No Causal Association Between Cholelithiasis and COVID-19: A Bidirectional Mendelian Randomization Study (preprint)

Background: Gallstone diseases and cholecystectomy are possibly associated with the severity of COVID-19 bidirectionally, yet the casual association remains unclear. Method: Applying genome-wide association study summary statistics of primarily European individuals, we utilized 2-sample Mendelian randomization to estimate the bidirectional causal effects of cholelithiasis, cholecystitis and cholecystectomy on three COVID-19 phenotypes: SARS-CoV-2 infection, COVID-19 hospitalization and severe COVID-19. Results: Inverse variance weighted Mendelian randomization results from the FinnGen consortium showed that none of cholelithiasis, cholecystitis and cholecystectomy was not causally associated with COVID-19 phenotypes, and vice versa. In addition, other methods including MR-Egger, weighted median, weight mode and simple mode exhibited approximate tendency as IVW. These results were all robust to sensitivity analysis. Conclusion:  The forward MR analysis showed no causally significant impact of cholelithiasis, cholecystitis and cholecystectomy on COVID-19 phenotypes. Similarly, reverse MR results also showed no causal association between COVID-19 and cholelithiasis events.

Factors Influencing Retention among Regional, Rural and Remote Undergraduate Nursing Students in Australia: A Systematic Review of Current Research Evidence.

BACKGROUND: This systematic review aimed to explore the factors influencing retention among regional, rural, and remote undergraduate nursing students who were enrolled in Australian universities. METHODS: Mixed-methods systematic review. A+ Education, CINAHL, Education Resources Information Center (ERIC), Education Research Complete, JBI EBP database, Journals@Ovid, Medline, PsycINFO, PubMed, and Web of Science were systematically searched from September 2017 to September 2022 to identify eligible English-language studies. The methodological quality of the included studies was critically assessed using the Joanna Briggs Institute's critical appraisal tools. Descriptive analysis with a convergent segregated approach was conducted to synthesize and integrate the results from the included studies. RESULTS: Two quantitative and four qualitative studies were included in this systematic review. Both the quantitative and qualitative findings demonstrated that additional academic and personal support was essential for improving retention among undergraduate nursing students from regional, rural, and remote areas in Australia. The qualitative synthesis also highlighted many internal (e.g., personal qualities, stress, ability to engage with classes and institutions, time management, lack of confidence, cultural well-being, and Indigenous identity) and external factors (e.g., technical difficulties, casual tutors, different competing demands, study facilities, and financial and logistical barriers) that influenced retention among undergraduate nursing students from regional, rural, and remote areas in Australia. CONCLUSIONS: This systematic review demonstrates that identifying potentially modifiable factors could be the focus of retention support programs for undergraduate nursing students. The findings of this systematic review provide a direction for the development of retention support strategies and programs for undergraduate nursing students from regional, rural and remote areas in Australia.

Clinical and immunological features of convalescent pediatric patients infected with the SARS-CoV-2 Omicron variant in Tianjin, China.

COVID-19 has spread surprisingly fast worldwide, and new variants continue to emerge. Recently, the World Health Organization acknowledged a new mutant strain "Omicron", with children were accounting for a growing share of COVID-19 cases compared with other mutant strains. However, the clinical and immunological characteristics of convalescent pediatric patients after Omicron infection were lacking. In this study, we comparatively analyzed the clinical data from pediatric patients with adult patients or healthy children and the effects of SARS-CoV-2 vaccine on the clinical and immune characteristics in convalescent pediatric patients. Our results indicated that convalescent pediatric patients had unique clinical and immune characteristics different from those of adult patients or healthy children, and SARS-CoV-2 vaccination significantly affected on the clinical and immune characteristics and the prevention of nucleic acid re-detectable positive (RP) in convalescent patients. Our study further deepens the understanding of the impact of Omicron on the long-term health of pediatric patients and provides a valuable reference for the prevention and treatment of children infected with Omicron.

Insomnia plays a key role in mental health problems of COVID-19 patients in Square Cabin Hospitals: a network analysis (preprint)

Background: While the emergence of the Coronavirus Disease 2019 (COVID-19) has greatly affected the mental health and wellbeing of people everywhere, the core symptoms of common syndromes of psychological distress remain unclear, especially among COVID-19 patients who have been quarantined in Square Cabin Hospitals. Using the method of network analysis, the current study explored the relations between stress, depression, anxiety and insomnia symptoms among COVID-19 patients in Shanghai Four-Leaf Clover Cabin Hospital. Method: The study used an online survey to gauge the mental health issues of COVID-19 patients at Shanghai Four-Leaf Clover Cabin Hospital from April 18 to May 19, 2022. The Perceived Stress Scale, Patient Health Questionnaire, Generalized Anxiety Disorder Scale, and Insomnia Severity Index were used to assess perceived stress symptoms, depressive symptoms, anxiety symptoms, and insomnia symptoms, respectively. The central symptoms and bridge symptoms were determined using a regularized partial correlation network. Results: A total of 1014 patients was included in this study. Overall, 61.5%, 49.2% , and 56.1% of all patients reported symptoms of depressive, anxiety, and insomnia, respectively. “Distress caused by the sleep difficulties” had the highest expected influence, followed by “Excessive worry”, “Severity of sleep onset”, “Overburden”, “Uncontrollable worry”, “Trouble relaxing”, “Restlessness”. Seven bridge symptoms were identified: “Sad Mood”, “Severity of sleep onset”, “Sleep”, “Motor”, “Feeling afraid”, “Nervousness”, “Appetite”. In addition, significant differences in network global strength were found between women and men. Conclusions: Psychological distress was prevalent among COVID-19 patients and insomnia symptoms played a key role in the network of psychological distress symptoms. As a result, specific insomnia symptoms should be closely monitored as potential intervention targets in alleviating or preventing common, frequently co-occurring psychiatric syndromes.

SARS-CoV-2 Pattern Provides a New Scoring System and Predicts the Prognosis and Immune Therapeutic Response in Glioma.

OBJECTIVE: Glioma is the most common primary malignancy of the adult central nervous system (CNS), with a poor prognosis and no effective prognostic signature. Since late 2019, the world has been affected by the rapid spread of SARS-CoV-2 infection. Research on SARS-CoV-2 is flourishing; however, its potential mechanistic association with glioma has rarely been reported. The aim of this study was to investigate the potential correlation of SARS-CoV-2-related genes with the occurrence, progression, prognosis, and immunotherapy of gliomas. METHODS: SARS-CoV-2-related genes were obtained from the human protein atlas (HPA), while transcriptional data and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Glioma samples were collected from surgeries with the knowledge of patients. Differentially expressed genes were then identified and screened, and seven SARS-CoV-2 related genes were generated by LASSO regression analysis and uni/multi-variate COX analysis. A prognostic SARS-CoV-2-related gene signature (SCRGS) was then constructed based on these seven genes and validated in the TCGA validation cohort and CGGA cohort. Next, a nomogram was established by combining critical clinicopathological data. The correlation between SCRGS and glioma related biological processes was clarified by Gene set enrichment analysis (GSEA). In addition, immune infiltration and immune score, as well as immune checkpoint expression and immune escape, were further analyzed to assess the role of SCRGS in glioma-associated immune landscape and the responsiveness of immunotherapy. Finally, the reliability of SCRGS was verified by quantitative real-time polymerase chain reaction (qRT-PCR) on glioma samples. RESULTS: The prognostic SCRGS contained seven genes, REEP6, CEP112, LARP4B, CWC27, GOLGA2, ATP6AP1, and ERO1B. Patients were divided into high- and low-risk groups according to the median SARS-CoV-2 Index. Overall survival was significantly worse in the high-risk group than in the low-risk group. COX analysis and receiver operating characteristic (ROC) curves demonstrated excellent predictive power for SCRGS for glioma prognosis. In addition, GSEA, immune infiltration, and immune scores indicated that SCRGS could potentially predict the tumor microenvironment, immune infiltration, and immune response in glioma patients. CONCLUSIONS: The SCRGS established here can effectively predict the prognosis of glioma patients and provide a potential direction for immunotherapy.

Clinical and immunological features of convalescent pediatric patients infected with the SARS-CoV-2 Omicron variant in Tianjin, China

COVID-19 has spread surprisingly fast worldwide, and new variants continue to emerge. Recently, the World Health Organization acknowledged a new mutant strain "Omicron", with children were accounting for a growing share of COVID-19 cases compared with other mutant strains. However, the clinical and immunological characteristics of convalescent pediatric patients after Omicron infection were lacking. In this study, we comparatively analyzed the clinical data from pediatric patients with adult patients or healthy children and the effects of SARS-CoV-2 vaccine on the clinical and immune characteristics in convalescent pediatric patients. Our results indicated that convalescent pediatric patients had unique clinical and immune characteristics different from those of adult patients or healthy children, and SARS-CoV-2 vaccination significantly affected on the clinical and immune characteristics and the prevention of nucleic acid re-detectable positive (RP) in convalescent patients. Our study further deepens the understanding of the impact of Omicron on the long-term health of pediatric patients and provides a valuable reference for the prevention and treatment of children infected with Omicron.

The risk factors and outcomes for radiological abnormalities in early convalescence of COVID-19 patients caused by the SARS-CoV-2 Omicron variant in Tianjin, China: a retrospective, multicenter follow-up study (preprint)

Background: The emergence of the SARS-CoV-2 Omicron variant has been triggering the new wave of COVID-19 globally. However, the risk factors and outcomes for radiological abnormalities in the early convalescent stage (1 month after onset) of Omicron infected patients are still unknown.Methods: Patients were retrospectively enrolled if they were admitted to the hospital due to COVID-19 and underwent chest CT scans during hospitalization between 8 January and 24 February 2022. The chest CTs and clinical data obtained at admission and 1 month after onset were longitudinally analyzed. Spearman rank correlation analysis was used to investigate the correlation between laboratory markers and CT scores. Uni-/multi-variable logistic regression tests were performed to explore independent risk factors for radiological abnormalities at admission and residual pulmonary abnormalities after 1 month. Results: We assessed 316 COVID-19 patients, including 47% with radiological abnormalities at admission and 23% with residual pulmonary abnormalities at 1-month follow-up. In a multivariate regression analysis, age ≥ 50 years, body mass index ≥ 23.87, days after vaccination ≥ 81 days, lymphocyte count ≤ 1.21×10-9/L, Interleukin-6 ≥ 10.05 pg/mL and IgG ≤ 14.140 S/CO were independent risk factors for CT abnormalities at admission (odds ratio = 2.870, 4.171, 2.360, 2.826, 3.886 and 2.828, respectively; P < 0.05 for each comparison). The presence of interlobular septal thickening and IL-6 ≥ 5.85 pg/mL were the independent risk factors for residual pulmonary abnormalities at 1-month follow-up (odds ratio = 3.619 and 3.197, respectively; P < 0.05 for each comparison). There were no significant changes in the number of involved lung lobes (P = 0.308) and total CT score (P = 0.068) during the early convalescent stage. And the level of IL-6 showed positive correlation with CT score at admission (spearman r = 0.202, P = 0.030).Conclusions: The higher IL-6 level was a common independent risk factor for CT abnormalities at admission and residual pulmonary abnormalities at 1-month follow-up. And there were no obvious radiographic changes during the early convalescent stage in patients with residual pulmonary abnormalities. 

Factors associated with COVID-19 vaccination intent in Singapore, Australia and Hong Kong.

BACKGROUND: COVID-19 pandemic has caused significant morbidity and mortality globally. As vaccines have been developed under expedited conditions, their safety and efficacy are being questioned by some populations leading to vaccine hesitancy, resulting in delayed vaccine uptake and herd immunity. This study aims to adopt a combination of Health Belief Model and other independent risk factors associated with high vaccine acceptance. METHODS: An anonymized cross-sectional survey was distributed between 15 January and 3 February 2021 across Singapore, Hong Kong and Australia among adult respondents through a certified online panel. Exploratory factor analysis and confirmatory factor analysis were carried out to assess perception constructs followed by multivariate regression modelling to assess factors associated with high vaccine acceptance against SARS_CoV-2. RESULTS: A total of 3,133 anonymised participants from Singapore (n = 1,009), Australia (n = 1,118) and Hong Kong (n = 1,006) completed the survey. While age and gender were not significantly associated, Asian ethnicity, current smokers and self-efficacy were significant associated factors of increased vaccine acceptance. While specific practices like taking micronutrients more frequently, cleaning and disinfecting their house more often were positively associated with increased vaccine acceptance, seeking medical help for COVID-19 symptoms like loss of smell/taste and overall COVID-19 knowledge score were negatively associated. Increased likelihood of vaccine acceptance was seen among those that obtained COVID-19 information less frequently and used digital media or non-health-related sources like influencers as a source of information. Among the eight perception constructs, perceived susceptibility and perceived response efficacy were positively associated, while perceived barriers were negatively associated with high vaccine acceptance. CONCLUSION: While demographic parameters have weak association with vaccine acceptance, perceptions and practices parameters can help to better understand and influence vaccine acceptance. Study findings should provide guidance on the risk communication strategy to enhance vaccine acceptance for vaccination and boosters against new SARS-CoV-2 variants.

Mask-wearing intentions on airplanes during COVID-19 - Application of theory of planned behavior model.

The COVID-19 pandemic has devastated the air transport industry, forcing airlines to take measures to ensure the safety of passengers and crewmembers. Among the many protective measures, mask mandate onboard the airplane is an important one, but travelers' mask-wearing intentions during flight remain uninvestigated especially in the US where mask use is a topic of on-going debate. This study focused on the mask use of airline passengers when they fly during COVID-19, using the theory of planned behavior (TPB) model to examine the relationship between nine predicting factors and the mask-wearing intention in the aircraft cabin. A survey instrument was developed to collect data from 1124 air travelers on Amazon Mechanical Turk (MTurk), and the data was statistically analyzed using structural equation modeling and logistic regression. Results showed that attitude, descriptive norms, risk avoidance, and information seeking significantly influenced the travelers' intention to wear a mask during flight in COVID-19. Group analysis further indicated that the four factors influenced mask-wearing intentions differently on young, middle-aged, and senior travelers. It was also found that demographic and travel characteristics including age, education, income, and travel frequency can be used to predict if the airline passenger was willing to pay a large amount to switch to airlines that adopted different mask policies during COVID-19. The findings of this study fill the research gap of air travelers' intentions to wear a mask when flying during a global pandemic and provide recommendations for mask-wearing policies to help the air transport industry recover from COVID-19.

Mask-wearing intentions on airplanes during COVID-19 – Application of theory of planned behavior model

The COVID-19 pandemic has devastated the air transport industry, forcing airlines to take measures to ensure the safety of passengers and crewmembers. Among the many protective measures, mask mandate onboard the airplane is an important one, but travelers' mask-wearing intentions during flight remain uninvestigated especially in the US where mask use is a topic of on-going debate. This study focused on the mask use of airline passengers when they fly during COVID-19, using the theory of planned behavior (TPB) model to examine the relationship between nine predicting factors and the mask-wearing intention in the aircraft cabin. A survey instrument was developed to collect data from 1124 air travelers on Amazon Mechanical Turk (MTurk), and the data was statistically analyzed using structural equation modeling and logistic regression. Results showed that attitude, descriptive norms, risk avoidance, and information seeking significantly influenced the travelers' intention to wear a mask during flight in COVID-19. Group analysis further indicated that the four factors influenced mask-wearing intentions differently on young, middle-aged, and senior travelers. It was also found that demographic and travel characteristics including age, education, income, and travel frequency can be used to predict if the airline passenger was willing to pay a large amount to switch to airlines that adopted different mask policies during COVID-19. The findings of this study fill the research gap of air travelers’ intentions to wear a mask when flying during a global pandemic and provide recommendations for mask-wearing policies to help the air transport industry recover from COVID-19.

COVID-19 and Tuberculosis Coinfection: An Overview of Case Reports/Case Series and Meta-Analysis.

Background: Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are two major infectious diseases posing significant public health threats, and their coinfection (aptly abbreviated COVID-TB) makes the situation worse. This study aimed to investigate the clinical features and prognosis of COVID-TB cases. Methods: The PubMed, Embase, Cochrane, CNKI, and Wanfang databases were searched for relevant studies published through December 18, 2020. An overview of COVID-TB case reports/case series was prepared that described their clinical characteristics and differences between survivors and deceased patients. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for death or severe COVID-19 were calculated. The quality of outcomes was assessed using GRADEpro. Results: Thirty-six studies were included. Of 89 COVID-TB patients, 19 (23.46%) died, and 72 (80.90%) were male. The median age of non-survivors (53.95 ± 19.78 years) was greater than that of survivors (37.76 ± 15.54 years) (p < 0.001). Non-survivors were more likely to have hypertension (47.06 vs. 17.95%) or symptoms of dyspnea (72.73% vs. 30%) or bilateral lesions (73.68 vs. 47.14%), infiltrates (57.89 vs. 24.29%), tree in bud (10.53% vs. 0%), or a higher leucocyte count (12.9 [10.5-16.73] vs. 8.015 [4.8-8.97] × 109/L) than survivors (p < 0.05). In terms of treatment, 88.52% received anti-TB therapy, 50.82% received antibiotics, 22.95% received antiviral therapy, 26.23% received hydroxychloroquine, and 11.48% received corticosteroids. The pooled ORs of death or severe disease in the COVID-TB group and the non-TB group were 2.21 (95% CI: 1.80, 2.70) and 2.77 (95% CI: 1.33, 5.74) (P < 0.01), respectively. Conclusion: In summary, there appear to be some predictors of worse prognosis among COVID-TB cases. A moderate level of evidence suggests that COVID-TB patients are more likely to suffer severe disease or death than COVID-19 patients. Finally, routine screening for TB may be recommended among suspected or confirmed cases of COVID-19 in countries with high TB burden.

Research progress of mechanisms of spike protein in SARS-CoV-2 infection

Human ACE2 receptors on cells binding to Spike(S) protein on the surface of SARS-CoV-2 may be the main cause of the viruses entering into human cells. In this article, the current situation of the research on the S protein related SARS-CoV-2 infection and its mechanisms were summarized. We focused on the effect of structure of S protein on the infection, the binding sites of S proteins on ACE2 receptors in various tissues and other proteins which may regulate the process of binding, in order to elucidate the mechanisms of the infection of SARS-CoV-2. The variation of the gene of S protein can affect the transmission and virulence of SARS-CoV-2, which may give some useful references to the comprehensive understanding of the new virus of SARS-CoV-2.

Work from Home, Managerial Sentiment, and Corporate Liquidity Management under COVID-19 (preprint)

COVID-19 pandemic lockdowns and mobility restrictions have forced many individuals to work from home, leading to diverse isolation-induced mental health consequences. Using the granularity of foot traffic data, we show that prolonged work from home during the COVID-19 outbreak dampens managerial sentiment. This baseline result is robust to the identification strategy exploiting the staggered implementation of stay-at-home orders across the United States. Further analyses indicate that the induced negative sentiment elevates managers' perceived risk, driving them to accumulate more cash in response to the unprecedented COVID-19 cash-flow shock. But this increase in cash destroys shareholder value.

Durable tracking anti-SARS-CoV-2 antibodies of cancer patients recovered from COVID-19 (preprint)

Cancer patients are more susceptible to SARS-CoV-2 infection and generally have higher mortality rate. Anti-SARS-CoV-2 IgG is an important consideration for the patients in this COVID-19 pandemic. Recent researches suggested the rapid decay of anti-SARS-CoV-2 antibodies in the general population, but the decline rate of the antibodies in cancer patients was unknown. In this observational study, we reported the clinical features of the 53 cancer patients infected by SARS-CoV-2 from two hospitals in Wuhan, China and tracked the presence of anti-SARS-CoV-2 antibodies in the patients for more than 12 months. We found the duration (days) of anti-SARS-CoV-2 IgG in the patients was significant longer in chemotherapy (mean: 175; range: 75 to 315) and radiotherapy groups (mean: 168; range: 85 to 265) than in non-chemo- or radio-therapy group (mean: 58; range:21 to 123) after their recovery from COVID-19. We also used single-cell RNA sequencing to track the immunologic changes in a representative patient infected by COVID-19 for more than one year, and found that CD8 + effective T cells, memory B cells and plasma cells were persistently activated in the patient undergoing chemotherapy. Together, our findings show that chemotherapy and radiotherapy might be beneficial to extend the duration of anti-SARS-CoV-2 IgG.

Synthetic Homogeneous Glycoforms of the SARS-CoV-2 Spike Receptor-Binding Domain Reveals Different Binding Profiles of Monoclonal Antibodies

SARS-CoV-2 attaches to its host receptor, angiotensin-converting enzyme 2 (ACE2), via the receptor-binding domain (RBD) of the spike protein. The RBD glycoprotein is a critical target for the development of neutralizing antibodies and vaccines against SARS-CoV-2. However, the high heterogeneity of RBD glycoforms may lead to an incomplete neutralization effect and impact the immunogenic integrity of RBD-based vaccines. Investigating the role of different carbohydrate domains is of paramount importance. Unfortunately, there is no viable method for preparing RBD glycoproteins with structurally defined glycans. Herein we describe a highly efficient and scalable strategy for the preparation of six glycosylated RBDs bearing defined structure glycoforms at T323, N331 and N343. A combination of modern oligosaccharide, peptide synthesis and recombinant protein engineering provides a robust route to deciphering carbohydrate structure?function relationships.

Evidence of SARS-CoV-2 Transmission Through the Ocular Route.

PURPOSE: Currently, the coronavirus disease 2019 (COVID-19) pandemic is raging around the world. However, the transmission of its pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is not fully clear. It is still controversial whether the ocular transmission of SARS-CoV-2 exists. This review aimed to summarize the evidence of SARS-CoV-2 ocular transmission. METHODS: Online articles were searched till October 23, 2020 in Pubmed, Embase, and websites of World Health Organization, Centers for Disease Control and Prevention COVID-19, American Academy of Ophthalmology, and American Society of Cataract and Refractive Surgery under the search strategy of (((("COVID-19"[Mesh]) OR ("SARS-CoV-2"[Mesh])) OR (2019 novel coronavirus)) OR (2019-nCoV)) AND (((("Conjunctivitis"[Mesh]) OR (Ocular Surface)) OR ("Eye"[Mesh])) OR ("Ophthalmology"[Mesh])). The language was not restricted. After screening, 1445 records were excluded and 168 references original articles were finally included. RESULTS: Cells of ocular surface express both the receptor of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), offering molecular bases for the ocular susceptibility to SARS-CoV-2. Accumulated COVID-19 patients presented conjunctivitis as the initial or the only symptom. Whether COVID-19 patients had ocular symptoms or not, SARS-CoV-2 was detectable on the ocular surface, and the isolated virus was infectious, proving that the ocular surface can not only be a reservoir but also a source of contagion. SARS-CoV-2 may reach the ocular surface by hand-eye contact and aerosols. Once SARS-CoV-2 reaches the ocular surface, it may transfer to other systems through the nasolacrimal system or hematogenous metastasis. CONCLUSION: The ocular surface can serve as a reservoir and source of contagion for SARS-CoV-2. SARS-CoV-2 can be transmitted to the ocular surface through hand-eye contact and aerosols, and then transfer to other systems through nasolacrimal route and hematogenous metastasis. The possibility of ocular transmission of SARS-CoV-2 cannot be ignored.

Feasibility to Reduce Swab RT-PCR Tests by Serum Proteomics for COVID-19 Disease Course Monitoring (preprint)

The diagnosis and disease course monitoring of COVID-19 are mainly based on RT-PCR analysis of RNAs extracted from pharyngeal or nasopharyngeal swabs with potential live virus, posing a high risk to medical practitioners. Here, we investigated the feasibility of applying serum proteomics to classify COVID-19 patients in the nucleic acid positive (NCP) and negative (NCN) stages. We analyzed the proteome of 320 inactivated serum samples from 144 COVID-19 patients, and 45 controls and shortlisted 42 regulated proteins in the severe group and 12 regulated proteins in the non-severe group. Together with several key clinical indexes including days after symptom onset, platelet counts and magnesium, we developed machine learning models to classify NCP and NCN with an AUC of 0.94 for the severe cases and 0.89 for the non-severe cases. This study suggests the feasibility of utilizing quantitative serum proteomics for NCP-NCN classification.Funding: This work was supported by grants from the National Key R&D Program of China(No. 2020YFE0202200), National Natural Science Foundation of China (81672086), Zhejiang Province Analysis Test Project (2018C37032), the National Natural Science Foundation of China (81972492, 21904107), Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars (LR19C050001), Zhejiang Medical and Health Science and Technology Plan (2021KY394), Hangzhou Agriculture andSociety Advancement Program (20190101A04), and Westlake Education Foundation, Tencent Foundation.Conflict of Interest: Tiannan Guo is shareholder of Westlake Omics Inc. W.G. and N.X. are employees of Westlake Omics Inc. The remaining authors declare no competing interests.Ethical Approval: This study has been approved by both the Ethical/Institutional Review Boards of Taizhou Hospital and Westlake University. Informed contents from patients were waived by the boards.