovarian, renal, breast and liver cancer. Real-time PCR and IHC results of collected clinical lung cancer samples confirmed that ZWINT is highly expressed in tumor tissues compared with adjacent non-tumor tissues. Additionally, high expression of ZWINT might predict poor OS and DFS in lung cancer patients. Moreover, disease stage and expression level of ZWINT were correlated with recurrence-free survival and OS in lung cancer. Analysis of protein-protein interaction based on STRING database gained 8 top genes which could interact with ZWINT, including PMF1, MIS12, DSN1, ZW10, BUB1, BUB1B, CASC5, NDC80, NSL1 and NUF2.Conclusion: ZWINT is aberrantly highly expressed in lung tumor tissues and might be involved in the pathogenesis of lung cancer. Keywords: ZWINT, lung cancer, prognosis, overall survival, recurrence-free survival

Yuanyuan Qiao,1,* Jun Li,2,* Chenghe Shi,1,* Wei Wang,2 Xiuhua Qu,1 Ming Xiong,1 Yulin Sun,3 Dandan Li,1 Xiaohang Zhao,1,3 Dajin Zhang1 1Center of Basic Medical Sciences, 2Department of Thoracic Surgery, Navy General Hospital of Chinese PLA, 3State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China *These authors contributed equally to this work Objective: Circulating tumor cells (CTCs) of patients with malignant tumors can be used as a prognostic marker. However, there are few relevant reports to date on esophageal squamous cell carcinoma (ESCC). Our study assesses the clinical significance of CTCs in ESCC patients. Patients and methods: CTCs were detected in 103 peripheral blood (PB) samples from 59 ESCC patients. Correlation between CTCs and clinical parameters was analyzed using the χ2 test or Fisher’s exact test. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier analysis and univariate and multivariate methods. Results: The CTC detection rate was 79.7% (47/59) at baseline. The frequency of CTC-positive patients increased as the disease stage advanced (88.0% in stages III–IV, 58.9% in stages I–II). CTC counts ≥0/7.5 mL of PB were correlated with the degree of tumor differentiation, tumor infiltration, and lymph node and distant metastases. Overall, the OS and PFS of patients with CTC counts ≥3 or ≥5/7.5 mL of PB before surgery were significantly shorter than those of patients with CTC counts

Mingmei Xiong,* Jian Wang,* Meihua Guo, Qipeng Zhou, Wenju Lu State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China *These authors contributed equally to this work Abstract: TRPM8 plays a key role in COPD. The development of pulmonary hypertension (PH) in COPD adversely affects survival and exercise capacity. Thus, the aim of this study was to evaluate the possible association between single nucleotide polymorphisms (SNPs) in TRPM8 and COPD or PH in COPD among the Chinese Han population. A total of 513 COPD patients and 506 controls were enrolled in the study. Six tag SNPs (tSNPs) were genotyped. The relationship between COPD or PH in COPD and the six tSNPs was evaluated using the χ2 test and genetic model analysis. In the rs9789398 polymorphism, the T/C genotype was associated with an increased risk for COPD (P=0.005). Under the assumption of models of inheritance, there was an association between the rs9789398 polymorphism and COPD. In the rs9789675 polymorphism, the G/A genotype was associated with an increased risk for COPD (P=0.021). Furthermore, by the χ2 test, we found that the minor allele “A” of rs9789675 (odds ratio [OR] =0.63, 95% confidence interval [CI], 0.42–0.97, P=0.034) and the minor allele “C” of rs9789398 (OR =1.59, 95% CI, 1.03–2.44, P=0.034) were associated with a decreased risk of PH in COPD in allele models. In genetic models, the genotypes “GA” and “AA” of rs9789675 were associated with a decreased risk of PH in COPD. The genotypes “TC” and “CC” of rs9789398 were associated with a decreased risk of PH in COPD. Moreover, “CG” of rs1004478 was significantly associated with a decreased risk of PH in COPD. There was a significant association between the five SNPs (rs2362290, rs9789675, rs9789398, rs1003540, and rs104478) in the TRPM8 gene and the risk of PH in COPD. Our findings indicated that rs9789398 in the TRPM8 gene was significantly associated with the risk of COPD in the Chinese Han population. Moreover, rs9789675, rs9789398, and rs1004478 were significantly associated with the risk of PH in COPD. This study provides a novel insight into COPD and PH in the development of COPD. Keywords: COPD, pulmonary hypertension, case–control study, single nucleotide polymorphism