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Objective The long-term epidemiological and etiological characteristics of hand, foot and mouth disease (HFMD) in Huai’an, Jiangsu were analyzed to provide scientific evidence for the prevention of HFMD. Methods The data of HFMD reports, etiological diagnosis and in Huai’an from 2009 to 2022 were described and analyzed. Results A total of 78 535 cases were reported from 2009 to 2022 , with 14-year average annual incidence rate of 114.71/100 000. Before 2020, the incidence rate of HFMD in Huai’an showed the epidemic intensity increased every other year on the whole, and the average annual incidence rate during the COVID-19 pandemic (2020-2022) (55.69/100 000) was significantly lower than that in previous years (2009-2019) (129.95/100 000). The joinpoint regression analysis showed that the best fitting model from 2009 to 2022 had no joinpoints, APC=AAPC=-1.24%. The overall trend showed a monotonously decreasing trend, but the trend was not statistically significant. The male-to-female distribution ratio was 1.53:1, and the age distribution was mainly under 5 years old, especially in scattered children. The epidemic season was from April to July. The results of etiological surveillance showed that the co-epidemic of Coxsackievirus A16 (CV-A16) and Enterovirus A71 (EV-A71) during the early stages had changed to the co-epidemic of CV-A16 and CV-A6 in the current period. Conclusion The burden of HFMD in Huai’an was large, and the epidemic intensity increased every other year was affected by the COVID-19 pandemic. The epidemiological features after the COVID-19 pandemic should be further monitored.
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Objective To understand the epidemiological characteristics of scrub typhus disease and to provide a scientific basis for the prevention and control of scrub typhus disease. Methods Descriptive epidemiological methods were used to analyze the population and regional distribution of scrub typhus. Seasonal characteristics were analyzed using concentration method and circular distribution method, and incidence trend was analyzed using joinpoint regression model. Results The annual incidence rate of scrub typhus was 0.95/100 000 from 2010 to 2022. The incidence rate of male was 0.77/100 000, lower than that of female 1.12/100 000 (χ2=18.89, P-=-62.3728, S=20.8960. The circular distribution results indicated that the peak day was October 19th, and the peak period was between October 7 to December 19. The average annual percentage change (AAPC) of the incidence rate from 2010 to 2022 was 13.70%, 95% CI (-8.62%~41.48%), and the incidence rate showed an upward trend (t=1.15, P=0.249). Conclusion The incidence of scrub typhus disease is strictly seasonal, and the incidence rate over the years shows an upward trend. It is necessary to strengthen monitoring and take various intervention measures to reduce the risk of scrub typhus disease.
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Purpose To investigate the effect of autophagy intervention on ferroptosis and drug resistance of colorectal canc-er cells and its molecular mechanism.Methods The human colorectal cancer cell lines HCT-8,COLO205,HCT-116,SW620,and SW480 were cultured.HCT-116 cells with moder-ate expression of LC3 were screened,and the expression differ-ences of LC3,p62,Keap1,Nrf2,GPX4 proteins,Fe2+,GSH,and MDA between them and OXA-resistant HCT-116/OXA cell lines were detected.The expression levels of LC3,p62,Keap1,Nrf2,GPX4,Fe2+,GSH and MDA were assessed in HCT-116/OXA cells through the intervention of autophagy and ferroptosis intervention agent combined with oxaliplatin.The proliferative activity and sensitivity to oxaliplatin in each group were detected by CCK-8 assay.Cell growth and invasion ability of each group were detected by plate cloning and Trans well assay.Results LC3,p62 and GPX4 expression levels of HCT-116 cells in the 5 groups were moderate.Compared with HCT-116 cells,HCT-116/OXA was less sensitive to oxaliplatin,and the proteins of p62,Nrf2 and GPX4 were highly expressed,LC3 and Keap1 were lowly expressed,and the expression of Fe2+,GSH and MDA were increased(P＜0.05).The levels of LC3,Keap1 protein,Fe2+and MDA in Rapa and Rapa+Fer-1 groups were higher than those in Fer-1 and control groups,while p62,Nrf2,GPX4 and GSH levels were lower.The expressions of GPX4 pro-tein and GSH in Rapa+Fer-1 group were lower than those in Rapa group(P＜0.05).In the autophagy inhibitor group,LC3,p62,Nrf2,GPX4 and GSH were highly expressed in the CQ and CQ+Erastin groups compared with the control and Eras-tin groups,while Keap1 protein,Fe2+and MDA were low.The levels of GPX4 protein and GSH in Erastin group were lower than those in the other three groups,and the levels of Fe2+and MDA were higher than those in the other three groups(P＜0.05).The combination of autophagy activator OXA showed that Rapa intervention group had higher chemical sensitivity to OXA,less number of migrating cells and lower cell proliferation activity than the other three groups.The sensitivity of Rapa+Fer-1 group to oxaliplatin was lower than that of Rapa group,but higher than that of Fer-1 group and control group(P＜0.05).There was no significant difference between Fer-1 group and con-trol group(P＜0.05).Compared with the control group,the cell activity,migration capacity and clonogenesis capacity of Erastin,CQ+Erastin and CQ groups were decreased when auto-phagy inhibitor was combined with OXA,and the Erastin group was the lowest,while the CQ+Erastin group was higher than the Erastin group,and lower than the CQ group(P＜0.05).Con-clusion In colorectal cancer,autophagy is involved in the regu-lation of ferroptosis,and intervention in autophagy can regulate ferroptosis in colorectal cancer cells through the p62-Keap1/Nrf2-GPX4 pathway,thereby reversing oxaliplatin resistance.
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Objective To investigate the value of qualitative and quantitative characteristics of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI in preoperative prediction of vessels encapsulating tumor clusters(VETC)pattern in hepatocellular carcinoma(HCC).Methods A total of 234 patients diagnosed with HCC by pathology were analyzed retrospectively.A total of 101 VETC-positive HCC patients and 133 VETC-negative HCC patients were included.All patients were divided into training group and validation group according to 7︰3.The training group data were used to construct a prediction model for VETC-positive HCC.Receiver operating characteristic(ROC)curve was drawn and the area under the curve(AUC)was calculated to verify the diagnostic efficiency of the model.Calibration curve was drawn to verify the calibration of the model.Results Multivariate logistic regression analysis predicted the independent risk factors for VETC-positive HCC:portal phase peripheral washout[odds ratio(OR)6.493],necrosis or severe ischemia(OR 4.756),targetoid transitional phase or hepatobiliary phase(OR 0.307),and lesion to liver signal intensity ratio(LLR)on arterial phase(OR 0.074).The AUC of the training group in predicting VETC-positive HCC was 0.790[95%confidence interval(CI)0.720-0.859].The AUC of the validation group in predicting VETC-positive HCC was 0.779(95%CI 0.668-0.889).The calibration curve diagram showed that the calibration curve(the slope was 0.91)almost coincides with the ideal curve,indicating that the prediction model had better calibration.Conclusion The qualitative and quantitative characteristics of Gd-EOB-DTPA enhanced MRI can be used to predict VETC-positive HCC preoperatively,the independent risk factors of VETC include portal phase peripheral washout,necrosis or severe ischemia,targetoid transitional phase or hepatobiliary phase,and LLR on arterial phase.
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OBJECTIVE To prepare and characterize curcumin nanomicelles （hereinafter referred to as Cur/mPEG-PBLA micelles）， and to evaluate the in vitro hepatoprotective activity against alcohol liver disease （ALD）. METHODS Cur/mPEG-PBLA micelles were prepared with the dialysis method using methoxy-poly（ethylene glycol）-poly（β-benzyl-L-aspartate） （mPEG-PLGA） as the carrier. The appearance and microscopic morphology of Cur/mPEG-PBLA micelles were observed， and particle size， polydispersity index， Zeta potential， encapsulation efficiency and drug loading content were all detected. The in vitro release， pH stability， thermal stability， dilution stability， storage stability， plasma stability tests， and hemolysis experiments were all performed. The cell model of ALD was established with anhydrous ethanol intervention using human liver cancer cells and normal liver cells as objects， Cur reference solution as reference， to evaluate in vitro preventive and ameliorative effects of Cur/mPEG- PBLA micelles on ALD. RESULTS The prepared Cur/mPEG-PBLA micelles exhibited a pale-yellow milky light， with a spherical shape and uniform distribution. The average particle size was about 140 nm， and the polydispersity index was less than 0.3. Zeta potential was （－8.15±0.05） mV； the encapsulation efficiency was （73.26±3.16）%， and the drug loading content was （4.87± 0.42）%. The cumulative release of Cur reference substance was close to 80% at 10 h； the cumulative release of Cur/mPEG-PBLA micelles at 8 h was 28.94% and only 48.25% at 48 h. pH stability and thermal stability of Cur/mPEG-PBLA micelles were better than those of Cur reference solution； Cur/mPEG-PBLA micelles showed good dilution stability， storage stability and plasma stability， and would not cause hemolysis. Cur reference solution and Cur/mPEG-PBLA micelles had varying degrees of in vitro preventive and ameliorative effects on ALD in two types of cells； after 48 h of application， the above effects of Cur/mPEG-PBLA micelles were significantly better than those of Cur reference solution at the same mass concentration （P＜0.05）. CONCLUSIONS Cur/mPEG-PBLA micelles can improve pH stability and thermal stability of Cur， delayits degradation rate， and have better in vitro hepatoprotective activity against ALD.
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OBJECTIVE To prepare venlafaxine hydrochloride and fluoxetine hydrochloride multiplayer tablets by stereolithography （SLA） 3D printing technology， and to conduct its quality evaluation and in vitro release investigation. METHODS Using venlafaxine hydrochloride/fluoxetine hydrochloride， photopolymerization monomer PEGDA 400， porogen PEG 300， photoinitiator TPO and light absorber citrine as formulation， SLA 3D printer technology was employed to prepare venlafaxine hydrochloride and fluoxetine hydrochloride multiplayer tablets， with outer diameter of 10 mm， inner diameter of 5 mm， and thickness of 6 mm. Moreover， the tablets’ appearance， three-dimensional dimensions， weight uniformity， drug content， internal structural characteristics and in vitro release characteristics were all investigated. RESULTS The multilayer tablets had good printing formability， smooth and round edges， and uniform size and thickness； the outer diameter， inner diameter and thickness were （10.06±0.26）， （4.94±0.06）， （5.80±0.12） mm （RSD＝2.58%， 1.21%， 2.07%，n＝20）， and the weight difference all met the requirements. The contents of venlafaxine hydrochloride and fluoxetine hydrochloride were （7.96±0.09） and （11.26±0.46） mg/tablet， respectively. The results of X-ray diffraction and scanning electron microscopy characterization showed that the two drug molecules in the multilayer film existed in an amorphous structure； after the dissolution of the venlafaxine hydrochloride layer， a clear pore structure was formed， while the fluoxetine hydrochloride layer did not show any pore structure. According to the release curve， 24 h accumulative release rates of venlafaxine hydrochloride layer and fluoxetine hydrochloride layer were（91.88±0.94）% and （106.25±1.28）%， which were in line with Rigter-Peppas release model. CONCLUSIONS This study successfully prepared venlafaxine hydrochloride and fluoxetine hydrochloride multilayer tablets using SLA 3D printing technology； the multilayer tablets have the advantages of excellent printing formability， which are in line with Rigter-Peppas release model.
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ObjectiveTo explore the clinical efficacy of Gandou decoction in treating Wilson's disease （WD） with dampness heat accumulation accompanied by rapid eye movement （REM） sleep behavior disorder （RBD）. MethodFrom April 2019 to August 2023，62 patients with dampness heat accumulation type WD accompanied by RBD who met the inclusion criteria were selected from the Department of Encephalopathy at the First Affiliated Hospital of Anhui University of Chinese Medicine. They were randomly divided into a control group and an observation group with 31 cases each using a computer distributor. The control group received routine copper removal treatment，while the observation group received additional treatment with Gandou decoction on the basis of the control group. Eight days was one course of treatment，totaling three courses. The scores of traditional Chinese medicine syndromes，RBD screening questionnaire （RBDSQ） scores，RBD questionnaire-Hong Kong （RBDQ-HK） scores，polysomnography （PSG） parameters，24-hour urine copper （24 h U-Cu） levels，and non-ceruloplasmin-bound copper （NCC） levels between the two groups before and after treatment were compared，and adverse reactions were observed. ResultSixty trial cases were ultimately completed，with 30 cases in each group. Before treatment，there was no statistically significant difference in various indicators between the two groups， and thus they were comparable. Compared with those before treatment，the traditional Chinese medicine syndrome scores，RBDSQ scores and RBDQ-HK scores of the two groups were significantly reduced，the 24 h U-Cu levels were significantly increased，and the NCC levels were significantly reduced （P<0.05，P<0.01）. Compared with the control group， the observation group showed better improvement in traditional Chinese medicine syndrome scores， RBDSQ scores， RBDQ-HK scores， and NCC levels （P<0.05，P<0.01）. Compared with those before treatment，the total sleep time （TST），sleep efficiency （SE），sleep/REM latency，the proportion of N1/N2/REM stages，arousal index （ARI），and proportion of phasic electromyographic activity （P-EMG-A） were significantly improved in both groups （P<0.05）. Compared with the control group after treatment，the observation group showed more significant improvements in the proportion of TST，SE，REM stages，ARI，and P-EMG-A proportion （P<0.05）. ConclusionGandou decoction can not only improve the traditional Chinese medicine syndrome of WD patients with dampness heat accumulation accompanied by RBD but also alleviate their RBD symptoms.
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ObjectiveDepression is a common mental illness with a profound impact on physical health. Depression has been associated with a higher risk of bacterial infection； however， whether this relationship is causal and how depression affects infection remains unclear. Therefore， we aimed to investigate the effects of depressive phenotype in infected mice by constructing a chronic unpredictable mild stress （CUMS） model. MethodsMice were induced with CUMS for 4 weeks. The depressive phenotype was evaluated using behavioral tests. Subsequently， the mice were intraperitoneally injected with Klebsiella pneumoniae to establish bacterial infection. Serum and abdominal tissues were collected 48 h after infection. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the tissues， and enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of inflammatory factors. In addition， the fecal samples collected before infection were analyzed for 16S rDNA gene of gut microbiota， and the expression levels of NF-κB/NLRP3 signaling pathway in colon tissues of uninfected mice were detected. ResultsBehavioral tests showed that compared with the control mice， CUMS mice had significantly lower body weight （P<0.000 1， t=5.426）， lower sucrose preference rate （P<0.001， t=4.937）， increased swimming stationary time （P<0.001， t=16.37）， and decreased time spent in the central area of the open field （P<0.01， t=3.575）. Survival analysis showed that compared with the control mice， the survival rate of CUMS mice significantly decreased after infection （P<0.05）. Additionally， histochemical staining showed that tissue damage in the liver （P<0.05， t=4.025）， kidney （P<0.05， t=2.828）， and mesentery （P<0.01， t=5.367） significantly increased. Furthermore， ELISA results showed that the levels of the inflammatory cytokines IL-6 （P<0.01， t=3.365）， IL-1β （P<0.01， t=4.061）， TNF-α （P<0.01， t=4.460） and LPS （P<0.000 1， t=27.24） were elevated. The difference was statistically significant. According to 16S rDNA sequencing， CUMS-induced changes in the intestinal bacterial community structure of mice， making them significantly different from the control mice. Compared with the control mice， the expression levels of NF-κB （P<0.01， t=6.825） and NLRP3 （P<0.001， t=9.561） were upregulated in CUMS mice. ConclusionThe CUMS model was successfully constructed and CUMS mice developed more severe bacterial infection. Gut microbiota was dysregulated and the expression of NF-κB/NLRP3 signaling pathway was up-regulated in CUMS mice， which was related to the susceptibility to bacterial infection.
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BACKGROUND@#Hepatic fibrosis (HF) is a common pathological feature of chronic hepatic diseases. We aimed to illuminate the significance of amniotic mesenchymal stem cells (AMSCs)-derived extracellular vesicles (AMSCs-EVs) in HF. @*METHODS@#Human AMSCs-EVs were isolated and identified. HF mice were constructed and treated with EVs. The fibrosis was observed by staining experiments and Western blot (WB) assay. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and hepatic hydroxyproline (Hyp) were detected to confirm liver function.For the in vitro experiments, human hepatic stellate cells were induced with transforming growth factor-b and treated with EVs. To measure the degree of HF, the expression of alpha-smooth muscle actin (a-SMA) and Collagen I was detected by WB assay, and cell proliferation was detected by cell counting kit 8 assay. The levels of miR-200a, Zinc finger E-box binding homeobox 1 (ZEB1), and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) were detected by WB and realtime quantitative polymerase chain reaction. The binding of ZEB1 to PIK3R3 and miR-200a to ZEB1 was analyzed by chromatin immunoprecipitation and dual luciferase assays to validate their relationships. @*RESULTS@#Human AMSCs and AMSCs-EVs were obtained. Serum ALT, AST, TBIL, and hepatic Hyp were increased, implying the fibrosis degree was aggravated in HF mice, which was decreased again after EV treatment. EVs inhibited HF degree by reducing a-SMA and Collagen I and promoting cell proliferation. AMSCs-EVs delivered miR-200a into hepatocytes, which up-regulated miR-200a expression, inhibited ZEB1 expression, and reduced its enrichment on the PIK3R3 promoter, therefore inhibiting PIK3R3 expression and alleviating HF. Overexpression of ZEB1 or PIK3R3 attenuated the anti-fibrotic effect of AMSCs-EVs. @*CONCLUSION@#Human AMSCs-derived EVs mediated miR-200a delivery and inhibition of intracellular ZEB1/PIK3R3 axis to exert anti-fibrosis effects.
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Objective To explore the effect of robotic training under position limitation on upper limb of patients with shoulder sub-luxation after stroke. Methods From March to December,2023,sixty patients with shoulder subluxation after stroke in the First Affiliated Hospital of Bengbu Medical University were randomized into conventional group(n = 20),robot group(n = 20)and position-limited group(n = 20).All the groups accepted conventional rehabilitation,while the robot group underwent robot training and the position-limited group underwent robot training under position limitation,for four weeks.Before and after treatment,Fugl-Meyer Assessment-Upper Extremities(FMA-UE)and modified Bar-thel Index(MBI)were used for evaluation,surface electromyography(sEMG)was used to measure the average electromyography(AEMG)and root mean square(RMS)of posterior deltoid fasciculus and supraspinatus during contraction,and musculoskeletal ultrasonography was used to determine the distance of acromion-greater tuber-osity(AGT)of the affected side. Results After treatment,FMA-UE score,MBI score,AEMG,RMS and the distance of AGT improved in all the groups(|t|>10.850,P<0.001),and all the indexes were optimal in the position-limited group(F>42.031,P<0.001). Conclusion Robotic training for upper limb under postural limitation can further improve upper limb function and sub-luxation status,activities of daily living,and peri-shoulder muscle in patients with shoulder subluxation after stroke.