When DNA-damage responses meet innate and adaptive immunity.

When cells proliferate, stress on DNA replication or exposure to endogenous or external insults frequently results in DNA damage. DNA-Damage Response (DDR) networks are complex signaling pathways used by multicellular organisms to prevent DNA damage. Depending on the type of broken DNA, the various pathways, Base-Excision Repair (BER), Nucleotide Excision Repair (NER), Mismatch Repair (MMR), Homologous Recombination (HR), Non-Homologous End-Joining (NHEJ), Interstrand Crosslink (ICL) repair, and other direct repair pathways, can be activated separately or in combination to repair DNA damage. To preserve homeostasis, innate and adaptive immune responses are effective defenses against endogenous mutation or invasion by external pathogens. It is interesting to note that new research keeps showing how closely DDR components and the immune system are related. DDR and immunological response are linked by immune effectors such as the cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) pathway. These effectors act as sensors of DNA damage-caused immune response. Furthermore, DDR components themselves function in immune responses to trigger the generation of inflammatory cytokines in a cascade or even trigger programmed cell death. Defective DDR components are known to disrupt genomic stability and compromise immunological responses, aggravating immune imbalance and leading to serious diseases such as cancer and autoimmune disorders. This study examines the most recent developments in the interaction between DDR elements and immunological responses. The DDR network's immune modulators' dual roles may offer new perspectives on treating infectious disorders linked to DNA damage, including cancer, and on the development of target immunotherapy.

Human MARCH1, 2, and 8 block Ebola virus envelope glycoprotein cleavage via targeting furin P domain.

Membrane-associated RING-CH (MARCH) family proteins were recently reported to inhibit viral replication through multiple modes. Previous work showed that human MARCH8 blocked Ebola virus (EBOV) glycoprotein (GP) maturation. Our study here demonstrates that human MARCH1 and MARCH2 share a similar pattern to MARCH8 in restricting EBOV GP-pseudotyped viral infection. Human MARCH1 and MARCH2 retain EBOV GP at the trans-Golgi network, reduce its cell surface display, and impair EBOV GP-pseudotyped virions infectivity. Furthermore, we uncover that the host proprotein convertase furin could interact with human MARCH1/2 and EBOV GP intracellularly. Importantly, the furin P domain is verified to be recognized by MARCH1/2/8, which is critical for their blocking activities. Besides, bovine MARCH2 and murine MARCH1 also impair EBOV GP proteolytic processing. Altogether, our findings confirm that MARCH1/2 proteins of different mammalian origins showed a relatively conserved feature in blocking EBOV GP cleavage, which could provide clues for subsequent MARCHs antiviral studies and may facilitate the development of novel strategies to antagonize enveloped virus infection.

The role of SARS-CoV-2 ORF7a in autophagy flux disruption: implications for viral infection and pathogenesis.

Although alterations in the autophagy-lysosome pathway have been observed in the SARS-CoV-2 infection and invasion process since the outbreak of the coronavirus disease in 2019, the in-depth mechanism of autophagic and lysosomal reprogramming by SARS-CoV-2 has yet to be well identified. Our recent study unveiled a pivotal role played by the open reading frame 7a (ORF7a) protein in the SARS-CoV-2 genome, particularly in the modulation of macroautophagy/autophagy flux and function during viral infection and pathogenesis. Our study elucidated the underlying molecular mechanisms by which SARS-CoV-2 ORF7a intercepts autophagic flux, evades host autophagy-lysosome degradation, and accelerates viral infection and progeny germination. Furthermore, our study highlights that ORF7a can be a therapeutic target, and glecaprevir may hold potential as a drug against SARS-CoV-2 by targeting ORF7a. The key observations revealed in this study also contribute to a growing understanding of the function of SARS-CoV-2 ORF7a and the mechanisms underlying COVID-2019 treatment.

The emerging roles of ac4C acetylation "writer" NAT10 in tumorigenesis: A comprehensive review.

The quick progress of epigenetic study has kindled new hope for treating many cancers. When it comes to RNA epigenetics, the ac4C acetylation modification is showing promise, whereas N-acetyltransferase 10 plays a wide range of biological functions, has a significant impact on cellular life events, and is frequently highly expressed in many malignant tumors. N-acetyltransferase 10 is an acetyltransferase with important biological involvement in cellular processes and lifespan. Because it is highly expressed in many malignant tumors, it is considered a pro-carcinogenic gene. The review aims to introduce NAT10, summarize the effects of ac4C acetylation on tumor growth from multiple angles, and discuss the possible therapeutic targeting of NAT10 and the future directions of ac4C acetylation investigations.

Designing a polyvalent vaccine targeting multiple strains of varicella zoster virus using integrated bioinformatics approaches.

The Varicella Zoster Virus (VZV) presents a global health challenge due to its dual manifestations of chickenpox and shingles. Despite vaccination efforts, incomplete coverage, and waning immunity lead to recurrent infections, especially in aging and immunocompromised individuals. Existing vaccines prevent chickenpox but can trigger the reactivation of shingles. To address these limitations, we propose a polyvalent multiepitope subunit vaccine targeting key envelope glycoproteins of VZV. Through bioinformatics approaches, we selected six glycoproteins that are crucial for viral infection. Epitope mapping led to the identification of cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B cell linear (LBL) epitopes. Incorporating strong immunostimulants, we designed two vaccine constructs, demonstrating high antigenicity, solubility, stability, and compatibility with Toll-like receptors (TLRs). Molecular docking and dynamics simulations underscored the stability and affinity of the vaccine constructs with TLRs. These findings lay the foundation for a comprehensive solution to VZV infections, addressing the challenges of incomplete immunity and shingles reactivation. By employing advanced immunoinformatics and dynamics strategies, we have developed a promising polyvalent multiepitope subunit vaccine candidate, poised to enhance protection against VZV and its associated diseases. Further validation through in vivo studies is crucial to confirm the effectiveness and potential of the vaccine to curb the spread of VZV. This innovative approach not only contributes to VZV control but also offers insights into tailored vaccine design strategies against complex viral pathogens.

SARS-CoV-2 ORF7a blocked autophagy flux by intervening in the fusion between autophagosome and lysosome to promote viral infection and pathogenesis.

The coronavirus disease 2019 (COVID-19) continues to pose a major threat to public health worldwide. Although many studies have clarified the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection process, the underlying mechanisms of viral invasion and immune evasion were still unclear. This study focused on SARS-CoV-2 ORF7a (open reading frame-7a), one of the essential open reading frames (ORFs) in infection and pathogenesis. First, by analyzing its physical and chemical characteristics, SARS-CoV-2 ORF7a is an unstable hydrophobic transmembrane protein. Then, the ORF7a transmembrane domain three-dimensional crystal structure model was predicted and verified. SARS-CoV-2 ORF7a localized in the endoplasmic reticulum and participated in the autophagy-lysosome pathway via interacting with p62. In addition, we elucidated the underlying molecular mechanisms by which ORF7a intercepted autophagic flux, promoted double membrane vesicle formation, and evaded host autophagy-lysosome degradation and antiviral innate immunity. This study demonstrated that ORF7a could be a therapeutic target, and Glecaprevir may be a potential drug against SARS-CoV-2 by targeting ORF7a. A comprehensive understanding of ORF7a's functions may contribute to developing novel therapies and clinical drugs against COVID-19.

Baduanjin exercise for chronic non-specific low back pain: protocol for a series of N-of-1 trials.

INTRODUCTION: Chronic non-specific low back pain (CNLBP) is one of the most common health problems worldwide. According to the clinical guideline released by the American College of Physicians, exercise has been recommended for the treatment of chronic LBP. In recent years, traditional Chinese medicine (TCM) is becoming increasingly popular for the management of chronic LBP. Baduanjin exercise is one of the exercise therapies in TCM. N-of-1 trial is a randomised cross-over self-controlled trial suitable for patients with this chronic disease. A series of similar N-of-1 trials can be pooled to estimate the overall and individual therapeutic effects synchronously by hierarchical Bayesian analysis. And N-of-1 trials are considered as a good tool for evaluating the therapeutic effect of TCM. Therefore, this study aims to conduct a series of N-of-1 trials with hierarchical Bayesian analysis for assessing whether Baduanjin exercise is effective and safe for CNLBP. METHODS AND ANALYSIS: This study conducts a series of N-of-1 trials on Baduanjin exercise for the management of CNLBP. Fifty participants will receive 1-3 treatment cycles. They will be randomised into a Baduanjin exercise or waiting list group for a week during the two periods of each treatment cycle. The primary outcome is the 10-point Visual Analogue Scale. The secondary outcomes include the Oswestry Disability Index, the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire and the Short Form Health Survey 12. Statistical analysis will be conducted with WinBUGS V.1.4.3 software. Overall and individual therapeutic effects will be estimated synchronously by hierarchical Bayesian analysis. ETHICS AND DISSEMINATION: This study is approved by the Medical Ethics Committee of Tianjin University of TCM (reference number TJUTCM-EC20220005). Our findings will be published in a peer-reviewed journal or international conference. TRIAL REGISTRATION NUMBER: ChiCTR2200063307.

Risk transboundary transmission areas and driving factors of brucellosis along the borders between China and Mongolia.

OBJECTIVE: Brucellosis is a common and neglected zoonotic infectious disease worldwide caused by Brucella. However, transboundary transmissions among countries, particularly those with high incidences, are seldom investigated. In the present study, by taking China and Mongolia as examples, we aim to identify transboundary transmission risk and driving factors of brucellosis along borders. METHODS: 167 brucellosis outbreak locations along the border between China and Mongolia were collected. Wildlife distribution and cross-border activities were mapped. Maximum entropy approach modeling was conducted to predict the potential risk of prevalence of brucellosis with meteorological factors, geographical environment, economic development, living habits et al. The accuracy of the models was assessed by the area under the receiver operating characteristic (ROC) curve (AUC), Kappa test, and correctly classified instances (CCI). RESULTS: The spatial model performed excellent predictive performance with the predictor variables of soils, pastures, goat density, mean precipitation of the wettest month, temperature seasonality, and population density, which with the contribution and permutation important in 27.2 %, 31.9; 23.3 %, 6.8; 18.0 %, 17.2; 11.2 %, 18.1; 10. 3 %, 15.2; 10.0 %, 10.8. The calculated AUC, SD, Kappa, and CCI are 0.870, 0.001, 0.882, and 0.883, respectively. The distribution map of brucellosis showed high-risk areas along the borders. CONCLUSIONS: Our study identified high-risk areas and the driving effect of brucellosis along the borders between China and Mongolia. Moreover, there is the possibility of cross-border wildlife activities in high-risk areas, which increases the risk of cross-border brucellosis transmission. The funding provides clues for cooperative prevention and control of brucellosis by reducing transboundary transmission.

Comparative application of droplet-based digital and quantitative real-time PCR for human brucellosis detection.

We evaluated the diagnostic value of droplet-based digital PCR (dd-PCR) by comparing it with the quantitative real-time PCR (RT-qPCR) for detecting Brucella DNA, 487 whole blood and serum samples collected from suspected human brucellosis, respectively. Sensitivity and specificity were 88.14% and 100% for RT-qPCR; 97.12% and 100% for dd-PCR. The positive rate detected by RT-qPCR and dd-PCR based on the nucleic acid extracted by simultaneous extraction method in serum and blood cells were 56.49% and 62.22%, respectively, which is higher than the commercial kit in 47.74% and 52.77%. Additionally, 32 false-negative samples of chronic patients analyzed by serological tests were positive in the detection from the blood cell nucleic acid. dd-PCR could be considered a valuable tool for detecting Brucella DNA, particularly in false-negative test results. The simultaneous extraction method is complementary to dd-PCR in diagnosing human brucellosis cases at different disease stages, especially in chronic and relapsed stages.

CRISPR-Cas12a test strip (CRISPR/CAST) package: In-situ detection of Brucella from infected livestock.

BACKGROUND: Brucellosis is a common zoonotic disease caused by Brucella, which causes enormous economic losses and public burden to epidemic areas. Early and precise diagnosis and timely culling of infected animals are crucial to prevent the infection and spread of Brucella. In recent years, RNA-guided CRISPR/Cas12a(Clustered Regularly Interspaced Short Palindromic Repeats and its associated protein 12a) nucleases have shown great promise in nucleic acid detection. This research aims to develop a CRISPR/CAST (CRISPR/Cas12a Test strip) package that can rapidly detect Brucella nucleic acid during on-site screening, especially on remote family pastures. The CRISPR/Cas12a system combined with recombinase polymerase amplification (RPA), and lateral flow read-out. RESULTS: We selected the conserved gene bp26, which commonly used in Brucella infection detection and compared on Genbank with other Brucella species. The genomes of Brucella abortus 2308, Brucella suis S2, Brucella melitansis 16 M, and Brucella suis 1330, et al. were aligned, and the sequences were found to be consistent. Therefore, the experiments were only performed on B. melitensis. With the CRISPR/CAST package, the assay of Brucella nucleic acid can be completed within 30 min under isothermal temperature conditions, with a sensitivity of 10 copies/µl. Additionally, no antigen cross-reaction was observed against Yersinia enterocolitica O:9, Escherichia coli O157, Salmonella enterica serovar Urbana O:30, and Francisella tularensis. The serum samples of 398 sheep and 100 cattle were tested by the CRISPR/CAST package, of which 31 sheep and 8 cattle were Brucella DNA positive. The detection rate was consistent with the qPCR results and higher than that of the Rose Bengal Test (RBT, 19 sheep and 5 cattle were serum positive). CONCLUSIONS: The CRISPR/CAST package can accurately detect Brucella DNA in infected livestock within 30 min and exhibits several advantages, including simplicity, speed, high sensitivity, and strong specificity with no window period. In addition, no expensive equipment, standard laboratory, or professional operators are needed for the package. It is an effective tool for screening in the field and obtaining early, rapid diagnoses of Brucella infection. The package is an efficient tool for preventing and controlling epidemics.

The emerging roles of MARCH8 in viral infections: A double-edged Sword.

The host cell membrane-associated RING-CH 8 protein (MARCH8), a member of the E3 ubiquitin ligase family, regulates intracellular turnover of many transmembrane proteins and shows potent antiviral activities. Generally, 2 antiviral modes are performed by MARCH8. On the one hand, MARCH8 catalyzes viral envelope glycoproteins (VEGs) ubiquitination and thus leads to their intracellular degradation, which is the cytoplasmic tail (CT)-dependent (CTD) mode. On the other hand, MARCH8 traps VEGs at some intracellular compartments (such as the trans-Golgi network, TGN) but without inducing their degradation, which is the cytoplasmic tail-independent (CTI) mode, by which MARCH8 hijacks furin, a cellular proprotein convertase, to block VEGs cleavage. In addition, the MARCH8 C-terminal tyrosine-based motif (TBM) 222YxxL225 also plays a key role in its CTI antiviral effects. In contrast to its antiviral potency, MARCH8 is occasionally hijacked by some viruses and bacteria to enhance their invasion, indicating a duplex role of MARCH8 in host pathogenic infections. This review summarizes MARCH8's antiviral roles and how viruses evade its restriction, shedding light on novel antiviral therapeutic avenues.

Efficacy and safety of Runzao Zhiyang capsule for chronic urticaria: a systematic review and meta-analysis of randomized controlled trials.

Background: Chronic urticaria (CU) is a commonly seen skin disorder featured by recurring wheals, with or without angioedema, lasting for at least 6 weeks. Runzao Zhiyang capsule (RZC) has been widely applied to treat patients with CU. This study is aimed at systematically evaluating the efficacy and safety of RZC in treating CU. Materials and Methods: Randomized controlled trials (RCTs) of RZC on treating CU from Chinese and English databases were searched. Data were collected by two independent researchers. The Cochrane Collaboration tool was adopted for evaluating the risk of bias. The meta-analysis was performed with Review Manager 5.3 software. Sensitivity analysis and publication bias assessment were conducted by Stata 14.0 software. Results: Totally 27 studies were included in the analysis, involving 2,703 patients. The pooled results showed that compared with second-generation H1-antihistamines (sgAHs) therapy alone, RZC combined with sgAHs is more effective in improving the total effective rate (RR = 1.32, 95% CI: 1.25 to 1.39, p < 0.00001), the quality of life measured by Dermatology Life Quality Index (DLQI) (MD = -2.63, 95% CI: -3.68 to -1.58, p < 0.00001) and the serum IFN-γ level (SMD = 3.10, 95% CI: 1.58 to 4.62, p < 0.0001), and reducing the recurrence rate (RR = 0.39, 95% CI: 0.27 to 0.55, p < 0.00001), the serum total IgE level (SMD = -2.44, 95% CI: -3.51 to -1.38, p < 0.00001), the serum IL-4 level (SMD = -2.96, 95% CI: -4.10 to -1.83, p < 0.00001), and the incidence of adverse events including dizziness, fatigue, dry mouth, and constipation (RR = 0.53, 95% CI: 0.33 to 0.85, p = 0.009; RR = 0.46, 95% CI: 0.26 to 0.84, p = 0.01; RR = 0.57, 95% CI: 0.34 to 0.95, p = 0.03; RR = 0.24, 95% CI: 0.07 to 0.85, p = 0.03). Conclusion: The current evidence indicates that RZC may be an efficient therapeutic regimen in patients with CU. Nevertheless, owing to the suboptimal quality of the included studies, more large-scale, well-designed RCTs are required to verify the obtained findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/; Identifier: CRD42022313177.

The binding profile of SARS-CoV-2 with human leukocyte antigen polymorphisms reveals critical alleles involved in immune evasion.

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), astonished the world and led to millions of deaths. Due to viral new mutations and immune evasion, SARS-CoV-2 ranked first in transmission and influence. The binding affinity of human leukocyte antigen (HLA) polymorphisms to SARS-CoV-2 might be related to immune escape, but the mechanisms remained unclear. In this study, we obtained the binding affinity of SARS-CoV-2 strains with different HLA proteins and identified 31 risk alleles. Subsequent structural predictions identified 10 active binding sites in these HLA proteins that may promote immune evasion. Particularly, we also found that the weak binding ability with HLA class I polymorphisms could contribute to the immune evasion of Omicron. These findings suggest important implications for preventing the immune evasion of SARS-CoV-2 and providing new insights for the vaccine design.

Methionine enkephalin inhibited cervical cancer migration as well as invasion and activated CD11b+ NCR1+ NKs of tumor microenvironment.

This study was to study the role of methionine enkephalin (menk) in cell invasion and migration as well as NK cells activation of tumor microenvironment in cervical cancer. The results showed that menk inhibited cervical cancer migration and invasion. In addition, we found menk affected epithelial to mesenchymal transition (EMT) related indicators, with increasing E-cadherin level, decreasing N-cadherin and vimentin level. Through in vivo mouse model, we found that menk IFNγ and NKP46 expression was upregulated in tumor tissues by menk compared with controls, while LAG3 expression was inhibited by menk, besides, there was an upregulation of CD11b+ NCR1+ NKs of tumor microenvironment in cervical cancer. Therefore, we concluded that menk inhibited cancer migration and invasion via affecting EMT related indicators and activated CD11b+ NCR1+ NKs of tumor microenvironment in cervical cancer, laying a theoretical foundation for the further clinical treatment of menk.

Application of immunomodulatory therapy in a human brucellosis patient with pancytopenia: A case report.

Brucellosis is a common zoonotic infectious disease with diverse and non-specific clinical manifestations caused by Brucella. Although Brucella can cause damage to multiple systems in the human body, hematological complications are relatively rare. We present a case of a 47-year-old male brucellosis patient with pancytopenia. In May 2018, the patient was diagnosed with brucellosis and recovered after receiving antibiotic treatment (rifampicin 600 mg/day and doxycycline 200 mg/day) for six weeks. However, after three years, the patient experienced a recurring high fever. Brucellosis relapse was confirmed based on the patient's clinical history, Rose Bengal plate agglutination test and standard tube agglutination test results. Routine blood examination revealed a decrease in the whole blood cell count, suggesting bone marrow suppression. Bone marrow aspiration and bacterial culture confirmed the diagnosis of brucellosis with pancytopenia. Antibiotic treatment failed to effectively improve the patient's condition. Therefore, a combination of immunomodulatory and antibiotic treatments was used. The antibiotic regimen included oral rifampicin 600 mg/day, intravenous doxycycline hydrochloride 200 mg/day, and subcutaneous injection of human granulocyte-stimulating factor (0.2 mg/day). Immunomodulatory therapy consisted of 20,000 mg/day intravenous human immunoglobulin (pH 4) for five days and 800 mg/day oral pidotimod liquid for 20 days. As the treatment progressed, the count gradually recovered to normal levels, and the symptoms of bone marrow suppression were alleviated. PCR testing revealed the absence of Brucella DNA in both monocyte and serum samples. Furthermore, negative standard tube agglutination test results were obtained. These findings indicate that the immunomodulatory therapy resulted in a complete clearance of Brucella. Therefore, immunomodulatory therapy could be an effective option in cases of brucellosis with pancytopenia that are unresponsive to conventional antibiotic treatment. Further research and clinical evidence are required to confirm and optimize the use of immunomodulatory therapies in patients with brucellosis.

Tumor necrosis factor-like cytokine 1A plays a role in inflammatory bowel disease pathogenesis.

The binding of tumor necrosis factor-like cytokine 1A (TL1A) to death receptor 3 (DR3) plays an important role in the interaction between dendritic cells (DCs) and T cells and contributes to intestinal inflammation development. However, the mechanism by which DCs expressing TL1A mediate helper T (Th) cell differentiation in the intestinal lamina propria (LP) during the pathogenesis of inflammatory bowel disease remains unclear. In this study, we found that TL1A/DR3 promoted Th1 and Th17 cell differentiation in T-T and DC-T cell interaction-dependent manners. TL1A-deficient CD4+ T cells failed to polarize into Th1/Th17 cells and did not cause colonic inflammation in a T cell transfer colitis model. Notably, TL1A was located in the cytoplasm and nuclei of DCs, positively regulated the DC-specific ICAM-grabbing nonintegrin/RAF1/nuclear factor κB signaling pathway, enhanced the antigen uptake ability of DCs, and promoted TLR4-mediated DC activation, inducing naive CD4+ T cell differentiation into Th1 and Th17 cells. Our work reveals that TL1A plays a regulatory role in inflammatory bowel disease pathogenesis.

NLRC4 promotes the cGAS-STING signaling pathway by facilitating CBL-mediated K63-linked polyubiquitination of TBK1.

TANK-binding kinase 1 (TBK1) is crucial in producing type Ⅰ interferons (IFN-Ⅰ) that play critical functions in antiviral innate immunity. The tight regulation of TBK1, especially its activation, is very important. Here we identify NLRC4 as a positive regulator of TBK1. Ectopic expression of NLRC4 facilitates the activation of the IFN-ß promoter, the mRNA levels of IFN-ß, ISG54, and ISG56, and the nuclear translocation of interferon regulatory factor 3 induced by cGAS and STING. Consistently, under herpes simplex virus-1 (HSV-1) infection, knockdown or knockout of NLRC4 in BJ cells and primary peritoneal macrophages from Nlrc4-deficient (Nlrc4-/- ) mice show attenuated Ifn-ß, Isg54, and Isg56 mRNA transcription, TBK1 phosphorylation, and augmented viral replications. Moreover, Nlrc4-/- mice show higher mortality upon HSV-1 infection. Mechanistically, NLRC4 facilitates the interaction between TBK1 and the E3 ubiquitin ligase CBL to enhance the K63-linked polyubiquitination of TBK1. Our study elucidates a previously uncharacterized function for NLRC4 in upregulating the cGAS-STING signaling pathway and antiviral innate immunity.

The short and long-term impact of nonpharmaceutical interventions on the prevalence of varicella in Xi'an during the COVID-19 pandemic.

Varicella is a highly prevalent infectious disease with a similar transmission pathway to coronavirus disease 2019 (COVID-19). In the context of the COVID-19 pandemic, anti-COVID-19 nonpharmaceutical interventions (NPIs) have been implemented to prevent the spread of the infection. This study aims to analyze varicella's epidemiological characteristics and further investigate the effect of anti-COVID-19 NPIs on varicella in Xi'an, northwestern China. Based on the varicella surveillance data, search engine indices, meteorological factors from 2011 to 2021 in Xi'an, and different levels of emergency response to COVID-19 during the pandemic, we applied Bayesian Structural Time Series models and interrupted time series analysis to predict the counterfactual incidence of varicella and quantify the impact of varying NPIs intensities on varicella. From 2011 to 2021, varicella incidence increased, especially in 2019, with a high incidence of 111.69/100 000. However, there was a sharp decrease of 43.18% in 2020 compared with 2019, and the peak of varicella incidence in 2020 was lower than in previous years from the 21st to the 25th week. In 2021, the seasonality of varicella incidence gradually returned to a seasonal pattern in 2011-2019. The results suggest that anti-COVID-19 NPIs effectively reduce the incidence of varicella, and the reduction has spatiotemporal heterogeneity.