Di- and tri-methylation of histone H3K36 play distinct roles in DNA double-strand break repair.

Histone H3 Lys36 (H3K36) methylation and its associated modifiers are crucial for DNA double-strand break (DSB) repair, but the mechanism governing whether and how different H3K36 methylation forms impact repair pathways is unclear. Here, we unveil the distinct roles of H3K36 dimethylation (H3K36me2) and H3K36 trimethylation (H3K36me3) in DSB repair via non-homologous end joining (NHEJ) or homologous recombination (HR). Yeast cells lacking H3K36me2 or H3K36me3 exhibit reduced NHEJ or HR efficiency. yKu70 and Rfa1 bind H3K36me2- or H3K36me3-modified peptides and chromatin, respectively. Disrupting these interactions impairs yKu70 and Rfa1 recruitment to damaged H3K36me2- or H3K36me3-rich loci, increasing DNA damage sensitivity and decreasing repair efficiency. Conversely, H3K36me2-enriched intergenic regions and H3K36me3-enriched gene bodies independently recruit yKu70 or Rfa1 under DSB stress. Importantly, human KU70 and RPA1, the homologs of yKu70 and Rfa1, exclusively associate with H3K36me2 and H3K36me3 in a conserved manner. These findings provide valuable insights into how H3K36me2 and H3K36me3 regulate distinct DSB repair pathways, highlighting H3K36 methylation as a critical element in the choice of DSB repair pathway.

A qualitative study on inner experience of self-management behavior among elderly patients with type 2 diabetes in rural areas.

BACKGROUND: As a chronic metabolic disease, diabetes poses a serious threat to human health and has become a major public health problem in China and worldwide. In 2020, 30% of Chinese people (aged ≥ 60 years) reported having diabetes mellitus. Moreover, individuals with diabetes living in rural areas face a significantly higher mortality risk compared to those in urban areas. In this study, we explored the inner experience of self-management behaviors in elderly patients with type 2 diabetes in rural areas to inform targeted interventions. METHODS: A phenomenological research design was used to explore the inner experience of self-management in rural elderly diabetes. Ten elderly diabetic patients were sampled from December 2022 to March 2023 in rural areas of Yangcheng County, Jincheng City, ShanXi Province, China. The seven-step Colaizzi phenomenological was used to analyze the interview data and generate themes. RESULTS: Four themes emerged: "Insufficient self-management cognition", "Negative self-management attitude", "Slack self-management behavior", and "No time for self-management". CONCLUSION: The level of self-management among elderly patients with type 2 diabetes in rural areas is low. Healthcare professionals should develop targeted interventions aimed at enhancing their cognitive levels, modifying their coping styles, and improving their self-management abilities to improve their quality of life.

Cemented vertebra and adjacent vertebra refractured in a chronic kidney disease-mineral and bone disorder patient: A case report.

BACKGROUND: Although percutaneous vertebral augmentation (PVA) is a commonly used procedure for treating vertebral compression fracture (VCF), the risk of vertebral refracture should be considered. Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a systemic disease of mineral and bone metabolism. It is associated with an increased risk of fracture. Few studies have reported the use of PVA in patients with CKD-MBD. We herein report a rare case wherein the cemented vertebra and the adjacent vertebra refractured simultaneously in a CKD-MBD patient after PVA. CASE SUMMARY: A 74-year-old man suffered from low back pain after taking a fall about 3 wk ago. According to physical examination, imaging and laboratory findings, diagnoses of T12 VCF, CKD-MBD, and chronic kidney disease stage 5 were established. He then received percutaneous vertebroplasty at T12 vertebra. Fourteen weeks later, he presented with T12 and L1 vertebral refractures caused by lumbar sprain. Once again, he was given PVA which was optimized for the refractured vertebrae. Although the short-term postoperative effect was satisfactory, he reported chronic low back pain again at the 3-month follow-up. CONCLUSION: It is necessary that patients with CKD-MBD who have received PVA are aware of the adverse effects of CKD-MBD. It may increase the risk of vertebral refracture. Furthermore, the PVA surgical technique needs to be optimized according to the condition of the patient. The medium- and long-term effects of PVA remain uncertain in patients with CKD-MBD.

MicroRNA-18a prevents senescence of mesenchymal stem cells by targeting CTDSPL.

Stem cell therapy requires massive-scale homogeneous stem cells under strict qualification control. However, Prolonged ex vivo expansion impairs the biological functions and results in senescence of mesenchymal stem cells (MSCs). We investigated the function of CTDSPL in the premature senescence process of MSCs and clarified that miR-18a-5p played a prominent role in preventing senescence of long-term cultured MSCs and promoting the self-renewal ability of MSCs. Over-expression of CTDSPL resulted in an enlarged morphology, up-regulation of p16 and accumulation of SA-ß-gal of MSCs. The reduced phosphorylated RB suggested cell cycle arrest of MSCs. All these results implied that CTDSPL induced premature senescence of MSCs. We further demonstrated that miR-18a-5p was a putative regulator of CTDSPL by luciferase reporter assay. Inhibition of miR-18a-5p promoted the expression of CTDSPL and induced premature senescence of MSCs. Continuous overexpression of miR-18a-5p improved self-renewal of MSCs by reducing ROS level, increased expression of Oct4 and Nanog, and promoted growth rate and differentiation capability. We reported for the first time that the dynamic interaction of miR-18a-5p and CTDSPL is crucial for stem cell senescence.

Synchronous occurrence of gastric cancer and gastrointestinal stromal tumor: A case report and review of the literature.

BACKGROUND: To evaluate the clinicopathological features and prognosis of gastric cancer (GC) occurring synchronously with gastrointestinal stromal tumor (GIST). CASE SUMMARY: We report 19 patients with concurrent GC and GIST (17 male and 2 female, median age 62 years). GC was most often located in the lower third of the stomach. GIST was diagnosed preoperatively in four patients. GIST was most often located in the gastric body (n = 8, 42%). The most common growth pattern in GIST was extraluminal (n = 12, 63%). The positive expression rates of CD117 and CD34 in GIST were 100% and 95%, respectively. Most patients with GIST (n = 17, 89%) were very low or low risk. There was no recurrence of GIST during follow-up. The 3-year cumulative survival rate was 73.9%, and the 5-year cumulative survival rate was 59.2%. The combined analysis of this study and literature reports (47 reports, 157 patients) found that GC and GIST were usually located in the lower third (42%) and middle third (51%) of the stomach. GC was usually early (stage I: 42%), poorly differentiated (42%) intestinal-type adenocarcinoma (51%). GISTs were primarily small in diameter (median: 1.2 cm) and very low or low risk (89%). CONCLUSION: Synchronous GC and GIST may not be rare. They have specific clinicopathological characteristics, and may have mutual inhibition in pathogenesis and progression.

Gcn5- and Bre1-mediated Set2 degradation promotes chronological aging of Saccharomyces cerevisiae.

Loss of transcription-coupled histone H3 lysine 36 trimethylation (H3K36me3) contributes to shorter lifespans in eukaryotes. However, the molecular mechanism of the decline of H3K36me3 during aging remains poorly understood. Here, we report that the degradation of the methyltransferase Set2 is the cause of decreased H3K36me3 levels during chronological aging in budding yeast. We show that Set2 protein degradation during cellular senescence and chronological aging is mainly mediated by the ubiquitin-conjugating E2 enzyme Ubc3 and the E3 ligase Bre1. Lack of Bre1 or abolishment of the ubiquitination stabilizes Set2 protein, sustains H3K36me3 levels at the aging-related gene loci, and upregulates their gene expression, thus leading to extended chronological lifespan. We further illustrate that Gcn5-mediated Set2 acetylation is a prerequisite for Bre1-catalyzed Set2 polyubiquitination and proteolysis during aging. We propose that two sequential post-translational modifications regulate Set2 homeostasis, suggesting a potential strategy to target the Gcn5-Bre1-Set2 axis for intervention of longevity.

Rh(III)-Catalyzed Dual C-H Functionalization and C-O/C-N Annulations of Monoamide Fumarates.

Pyrano[4,3-c]pyridine-diones, which are the key skeleton of bioactive compounds and functional materials, are usually prepared via a multistep synthesis using expensive substrates. This work demonstrates that Rh(III)-catalyzed dual C(sp2)-H functionalization and C-O/C-N annulation of monoamide fumarates can produce pyrano[4,3-c]pyridine-1,5(6H)-diones in high yield (up to 82%) in a single step. The substrates of monoamide fumarates and acetylenes are structurally simple, readily available, and inexpensive. The additive AgSbF6 effectively raised the yields. On account of easier dehydrogenation of OH in the COOH group than NH in the amide group in the reaction, the process first undergoes C-O annulation and then is succeeded by C-N annulation.

Overcome tumor relapse in CAR T cell therapy

Chimeric antigen receptor (CAR) T cell therapy is a novel therapeutic approach that uses gene editing techniques and lentiviral transduction to engineer T cells so that they can effectively kill tumors. However, CAR T cell therapy still has some drawbacks: many patients who received CAR T cell therapy and achieve remission, still had tumor relapse and treatment resistance, which may be due to tumor immune escape and CAR T cell dysfunction. To overcome tumor relapse, more researches are being done to optimize CAR T cell therapy to make it more precise and personalized, including screening for more specific tumor antigens, developing novel CAR T cells, and combinatorial treatment approaches. In this review, we will discuss the mechanisms as well as the progress of research on overcoming plans. (AU)

Hypertension Exacerbates Severity and Outcomes of COVID-19 in Elderly Patients: A Retrospective Observational Study.

OBJECTIVE: To evaluate the impact of hypertension on the clinical outcome of COVID-19 patients aged 60 years old and older. METHODS: This single-center retrospective cohort study enrolled consecutive COVID-19 patients aged 60 years old and older, who were admitted to Liyuan Hospital from January 1, 2020 to April 25, 2020. All included patients were divided into two groups: hypertension and nonhypertension group. The baseline demographic characteristics, laboratory test results, chest computed tomography (CT) images and clinical outcomes were collected and analyzed. The prognostic value of hypertension was determined using binary logistic regression. RESULTS: Among the 232 patients included in the analysis, 105 (45.3%) patients had comorbid hypertension. Compared to the nonhypertension group, patients in the hypertension group had higher neutrophil-to-lymphocyte ratios, red cell distribution widths, lactate dehydrogenase, high-sensitivity C-reactive protein, D-dimer and severity of lung lesion, and lower lymphocyte counts (all P<0.05). Furthermore, the hypertension group had a higher proportion of intensive care unit admissions [24 (22.9%) vs. 14 (11.0%), P=0.02) and deaths [16 (15.2%) vs. 3 (2.4%), P<0.001] and a significantly lower probability of survival (P<0.001) than the nonhypertension group. Hypertension (OR: 4.540, 95% CI: 1.203-17.129, P=0.026) was independently correlated with all-cause in-hospital death in elderly patients with COVID-19. CONCLUSION: The elderly COVID-19 patients with hypertension tend to have worse conditions at baseline than those without hypertension. Hypertension may be an independent prognostic factor of poor clinical outcome in elderly COVID-19 patients.

Overcome tumor relapse in CAR T cell therapy.

Chimeric antigen receptor (CAR) T cell therapy is a novel therapeutic approach that uses gene editing techniques and lentiviral transduction to engineer T cells so that they can effectively kill tumors. However, CAR T cell therapy still has some drawbacks: many patients who received CAR T cell therapy and achieve remission, still had tumor relapse and treatment resistance, which may be due to tumor immune escape and CAR T cell dysfunction. To overcome tumor relapse, more researches are being done to optimize CAR T cell therapy to make it more precise and personalized, including screening for more specific tumor antigens, developing novel CAR T cells, and combinatorial treatment approaches. In this review, we will discuss the mechanisms as well as the progress of research on overcoming plans.

Fatal systemic emphysematous infection caused by Klebsiella pneumoniae: A case report.

BACKGROUND: Systemic emphysematous infection caused by Klebsiella pneumoniae (K. pneumo niae) is a rare but severe infection which can be lethal if the diagnosis is delayed. CASE SUMMARY: We report a rare case of systemic emphysematous infection via hematogenous dissemination from a liver abscess caused by K. pneumoniae, complicated by multiple organ dysfunction syndrome, septic shock, bacteremia, emphysematous cystitis, prostate and left seminal vesicle abscesses in a diabetic patient. The patient simultaneously presented with spontaneous pneumoperitoneum secondary to rupture of the emphysematous liver abscess. His condition after admission deteriorated rapidly and he died within a short period. This disease is a great challenge for the clinician as K. pneumoniae can cause multifocal emphysematous infections and fulminant septic shock. Pneumoperitoneum following spontaneous rupture of the liver abscess can result in intra-abdominal sepsis that further increases mortality rate. Moreover, appropriate site-specific intervention and adequate drainage of numerous emphysematous liver lesions are difficult. CONCLUSION: Early diagnosis followed by efficient antibiotic therapy and surgical management are essential for systemic emphysematous infection.

Identification of differentially expressed miRNAs derived from serum exosomes associated with gastric cancer by microarray analysis.

AIMS: To explore the differentially expressed microRNAs (DEMs) in serum exosomes between gastric cancer (GC) patients and healthy people to provide new targets for GC diagnosis and treatment. METHODS: DEMs in serum exosomes were screened by microarray analysis and verified by RT-qPCR. The target genes of DEMs were predicted using Targetscan and miRTarBase databases and then overlapped with the DEGs of STAD in TCGA database to obtain the common target genes. Biological function and pathway enrichment were analyzed using enrichr database, and a PPI network was constructed using STRING database. The potential target genes of DEMs were identified using the MCODE and cytoHubba plug-ins of Cytoscape software. Survival analysis were conducted using KMP and TCGA databases. The DEMs -target genes-pathways network was established using Cytoscape software. A Cox proportional hazards regression model formed by optimal target genes was used to access the reliability of this prediction process. RESULTS: Three serum exosomal microRNAs (exo-miRNAs, has-miR-1273 g-3p, has-miR-4793-3p, has-miR-619-5p) were identified to be highly expressed in GC patients and performed excellent diagnostic ability. A total of 179 common target genes related to GC were predicted. They were mainly involved in 79 GO functional annotations and 6 KEGG pathways. The prognostic model formed by eight optimal target genes (TIMELESS, DNA2, MELK, CHAF1B, DBF4, PAICS, CHEK1 and NCAPG2), which were low-risk genes of GC, also performed perfect prognostic ability. CONCLUSIONS: Serum exosomal has-miR-1273 g-3p, has-miR-4793-3p and has-miR-619-5p can be used as new diagnostic biomarkers for GC. Among them, serum exosomal hsa-miR-1273 g-3p / hsa-miR-4793-3p targets MELK and hsa-miR-619-5p targets NCAPG2 were identified as novel mechanisms involved in the development of GC. It provides new targets for the diagnosis and treatment of GC by exo-miRNAs.

Damage Control Surgery Saves Patient with Gastric Lymphoma from Radical Gastrectomy.

The concept of damage control surgery was first introduced in the 1990s. It has great significance in the treatment for critically ill patients, which not only greatly improves survival rate, but also helps doctors avoiding misdiagnosis and mistreatment. Herein, we present a case of gastric perforation caused by neoplasm with critical condition of the patient. According to the concept of damage control surgery, the patient was subjected to perforation repair and tumor biopsy instead of conventional radical gastrectomy. Then, diffuse large B cell lymphoma was diagnosed on pathologic examination. After surgery, the patient received R-CHOP chemotherapy according to the clinical guidelines and is alive till now. Our experience might be helpful for understanding the value of damage control surgery in avoiding misdiagnosis and mistreatment for critical emergency patients. Key Words: Lymphoma, Stomach, Perforation, Damage control surgery.

Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression.

Correction to "Liu LP, Sheng XP, Shuai TK, Zhao YX, Li B, Li YM. Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression. World J Gastroenterol 2018; 24: 4565-4577 [PMID: 30386106 DOI: 10.3748/wjg.v24.i40.4565]." In this article, we have identified some of the images in Figure 2A, C, E, G, and I are identical to the images in Figures 1B, 2A, 3B, 3E, and 3G of another paper entitled "Liu L, Zhao Y, Fan G, Shuai T, Li B, Li Y. Helicobacter pylori infection enhances heparanase leading to cell proliferation via mitogenactivated protein kinase signalling in human gastric cancer cells.", which was published by us in the Molecular Medicine Reports in December, 2018 [PMID: 30320396 DOI: 10.3892/mmr.2018.9558]. The reason why we asked to replace the pictures was that when we were simultaneously preparing to submit our two different articles to the World Journal of Gastroenterology (WJG) and Molecular Medicine Reports, we uploaded the wrong pictures to the WJG, which were same as those submitted to the Molecular Medicine Reports. We apologize for this negligence and any inconvenience that this may cause. We would be grateful if you could replace the wrong pictures with the correct ones attached.

Set2-mediated H3K36 methylation states redundantly repress the production of antisense transcripts: role in transcription regulation.

Methyltransferase Set2-mediated methylation of histone H3 lysine 36 (H3K36), which involves the addition of up to three methyl groups at this site, has been demonstrated to function in many chromatin-coupled events. The methylation of H3K36 is known to recruit different chromatin effector proteins, affecting transcription, mRNA splicing and DNA repair. In this study, we engineered two yeast set2 mutants that lack H3K36 mono/dimethylation (H3K36me1/2) and trimethylation (H3K36me3), respectively, and characterized their roles in the production of antisense transcripts under nutrient-rich conditions. Using our new bioinformatics identification pipeline analysis, we are able to identify a larger number of antisense transcripts in set2∆ cells than has been published previously. We further show that H3K36me1/2 or H3K36me3 redundantly repressed the production of antisense transcripts. Moreover, gene ontology (GO) analysis implies that H3K36me3-mediated antisense transcription might play a role in DNA replication and DNA damage repair, which is independent of regulation of the corresponding sense gene expression. Overall, our results validate a coregulatory mechanism of different H3K36 methylation states, particularly in the repression of antisense transcription.

Construction of PD1/CD28 chimeric-switch receptor enhances anti-tumor ability of c-Met CAR-T in gastric cancer.

Chimeric antigen receptor (CAR) T cell is a promising method in cancer immunotherapy but faces many challenges in solid tumors. One of the major problems was immunosuppression caused by PD-1. In our study, the expression of c-Met in GC was analyzed from TCGA datasets, GC tissues, and cell lines. The c-Met CAR was a second-generation CAR with 4-1BB, cMet-PD1/CD28 CAR was c-Met CAR adding PD1/CD28 chimeric-switch receptor (CSR). In vitro, we measured the changes of different subgroups, phenotypes and PD-1 expression in CAR-T cells. We detected the secretion levels of different cytokines and the killing ability of CAR-Ts. In vivo, we established a xenograft GC model and observed the anti-tumor effect and off-target toxicity of different CAR-Ts. We find that the expression of c-Met was increased in GC. CD3+CD8+ T cells and CD62L+CCR7+ central memory T cells (TCM) were increased in two CAR-Ts. The stimulation of target cells could promote the expression of PD-1 in c-Met CAR-T. Compared with Mock T, the secretion of cytokines as IFN-γ, TNF-α, IL-6, IL-10 secreted by two CAR-Ts was increased, and the killing ability to c-Met positive GC cells was enhanced. The PD1/CD28 CSR could further enhance the killing ability, especially the long-term anti-tumor effect of c-Met CAR-T, and reduce the release level of IL-6. CAR-Ts target c-Met had no obvious off-target toxicity to normal organs. Thus, the PD1/CD28 CSR could further enhance the anti-tumor ability of c-Met CAR-T, and provides a promising design strategy to improve the efficacy of CAR-T in GC.

Biomechanical analysis of the closed reduction internal fixation with cannulated screw of femoral neck fractures.

ABSTRACT: The influencing factors in closed reduction internal fixation with cannulated screw of femoral neck fractures have not been well investigated. This study evaluated these factors in patients with femoral neck fractures.Fifty-seven patients (36 males and 21 females) diagnosed with femoral neck fracture with the average age of 52.44 ±â€Š15.04 years who underwent closed reduction internal fixation with cannulated screw were included in this study. Data were collected through case report reviews, phone call follow-ups, and outpatient follow-ups to evaluate pre- and postoperative radiograph images. Statistical analysis was performed using Garden classification, binary and multinomial logistic regression analysis by including factors such as patient's age, gender, fracture type, time to fixation, reduction quality, functional recovery period, removal of cannulated screw, and preoperative traction. Logistic regression analysis revealed that age and reduction quality was statistically significant (P < .05) to clinical outcome and other factors were not statistically significant.The main factors affecting clinical outcomes were functional recovery and reduction quality. The biomechanical effects of fixation provide a good foundation for fracture healing. Patient's conditions should be carefully evaluated before selecting reduction procedures to reach an optimal surgical outcome.

The Paf1 complex transcriptionally regulates the mitochondrial-anchored protein Atg32 leading to activation of mitophagy.

Mitophagy is a critical process that safeguards mitochondrial quality control in order to maintain proper cellular homeostasis. Although the mitochondrial-anchored receptor Atg32-mediated cargo-recognition system has been well characterized to be essential for this process, the signaling pathway modulating its expression as a contribution of governing the mitophagy process remains largely unknown. Here, bioinformatics analyses of epigenetic or transcriptional regulators modulating gene expression allow us to identify the Paf1 complex (the polymerase-associated factor 1 complex, Paf1C) as a transcriptional repressor of ATG genes. We show that Paf1C suppresses glucose starvation-induced autophagy, but does not affect nitrogen starvation- or rapamycin-induced autophagy. Moreover, we show that Paf1C specifically regulates mitophagy through modulating ATG32 expression. Deletion of the genes encoding two core subunits of Paf1C, Paf1 and Ctr9, increases ATG32 and ATG11 expression and facilitates mitophagy activity. Although Paf1C is required for many histone modifications and gene activation, we show that Paf1C regulates mitophagy independent of its positive regulatory role in other processes. More importantly, we also demonstrate the mitophagic role of PAF1C in mammals. Overall, we conclude that Paf1C maintains mitophagy at a low level through binding the promoter of the ATG32 gene in glucose-rich conditions. Dissociation of Paf1C from ATG32 leads to the increased expression of this gene, and mitophagy induction upon glucose starvation. Thus, we uncover a new role of Paf1C in modulating the mitophagy process at the transcriptional level. ABBREVIATIONS: AMPK: AMP-activated protein kinase; ATP5F1A: ATP synthase F1 subunit alpha; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CCCP: chlorophenylhydrazone; DFP: chelator deferiprone; GFP: green fluorescent protein; H2B-Ub1: H2B monoubiquitination; HSPD1/HSP60: heat shock protein family D (Hsp60) member 1; KD: kinase dead; OPTN, optineurin; Paf1: polymerase-associated factor 1; PINK1: PTEN induced kinase 1; PRKN/Parkin: parkin RBR E3 ubiquitin protein ligase; RT-qPCR: real-time quantitative PCR; SD-N: synthetic dropout without nitrogen base; TIMM23: translocase of inner mitochondrial membrane 23; TOMM20: translocase of outer mitochondrial membrane 20; WT: wild-type; YPD: yeast extract peptone dextrose; YPL: yeast extract peptone lactate.

Characteristics of COVID-19 clusters in Lishui / 预防医学

Objective@#To analyze the epidemiological characteristics of coronavirus disease 2019 ( COVID-19 ) clusters in Lishui, so as to provide basis for the prevention and control of COVID-19 clusters.@*Methods@#The data of COVID-19 clusters in Lishui from January 23 to March 29, 2020 were collected through China Disease Control and Prevention Information System-Public Health Emergency Information System, and analyzed time, space, scale, source of infection, exposure and transmission route by descriptive epidemiological method. @*Results@#There were 31 cases in 8 clusters ( about 4 cases per cluster ), with no death. The report time was bimodal, peaked first from January 20 to February 10 with 4 clusters imported from domestic and peaked second from March 1 to 29 with 4 clusters imported from overseas. Qingtian County reported 4 clusters, Liandu District, Yunhe County, Qingyuan County and Jingning County each reported 1 cluster. Thirteen cases were restaurant employees, accounting for 41.94%. The cases were mainly occurred in the condition that exposed in the same family ( 6 clusters ), in the same dinner and car ( 1 clusters ), and in the same party ( 1 clusters ). The exposure modes that caused more cases infected were through the same family (9 cases) and through the same dinner and car ( 6 cases ). There were 3 clusters with first-generation cases, 3 clusters with second-generation cases and 2 clusters with third-generation cases. The recurrence rate of the 8 clusters ranged from 1.49% to 7.69%, with a median of 3.47%. @*Conclusions@#The COVID-19 clusters in Lishui imported from domestic in the early stage and later from overseas. Most cases were reported from Qingtian County, were engaged in catering business, and exposed by living with families.