Objective To investigate the effect of miR-10a-5p downregulation on cisplatin(DDP)resistance in bladder cancer T24 cells and elucidate the underlying molecular mechanism.Methods Quantitative real-time PCR quantified the expression of miR-10a-5p in the cisplatin-resistant bladder cancer cell line T24/DDP and its parental cell line T24.T24/DDP cells were divided into control,inhibitor NC,miR-10a-5p inhibitor,miR-10a-5p inhibitor+si-NC,and miR-10a-5p inhibitor+si-Apaf1 groups.Different concentrations of DDP were administered for 24 h.Cell proliferative activity was detected using the MTT assay,and the drug resistance index was calculated.Apop-tosis was analyzed using flow cytometry.The protein expression levels of Apaf1,cleaved caspase-9,cleaved caspase-3,and cytochrome C(Cyt C)were analyzed using Western blotting.A dual-luciferase reporter gene assay confirmed the target binding relationship between miR-10a-5p and Apaf1.Results The expression of miR-10a-5p was significantly higher in drug-resistant T24/DDP cells than in parental T24 cells(P<0.05).Compared with the inhibitor NC group,the miR-10a-5p inhibitor group exhibited increased T24/DDP cells sensitivity to DDP,decreased drug resistance index,and elevated apoptosis levels.The protein expression levels of Apaf1,cleaved caspase-9,cleaved caspase-3,and cytoplasmic Cyt C proteins were upregulated in the miR-10a-5p inhibitor group compared with the inhibitor NC group(all P<0.05).The DDP sensitivity of T24/DDP cells was reduced in the miR-10a-5p inhibitor+si-Apaf1 group compared to the miR-10a-5p inhibitor+si-NC group,accompanied by an increase in the drug resistance index and a decrease in apoptosis(all P<0.05).The double-lu-ciferase reporter gene assay results confirmed that Apaf1 was a downstream target gene regulated by miR-10a-5p.Conclusion miR-10a-5p knockdown targeting the upregulation of Apaf1reversed DDP resistance in T24/DDP cells.

Objective:To establish graded forecast models of pollen concentration in spring and summer-autumn in northern China, based on long-term data of pollen and allergic rhinitis (AR) medical visits in 8 cities of northern China.Methods:Pollen concentration and the characteristics of AR patients from 8 cities of northern China, including Beijing, Baotou, Hohhot, Xi′an, Xining, Cangzhou, Liaocheng and Zibo, were analyzed. Spearman′s correlation was used to examine the relationship between pollen concentration and daily AR patient visits. A pollen concentration grading was establish, and a pollen forecast model was created using the eXtreme gradient boosting (XGBoost) algorithm. The model incorporated meteorological factors and the 3-day moving average of pollen concentrations.Results:The spring pollen period started early and lasted long in Beijing and Xi ′an, while the summer-autumn pollen period started earlier and persisted longer in Xining, Baotou and Hohhot. During summer-autumn pollen period, and the spring period in most cities (except Baotou and Cangzhou), average daily patient visits were significantly higher than those in non-pollen periods. A strong correlation was observed between daily AR patient visits and the 3-day moving average of pollen concentrations in both the spring and summer-autumn periods across all cities. Based on the correlation, a pollen concentration grading standard of northern China was established. The accuracy evaluation of pollen concentration prediction model showed that the percentage of forecasts with either completely accurate or within one level difference exceeded 91% in spring and 95% in summer-autumn. The most important predictive variable in the model was the pollen level from previous day, followed by the temperature and humidity.Conclusion:The grading prediction model for pollen concentration provides guidance for AR patients in term of travel, early defense and treatment, as well as the determining medication schedules for clinical drug research and specific immunotherapy.

Objective To investigate the effect of miR-10a-5p downregulation on cisplatin(DDP)resistance in bladder cancer T24 cells and elucidate the underlying molecular mechanism.Methods Quantitative real-time PCR quantified the expression of miR-10a-5p in the cisplatin-resistant bladder cancer cell line T24/DDP and its parental cell line T24.T24/DDP cells were divided into control,inhibitor NC,miR-10a-5p inhibitor,miR-10a-5p inhibitor+si-NC,and miR-10a-5p inhibitor+si-Apaf1 groups.Different concentrations of DDP were administered for 24 h.Cell proliferative activity was detected using the MTT assay,and the drug resistance index was calculated.Apop-tosis was analyzed using flow cytometry.The protein expression levels of Apaf1,cleaved caspase-9,cleaved caspase-3,and cytochrome C(Cyt C)were analyzed using Western blotting.A dual-luciferase reporter gene assay confirmed the target binding relationship between miR-10a-5p and Apaf1.Results The expression of miR-10a-5p was significantly higher in drug-resistant T24/DDP cells than in parental T24 cells(P<0.05).Compared with the inhibitor NC group,the miR-10a-5p inhibitor group exhibited increased T24/DDP cells sensitivity to DDP,decreased drug resistance index,and elevated apoptosis levels.The protein expression levels of Apaf1,cleaved caspase-9,cleaved caspase-3,and cytoplasmic Cyt C proteins were upregulated in the miR-10a-5p inhibitor group compared with the inhibitor NC group(all P<0.05).The DDP sensitivity of T24/DDP cells was reduced in the miR-10a-5p inhibitor+si-Apaf1 group compared to the miR-10a-5p inhibitor+si-NC group,accompanied by an increase in the drug resistance index and a decrease in apoptosis(all P<0.05).The double-lu-ciferase reporter gene assay results confirmed that Apaf1 was a downstream target gene regulated by miR-10a-5p.Conclusion miR-10a-5p knockdown targeting the upregulation of Apaf1reversed DDP resistance in T24/DDP cells.

Circular RNA(circRNA)is a single-stranded RNA with a covalently closed loop structure,which has a more stable structure and lower immunogenicity than linear RNA.Many studies have shown that circRNA has characteristics such as conservation,stability,and tissue specificity,and can act as a microRNA(miRNA)sponge to interact with proteins and translation templates,and regulate biological functions such as gene expression and signal transduction.Based on the characteristics and various bio-logical functions of circRNA,some endogenous circRNA plays an important regulatory role in the occur-rence and development of tumors and has the potential to be used as biomarkers and therapeutic targets.In addition,mRNA drugs have limitations such as instability,easy degradation,low translation efficien-cy,and immunogenicity in practical applications.Engineered translatable exogenous circRNA can solve some of the limitations of linear mRNA application and become a new type of potential efficient drug.In this paper,we introduce the circRNA biogenesis mechanisms,specific biological functions,and the cur-rent status of diagnosis and treatment applications in tumors.This includes the diagnostic application of endogenous circRNA in tumors,the design and synthesis strategies of exogenous circRNA,and the cur-rent progress in the design and application of engineered circRNA vaccines using their stable and efficient protein expression functions in the treatment of tumors.Finally,we discuss the current clinical diagnostic application problems of circRNA,the challenges of exogenous circRNA therapeutic applications,and the prospects of the field.

Circular RNA(circRNA)is a single-stranded RNA with a covalently closed loop structure,which has a more stable structure and lower immunogenicity than linear RNA.Many studies have shown that circRNA has characteristics such as conservation,stability,and tissue specificity,and can act as a microRNA(miRNA)sponge to interact with proteins and translation templates,and regulate biological functions such as gene expression and signal transduction.Based on the characteristics and various bio-logical functions of circRNA,some endogenous circRNA plays an important regulatory role in the occur-rence and development of tumors and has the potential to be used as biomarkers and therapeutic targets.In addition,mRNA drugs have limitations such as instability,easy degradation,low translation efficien-cy,and immunogenicity in practical applications.Engineered translatable exogenous circRNA can solve some of the limitations of linear mRNA application and become a new type of potential efficient drug.In this paper,we introduce the circRNA biogenesis mechanisms,specific biological functions,and the cur-rent status of diagnosis and treatment applications in tumors.This includes the diagnostic application of endogenous circRNA in tumors,the design and synthesis strategies of exogenous circRNA,and the cur-rent progress in the design and application of engineered circRNA vaccines using their stable and efficient protein expression functions in the treatment of tumors.Finally,we discuss the current clinical diagnostic application problems of circRNA,the challenges of exogenous circRNA therapeutic applications,and the prospects of the field.

Objective:To establish graded forecast models of pollen concentration in spring and summer-autumn in northern China, based on long-term data of pollen and allergic rhinitis (AR) medical visits in 8 cities of northern China.Methods:Pollen concentration and the characteristics of AR patients from 8 cities of northern China, including Beijing, Baotou, Hohhot, Xi′an, Xining, Cangzhou, Liaocheng and Zibo, were analyzed. Spearman′s correlation was used to examine the relationship between pollen concentration and daily AR patient visits. A pollen concentration grading was establish, and a pollen forecast model was created using the eXtreme gradient boosting (XGBoost) algorithm. The model incorporated meteorological factors and the 3-day moving average of pollen concentrations.Results:The spring pollen period started early and lasted long in Beijing and Xi ′an, while the summer-autumn pollen period started earlier and persisted longer in Xining, Baotou and Hohhot. During summer-autumn pollen period, and the spring period in most cities (except Baotou and Cangzhou), average daily patient visits were significantly higher than those in non-pollen periods. A strong correlation was observed between daily AR patient visits and the 3-day moving average of pollen concentrations in both the spring and summer-autumn periods across all cities. Based on the correlation, a pollen concentration grading standard of northern China was established. The accuracy evaluation of pollen concentration prediction model showed that the percentage of forecasts with either completely accurate or within one level difference exceeded 91% in spring and 95% in summer-autumn. The most important predictive variable in the model was the pollen level from previous day, followed by the temperature and humidity.Conclusion:The grading prediction model for pollen concentration provides guidance for AR patients in term of travel, early defense and treatment, as well as the determining medication schedules for clinical drug research and specific immunotherapy.

Toxin-antitoxin system (TA) is a genetic element widely found in chromosomes and plasmids of bacteria, archaea and prophages. TA usually consists a toxin that inhibits the growth of bacteria and an antitoxin that neutralizes its toxicity. Since the discovery of the first CcdB / CcdA TA in the 1980s, TA has been proved to exist in almost all sequenced microorganisms and plays an important role in maintaining plasmid stability, anti-phage and promoting biofilm formation. At present, TA is divided into type I-VIII, among which type IITA is the most widely studied. HipBA is a type II TA. The toxin HipA in Escherichia coli HipBA is a serine / threonine kinase, which inhibits protein translation by phosphorylating bacterial Glutamyl tRNA synthetase (GltX), and its toxicity can be specifically neutralized by HipB. Recently, it has been found that Escherichia coli HipA homologous proteins exist widely in microorganisms, and they form a potential novel TA with genes of the same promoter, in which HipBST has been confirmed by experiments. The toxin HipT and the antitoxin HipS in this TA are similar to the C-terminal and N-terminal of E. coli HipA respectively, and the neutralization mechanism and the substrate of the toxin are different from that of E. coli toxin HipA. This study summarizes the recent discovery of special TA, especially the neutralization mechanism of HipBST which widely exists in prokaryotes.

Bunyavirus is widely distributed, highly contagious, and has a high fatality rate. It is a negative- strand RNA virus that has a major impact on public health around the world. The development of vaccines and the search for drugs are the key to prevent bunyavirus infection. The nucleoprotein (NP) of viruses is necessary for the synthesis of viral RNA, which combines with viral RNA to form the nucleocapsid, participates in viral assembly and RNA transcription, and plays an important role in viral proliferation. In addition, NP also has B cell and T cell epitopes, which can induce cellular and humoral immunity, so NP is an ideal target for vaccine design and drug development. Given its abundance and specificity, NP is also commonly used in the detection of viral diseases. More and more bunyavirus NP structures and structures of NP-RNA complexes have been resolved. Researchers have discovered two important antiviral targets through these structures, the terminal arm and the RNA binding cleft. This paper reviews the function and three-dimensional structure of the bunyavirus NP and the research progress of NP as an antiviral target, in order to provide a theoretical basis for the prevention and treatment of the bunyavirus disease.

Objective: To investigate the clinical value of the bipolar tweezers-clamp for the hepatic parenchymal transection in the resection of hepatocellular carcinoma. Methods: From January 2020 to January 2021,63 patients with the hepatocellular carcinoma for hepatectomy at Department of Hepatopancreatobiliary Surgery,Yuebei People's Hospital Affiliated to Shantou University Medical College were analyzed retrospectively.According to the different instruments used in the hepatic parenchymal transection,the patients were divided into bipolar tweezers-clamp group and ultrasonic scalpel group.There were 32 patients in bipolar tweezers-clamp group,with age of (55.5±10.5)years(range:37 to 78 years),including 22 males and 10 females,tumor size was (6.0±3.4)cm(range:2.4 to 13.4 cm). There were 6 patients with portal vein tumor thrombus and 5 patients with portal hypertension. There were 31 patients in ultrasonic scalpel group,with aged(57.8±10.1)years(range:37 to 79 years),including 27males and 4 females,tumor size was(7.9±5.1)cm(range: 2.4 to 21.3 cm),3 patients with portal vein tumor thrombus and 2 patients with portal hypertension. The preoperative baseline data,operation time,blood loss,postoperative liver function and the complications were compared between two groups using t test,χ² test and Fisher exact probabilityrespectively. Results: The operation was successfully completed in both groups.Compared with the ultrasonic scalpel group,the operation time was significantly shorter((219.3±76.4)minutes vs.(294.0±100.8)minutes,t=-3.322,P=0.002),the blood loss was less((250(475)ml vs. 500(1 050)ml,t=-2.307,P=0.026),the concentrate red blood cells transfusion volume was less(0.92(0.88)U vs. 2.32(4.00)U,Z=-1.987,P=0.047) in the bipolar tweezers-clamp group.The postoperative serum ALB level was higher in the bipolar tweezers-clamp group than that in the ultrasonic scalpel group((33.5±6.1)g/L vs. (29.5±4.2)g/L,t=3.226,P=0.020) on postoperative day 1;((35.7±4.5)g/L vs.(30.1±3.2)g/L,t=5.575,P<0.01) on postoperative day 3;((33.2±3.7)g/L vs. (31.0±4.4)g/L,t=3.020,P=0.004) on postoperative day 7. There was no significant difference in serum ALT,TBIL and PT level between the two groups(all P>0.05).No postoperative bile leakage occurred in both groups.The postoperative complications occurred in 8 cases(25.0%)in the bipolar tweezers-clamp group,including liver failure in one,and in 11 cases(35.5%)in the ultrasonic scalpel group,including liver failure in two(P>0.05). Conclusion: The bipolar tweezers-clamp is a safe and reliable method for the hepatic parenchymal transaction,which is quick and less bleeding during the hepatic resection.
Blood Loss, Surgical ; Carcinoma, Hepatocellular/surgery* ; Female ; Hemorrhage ; Hepatectomy/methods* ; Humans ; Hypertension, Portal/surgery* ; Liver Failure ; Liver Neoplasms/surgery* ; Male ; Retrospective Studies ; Treatment Outcome

Objective:To analyze the incidence and epidemiological characteristics of traumatic spinal cord injury in China in 2018.Methods:Multi-stage stratified cluster sampling was used to randomly select hospitals capable of treating patients with spinal cord injury from 3 regions，9 provinces and 27 cities in China to retrospectively investigate eligible patients with traumatic spinal cord injury admitted in 2018. National and regional incidence rates were calculated. The data of cause of injury，injury level，severity of injury，segment and type of fracture，complications，death and other data were collected by medical record questionnaire，and analyzed according to geographical region，age and gender.Results:Medical records of 4，134 patients were included in this study，with a male-to-female ratio of 2.99∶1. The incidence of traumatic spinal cord injury in China in 2018 was 50.484 / 1 million （95% CI 50.122-50.846）. The highest incidence in the Eastern region was 53.791 / 1 million （95% CI 53.217-54.365）. In the whole country，the main causes of injury were high falls （29.58%），as well as in the Western region （40.68%），while the main causes of injury in the Eastern and Central regions were traffic injuries （31.22%，30.10%）. The main injury level was cervical spinal cord in the whole country （64.49%），and the proportion of cervical spinal cord injury in the Central region was the highest （74.68%），and the proportion of lumbosacral spinal cord injury in the Western region was the highest （32.30%）. The highest proportion of degree of injury was incomplete quadriplegia （55.20%），and the distribution pattern was the same in each region. A total of 65.87% of the patients were complicated with fracture or dislocation，77.95% in the Western region and only 54.77% in the Central region. In the whole country，the head was the main combined injury （37.87%），as well as in the Eastern and Central regions，while the proportion of chest combined injury in the Western region was the highest （38.57%）. A total of 32.90% of the patients were complicated with respiratory complications. There were 23 patients （0.56%） died in hospital，of which 17（73.91%） died of respiratory dysfunction. Conclusions:The Eastern region of China has a high incidence of traumatic spinal cord injury. Other epidemiological features include high fall as the main cause of injury cervical spinal cord injury as the main injury level，incomplete quadriplegia as the main degree of injury，head as the main combined injury，and respiratory complications as the main complication.