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    Academic Frontiers
    Expert consensus of practical clinical classification system with optimal surgical strategy for cesarean scar pregnancy
    Yanli BAN, Ying Yanli Writing experts: ZHAO, Hua LI, Wei LIU, Fengnian RONG, Shuping ZHAO, Baoxia CUI
    Journal of Shandong University (Health Sciences). 2023, 61(11):  1-10.  doi:10.6040/j.issn.1671-7554.0.2023.0988
    Abstract ( 267 )   HTML ( 56 )   PDF (6842KB) ( 212 )   Save
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    Cesarean scar pregnancy (CSP) is a special type of ectopic pregnancy in which a pregnancy sac is implanted at the scar of a previous caesarean section. Without appropriate diagnosis or treatment, it can lead to severe morbidity such as life-threatening massive hemorrhage, and uterine rupture, with subsequent effect of fertility, physical and mental health of patients. Although many different treatment options have been described, there is still no consensus on the optimal surgical treatment strategy. In recent years, treatment of CSP based on classification has drawn more and more attention. The practical clinical classification system with optimal surgical strategy for CSP has been widely validated in Shandong Province, which shows good application value and reliable therapeutic effects. Based on this classification system, and combined with clinical experience and the latest clinical research results, the expert consensus of clinical classification system and surgical strategy for CSP is formulated, aiming to standardize the clinical diagnosis and treatment, and to guide clinical work.

    Technical procedure of CT-guided intratumoral chemotherapy for lung tumor
    Mingyong HAN,Xiaoli YU,Fangping ZENG,Bing XIE,Lan LU,Jiaquan QU,Bifeng JIANG,Sihan TANG,Jie TAN,Jin LIANG,Longhui ZHONG,Liu WANG,Xuanzhi ZHAO
    Journal of Shandong University (Health Sciences). 2023, 61(11):  11-19.  doi:10.6040/j.issn.1671-7554.0.2023.0981
    Abstract ( 189 )   HTML ( 42 )   PDF (6630KB) ( 141 )   Save
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    The incidence and mortality rates of lung cancer in China rank the first of all tumors. At present, there are many effective treatment methods, including surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy and other local and systematic treatments. In recent years, intratumoral chemotherapy, which combines the advantages of local therapy and systemic therapy, has gradually become the focus. By using ultrasound, bronchoscope, ultrasonic bronchoscope, endoscopic ultrasonography or CT and other imaging and interventional modalities, chemotherapeutics such as cisplatin, carboplatin, mitomycin, paclitaxel liposomes, fluorouracil in stock or diluted solutions are directly injected into the cancer tissue through the puncture needle. Intratumoral chemotherapy can increase the concentration of chemotherapeutics in the tumor tissue, reduce the systemic toxicity and side effects, and improve the local control rate of cancers. We have carried out clinical application and exploratory research on intratumoral chemotherapy for lung cancer, liver metastasis and bone metastasis, and observed patients' benefits and primary efficacy. This paper will summarize the technical procedure of CT-guided intratumoral chemotherapy.

    Progress in the establishment and application of organoids of bladder cancer
    Andong GUO,Sentai DING
    Journal of Shandong University (Health Sciences). 2023, 61(11):  20-26.  doi:10.6040/j.issn.1671-7554.0.2023.0900
    Abstract ( 192 )   HTML ( 15 )   PDF (2324KB) ( 192 )   Save
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    Bladder cancer is a common disease of the urinary system. Cisplatin-based chemotherapy is the first-line treatment for inoperable and metastatic myometrial invasive bladder cancer. However, due to resistance, a large number of patients fail in chemotherapy, which leads to tumor recurrence and progression. In recent years, organoid models have become a hot spot in the research of pathogenesis, metastasis and drug sensitivity. The successful establishment of bladder cancer organoids is a breakthrough in the clinical treatment of bladder cancer, because organoids and primary tissues have a high degree of genetic and phenotypic consistency, which can help us better understand the genomic changes of bladder cancer, and detect drug sensitivity and resistance. This article aims to review and analyze the construction process, characteristics, advantages and applications of bladder cancer organoids as preclinical models.

    Preclinical Medicine
    Structural variation and expression analysis of mRNAome and lncRNAome in cortex of rat Middle Cerebral Artery Occlusion model
    YUAN Shan, YANG Yuying, XU Meimei, HU Guangze, TANG Juan, GAO Rui
    Journal of Shandong University (Health Sciences). 2023, 61(11):  27-37.  doi:10.6040/j.issn.1671-7554.0.2023.0291
    Abstract ( 135 )   PDF (9282KB) ( 100 )   Save
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    Objective To explore the basic characteristics and expression patterns of mRNA transcriptome(mRNAome)and lncRNA transcriptome(lncRNAome)in the cortex tissue of middle cerebral artery occlusion(MCAO)rats by using deep sequencing technology, so as to provide available target genes and molecular markers for ischemic stroke. Methods After the hypoxic-ischemia and reperfusion injury model of MCAO rat model was established with thread embolism method, the availability was estimated with behavioral scoring and TTC staining. The full transcriptome of 10 cortical samples from the MCAO and sham groups were sequenced with deep sequencing technology. The mRNAome, lncRNAome, and their structural variations were identified with bioinformatics methods. The differentially expressed genes(DEGs)were verified with qRT-PCR. Results The MCAO model was successfully established. The brain tissue in the ischemic and hypoxic area showed pale after TTC staining, which was in sharp contrast to the ruddy color of the non-infarcted area. A total of 108.54 G clean sequencing data were obtained from high-throughput sequencing, and 30,829 and 311,183 mRNA and lncRNA transcripts were identified respectively. The total numbers of SNP and Indel produced by the MCAO group were significantly fewer than those by the sham group. However, there was no significant difference in the number of mRNA Indel between the two groups. The number of variants of mRNAome was significantly greater than that of lncRNAome, but there was no significant difference in the total number of variants of transcripts between the two groups. A total of 2,608 differentially expressed mRNA and 551 differentially expressed lncRNA were screened out. Altogether 9 known genes responding to ischemia and hypoxia were identified as the double-blind testers, which were verified in the up-regulated gene dataset in the MCAO group. The qRT-PCR results further confirmed that the expression trends of the 9 genes were the same as the sequencing data, indicating that the sequencing data were reliable. Conclusion A part of mRNA and lncRNA affecting the processing and splicing of transcripts are activated after hypoxic-ischemic and reperfusion injury, which may inhibit the transcription of some transcripts and the ability of RNA editing and processing, and then affect the expression of key target genes in ischemic stroke.
    Effects of NR4A1 on thapsigargin-induced glucose metabolism dysfunction in C2C12 myotube cells
    LU Xingchen, QIANG Ye, LIU Xinyu, ZUO Dan, JIANG Zihan, ZHANG Yuchao, LIU Yuantao, MA Xiaoli
    Journal of Shandong University (Health Sciences). 2023, 61(11):  38-47.  doi:10.6040/j.issn.1671-7554.0.2023.0753
    Abstract ( 139 )   PDF (7799KB) ( 95 )   Save
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    Objective To explore the effects and mechanism of NR4A1 on thapsigargin(TG)-induced glucose metabolism dysfunction in C2C12 myotube cells. Methods C2C12 cells were induced to differentiate into mature myotube cells in vitro. Cells stimulated with 20 nmol/L insulin for 10 minutes were labeled as insulin group, while cells without special treatment were labeled as control group. The phosphatidyl inositol-3-kinase/protein kinase B(PI3K/AKT)signaling pathway and protein expression of NR4A1 were determined with Western blotting. The viability of C2C12 myotube cells treated with TG concentration gradient was detected with CCK8. After a glucose metabolism impaired cell model was established, the cells were divided into control group, ethanol(EtOH)group, and TG group. After treatment, insulin was added, then glucose consumption level was measured with a glucose assay kit. The protein expressions of NR4A1, p-PI3K and p-AKT were detected with Western blotting. After the cells were infected with lentivirus and screened, those with stable overexpression of NR4A1 were obtained and subjected to TG treatment. After that, the cells were divided into Ad-NC group, Ad-NC+TG group, and Ad-NR4A1+TG group. After differentiation and maturation, insulin was added to detect the glucose consumption level and the expressions of NR4A1, p-PI3K and p-AKT. Results Compared with the control group, the insulin group showed significantly higher phosphorylation of the PI3K/AKT pathway and NR4A1 expression(P<0.01). CCK-8 results showed that the cell viability significantly decreased after 1 μmol/L of TG treatment(P<0.01). Compared with the EtOH group, the TG group showed decreased glucose consumption, reduced NR4A1 expression, and inhibited PI3K/AKT phosphorylation(P<0.01). Compared with the Ad-NC+TG group, the Ad-NR4A1+TG group showed an increase in glucose consumption with insulin stimulation(P<0.05), and significant activation of PI3K/KT signaling pathway(P<0.05). Conclusion TG induces glucose metabolism dysfunction in C2C12 myotube cells, while NR4A1 can improve such dysfunction, which may be mediated through the PI3K/AKT signaling pathway.
    Applying Typodont to compare the dentition changes in closing space of extractions between sliding straight wire technique and double keyhole loops
    HAN Di, GUO Jing
    Journal of Shandong University (Health Sciences). 2023, 61(11):  48-58.  doi:10.6040/j.issn.1671-7554.0.2022.1397
    Abstract ( 117 )   PDF (9312KB) ( 23 )   Save
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    Objective To observe the three-dimensional(3D)changes of the dentition between sliding straight wire technique and double keyhole loops with heat-induced Typodont system and scanner, and to explore the effects of loading forces on the dentition under the same methodology. Methods Brackets were bonded onto a standard Typodont maxillary model, with the first premolar extracted. The sliding technique group was divided into two subgroups: straight arch group and cruve arch group. The double keyhole group was also divided into two subgroups: tip-forward group and tip-back group. The initial and post-experiment digital models were overlapped, and 3D changes were analyzed using crown marker points. Results (1)Sagittal Changes: in the straight arch group, at 250 g force value, there was significant difference in U1 between the curve arch group and tip-forward group, and in U3 and U7 between tip-back group(P<0.05). At 300 g force value, only U7 in the curve arch group and U1-U6 in the tip-back group had statistical differences(P<0.05). When the force was increased, there was no significant increase in the anterior teeth retrusion, and the advancement of posterior teeth increased accordingly in all groups. However, there were no significant differences between posterior tooth changes, except for U6 in the curve arch group and U7 in the tip-back group(P<0.05). (2)Crown inclination lip(cheek)tongue degree: the amount of anterior lingual displacement in the straight arch group was more significant than that in the curve arch group. Crown lingual displacement increased in both groups with increasing force. Under two force values, only the tip-forward group's anterior teeth showed lip inclination displacement. The tip-back group anterior teeth were close to overall movement at 250 g. Under 250 g at the posterior tooth region, only the curve arch group shifted to the inclination of crown tongue, while the remaining three groups showed buccal displacement. Under 300 g, U5 and U6 in the sliding technique group showed crown tongue inclination, and U7 tooth showed crown buccal inclination. All posterior teeth in the double keyhole group showed buccal inclination. (3)Vertical changes: at 250 g, the straight arch group elongated all anterior and posterior teeth except U7. At 300 g, the posterior tooth elongation significantly increased(U6, U7: P<0.05). At 250 g, the curve arch group achieved a certain degree of intrusion in anterior and posterior teeth. At 300 g, anterior teeth showed elongation, and posterior teeth intrusion decreased. The tip-forward group significantly lowered the anterior teeth and slightly elongated the posterior teeth. When the force was increased, the anterior tooth intrusion reduced, while posterior tooth elongation increased significantly(P<0.05). The tip-back group exhibited significant posterior tooth intrusion and minor anterior tooth extrusion. The changes in anterior and posterior teeth were not statistically significant with increasing force(P>0.05). Conclusion (1)The sliding technique group using the rocking chair reduces the degree of anterior tooth tongue inclination, posterior tooth advancement and elongation to some extent. The double keyhole group with a preset backward inclination provides relatively firm posterior tooth anchorage, while the preset forward inclination provides relatively firm anterior tooth anchorage. The double keyhole group effectively controls anterior and posterior teeth independently and prevents anterior crown tongue inclination during adduction due to front and back tilts. (2) Using larger forces does not lead to an increase in anterior tooth retrusion, but it adversely affects posterior tooth anchorage and anterior tooth torque.
    Clinical Medicine
    Effects of high expressions of hypoxia inducible factor-1 and vascular endothelial growth factor induced by Fusobacterium nucleatum on survival and prognosis of patients with esophageal squamous cell carcinoma
    HUA Yuefan, HE Keyao, ZHANG Jiahao, QIAN Mengfan, LIU Yiwen, KONG Jinyu, YANG Haijun, ZHOU Fuyou
    Journal of Shandong University (Health Sciences). 2023, 61(11):  59-67.  doi:10.6040/j.issn.1671-7554.0.2023.0655
    Abstract ( 133 )   PDF (4881KB) ( 127 )   Save
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    Objective To investigate the induction effect of Fusobacterium nucleatum(Fn)on hypoxia inducible factor-1(HIF-1α)and vascular endothelial growth factor(VEGF)in esophageal squamous cell carcinoma(ESCC), and to explore the influence of the above three indexes on the survival and prognosis of ESCC patients. Methods ESCC cells(KYSE30 and KYSE150)were divided into control and Fn infection groups. The expressions of HIF-1α and VEGF, the response efficacy of paclitaxel(PTX)and cisplatin(CDDP), and the in vitro proliferation ability of cells were detected with Western blotting, CCK8 and plate cloning, respectively. The Fn infection and expressions of HIF-1α and VEGF in 309 ESCC tissues were determined with RNA scope and immunohistochemistry. The difference in survival between Fn+HIF-1α+VEGF high-risk and low-risk groups were compared with Kaplan-Meier survival analysis. Results Compared with the control group, the Fn infection group had increased expressions of HIF-1α and VEGF, the 50% inhibitory concentration of PTX and CDDP, and the proliferation capacity(P<0.05). The Fn infection rate, HIF-1α and positive rate of VEGF in ESCC tissues were 43.04%, 65.37% and 60.52%, respectively, with significant consistency(P<0.05). Compared with Fn+HIF-1α+VEGF low-risk group, the high-risk group had significantly shortened 5-year survival(P<0.05). Conclusion Fn infection can induce the high expression of HIF-1α and VEGF, reduce the sensitivity of ESCC cells to chemotherapy drugs, promote their malignant proliferation, and lead to poor prognosis of ESCC patients.
    Risk factors of mortality of maintenance hemodialysis patients with COVID-19 pneumonia
    WANG Yuanyuan, SUN Yun
    Journal of Shandong University (Health Sciences). 2023, 61(11):  68-73.  doi:10.6040/j.issn.1671-7554.0.2023.0386
    Abstract ( 141 )   PDF (979KB) ( 99 )   Save
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    Objective To explore the risk factors of in-hospital mortality of maintenance hemodialysis(MHD)patients with COVID-19 pneumonia. Methods A case-control study was conducted on MHD patients admitted due to COVID-19 pneumonia during Dec. 1, 2022 and Feb. 28, 2023. A total of 54 patients were included in the study. According to whether the patients died during the hospitalization, they were divided into two groups: the death group(n=21)and the survival group(n=33). The patients had a mean age of(66.5±11.4)years, with a male proportion of 74.1%. The clinical and laboratory characteristics of the two groups were compared, and the multivariable Logistic regression models were applied to identify the independent risk factors of in-hospital mortality. Results Mean survival time of patients in the death group was(8.8±6.7)days. The causes of death were severe pneumonia secondary to COVID-19(15 cases, 71.4%), cardiovascular disease(4 cases, 19.0%), and cerebrovascular disease(2 cases, 9.5%). Compared with the survival group, more patients in the death group were ≥75 years of age(P=0.024); had a positive history of diabetes mellitus(P=0.030); had lower albumin(ALB)level in the 6 months before COVID-19 pneumonia(P=0.046); had higher levels of D-dimer, white blood cell(WBC)count, neutrophil(NEUT)count, C-reactive protein(CRP), interleukin-6(IL-6)and procalcitonin(PCT)within 24 hours of admission(all P<0.05); had lower levels of lymphocyte(LYM)count, ALB and prealbumin(PA)(all P<0.05). Multivariable Logistic regression analysis showed that ≥75 years of age and elevated IL-6 level were independent risk factors of in-hospital mortality. Elevated IL-6 level was independent influencing factor of oxygen partial pressure ≤60 mmHg and progression of chest imaging lesions >50% during hospitalization. Conclusion MHD patients with COVID-19 pneumonia have a high mortality during hospitalization, most of whom die of severe pneumonia. Advanced age, history of diabetes mellitus, poor nutritional status, high inflammatory levels and hypercoagulability, especially IL-6 level, are risk factors of mortality in these patients.
    A nomogram analysis of the risk of kinesiophobia in patients with hip fracture after surgery
    ZHANG Minghui, WANG Liyun, WANG Yun, ZHANG Xinyue, SHA Kaihui
    Journal of Shandong University (Health Sciences). 2023, 61(11):  74-81.  doi:10.6040/j.issn.1671-7554.0.2023.0792
    Abstract ( 120 )   PDF (1244KB) ( 135 )   Save
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    Objective To investigate the incidence of kinesiophobia after hip fracture(HF), and explore the risk factors and construct a nomogram prediction model. Methods A total of 328 patients treated during Jan. 2022 and May 2023 who met the inclusion and exclusion criteria were collected with convenience sampling. The general information, kinesiophobia score, psychological resilience and sleep disorder of patients were investigated. The risk factors of kinesiophobia after HF were analyzed with Logistic regression. A nomogram prediction model was established and its prediction effects were verified. Results The probability of kinesiophobia after HF was 39.94%. Logistic regression showed that age, pain and sleep disorder were risk factors, while social support and psychological resilience were protective factors. The internal verification of the nomogram model showed that the C-index was 0.880; the area under the receiver operating characteristic(ROC)curve was 0.880(95%CI: 0.845-0.915). H-L test showed P=0.181, the correction curve was close to the ideal curve, and the net benefit value of decision curve in clinical application was high. Conclusion Age, pain, sleep disorder, social support and psychological resilience are independent influencing factors for kinesiophobia after HF. The nomogram model has good predictive efficiency and certain clinical value.
    SMARCA2-deficient undifferentiated bowel cancer: a report of 4 cases and literature review
    LI Zhe, ZHANG Zhenkun, ZHANG Shukun
    Journal of Shandong University (Health Sciences). 2023, 61(11):  82-88.  doi:10.6040/j.issn.1671-7554.0.2023.0510
    Abstract ( 123 )   PDF (5394KB) ( 143 )   Save
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    Objective To explore the clinicopathological features of SMARCA2-deficient undifferentiated bowel cancer. Methods Clinical data of patients with undifferentiated bowel cancer and negative SMARCA2 expression diagnosed in Weihai Municipal Hospital during Jan. 2016 and Dec. 2020 were collected. The sections of HE staining were re-examined, the histological morphology was re-observed, and the undifferentiated morphology was re-determined by senior pathologists. The representative sections extracted from paraffin-embedded formalin-fixed tissue blocks were stained with automatic immunohistochemical staining machine. Results All four patients died within 1 year. HE staining showed highly malignant morphology. Conclusion SMARCA2 depletion is an indicator of poor prognosis and may be involved in tumor dedifferentiati
    Clinical analysis of 9 cases with group A streptococcus infection in obstetrics
    SONG Min, CAO Luquan, WU Lilong, WU Shuxia, LIU Jing, ZHANG Juan, LIU Cuiying
    Journal of Shandong University (Health Sciences). 2023, 61(11):  89-95.  doi:10.6040/j.issn.1671-7554.0.2023.0823
    Abstract ( 97 )   PDF (969KB) ( 100 )   Save
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    Objective Abstract: Objective To analyze the clinical data of pregnancy-associated group A streptococcus(GAS)infection in pregnant women with high risk of perinatal infection, and to explore the prevention and treatment strategies. Methods General data of pregnant women at high risk of perinatal infection treated in Jinan Maternal and Child Health Hospital during Jan. 2018 and Jun. 2022 were collected. The source of disease, clinical characteristics, treatment process, maternal and infant outcomes and follow-up of 9 patients diagnosed with GAS infection were analyzed and the prevention and treatment strategies were discussed. Results A total of 27,518 bacterial cultures were obtained. Of the 4,289 positive bacterial specimens, 15 were GAS positive(9 cases), accounting for 0.055% of the total number of bacterial cultures, including 9 from vaginal secretions, 1 from throat swab, 1 from urine culture, 2 from blood cultures, 1 from endometrium, and 1 from perineal incision secretion. Two cases of prenatal onset occurred in the third trimester, and both of the mother and fetus died. Six out of seven cases of postpartum onset had good maternal and infant outcomes after active treatment except for one with malformative induction. During the follow-up, except for 1 case who had another positive GAS culture due to poor perineal incision healing 8 days after discharge, the other 6 cases had no recurrent infections. The initial symptom was 39 ℃ fever, and the ratio of neutrophils in blood was over 90%. Conclusion GAS infection is closely related to obstetrics, and pregnant and postpartum women are at high risk. Obstetric infection can be divided into two types: prenatal and postpartum. Prenatal infection is relatively severe, resulting in a higher mortality rate. Perinatal GAS infection is an important cause of severe infection and death in pregnant and postpartum women. Screening high-risk populations and early identification and treatment can help improve the maternal and fetal outcomes.
    Clinical analysis of 9 cases of mycoplasma pneumoniae pneumonia complicated with pulmonary embolism in children and literature review
    SONG Shaoxiu, XU Yongsheng
    Journal of Shandong University (Health Sciences). 2023, 61(11):  96-103.  doi:10.6040/j.issn.1671-7554.0.2023.0377
    Abstract ( 118 )   PDF (4967KB) ( 52 )   Save
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    Objective To analyze the clinical characteristics and treatment of mycoplasma pneumoniae pneumonia(MPP)complicated with pulmonary embolism(PE)in children. Methods The general data, clinical manifestations, laboratory tests, imaging features, treatment and prognosis of 9 cases of children with MPP complicated with PE treated during Jan. 2018 and Dec. 2021 were retrospectively analyzed, and relevant literature was reviewed. Results The median age of patients was 3-8 years, with a median of 7.5 years; the median days from onset to PE was 14 days. All cases were refractory MPP(RMPP). Chest pain occurred in 3 cases, hemoptysis in 1 case, dyspnea in 5 cases, and radiating pain at atypical sites in 6 cases. The C-reactive protein(CRP), D-dimer and fibrinogen(FIB)increased in all cases; the platelet(PLT)count and IL-6 levels increased in 7 cases. Screening of thrombophilia-related indexes showed 5 cases of positive lupus anticoagulant(LA), 5 cases of positive anti-cardiolipin antibody(ACA), 3 cases of positive anti-β2-glycoprotein antibody IgM, 3 cases of reduced protein S activity, 3 cases of elevated coagulation factor VIII, and 6 cases of positive antinuclear antibody. CT pulmonary arteriogram showed filling defects at the embolization site with pleural effusion. All cases were positive for bronchoalveolar lavage fluid resistance mutation site 2063/2064. After treatment with sequential low-molecular heparin anticoagulation plus rivaroxaban, all patients recovered well, and 2 children with cardiac embolism received thrombolysis. During the follow-up of 0.5-9 months, all children had slow absorption of emboli, no recurrence occurred, and the autoantibodies and thrombophilia indexes returned to normal. Conclusion MPP complicated with PE is mostly RMPP cases. The onset of PE does not necessarily coincide with the extreme stage of disease. Most patients will have transient autoantibody positivity, leading to imbalance of coagulation and anticoagulation fibrinolytic system. Timely treatment will result in good prognosis, and rivaroxaban is effective in the treatment of the disease.
    Spatio-temporal distribution and influencing factors of hantavirus hemorrhagic fever with renal syndrome in Shandong Province, 2011—2019
    ZHENG Liang, SUN Minghao, SHI Yuan, YU Shengnan, WANG Zhiqiang, LI Xiujun
    Journal of Shandong University (Health Sciences). 2023, 61(11):  104-110.  doi:10.6040/j.issn.1671-7554.0.2023.0798
    Abstract ( 315 )   PDF (1558KB) ( 76 )   Save
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    Objective To analyze the epidemiological characteristics, spatial-temporal distribution and influencing factors of hemorrhagic fever with renal syndrome(HFRS)in Shandong Province from 2011 to 2019, so as to provide a scientific basis for the prevention and control of this disease. Methods The data of HFRS were collected and the epidemiological characteristics were described. The spatial-temporal distribution characteristics were analyzed with spatial autocorrelation and space-time scanning. Geodetector were used to analyze the influence of environmental factors and the interactions on HFRS. Results A total of 11,310 HFRS cases were reported, with an average annual incidence of 1.24/100,000; 142 deaths were reported, with a fatality rate of 1.26%. The male-to-female ratio was 2.6∶1. The key population was farmers aged 30 to 70 years. The incidence showed seasonal and spatial-temporal clustering, with spring peak(April-June)and autumn-winter peak(October-December). The spatial distribution was higher in the southeast and lower in the northwest. Temperature, precipitation, altitude, and other factors could affect the incidence of HFRS(q=0.349, 0.251, 0.203). The pairwise interactions between factors could enhance the risk of HFRS. The interaction between temperature and slope was the strongest(q=0.627). Conclusion The incidence of HFRS shows spatial-temporal clustering in Shandong Province, which is influenced by various social and natural factors. The interaction between factors can enhance the impact on HFRS. The central mountainous area with high altitude, abundant precipitation and wide vegetation coverage, and the southeast coastal area have higher risk of HFRS and need pay more attention to the prevention and control of this disease.