The clinical application of chemotherapeutic drugs has been limited due to the lack of tumor selectivity which causes different degrees of adverse reactions. Transferrin receptor(TfR) is one of the targets for tumor targeted drug delivery system because it is over-expressed in many kinds of tumor cells and tumor-associated blood vessels, but is low-expressed in normal cells. By modifying drug carriers or coupling antitumor drugs with ligands that have high specific affinity for TfR, it is expected to achieve targeted therapy of TfR over-expressed tumors. In this paper, the application progress of TfR functional ligands in tumor targeted drug delivery in recent years is summarized, in order to provide reference for the research of TfR targeted drug delivery systems.

Objective Genotypes(G)1,3,and 5 of the Japanese encephalitis virus(JEV)have been isolated in China,but the dominant genotype circulating in Chinese coastal areas remains unknown.We searched for G5 JEV-infected cases and attempted to elucidate which JEV genotype was most closely related to human Japanese encephalitis(JE)in the coastal provinces of China. Methods In this study,we collected serum specimens from patients with JE in three coastal provinces of China(Guangdong,Zhejiang,and Shandong)from 2018 to 2020 and conducted JEV cross-neutralization tests against G1,G3,and G5. Results Acute serum specimens from clinically reported JE cases were obtained for laboratory confirmation from hospitals in Shandong(92 patients),Zhejiang(192 patients),and Guangdong(77 patients),China,from 2018 to 2020.Seventy of the 361 serum specimens were laboratory-confirmed to be infected with JEV.Two cases were confirmed to be infected with G1 JEV,32 with G3 JEV,and two with G5 JEV. Conclusion G3 was the primary infection genotype among JE cases with a definite infection genotype,and the infection caused by G5 JEV was confirmed serologically in China.

Objective To compare the effects of angular and unilateral vertebroplasty on spinal compression fractures in the elderly.Methods A total of 122 elderly patients with spinal compression fractures admitted to the Department of Orthopedics,Handan First Hospital from January 2018 to January 2021 were selected as the research subjects.They were divided into a control group and an observation group according to the surgical method,with 61 patients in each group.Patients in the control group were treated with unilateral vertebroplasty,while patients in the observation group were treated with angular vertebroplasty.The operation time,intraoperative blood loss and bone cement injection volume,bone cement distribution,bone cement leakage,spinal-pelvic parameters,visual analogue score(VAS),Barthel index score,and the occurrence of complications were compared between the two groups.Results There was no statistically significant different in the operation time,intraoperative blood loss and bone cement injection volume between the two groups(P＞0.05).The proportions of grade Ⅰ,grade Ⅱ,grade Ⅲ and grade Ⅳ bone cement distribution also showed no significant difference between the two groups(P＞0.05).The total proportion of grade Ⅰ and grade Ⅱ bone cement distribution in the observation group was significantly higher than that in the control group(P＜0.05).The incidence of bone cement leakage in the observation group was significantly lower than that in the control group(P＜0.05).Before operation,there was no statistically significant difference in sagittal balance,thoracic kyphosis angle,pel vic tilt angle,lumbar lordosis angle,and sacral slope angle between the two groups(P＞0.05).After operation,the sagittal balance,thoracic kyphosis angle and pelvic tilt angle significantly decreased in the two groups compared to before operation,and the sagittal balance,thoracic kyphosis angle and pelvic tilt angle of patients in the observation group were significantly smaller than those in the control group(P＜0.05);the lumbar lordosis angle and sacral slope angle significantly increased in the two groups compared to before operation,and the lumbar lordosis angle and sacral slope angle of patients in the observation group were significantly greater than those in the control group(P＜0.05).Before operation,there was no statistically significant difference in the VAS score and Barthel index between the two groups(P＞0.05).Three months after operation,the VAS score of patients in the two groups decreased,while the Barthel index increased compared to before operation(P＜0.05);the Barthel index of patients in the observation group was significantly higher than that in the control group(P＜0.05),while the VAS score showed no significant difference between the two groups(P＞0.05).During treatment,1 case of extraspinal hematoma occurred in the observation group,and the complication rate was 1.64％(1/61);in the control group,2 cases of extraspinal hematoma and 1 case of incision infection occurred,and the complication rate was 4.92％(3/61).There was no statistically significant difference in the incidence of complications between the two groups(x2=1.034,P=0.309).Conclusion Compared with unilateral vertebroplasty,angular vertebroplasty has better effect of bone cement distribution in treating elderly patients with spinal compression fractures,and it can improve the spiral balance and enhance the postoperative quality of life.

The aim of this study was to evaluate the roles of interleukin (IL)-17A in risk stratification and prognosis of patients with sepsis-associated acute kidney injury (SAKI). Methods: We enrolled 146 sepsis patients (84 non-SAKI and 62 SAKI patients) admitted to the emergency department from November 2020 to November 2021. Patients with SAKI were differentiated based on the severity of acute kidney injury. All clinical parameters were evaluated upon admission before administering antibiotic treatment. Inflammatory cytokines were assessed using flow cytometry and the Pylon 3D automated immunoassay system (ET Healthcare). In addition, a receiver operating characteristic (ROC) curve was utilized to determine the prognostic values of IL-17A in SAKI. Results: The levels of creatinine, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor alpha, C-reactive protein, and procalcitonin (PCT) were significantly higher in the SAKI group than in the non-SAKI group (p < 0.05). The level of IL-17A revealed significant differences among stages 1, 2, and 3 in SAKI patients (p < 0.05). The mean levels of PCT, IL-4, and IL-17A were significantly higher in the non-survival group than in the survival group in SAKI patients (p < 0.05). In addition, the area under the ROC curve of IL-17A was 0.811. Moreover, the IL-17A cutoff for differentiating survivors from non-survivors was 4.7 pg/mL, of which the sensitivity and specificity were 77.4% and 71.0%, respectively. Conclusion: Elevated levels of IL-17A could predict that SAKI patients are significantly prone to worsening kidney injury with higher mortality. The usefulness of IL-17A in treating SAKI requires further research.

ObjectiveTo analyze the mental health status and its influencing factors in middle school students under the regular prevention and control of COVID-19， so as to provide references for the intervention and management of their mental health problems. MethodsFrom March 7 to 21， 2021， a stratified random sampling method was used to select 19 352 students from 17 schools in 3 districts and 9 counties of Linyi City， Shandong Province. Basic data were collected through a self-designed questionnaire. All students completed the Symptom Checklist 90 （SCL-90） to assess their mental health status. Then the factors affecting the mental health status of middle school students were screened using independent sample t-test， one-way ANOVA test and multiple stepwise regression analysis. Results① A total of 6 350 （32.81%） middle school students were found to have mental health problems. ② Each SCL-90 factor score and total average score yielded statistical difference among middle school students of different genders， relationships with classmate， closeness to friends， concerns about the epidemic， and pressure exerted by schoolwork （P<0.01）. Each SCL-90 factor score and total average score of middle school students were significant different in terms of the hours of smartphone usage for recreation per day， sleep duration per night in hours and exercise frequency （P<0.01）. ③ Multiple stepwise regression analysis denoted that female gender， poor relationship with classmate， no close friend and long hours of smartphone usage for recreation were the risk factors for mental health of middle school students （β=0.096， 0.183， 0.064， 0.232， P<0.01）. ConclusionThe prevalence rate of mild mental health problems is quite high among middle school students under the regular epidemic prevention and control. Additionally， female gender， poor relationship with classmate， no close friend and long hours of smartphone usage for recreation have a negative impact on middle school students' mental health.

Objective: To investigate the expression of miR-155 in peripheral blood of type 2 diabetes patients(T2 DM) associated with diabetic foot ulcer(DFU) and its relationship with the onset of DFU. Methods: Sixty newly diagnosed T2 DM patients without DFU(T2 DM group), 112 T2 DM patients with DFU(DFU group), and 60 healthy controls with normal glucose tolerance(NC group) were included. MiR-155 levels were determined by quantitative real-time PCR, while clinical features and risk factors of DFU were explored. Results: A significant decrease in the expression level of miR-155 in peripheral blood was observed in T2 DM group compared with NC group(P<0.05), and a markedly increased miR-155 expression level was noted in DFU group compared with T2 DM group(P<0.01). Moreover, there was a positive correlation between the expression level of miR-155 in peripheral blood and the course of foot ulcer and Wagner grade of foot ulcer(P=0.02,P=0.01) while a negative correlation in the expression level of miR-155 with healing rate of DFU after eight weeks(P=0.04). The multiple stepwise logistic regression analysis confirmed that a high expression of miR-155 was an independent risk factor for DFU(OR=3.98,P=0.002). Conclusion An increased expression of miR-155 in peripheral blood of T2 DM patients is an independent risk factor for DFU and is closely related to the prognosis of DFU.

AIM: To investigate the protective affect of salvianolic acid A on palmitic acid-induced lipotoxicity in hepatocyte and its potential molecular mechanism. METHODS: The lipotoxicity model of AML12 hepatocytes induced by PA was established. Different concentrations of Sal A (20, 40, 80, 120 μmol/L) were intervened. The hepatocyte injury was detected by the Lactate dehydrogenase (LDH) method, the intracellular triglyceride (TG) content was detected by enzyme assay and the lipid droplets were observed by Bodipy staining, cell viability was detected by MTT, Intracellular reactive oxygen species (ROS) were detected by 2'eci'- dichlorofluorescein diacetate (DCFH-DA) and fluorescence microscope. Mitochondrial membrane potential was detected by rhodamine 123 and fluorescence microscope. The expression of phosphorylation of AMP-activated protein kinase (AMPK) protein and silent information regulator 1 (SIRT1) protein were observed by Western blot. RESULTS: Model of hepatocyte lipotoxicity was established after intervented for 12 h in vitro with PA (0.5 mmol/L). Different concentrations of Sal A could significantly reduce the lipid deposition and hepatocytes injury induced by PA (P<0.05), and the protective effect was dose-dependent. Secondly, Sal A could significantly improve cell mitochondrial membrane potential (P<0.01) and abate the ROS level of hepatocytes induced by PA (P<0.01). In addition, PA could significantly inhibit AMPK and SIRT1 protein expression (P<0.05). Salvianolic acid A can significantly up-regulate SIRT1 and AMPK protein expression (P<0.05). CONCLUSION: Sal A improves PA induced lipotoxicity in hepatocyte, AMPK and SIRT1 may be a potential molecular target.

Objective:To establish a sensitive and specific real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) method for rapid detection of Getah virus (GETV).Methods:All the gene sequences of GETV were downloaded from GenBank database. Clustal X was used for sequence alignment, and specific primers and probes were designed according to highly conserved regions; we established a standard curve using the nucleic acid of GETV as a standard, and the sensitivity, specificity and stability of this method were evaluated respectively.Results:This method could specifically detect GETV and has no cross-reactivity with multiple arboviruses; the sensitivity was 1.0×10 pfu/ml, and the intra-assay and inter-assay coefficients of variation were less than 1%. One case was GETV positive in 196 batches of mosquitoes collected from Hunan province, Hebei province, Fujian province and Chongqing city.Conclusions:We established a TaqMan probe real-time quantitative RT-PCR with high sensitivity and specificity which can be used for screening.

Objective:A highly sensitive and specific real-time quantitative TaqMan reverse transcription-polymerase chain reaction (RT-PCR) assay was developed for rapid and accurate detection of Tibet orbivirus (TIBOV).Methods:The TIBOV genomic sequences from GenBank were analyzed by Clustal X 2.1 and the specific primers and probe were designed in the conserved segment of VP4 gene. RNA standard was obtained from in vitro transcription and a TaqMan RT-PCR assay for TIBOV was established. The sensitivity, specificity and repeatability of this method were evaluated. Results:The assay showed a good amplification curve within the range of 1.0×10 2~8 copies/reaction template, the detection limit was 1.0×10 2 copies/reaction, the coefficients of variation of Ct values in repeat detections were all less than 1.5%. No cross-reaction was found in this assay. Variable mosquito samples were screened by this assay and the result showed TIBOV negative. The prepared TIBOV simulated positive samples were 100% detected. Conclusions:The assay developed in this study is specific and sensitive for detection of TIBOV and can be used for laboratory detection and routine surveillance.

Prostate cancer (PCa) patients who progress to metastatic castration-resistant PCa (mCRPC) mostly have poor outcomes due to the lack of effective therapies. Our recent study established the orphan nuclear receptor ROR