Objective To analyze the spatial and temporal distribution characteristics of hand-foot-mouth disease (HFMD) in Zibo City, to explore the key incidence areas, and to find a suitable prediction model, so as to provide reference for the prevention and control of HFMD. Methods The spatiotemporal clustering characteristics of HFMD in Zibo City from 2018 to 2023 were analyzed by using SaTScan 10.0.2 software and ArcGIS 10.7 software. A combination model of ARIMA and SVM was established, and the prediction results were verified and compared. Results Spatial clustering analysis showed that there was spatial clustering of the incidence of HFMD in various townships of Zibo City from 2020 to 2022. The high-high clustering areas and Getis-Ord hot spot areas were mainly concentrated in some main urban areas of Zhangdian District, Zichuan District, and Huantai County. A total of 2-5 aggregation areas were detected by spatiotemporal scanning analysis. The first-type aggregation areas were mainly concentrated in the towns of Zhangdian District, Huantai County, Linzi District, Zhoucun District and Gaoxin District. The aggregation months were July, August, September and November. The model prediction results showed that the ARIMA-SVM combined model was more accurate than the traditional ARIMA model. Conclusion There is a spatiotemporal clustering of hand-foot-mouth disease in Zibo City. The ARIMA-SVM combined model can be used to predict the incidence of hand-foot-mouth disease in Zibo City, and to strengthen health education and disease monitoring in high-risk areas and populations during the epidemic months.

Objective:To investigate the distribution rules of artemisia pollen and the clinical sensitization characteristics of allergic rhinitis (AR) induced by artemisia pollen in three urban and rural areas of Inner Mongolia.Methods:From March to October 2019, in 3 central cities (Chifeng, Hohhot, Ordos) and rural areas of Inner Mongolia, an epidemiological investigation method combining multi-stage stratified random sampling and face-to-face questionnaire survey was adopted to screen suspected AR patients, and skin prick test (SPT) was applied for diagnosis. At the same time, pollen monitoring was carried out in 3 areas to analyze the distribution and clinical sensitization characteristics of artemisia pollen.SPSS26.0 statistical software was used to process all the data. Chi-square test was used to compare rates among different age, sex, region and nationality, Spearman test was used to describe correlation analysis, and pairwise comparison of positive rates among multiple samples was used Bonferroni method.Results:Among the 6 393 subjects, 1 093 cases were diagnosed with AR, and the prevalence of AR was 17.10% (1 093/6 393). Among them, pollen-induced allergic rhinitis, the prevalence of PiAR was 10.97% (701/6 393), accounting for 64.14%(701/1 093).The highest incidence was in the youth group (20-39 years old), accounting for 46.94% (329/701).The diagnosed prevalence was higher in females than in males (11.35% vs. 10.64%, χ2 value 12.304, P<0.001).The prevalence rate of ethnic minority was higher than that of Han nationality (13.01% vs. 10.65%, χ2 value 6.296, P=0.008).The prevalence in urban areas was also significantly higher than that in rural areas (18.40% vs. 5.50%, χ2 value 10.497, P<0.001).There was significant difference in prevalence rate among the three regions in Inner Mongolia (6.06% in Chifeng, 13.46% in Hohhot, 16.39% in Ordos, χ2 value 70.054, P<0.001).The main clinical symptoms of artemisia PiAR were sneezing (95.58%), nasal congestion (91.73%) and nasal itching (89.30%).Allergic conjunctivitis accounted for 79.60% (558/701), chronic sinusitis for 55.63% (390/701), asthma for 23.25% (163/701).The pattern of artemisia pollen sensitization was mainly multiple sensitization, and the frequency of clinical symptoms and clinical diseases induced by hypersensitization with other allergens accounted for more than that caused by single artemisia pollen. The spread period of Artemisia pollen in the three regions was from June to October, and the peak state was in August in summer. The peak time of clinical symptoms in artemisia PiAR patients was about 2 weeks earlier than the peak time of pollen concentration, and the two were significantly positively correlated ( R=0.7671, P<0.001). Conclusion:Artemisia pollens are the dominant pollens in late summer and early autumn in Inner Mongolia, and the prevalence of artemisia PiAR is high. Controlling the spread of Artemisia pollens is of great significance for the prevention and treatment of AR.

Objective:To investigate the distribution rules of artemisia pollen and the clinical sensitization characteristics of allergic rhinitis (AR) induced by artemisia pollen in three urban and rural areas of Inner Mongolia.Methods:From March to October 2019, in 3 central cities (Chifeng, Hohhot, Ordos) and rural areas of Inner Mongolia, an epidemiological investigation method combining multi-stage stratified random sampling and face-to-face questionnaire survey was adopted to screen suspected AR patients, and skin prick test (SPT) was applied for diagnosis. At the same time, pollen monitoring was carried out in 3 areas to analyze the distribution and clinical sensitization characteristics of artemisia pollen.SPSS26.0 statistical software was used to process all the data. Chi-square test was used to compare rates among different age, sex, region and nationality, Spearman test was used to describe correlation analysis, and pairwise comparison of positive rates among multiple samples was used Bonferroni method.Results:Among the 6 393 subjects, 1 093 cases were diagnosed with AR, and the prevalence of AR was 17.10% (1 093/6 393). Among them, pollen-induced allergic rhinitis, the prevalence of PiAR was 10.97% (701/6 393), accounting for 64.14%(701/1 093).The highest incidence was in the youth group (20-39 years old), accounting for 46.94% (329/701).The diagnosed prevalence was higher in females than in males (11.35% vs. 10.64%, χ2 value 12.304, P<0.001).The prevalence rate of ethnic minority was higher than that of Han nationality (13.01% vs. 10.65%, χ2 value 6.296, P=0.008).The prevalence in urban areas was also significantly higher than that in rural areas (18.40% vs. 5.50%, χ2 value 10.497, P<0.001).There was significant difference in prevalence rate among the three regions in Inner Mongolia (6.06% in Chifeng, 13.46% in Hohhot, 16.39% in Ordos, χ2 value 70.054, P<0.001).The main clinical symptoms of artemisia PiAR were sneezing (95.58%), nasal congestion (91.73%) and nasal itching (89.30%).Allergic conjunctivitis accounted for 79.60% (558/701), chronic sinusitis for 55.63% (390/701), asthma for 23.25% (163/701).The pattern of artemisia pollen sensitization was mainly multiple sensitization, and the frequency of clinical symptoms and clinical diseases induced by hypersensitization with other allergens accounted for more than that caused by single artemisia pollen. The spread period of Artemisia pollen in the three regions was from June to October, and the peak state was in August in summer. The peak time of clinical symptoms in artemisia PiAR patients was about 2 weeks earlier than the peak time of pollen concentration, and the two were significantly positively correlated ( R=0.7671, P<0.001). Conclusion:Artemisia pollens are the dominant pollens in late summer and early autumn in Inner Mongolia, and the prevalence of artemisia PiAR is high. Controlling the spread of Artemisia pollens is of great significance for the prevention and treatment of AR.

Objective:To investigate the clinical features, diagnostic methods and treatments of left ventricular apical fibroma.Methods:The clinical manifestations, ECG, imaging features and treatment plans of 2 patients with giant fibroma of left ventricular apex diagnosed in September 2020 and May 2022 were analyzed retrospectively, and the related literature was reviewed.Results:Both patients had slight chest distress and discomfort after activities. The ECG showed T-wave inversion of different degrees, which were misdiagnosed as “myocarditis” and “coronary heart disease” respectively. The cardiac magnetic resonance imaging and echocardiography showed left ventricular apical mass. Coronary artery stenosis was not found in coronary angiography. One patient required conservative treatment, and there was no significant change in clinical symptoms and tumor size in the follow-up for half a year; Another patient underwent cardiac mass removal, and the pathological examination after operation confirmed that it was cardiac fibroma, and there was no recurrence in the follow-up 2 years.Conclusion:Fibroma of left ventricular apex is a rare cardiac tumor, which is easy to be missed and misdiagnosed, and is one of the rare causes of T-wave inversion. Cardiac magnetic resonance imaging, CT and echocardiography are commonly used imaging methods to diagnose cardiac fibroma, and surgical resection is an effective treatment.

Objective To investigate the effect of SMAD family member 3(SMAD3) silenced by small interfering RNA (siRNA) on macrophage polarization and transforming growth factor β1 (TGF-β1)/ SMAD family signaling pathway in rheumatoid arthritis (RA). Methods RA macrophages co-cultured with rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) were used as a cell model. TGF-β1 was used to stimulate macrophages, and SMAD3-specific siRNA (si-SMAD3) and negative control siRNA (si-NC) were transfected into human RA macrophages co-cultured in Transwell^TM chamber. The expression of SMAD3 mRNA was detected by real-time fluorescence quantitative PCR, and the expression of TGF-β1, SMAD3 and SMAD7 protein was detected by Western blot analysis. The contents of TGF-β1 and IL-23 in cell culture supernatant were determined by ELISA. Cell proliferation was detected by CCK-8 assay. Transwell^TM chamber was used to measure cell migration. Results Compared with the model group and the si-NC group, the expression of TGF-β1, SMAD3 mRNA and protein in RA macrophages decreased significantly after silencing SMAD3. In addition, the secretion of IL-23 decreased significantly, and the cell proliferation activity and cell migration were inhibited, with high expression of SMAD7. Conclusion Knockdown of SMAD3 can promote M2 polarization and SMAD7 expression in RA macrophages.
Humans ; Arthritis, Rheumatoid/genetics* ; Interleukin-23 ; Macrophages ; RNA, Messenger ; RNA, Small Interfering/genetics* ; Smad7 Protein/genetics* ; Transforming Growth Factor beta1/genetics* ; Smad3 Protein/genetics* ; Gene Silencing

Objective This study aimed to establish a pre-metastatic niche mouse model utilizing luciferase-labeled Lewis (Luc-Lewis) lung cancer cells and to assess the efficacy of this model employing both qualitative and quantitative methods. Methods C57BL/6 mice were categorized into two groups: a normal control group and a model group, each containing 15 individual mice. The pre-metastatic niche model was established via tail vein injection of Luc-Lewis lung cancer cells. Body mass were measured daily for all groups. Tumor fluorescence signals within the mice were detected using a high-throughput enzyme marker instrument. Lung tissue specimens were harvested to evaluate metastatic progression. HE staining was used to assess histopathological changes. Real-time quantitative PCR and Western blot analysis were used to detect the mRNA and protein expression of lysyl oxidase (LOX), matrix metalloproteinase 9 (MMP9), versican (VCAN), and fibronectin (FN), which are the specific markers for the formation of the microenvironment of lung tissues before metastasis. Results Significant declines in body mass and observable lethargy were noted in the model group when compared to the control group. Distinct fluorescence signals were observed in the lung tissue of the model group, demonstrating a positive correlation with the duration of model establishment. By day 14, elevated mRNA and protein expression levels of LOX, MMP9, VCAN, and FN were significantly evident. In addition, histopathological evaluations revealed augmented interstitial thickness, alveolar atrophy and significant inflammatory cell infiltration within the lung tissues of the model group. By the 21st day, metastatic lesions manifested in the lung tissues of the model group, suggesting an approximate pre-metastatic niche maturation timeline of 14 days. Conclusion A pre-metastatic niche mouse model for Lewis lung cancer is successfully established.
Mice ; Animals ; Lung Neoplasms/pathology* ; Matrix Metalloproteinase 9 ; Mice, Inbred C57BL ; Carcinoma, Lewis Lung ; Disease Models, Animal ; RNA, Messenger ; Tumor Microenvironment

Objective: To observe the pathological changes of brain tissue in neonatal rats after hypoxic-ischemic brain damage(HIBD), the distribution and expression changes of endoplasmic reticulum stress(ERS) related factors includingactivated transcription factor 6(ATF6), inositol demand factor 1(IRE1) and double-stranded RNA-activated protein kinase-likeendoplasmic reticulum kinase(PERK) in brain tissue. Methods : Seven-day-old newborn rats were divided into sham operation group(Sham group) and hypoxic-ischemic brain damage group(HIBD group). The modified rice method was used to establish the HIBD model. Hematoxylin-eosin(HE) staining was performed on the brain tissue at the 72 h point of modeling to observe the pathological changes of the brain, Nissl staining was used to observe the neuron damage in the cortex and hippocampus, and immunohistochemistry was used to detect the expression of ATF6, IRE1 and PERK in the cerebral cortex and hippocampus of rats in each group. The models were sacrificed at 6 h, 24 h, and 72 h respectively, Western blot was used to detect the protein expression of ATF6, IRE1, and PERK at each time point at 6 h, 24 h, and 72 h. Results: 72 hours after HIBD, HE staining showed that no nerve cell injury was observed in the Sham group, while nerve cell injury was observed in the brain tissue of the HIBD group, and the main injury sites were the cerebral cortex and hippocampus. Nissl staining showed that the proportion of damaged neurons in the cortex and hippocampus of the HIBD group was higher than that in the Sham group, and the difference was statistically significant(P<0.001). Immunohistochemical staining showed that compared with the Sham group, the number of ATF6, IRE1, and PERK positive cells(brown-yellow) in the cerebral cortex and hippocampus of the HIBD group increased(P<0.001). In the HIBD group, the expression of ATF6 in the cytoplasm and nucleus of nerve cells increased, and the expression of IRE1 in the nucleus and PERK in the cytoplasm increased. The relative protein expression levels of ATF6, IRE1, and PERK at each time point in the HIBD group were higher than those in the Sham group, and the differences were statistically significant(allP<0.05). Conclusion The brain damage of neonatal rats after hypoxic-ischemic brain injury is mainly in the cerebral cortex and hippocampus, and the expression of ER stress factors in cerebral cortex and hippocampus is increased, suggesting that ER stress related factors are involved in its pathological injury.

Objectives:To summarize the clinical and genetic characteristics of the patients with isolated methylmalonic acidemia and investigate the strategies for the diagnosis, treatment and prevention.Methods:Three hundred and fourteen patients (180 males, 134 females) with isolated methylmalonic acidemia were ascertained from 26 provinces or cities across the mainland of China during January 1998 to March 2020. Genetic analysis was performed by Sanger sequencing, gene panel sequencing, whole exome sequencing, multiplex ligation-dependent probe amplification or quantitative PCR. According to the age of onset, the patients were divided to early-onset group (≤12 months of age) and the late-onset group (>12 months of age). They were treated by cobalamin, L-carnitine and (or) special diet and symptomatic treatment. Statistical analysis was done using Chi-square test.Results:Fifty-eight of 314 (18.5%) patients were detected by Newborn screening using liquid chromatography tandem mass spectrometry. Five cases (1.6%) had a postmortem diagnosis. Two hundred and fifty-one patients (79.9%) were clinically diagnosed with an age of onset ranged from 3 hours after birth to 18 years. One hundred and fifty-nine patients (71.0%) belonged to early-onset groups, 65 patients (29.0%) belonged to the late-onset group. The most common symptoms were metabolic crises, psychomotor retardation, epilepsy, anemia and multiple organ damage. Metabolic acidosis and anemia were more common in early-onset patients than that in late-onset patients (20.8%(33/159) vs. 9.2% (6/65), 34.6% (55/159) vs. 16.9% (11/165), χ 2=4.261, 6.930, P=0.039, 0.008). Genetic tests were performed for 236 patients (75.2%), 96.2%(227/236) had molecular confirmation. One hundred and twenty-seven variants were identified in seven genes (MMUT, MMAA, MMAB, MMADHC, SUCLG1, SUCLA2, and MCEE), of which 49 were novel. The mut type, caused by the deficiency of methylmalonyl-CoA mutase, was the most common ( n=211, 93%) cause of this condition. c.729_730insTT, c.1106G>A and c.914T>C were the three most frequent mutations in MMUT gene. The frequency of c.914T>C in early-onset patients was significantly higher than that in late-onset patients (8.3% (18/216) vs. 1.6% (1/64), χ 2=3.859, P=0.037). Metabolic crisis was more frequent in mut type than the other types (72.6% (114/157) vs. 3/13, χ 2=13.729, P=0.001),developmental delay and hypotonia were less frequent in mut type (38.2% (60/157) vs. 9/13, 25.5% (40/157) vs. 8/13, χ 2=4.789, 7.705, P=0.030, 0.006). Of the 58 patients identified by newborn screening, 44 patients (75.9%) who were treated from asymptomatic phase developed normally whereas 14 patients (24.1%) who received treatment after developing symptoms exhibited varying degrees of psychomotor retardation. Conclusions:The characteristics of phenotypes and genotypes among Chinese patients with isolated methylmalonic acidemia were analyzed. Expanded the mutation spectrum of the associated genes. Because of the complex clinical manifestations and severe early onset of isolated methylmalonic acidemia, Newborn screening is crucial for early diagnosis and improvement of prognosis. MMUT gene is recommended for carrier screening as an effort to move the test earlier as a part of the primary prevention of birth defects.

Objective To observe the clinical features of retinal arterial occlusion (RAO) in youth.Methods This is a retrospective case review.Nine patients (9 eyes) with RAO were enrolled in this study.There were 6 males (6 eyes) and 3 females (3 eyes).The average age was (14.22± 3.93) years.The best-corrected visual acuity (BCVA),indirect ophthalmoscopy,fundus color photography and fundus fluorescein angiography were performed.All patients underwent systemic evaluation including blood routine,erythrocyte sedimentation rate,blood lipids,vasculitis screening,homocysteine level,antiphospholipid antibody,blood coagulation,neck vascular ultrasound,and cardiac color ultrasound and electrocardiogram examination.All patients received oxygen therapy,blood medications and symptomatic treatment.Meanwhile,the patients with autoimmune diseases were received systemic glucocorticoid therapy.The follow-up was ranged from 6 to 12 months.The visual acuity and fundus change before and after treatment were compared.Results among 9 patients,one patient had systemic lupus erythematosus,one patient had congenital heart disease,one patient had hypergammaglobulinemia,and carotid artery color ultrasonography showed that the internal carotid artery vessels faltered in 2 cases.The BCVA was 0.01-0.12.Among 9 eyes,there were 5 eyes (55.6％) with retinal branch artery occlusion (BRAO),2 eyes (22.2％) with central retinal artery occlusion (CRAO),2 eyes (22.2％) with ciliary retinal artery occlusion (CLAO).CRAO eyes showed positive RAPD (relative afferent pupillary defect),fine retinal artery and the corresponding vein,pale white retinal edema in posterior area and macular cherry-red spot.BRAO eyes manifested as inferior temporal artery occlusion and pale white retinal edema around them.CLAO eyes showed temporal ligulate grey-white retinal edema.At the last follow-up,BCVA improved and retinal vessels returned to normal in 7 eyes (77.8％);BCVA unchanged and no improvement in fundus in 2 eyes (22.2％).Conclusion Adolescent RAO is mostly partial occlusion,the prognosis is generally good after early active treatment.

Objective To investigate the application value of lung ultrasonic on severe high altitude pulmonary edema.Methods A prospective, single-blind, case-control study was conducted. Sixty patients with severe high altitude pulmonary edema admitted to Qinghai University Affiliated Hospital from February 2015 to May 2017 were enrolled. The patients were divided into 2500-3000 m group, 3000-3500 m group and 3500-4200 m group according to different altitudes,with 20 patients in each group. The acute physiology and chronic health evaluationⅡ(APACHEⅡ) score was recorded before and 12 hours and 24 hours after treatment. The arterial partial pressure of oxygen (PaO2) was determined by blood gas analysis, and the oxygenation index (PaO2/FiO2) was calculated. Bedside ultrasound scanning was used to determine B line number and pulmonary artery pressure (PAP), and B line score was calculated to reflect lung water content. The correlation between B line score and PaO2/FiO2, PAP and APACHEⅡ scores at each time point was analyzed by Pearson correlation analysis.Results None of 60 patients died or exited, all of them were enrolled in the final analysis. There was no significant difference in PaO2/FiO2, PAP, APACHEⅡ score or B line score among different altitudes groups (allP > 0.05). Repeated measurement variance analysis showed that the effects of different altitudes on PaO2/FiO2, PAP, APACHEⅡ score and B line score were not statistically significant (F value was 0.312, 0.014, 1.098, 0.236, andP value was 0.340, 0.791, 0.733, and 0.986, respectively). The PaO2/FiO2, PAP, APACHEⅡ score and B line score in all groups were improved obviously from 12 hours after treatment, and the improvements at 24 hours were more than those at 12 hours (allP < 0.05). Repeated measurement variance analysis showed that the effect at different time points on PaO2/FiO2, PAP, APACHEⅡ score and B line score was statistically significant (F value was 1844.270, 121.690, 1173.175, 19426.968, allP < 0.001). The interaction effects of different altitudes and different time points on PaO2/FiO2, PAP, APACHEⅡ score and B line score were not statistically significant (F value was 0.304, 0.404, 1.172, 1.403, andP value was 0.875, 0.805, 0.327, and 0.591, respectively). Pearson correlation analysis showed that there was a significant negative correlation between B line score and PaO2/FiO2 before and after treatment (r value was -0.579, -0.522, and -0.386, allP < 0.01), indicating that the more the B line, the more severe the pulmonary edema, and the worse the oxygenation; with the decrease in B line after treatment, the pulmonary edema was gradually alleviated, and oxygenation was gradually improved. There was a significant positive correlation between B line score and APACHEⅡ score before and 24 hours after treatment (r value was 0.484 and 0.536, bothP < 0.01), indicating that the more the B line, the more severe the patient; with the decrease in B line after treatment, the patient's condition improved after treatment. There was only a weak correlation between B line score and PAP at 24 hours after treatment (r = 0.317,P = 0.014), indicating that PAP was not a sensitive indicator in the degree of pulmonary edema in patients.Conclusions The more the B line in patients with severe high altitude pulmonary edema,the more severe of the pulmonary edema, and the more severe of the patient. There was no significant correlation between the B line score and PAP. Pulmonary ultrasonography can still be used not only in the plain and low elevation areas, but in the high altitude areas, as a reliable method to evaluate the severity of pulmonary edema.