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Hang Yi,1 Ruiping Ye,2 Jinfeng Wang,3 Lin Gao,4 Weiwei Zhang,4 Chao Liu4 1Department of Intensive Care Medicine, Qianjiang Central Hospital, Qianjiang City, Hubei Province, 433100, People’s Republic of China; 2Department of Intensive Care Medicine, The First People’s Hospital of Dingnan County, Ganzhou City, Jiangxi Province, 341900, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Gannan Medical University, Ganzhou City, Jiangxi Province, 341000, People’s Republic of China; 4Department of Intensive Care Medicine, Ganzhou People’s Hospital, Ganzhou City, Jiangxi Province, 341000, People’s Republic of ChinaCorrespondence: Chao Liu, Department of Intensive Care Medicine, Ganzhou People’s Hospital, No. 16, Meiguan Avenue, Zhanggong District, Ganzhou City, Jiangxi Province, People’s Republic of China, Email a15116461784@126.comObjective: To investigate the diagnostic value of serum fibrinogen domain-containing lectin-3 (Ficolin-3) and galectin-3 (Gal-3) in sepsis-associated acute kidney injury (SA-AKI).Methods: This study retrospectively analyzed 126 SA-AKI patients with SA-AKI and 103 septic patients without AKI as controls. Based on the severity of renal injury, the SA-AKI patients were divided into three groups: mild (41 cases), moderate (53 cases), and severe (32 cases). Serum levels of Ficolin-3 and Gal-3 were measured using ELISA, and their correlation was determined through Pearson analysis. Multivariate logistic regression was used to identify factors associated with the occurrence of SA-AKI.Results: The serum creatinine (SCr), blood urea nitrogen (BUN), as well as the expression levels of serum Ficolin-3 and Gal-3 in the SA-AKI group were higher than those in the non SA-AKI group (P< 0.05). The expression levels of Ficolin-3 and Gal-3 in the serum of the SA-AKI group were also higher than those of the non SA-AKI group (P< 0.05). The expression levels of Ficolin-3 and Gal-3 in serum gradually increased with the severity of renal injury in SA-AKI patients (P< 0.05). The expression levels of Ficolin-3 and Gal-3 in serum were greatly positively correlated (P< 0.001). Elevated levels of BUN, Ficolin-3, and Gal-3 were risk factors affecting the occurrence of SA-AKI (P< 0.05). The area under the curve (AUC) of serum Ficolin-3 and Gal-3 for individual diagnosis of SA-AKI was 0.877 and 0.867, respectively, the AUC of their combined diagnosis was 0.953, and the diagnostic sensitivity was higher than that of their individual diagnosis (P< 0.001).Conclusion: The expression levels of serum Ficolin-3 and Gal-3 are closely related to associated with the onset and progression of SA-AKI and hold diagnostic value for its detection. Furthermore, the combined use of both markers provides a more accurate diagnosis than either marker alone.Keywords: Sepsis complicated with acute kidney injury, Fibrinogen domain-containing lectin-3, Galectin-3

Zemin Ou, Yun You, Hong Yi, Xiaoqian Liu, Yan Tong, Dewen Liu, Jinyu Wang Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Dewen Liu; Jinyu Wang, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 10700, People’s Republic of China, Email dwliu@icmm.ac.cn; wangjinyu@icmm.ac.cnIntroduction: Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra. The precise molecular mechanisms underlying neuronal loss in PD remain unknown, and there are currently no effective treatments for PD-associated neurodegeneration. Echinacoside (ECH) is known for its neuroprotective effects, which include scavenging cellular reactive oxygen species and promoting mitochondrial fusion. However, the blood-brain barrier (BBB) limits the bioavailability of ECH in the brain, posing a significant challenge to its use in PD treatment.Methods: We synthesized and characterized PEGylated ECH liposomes (ECH@Lip) and peptide angiopep-2 (ANG) modified liposomes (ECH@ANG-Lip). The density of ANG in ANG-Lip was optimized using bEnd.3 cells. The brain-targeting ability of the liposomes was assessed in vitro using a transwell BBB model and in vivo using an imaging system and LC-MS. We evaluated the enhanced neuroprotective properties of this formulation in a the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model.Results: The ECH@ANG-Lip demonstrated significantly higher whole-brain uptake compared to ECH@Lip and free ECH. Furthermore, ECH@ANG-Lip was more effective in mitigating MPTP-induced behavioral impairment, oxidative stress, dopamine depletion, and dopaminergic neuron death than both ECH@Lip and free ECH.Conclusion: The formulation used in our study significantly enhanced the neuroprotective efficacy of ECH in the MPTP-induced PD model. Thus, ECH@ANG-Lip shows considerable potential for improving the bioavailability of ECH and providing neuroprotective effects in the brain.Keywords: nanomedicine, brain delivery, angiopep-2, echinacoside, Parkinson’s disease, liposomes

Qiying Zeng,1,&ast; Wenjun Xue,2,&ast; Zhicheng Wei,1 Hangdong Shen,1 Huajun Xu,1 Huaming Zhu,1 Jian Guan,1 Hongliang Yi,1 Yunhai Feng,2 Xinyi Li,1 Haibo Ye1 1Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai Jiao Tong University, Shanghai, 200233, People’s Republic of China; 2Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Eighth People’s Hospital Affiliated to Jiangsu University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinyi Li; Haibo Ye, Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, 200233, People’s Republic of China, Tel/Fax +86-2164834143, Email lixinyilixinyi123@163.com; yehaibo_2012@163.comBackground: Sleep-disordered breathing is more prevalent in individuals with allergic rhinitis (AR) than in those without AR. In addition to increased risk for sleep-disordered breathing, AR is associated with greater severity of obstructive sleep apnea (OSA) symptoms. The aim of this research study was to evaluate the association of multiple single nucleotide polymorphism (SNP) variations in AR with sleep- and breathing-related parameters in men with OSA.Methods: Men who had complained of snoring were consecutively enrolled in the Shanghai Sleep Health Study of Shanghai Sixth People’s Hospital from 2007 to 2018. After rigorous screening, 5322 men were included in the analysis. Anthropometric, fasting biochemical, and polysomnographic parameters, along with 27 AR-associated SNPs were analyzed. The associations between AR-related genetic polymorphisms and OSA were determined via linear, binary, and multinomial logistic regression analyses.Results: Rs12509403 had significantly positive associations with most sleep-breathing parameters. While the risk for OSA was increased by rs12509403, it was decreased by rs7717955 [odds ratio (OR) = 1.341, 95% confidence interval [CI] = 1.039– 1.732, P = 0.024; OR = 0.829, 95% CI = 0.715– 0.961, P = 0.013, respectively]. A graded increase in the risk of being in the highest quartile (Q4) vs the reference category (Q1) for sleep breathing indicators, especially REM-AHI and NREM-AHI, was identified by rs12509403 (OR = 1.496, 95% CI = 1.175– 1.904, P = 0.001; OR = 1.471, 95% CI = 1.151– 1.879, P < 0.001, respectively).Conclusion: The association of multiple AR SNPs with OSA-related hypoxia and sleep indices provides a genetic explanation for the higher AR susceptibility of OSA patients. Understanding the AR-related genetic underpinnings of OSA may lead to more personalized treatment approaches.Keywords: allergic rhinitis, obstructive sleep apnea, single nucleotide polymorphism, polysomnography

Qiaofei Tang,1,2 Honggan Yi,1,2 Siping Chen,1,2 Yantian Zheng,1,2 Yitao Wen,1,2 Man Yang1,2 1Reproductive Medicine Center, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Meizhou Municipal Engineering and Technology Research Center for Molecular Diagnostics of Major Genetic Disorders, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Man Yang, Reproductive Medicine Center, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meizhou, Meijiang District, People’s Republic of China, Email 13751992388@163.comBackground: The causes of pregnancy failure after intrauterine insemination (IUI) are controversial. The purpose of this study was to investigate the influencing factors on clinical pregnancy after IUI.Methods: This study retrospectively analyzed 1464 cycles of IUI performed at the Meizhou People’s Hospital between March 2014 and June 2023. The χ2 test and logistic regression analysis was applied to assess the associations between the some factors (maternal age, paternal age, cycle type (natural cycle or ovulation induction cycle), hormone level on the day of endometrial transformation (estradiol (E2), luteinizing hormone (LH), and progesterone (P)), endometrial thickness on the day of endometrial transformation, and forward motile sperm concentration after treatment) and pregnancy failure.Results: Among the 1464 IUI cycles in this study, 268 cycles of assisted reproduction resulted in clinical pregnancy, with a clinical pregnancy rate of 18.3%. During the cycles with clinical pregnancy, there were 25 (12.9%) preterm births and 169 (87.1%) full-term births. The E2 level on the day of endometrial transformation in clinical pregnancy group was higher than that in the pregnancy failure group (658.79± 656.02 vs 561.21± 558.83 pg/mL)(P=0.025). The clinical pregnancy group had a higher percentage of endometrial thickness between 8 and 13mm on the day of endometrial transformation than the pregnancy failure group (83.2% vs 75.0%)(P=0.002). The results of regressions analysis showed that low E2 level on the day of endometrial transformation (< 238.3 pg/mL vs ≥ 238.3 pg/mL: OR 1.493, 95% CI: 1.086– 2.052, P=0.014), and endometrial thickness < 8mm on the day of endometrial transformation (< 8mm vs 8– 13mm: OR 1.886, 95% CI: 1.284– 2.771, P=0.001) may increase risk of pregnancy failure performed IUI.Conclusion: Low estradiol level, and endometrial thickness on the day of endometrial transformation may increase risk of pregnancy failure performed intrauterine insemination.Keywords: intrauterine insemination, pregnancy failure, estradiol, endometrial thickness

Xinyi Li,1,&ast; Tao Wang,2,&ast; Li Jin,3 Zhiqiang Li,4 Cheng Hu,3 Hongliang Yi,1 Jian Guan,1 Huajun Xu,1 Xiaolin Wu5 1Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, People’s Republic of China; 2Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 4Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Ministry of Education, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 5Central Laboratory of Shanghai Eighth People’s Hospital, Xuhui Branch of Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huajun Xu, Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, 200233, People’s Republic of China, Email sunnydayxu2010@163.com Xiaolin Wu, Central Laboratory of Shanghai Eighth People’s Hospital, Xuhui Branch of Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China, Email wuxiaolin999@hotmail.comObjective: Both obstructive sleep apnea (OSA) and obesity are highly prevalent worldwide, and are intrinsically linked. Previous studies showed that obesity is one of the major risk factors for OSA, but the causality of the relationship is still unclear. The study was to investigate the causal relationships of overall obesity and abdominal obesity with OSA and its quantitative traits.Methods: In this case-control study, a total of 7134 participants, including 4335 moderate-to-severe OSA diagnosed by standard polysomnography and 2799 community-based controls were enrolled. Anthropometric and biochemical data were collected. Mendelian randomization (MR) analyses were performed using the genetic risk score, based on 29 body mass index (BMI)- and 11 waist-hip-ratio (WHR)-associated single nucleotide polymorphisms as instrumental variables. The causal associations of these genetic scores with OSA and its quantitative phenotypes were analyzed.Results: Obesity was strongly correlated with OSA in observational analysis (β= 0.055, P = 3.7 × 10− 5). In MR analysis, each increase by one standard deviation in BMI was associated with increased OSA risk [odds ratio (OR): 2.21, 95% confidence interval (CI): 1.62– 3.02, P = 5.57 × 10− 7] and with 2.72-, 4.68-, and 3.25-fold increases in AHI, ODI, and MAI, respectively (all P

Xuejiao Liao,1,&ast; Yuan Guan,1,2,&ast; Zixun Lin,1 Qingrong Tang,3 Zhenghua Ma,1 Shuting Wu,1 Xiaobin Wang,1 Jingke Dong,1 Liping Zhang,1 Jiayu Deng,1 Zhonghui Liao,1,4 Sumei Yang,1,4 Cheng Wang,1,4 Shuo Song,1 Hongyang Yi,1 Song Wu,5 Tetsuya Asakawa,6 Hongzhou Lu1 1Institute for Hepatology, National Clinical Research Center for Infectious Disease, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 2Department of Epidemiology, School of Public Health Fudan University, Shanghai, People’s Republic of China; 3The First Hospital of Changsha, Infectious Diseases Department, Changsha, People’s Republic of China; 4School of Public Health, Bengbu Medical College, Bengbu, People’s Republic of China; 5Department of Central Laboratory, South China Hospital, Medical School, Shenzhen University, Shenzhen, People’s Republic of China; 6Institute of Neurology, National Clinical Research Center for Infectious Diseases, the Third People’s Hospital of Shenzhen, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongzhou Lu, Institute for Hepatology, National Clinical Research Center for Infectious Disease, The Third People’s Hospital of Shenzhen, The Second Hospital Affiliated with the School of Medicine, Southern University of Science and Technology, No. 29 Bulan Road, Long Gang District, Shenzhen, Guangdong, 518112, People’s Republic of China, Email luhongzhou@fudan.edu.cn Tetsuya Asakawa, Institute of Neurology, National Clinical Research Center for Infectious Diseases, the Third People’s Hospital of Shenzhen, No. 29 Buji Bulan Road, Shenzhen, Guangdong, 518112, People’s Republic of China, Email asakawat1971@gmail.comPurpose: The purpose was to review relevant clinical data and formulate recommendations supporting the use of saline as a simple rinse for an early reassuring intervention to reduce the occurrence of re-positive COVID-19 patients.Methods: We conducted a single-centre retrospective cohort study, which enrolled patients with confirmed re-testing positive COVID-19 during 7– 60 days after discharge from Third People’s Hospital of Shenzhen. By one-to-two propensity score matching for age and sex, the control group of those not re-testing positive during the same period served as matched control.Results: A total of 223 patients were included in our study, 94 in re-positive group and 129 in non-re-positive group. The result shows that the rates of nasal douche treatment in the non-re-positive group were considerably higher than that of the re-positive group. And the Ct value of nasal douche group increased faster than that of non-nasal douche group after the Ct value reaching ≥ 35. Further analysis revealed that the higher the Ct value at the time of readmission, the shorter the time of average Ct values to reach ≥ 35.Conclusion: These findings suggest that nasal douche is beneficial to shorten the time of virus nucleic acid turning negative, thereby reducing the incidence of re-positive. The prevention and control of epidemics focuses on re-positive patients with Ct values < 35.Keywords: COVID-19, nasal douche, re-positive, RT-PCR

Yali Liu,1,&ast; Zhihong Qi,2,&ast; Meirong Bai,1,&ast; Jianle Kang,1 Jinxin Xu,1 Huochun Yi3 1Department of Thoracic Surgery, Zhongshan Hospital Xiamen University, Xiamen, Fujian, 361012, People’s Republic of China; 2Department of Urologic Surgery, Zhongshan Hospital Xiamen University, Xiamen, Fujian, 361012, People’s Republic of China; 3Clinical Laboratory, Zhongshan Hospital Xiamen University, Xiamen, Fujian, 361012, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinxin Xu, Department of Thoracic Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, No. 201 Hubin South Road, Siming District, Xiamen, People’s Republic of China, Email 2297203944@qq.com Huochun Yi, Centre of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, No. 201 Hubin South Road, Siming District, Xiamen, People’s Republic of China, Email yhc1818@xmu.edu.cnObjective: This study aims to investigate the independent prognostic factors of patients with coronavirus disease 2019 (COVID-19) and thereafter construct a related prognostic model.Methods: The subjects were screened following the COVID-19 diagnostic criteria. The independent prognostic factors were selected based on the indicators, including medical history, clinical manifestation, laboratory tests, imaging examination and clinical prognosis. Subsequently, we constructed a nomogram model to predict short-term prognosis.Results: Clinical information was obtained from 393 COVID-19 patients admitted to Zhongshan Hospital at Xiamen University between December 2022 and January 2023. The independent risk factors determined by Cox multivariate regression analysis included gender (OR: 0.355, 95% CI: 0.16~0.745), age (OR: 3.938, 95% CI: 1.221~15.9), pectoral muscle index (PMI, OR: 4.985, 95% CI: 2.336~11.443), pneumonia severity score (PSS, OR: 6.486, 95% CI: 2.082~21.416) and lactate dehydrogenase (LDH, OR: 3.857, 95% CI: 1.571~10.266). A short-term prognostic nomogram was developed based on the five independent risk factors above. The area under the receiver operating characteristic (ROC) curve (AUC) of the nomogram model was 0.857. The calibration curve confirmed the outcomes of the prognostic model, which exhibited excellent consistency with the actual results.Conclusion: In summary, gender, age, pectoral muscle index, pneumonia severity score, and lactate dehydrogenase are all independent risk factors for COVID-19 mortality. Thus, the nomogram based on the above indicators can predict the risk of mortality in COVID-19 patients. This may have the potential of being clinical application in prognostic evaluation of COVID-19.Keywords: COVID-19, risk factors, nomogram, prognoses, evaluation study

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

Wangxing Lu,1,&ast; Wenjie Liu,1,&ast; Anna Hu,1 Jian Shen,1 Hanxi Yi,2 Zeneng Cheng1 1Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410000, People’s Republic of China; 2School of Basic Medical Science, Central South University, Changsha, 410000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hanxi Yi; Wenjie Liu, Email hanxiyi2022@csu.edu.cn; wenjie.liu@csu.edu.cnIntroduction: Drug delivery systems (DDSs) based on liposomes are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve biosafe, accurate, and efficient cancer therapy of liposomes with single function or single mechanism. To solve this problem, we designed a multifunctional and multimechanism nanoplatform based on polydopamine (PDA)-coated liposomes for accurate and efficient combinatorial cancer therapy of chemotherapy and laser-induced PDT/PTT.Methods: ICG and DOX were co-incorporated in polyethylene glycol modified liposomes, which were further coated with PDA by a facile two-step method to construct PDA-liposome nanoparticles (PDA@Lipo/DOX/ICG). The safety of nanocarriers was investigated on normal HEK-293 cells, and the cellular uptake, intracellular ROS production capacity, and combinatorial treatment effect of the nanoparticles were assessed on human breast cancer cells MDA-MB-231. In vivo biodistribution, thermal imaging, biosafety assessment, and combination therapy effects were estimated based on MDA-MB-231 subcutaneous tumor model.Results: Compared with DOX·HCl and Lipo/DOX/ICG, PDA@Lipo/DOX/ICG showed higher toxicity on MDA-MB-231 cells. After endocytosis by target cells, PDA@Lipo/DOX/ICG produced a large amount of ROS for PDT by 808 nm laser irradiation, and the cell inhibition rate of combination therapy reached up to 80.4%. After the tail vein injection (DOX equivalent of 2.5 mg/kg) in mice bearing MDA-MB-231 tumors, PDA@Lipo/DOX/ICG significantly accumulated at the tumor site at 24 h post injection. After 808 nm laser irradiation (1.0 W/cm2, 2 min) at this timepoint, PDA@Lipo/DOX/ICG efficiently suppressed the proliferation of MDA-MB-231 cell and even thoroughly ablated tumors. Negligible cardiotoxicity and no treatment-induced side effects were observed.Conclusion: PDA@Lipo/DOX/ICG is a multifunctional nanoplatform based on PDA-coated liposomes for accurate and efficient combinatorial cancer therapy of chemotherapy and laser-induced PDT/PTT.Keywords: reactive oxygen species, photodynamic therapy, photothermal therapy, polydopamine, liposome

Yuying Lu,1– 5 Qianlin Li,1– 5 Huahao Fan,6 Conghui Liao,1– 5 Jingsong Zhang,1– 5 Huan Hu,1– 5 Huaimin Yi,1– 5 Yuanli Peng,1– 5 Jiahai Lu,1– 5 Zeliang Chen1– 3,7 1One Health Center of Excellence for Research and Training, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2National Medical Products Administration Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products, Guangzhou, People’s Republic of China; 3Key Laboratory of Tropical Diseases Control, Sun Yat-Sen University, Ministry of Education, Guangzhou, People’s Republic of China; 4Research Institute of Sun Yat-Sen University in Shenzhen, Shenzhen, People’s Republic of China; 5Hainan Key Novel Thinktank “Hainan Medical University ‘One Health’ Research Center”, Haikou, People’s Republic of China; 6College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, People’s Republic of China; 7Key Laboratory of Zoonose Prevention and Control at Universities of Inner Mongolia Autonomous Region, Medical College, Inner Mongolia Minzu University, Tongliao, People’s Republic of ChinaCorrespondence: Jiahai Lu; Zeliang Chen, One Health Center of Excellence for Research and Training, School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China, Email lujiahai@mail.sysu.edu.cn; chenzliang5@mail.sysu.edu.cnBackground: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants have risen to dominance, which contains far more mutations in the spike protein in comparison to previously reported variants, compromising the efficacy of most existing vaccines or therapeutic monoclonal antibodies. Nanobody screened from high-throughput naïve libraries is a potential candidate for developing preventive and therapeutic antibodies.Methods: Four nanobodies specific to the SARS-CoV-2 wild-type receptor-binding domain (RBD) were screened from a naïve phage display library. Their affinity and neutralizing activity were evaluated by surface plasmon resonance assays, surrogate virus neutralization tests, and pseudovirus neutralization assays. Preliminary identification of the binding epitopes of nanobodies by peptide-based ELISA and competition assay. Then four multivalent nanobodies were engineered by attaching the monovalent nanobodies to an antibody-binding nanoplatform constructed based on the lumazine synthase protein cage nanoparticles isolated from the Aquifex aeolicus (AaLS). Finally, the differences in potency between the monovalent and multivalent nanobodies were compared using the same methods.Results: Three of the four specific nanobodies could maintain substantial inhibitory activity against the Omicron (B.1.1.529), of them, B-B2 had the best neutralizing activity against the Omicron (B.1.1.529) pseudovirus (IC50 = 1.658 μg/mL). The antiviral ability of multivalent nanobody LS-B-B2 was improved in the Omicron (B.1.1.529) pseudovirus assays (IC50 = 0.653 μg/mL). The results of peptide-based ELISA indicated that LS-B-B2 might react with the linear epitopes in the SARS-CoV-2 RBD conserved regions, which would clarify the mechanisms for the maintenance of potent neutralization of Omicron (B.1.1.529) preliminary.Conclusion: Our study indicated that the AaLS could be used as an antibody-binding nanoplatform to present nanobodies on its surface and improve the potency of nanobodies. The multivalent nanobody LS-B-B2 may serve as a potential agent for the neutralization of SARS-CoV-2 variants.Keywords: COVID-19, bio-nanotechnology, self-assembly, nanobody multimers, thermal stability

Haiyu Tang,1,2 Man Yang,1,2 Honggan Yi,1,2 Mei Lin1,2 1Reproductive Medicine Center, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Haiyu Tang, Reproductive Medicine Center, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 Huang tang Road, Meijiang District, Meizhou, People’s Republic of China, Tel +86 753-2131-883, Email tanghaiyu666@163.comBackground: The risks of adverse perinatal outcomes in offspring conceived following frozen-thawed embryo transfer (FET) assisted reproductive technology (ART) are inconsistent. The aim of this study was to analyze the risk factors for preterm birth and low birth weight in singletons after FET.Methods: 386 FET cycles was conducted at the Reproductive Medicine Center of Meizhou People’s Hospital. The relationship between clinical characteristics and outcomes (term birth and preterm birth, normal birth weight and low birth weight) was analyzed.Results: The rate of primary infertility, basal FSH and T levels, gestational age, birth weight, and proportion of male fetuses were significantly different in the preterm and full-term groups. Logistic regression analysis showed that high maternal age (≥ 35 years) (OR 3.652, 95% CI: 1.683– 7.925, P=0.001), primary infertility (OR 2.869, 95% CI: 1.461– 5.632, P=0.002), low FSH level (< 6.215 mIU/mL) (OR 3.272, 95% CI: 1.743– 6.144, P< 0.001), and hormone replacement therapy (HRT) method (OR 2.780, 95% CI: 1.088– 7.100, P=0.033) may increase risk of preterm birth after FET. Gestational age and birth weight were significantly different in fetuses with low birth weight (< 2500g, n=38) and normal birth weight (≥ 2500g and < 4000g, n=333). Logistic regression analysis showed that low basal FSH level (< 6.215 mIU/mL) (OR 0.425, 95% CI: 0.209– 0.865, P=0.018), and HRT method of endometrial preparation for FET (OR 0.272, 95% CI: 0.079– 0.934, P=0.039) may reduce the risk of low birth weight after FET.Conclusion: High maternal age, primary infertility, low FSH level, HRT method of endometrial preparation for FET, and male fetus may increase risk of preterm birth after FET. In addition, primary infertility, low basal FSH level, and HRT method of endometrial preparation may reduce the risk of low birth weight after FET.Keywords: frozen embryo transfer, preterm birth, low birth weight, risk factors, assisted reproductive technology

Honggan Yi,1,2 Man Yang,1,2 Haiyu Tang,1,2 Mei Lin1,2 1Reproductive Medicine Center, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Honggan Yi, Reproductive Medicine Center, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, People’s Republic of China, Tel +86 753-2131-883, Email yihonggan6@163.comBackground: Infertile couples need to use assisted reproductive technology (ART) to give birth. However, pregnancy failure after ART is not uncommon. At present, the results of studies on the causes of pregnancy failure after ART are inconsistent.Methods: A retrospective cohort study involving 715 embryo transfer cycles was conducted at the Reproductive Medicine Center of Meizhou People’s Hospital, from December 2015 to June 2022. According to the pregnancy, they were divided into clinical pregnancy group and pregnancy failure group. The relationship between demographic characteristics and pregnancy status between the two groups was analyzed.Results: The pregnancy failure rate after ART was 49.7% (355/715). There were statistically significant distribution differences of maternal age, paternal age, COH protocols, and number of embryos transferred between clinical pregnancy and pregnancy failure groups (all P< 0.01). Multiple logistic regression analysis shows that high maternal age (> 35 years old vs ≤ 35 years old: OR 2.173, 95% CI: 1.386– 3.407, P=0.001), and GnRH-a short protocol (GnRH-a short protocol vs GnRH-a long protocol: OR 2.139, 95% CI: 1.127– 4.058, P=0.020) may increase risk of pregnancy failure in ART pregnancies, while two embryos transferred (two embryos transferred vs one embryo transferred: OR 0.563, 95% CI: 0.377– 0.839, P=0.005) may reduce risk of pregnancy failure. In addition, high maternal age, GnRH antagonist protocol, and GnRH-a short protocol may increase risk of implantation failure, while two embryos transferred may reduce risk of implantation failure. And high maternal age may increase risk of biochemical pregnancy.Conclusion: The risk of pregnancy failure increased in ART cycles with maternal age > 35 years old and GnRH-a short protocol, while reduced with two embryos transferred.Keywords: assisted reproductive technology, risk factors, pregnancy failure, infertility, miscarriage

Qian Liu, Ran Wei, Jian Lu, Hongke Ding, Hui Yi, Li Guo, Jing Wu Department of Medical Genetics Center, Guangdong Women and Children Hospital, Guangzhou City, Guangdong Province, People’s Republic of ChinaCorrespondence: Jing Wu, Department of Medical Genetics Center, Guangdong Women and Children Hospital, NO. 521 Xingnan Road, Panyu District, Guangzhou city, Guangdong Province, People’s Republic of China, Tel +86 20-39151548, Email wujing020@126.comObjective: To analyse the risk of clinical chromosomal abnormalities in foetuses with umbilical cord cysts.Methods: Data from all genetic assays that were performed as part of invasive prenatal diagnoses of umbilical cord cysts between October 2014 and June 2021 were retrospectively collected from Guangdong Women and Children Hospital. We compared the differences in genetic assay findings in isolated and nonisolated umbilical cord cyst cohorts.Results: A total of 49 singleton pregnancies and 2 foetuses that were one of the cotwins in monochorionic twin pregnancies were enrolled in the cohort; 20 isolated and 31 nonisolated umbilical cord cysts were identified in the cohort. One foetus (5%, 1/20) in the isolated umbilical cord cyst group showed chromosomal abnormalities and 17p12 microduplication. Twelve cases (38.7%, 12/31) of chromosomal abnormalities, including seven cases of trisomy 18, two cases of trisomy 13 and three cases of microdeletion, were identified in the nonisolated umbilical cord cyst group. The incidences of chromosomal abnormalities between the two groups were significantly different (1/20, 5% vs 13/31, 38.7%, p=0.003). There was no relative pathological medical exome sequencing finding in the three foetuses suffering from nonisolated umbilical cord cysts whose parents chose to undergo chromosomal microarray analysis (CMA) and medical exome sequencing.Conclusion: This retrospective cohort study evaluated the value of CMA in foetuses with umbilical cord cysts and suggested that copy number variants (CNVs) may be the basic genetic aetiological factors that should be considered for diagnostic evaluation. We recommended CMA as a basic genetic evaluation in cases of umbilical cord cysts, especially in nonisolated cases.Graphical Abstract: Keywords: chromosomal microarray analyses, CMA, umbilical cord cyst, G banding karyotype

Ruhan Liu,1,2,&ast; Chenyang Li,1,&ast; Huajun Xu,1 Kejia Wu,1 Xinyi Li,1 Yupu Liu,1 Jie Yuan,1 Lili Meng,1 Jianyin Zou,1 Weijun Huang,1 Hongliang Yi,1 Bin Sheng,2 Jian Guan,1 Shankai Yin1 1Department of Otolaryngology Head and Neck Surgery and Shanghai Key Laboratory of Sleep Disordered Breathing & Otolaryngological Institute of Shanghai Jiao Tong University, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Computer Science and Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Sheng; Jian Guan, Tel +86 13124853285, Email shengbin@sjtu.edu.cn; guanjian0606@sina.comPurpose: Misdiagnosis and missed diagnosis of sleep-disordered breathing (SDB) is common because polysomnography (PSG) is time-consuming, expensive, and uncomfortable. The use of recording methods based on the oxygen saturation (SpO2) signals detected by wearable devices is impractical and inaccurate for extracting signal features and detecting apnoeic events. We propose a method to automatically detect the apnoea-based SpO2 signal segments and compute the apnoea–hypopnea index (AHI) for SDB screening and grading.Patients and Methods: First, apnoea-related desaturation segments in raw SpO2 signals were detected; global features were extracted from whole night signals. Then, the SpO2 signal segments and global features were fed into a bi-directional long short-term memory convolutional neural network model to identify apnoea-related and non-apnoea-related events. The apnoea-related segments were used to assess the AHI.Results: The model was trained on 500 individuals and tested on 8131 individuals from two public hospitals and one private centre. In the testing data, the classification accuracy for apnoea-related segments was 84.3%. Individuals with SDB (AHI 15) were identified with a mean accuracy of 88.95%.Conclusion: Using automatic SDB detection based on SpO2 signals can accurately screen for SDB.Keywords: sleep apnea hypopnea syndrome, AHI, SDB severity classification, Bi-LSTM-CNN, desaturation events

Ziyu Li, Yuling An, Lijuan Li, Huimin Yi Department of Surgical Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, People’s Republic of ChinaCorrespondence: Huimin Yi, Department of Surgical Intensive Care Unit, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, People’s Republic of China, Email yhmsysu@163.comPurpose: Intracranial infection after neurosurgery is one of the most serious complications, especially extensively drug-resistant (XDR) Acinetobacter baumannii (A. baumannii) seriously affects the prognosis of patients. At present, there is little experience in the treatment of this infection and limited effective treatment options, like tigecycline or polymyxin B. Therefore, this report aims to describe the efficacy of tigecycline combined with polymyxin B by intrathecal (ITH) injection in the treatment of XDR intracranial infection with A. baumannii.Methods: We report a case of intracranial infection with XDR A. baumannii after ventricular drainage, treated by daily ITH and intravenous (IV) tigecycline, combined with polymyxin B ITH route. Moreover, tigecycline and polymyxin B treatments for XDR intracranial infection with A. baumannii that were reported in the literature were also reviewed and summarized.Results: The white blood cells (WBCs) of the patient’s cerebrospinal fluid dropped to normal, and the symptoms of intracranial infection disappeared. The patient finally obtained good clinical results and transferred to the local hospital.Conclusion: The polymyxin B ITH route is an ideal treatment strategy for XDR A. baumannii. The IV plus ITH tigecycline may be an effective treatment option. However, more researches should be conducted to confirm our observation.Keywords: intracranial infection, Acinetobacter baumannii, intrathecal injection of polymyxin B, tigecycline

Xiaoming Li,1,2 Chao Liu,2 Xiaoli Wang,1 Zhi Mao,2 Hongyu Yi,1 Feihu Zhou2 1Medical School of Chinese PLA, Beijing, People’s Republic of China; 2Department of Critical Care Medicine, The First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Feihu ZhouCritical Care Medicine, The First Medical Centre, Chinese People’s Liberation Army General Hospital, 28 Fu-Xing Road, Beijing, 100853, People’s Republic of China, Tel +86-10-66938148, Fax +86-10-88219862, Email feihuzhou301@126.comBackground: Sepsis is a systemic inflammatory response due to infection, resulting in organ dysfunction. Timely targeted interventions can improve prognosis. Inflammation plays a crucial role in the process of sepsis. To identify potential sepsis early, we developed and validated a nomogram model and a simple risk scoring model for predicting sepsis in critically ill patients.Methods: The medical records of adult patients admitted to our intensive care unit (ICU) from August 2017 to December 2020 were analyzed. Patients were randomly divided into a training cohort (70%) and a validation cohort (30%). A nomogram model was developed through multivariate logistic regression analysis. The continuous variables included in nomogram model were transformed into dichotomous variables. Then, a multivariable logistic regression analysis was performed based on these dichotomous variables, and the odds ratio (OR) for each variable was used to construct a simple risk scoring model. The receiver operating characteristic curves (ROC) were constructed, and the area under the curve (AUC) was calculated.Results: A total of 2074 patients were enrolled. Finally, white blood cell (WBC), C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT) and neutrophil-to-lymphocyte ratio (NLR) were included in our models. The AUC of the nomogram model and the simple risk scoring model were 0.854 and 0.842, respectively. The prediction performance of the two models on sepsis is comparable (p = 0.1298).Conclusion: This study combining five commonly available inflammatory markers (WBC, CRP, IL-6, PCT and NLR) developed a nomogram model and a simple risk scoring model to predict sepsis in critically ill patients. Although the prediction performance of the two models is comparable, the simple risk scoring model may be simpler and more practical for clinicians to identify potential sepsis in critically ill patients at an early stage and strategize treatments.Keywords: nomogram, score, model, prediction, inflammatory marker, sepsis

Xiaolong Zhao,1– 3,&ast; Huajun Xu,1,3,&ast; Chuan Dong,2,&ast; Jiangang Fan,2 Gang He,2 Jianyin Zou,1,3 Lili Meng,1,3 Huaming Zhu,1,3 Kaiming Su,1,3 Mingpo Yang,4 Hongliang Yi,1,3 Jian Wang,5 Shankai Yin,1,3 Jian Guan1,3 1Department of Otolaryngology Head and Neck Surgery & Center of Sleep Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, People’s Republic of China; 4Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China; 5School of Communication Science and Disorders/Physiol & Biophysics, Dalhousie University, Halifax, NS, Canada&ast;These authors contributed equally to this workCorrespondence: Shankai Yin; Jian Guan Email skyin@sjtu.edu.cn; guanjian0606@sina.comBackground: Cardiac autonomic dysfunction (CAD) is a common pathology in cardiovascular diseases; however, the role of glycolipid metabolic disorders in CAD development in obstructive sleep apnea (OSA) remains poorly understood.Methods: In total, 4152 patients with suspected OSA were recruited in our sleep center. Metabolic characteristics including anthropometric and glycolipid data were collected. Heart rate variability (HRV) was measured to assess the risk of CAD; its dose–response relationship with OSA severity was evaluated via restricted cubic spline (RCS) analysis. A segmented multivariate linear regression (SMLR) model was used to evaluate the roles of metabolic variables in different stages of OSA.Results: The RCS showed that CAD risk increased in a nonlinear relationship pattern with OSA severity, from slow fluctuation at earlier stages to rapid change in later stages. After integrating the clinical definition and RCS selected knots, we obtained the new four OSA severity stages. SMLR model showed that the overall value of glycolipid variables for prediction of HRV abnormalities was greater than the value of OSA variables at earlier stages, while OSA variables were more effective predictors in more severe stages. The discordance in respective relationship of HRV with metabolic and OSA variables sheds the light how metabolic disorders promoted the development of CAD in OSA, the later further in turn deteriorates cardiac function.Conclusion: These results are indicative of stage-specific involvement of glycolipid metabolic factors underlying CAD nonlinear changes in patients with OSA. Early control glycolipid disorders may help the control of CAD development in patients with OSA.Keywords: obstructive sleep apnea, autonomic nervous system, cardiac autonomic neuropathy, metabolism, heart rate variability

Haihong Zhang,1 Fang Wu,1 Hongli Yi,2 Dongjuan Xu,3 Nana Jiang,4 Yonghong Li,5 Ming Li,1 Kefang Wang1 1School of Nursing and Rehabilitation, Shandong University, Jinan City, Shandong Province, People’s Republic of China; 2Department of Respiratory Medicine, Shandong Provincial Hospital, Jinan City, Shandong Province, People’s Republic of China; 3School of Nursing, Purdue University, West Lafayette, IN, USA; 4Department of Respiratory Medicine, Dongfang Hospital Affiliated to Tongji University, Shanghai City, People’s Republic of China; 5Department of Respiratory Medicine, Jinan Central Hospital, Jinan City, Shandong Province, People’s Republic of ChinaCorrespondence: Ming LiSchool of Nursing and Rehabilitation, Shandong University, No.44 Wenhua Xi Road, Lixia District, Jinan City, Shandong Province, 250012, People’s Republic of ChinaTel +86-531-88382000Email liming74@sdu.edu.cnPurpose: Previous research has indicated that female and male patients may experience different levels of symptoms. However, no studies of chronic obstructive pulmonary disease (COPD) patients have compared the number and types of symptom clusters identified in male and female patients. Therefore, the purpose of this study was to investigate gender differences in symptom clusters among COPD patients.Patients and Methods: A total of 371 eligible patients were enrolled in the study. We assessed nine COPD symptoms, namely, dyspnea, cough, sputum, chest tightness, sleep quality, fatigue, frailty, anxiety, and depression. Exploratory factor analyses were used to explore the underlying clusters of the COPD symptoms.Results: Underlying the nine symptoms, female patients had 2 clusters, and male patients had 3 clusters. Specifically, the three general symptoms poor sleep, fatigue, and frailty loaded on the same symptom cluster with anxiety and depression in female patients, while the same 3 general symptoms loaded on the same symptom cluster with chest tightness and dyspnea in male patients. Moreover, cough and sputum not only were more common in male patients but also loaded together on a separate symptom cluster.Conclusion: Our findings suggest that in order to improve fatigue, frailty, and poor sleep quality, symptom management strategies should more closely address anxiety and depression in female patients as well as chest tightness and dyspnea in male patients. Smoking cessation is particularly important in male COPD patients because they account for a much higher proportion of smokers and are more likely to have cough and sputum. These findings signify the importance of identifying and implementing gender-tailored symptom management strategies to relieve symptom burden in COPD patients to enhance their quality of life.Keywords: quality of life, symptom burden, symptom management, factor analysis