Neuraminidase(NA),a glycoprotein on the surface of the influenza virus,plays a crucial role in viral escape and serves as a stable target for drug candidates.Monoclonal antibodies targeting the NA active site can bind to multiple influenza virus subtypes and inhibit the spread of influenza virus through various mechanisms,such as neutralizing,mediating antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotox-icity.In vivo experiments have shown that human monoclonal antibodies targeting the influenza virus NA can ef-fectively exert preventive and therapeutic effects,rescuing mice infected with lethal doses and reducing viral ti-ters in lungs of mice.This article provides a review of the currently reported human monoclonal antibodies targe-ting NA of Influenza A and Influenza B viruses,providing new ideas and prospects for the subsequent development of anti-influenza drugs.

Objective:To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and 24-h urinary calcium excretion (24-h UCaE) and hypercalciuria in Chinese adults.Methods:This cross-sectional study was conducted from March 2022 to March 2023 in nine cities in China and included 1 239 residents. Demographic characteristics were collected through questionnaires and physical examinations, fasting blood samples were assessed for bone metabolism indicators, and 24-h urine samples were used to determine the 24-h UCaE. Multiple linear regression analysis was used to explore the relationship between serum 25(OH)D and 24-h UCaE and bone metabolism indexes. The relationship between serum 25(OH)D and hypercalciuria was analyzed using a multiple logistic regression model combined with restricted cubic spline modeling.Results:The mean participant age was (47.9±18.1) years, of which 453 (36.6%) were male. The percentages of vitamin D sufficiency, insufficiency, and deficiency were 7.6% (94/1 239), 29.0% (359/1 239), and 63.4% (786/1 239), respectively. The multiple linear regression model showed that after adjusting for the covariates the 24-h UCaE gradually increased with higher levels of 25(OH)D ( P overall <0.001, P nonlinear <0.001). The logistic regression analysis revealed that compared with the vitamin D deficient group, the OR for the prevalence of hypercalciuria in the vitamin D sufficient and vitamin D insufficient groups were 3.290 (95% CI 1.745 to 6.202) and 3.742 (95% CI 2.458 to 5.697), respectively. The results of the restricted cubic spline modeling showed a positive nonlinear relationship between 25(OH)D and the prevalence of hypercalciuria ( P overall <0.001, P nonlinear <0.001). The prevalence of hypercalciuria increased when 25(OH)D was >17.00 μg/L and peaked at 26.71 μg/L, after which there was a decreasing trend in the prevalence of hypercalciuria with increasing 25(OH)D. Conclusion:Associations between serum 25(OH)D levels and urinary calcium excretion and the prevalence of hypercalciuria were observed in the Chinese adult population.

Objective To explore the clinical characteristics,antimicrobial resistance,virulence and molecular epi-demiology characteristics of carbapenem-resistant hypervirulent Klebsiella pneumoniae(CR-hvKP).Methods Car-bapenem-resistant Klebsiella pneumoniae(CRKP)strains isolated from clinical specimens in a tertiary first-class teaching hospital from 2018 to 2021 were collected.ST1 1 CR-hvKP strains were screened through the detection of antimicrobial resistance genes and virulence genes as well as multilocus sequence typing(MLST).Basic clinical in-formation,antimicrobial resistance genes and virulence genes were analyzed.Twenty-three strains of ST1 1 CR-hvKP were randomly selected for virulence phenotype analysis;45 strains of CR-hvKP were randomly selected for homology analysis by pulsed-field gel electrophoresis(PFGE).Results There were a total of 124 clinically isolated strains of ST11 CR-hvKP from 2018 to 2021,mainly from the department of neurosurgery(33.87％).The major specimen source was sputum(56.45％),the average age of infected patients were(55.2±16.4)years old,and the majority were male patients(77.42％).Antimicrobial susceptibility testing results showed these strains were resis-tant to most clinically commonly used antimicrobial agents.Virulence detection showed that virulence varied among these strains,but most of them were hypervirulence strains.PFGE analysis results showed that the strains were mainly subtype A1(63.4％).Conclusion ST1 1 CR-hvKP presents multidrug resistance and hypervirulence.Clonal transmission of some strains exists in this hospital,which poses great challenges for clinical anti-infection treatment as well as prevention and control.It is necessary to strengthen the prevention and control of healthcare-associated infection.

Objective To explore the clinical characteristics,antimicrobial resistance,virulence and molecular epi-demiology characteristics of carbapenem-resistant hypervirulent Klebsiella pneumoniae(CR-hvKP).Methods Car-bapenem-resistant Klebsiella pneumoniae(CRKP)strains isolated from clinical specimens in a tertiary first-class teaching hospital from 2018 to 2021 were collected.ST1 1 CR-hvKP strains were screened through the detection of antimicrobial resistance genes and virulence genes as well as multilocus sequence typing(MLST).Basic clinical in-formation,antimicrobial resistance genes and virulence genes were analyzed.Twenty-three strains of ST1 1 CR-hvKP were randomly selected for virulence phenotype analysis;45 strains of CR-hvKP were randomly selected for homology analysis by pulsed-field gel electrophoresis(PFGE).Results There were a total of 124 clinically isolated strains of ST11 CR-hvKP from 2018 to 2021,mainly from the department of neurosurgery(33.87％).The major specimen source was sputum(56.45％),the average age of infected patients were(55.2±16.4)years old,and the majority were male patients(77.42％).Antimicrobial susceptibility testing results showed these strains were resis-tant to most clinically commonly used antimicrobial agents.Virulence detection showed that virulence varied among these strains,but most of them were hypervirulence strains.PFGE analysis results showed that the strains were mainly subtype A1(63.4％).Conclusion ST1 1 CR-hvKP presents multidrug resistance and hypervirulence.Clonal transmission of some strains exists in this hospital,which poses great challenges for clinical anti-infection treatment as well as prevention and control.It is necessary to strengthen the prevention and control of healthcare-associated infection.

Neuraminidase(NA),a glycoprotein on the surface of the influenza virus,plays a crucial role in viral escape and serves as a stable target for drug candidates.Monoclonal antibodies targeting the NA active site can bind to multiple influenza virus subtypes and inhibit the spread of influenza virus through various mechanisms,such as neutralizing,mediating antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotox-icity.In vivo experiments have shown that human monoclonal antibodies targeting the influenza virus NA can ef-fectively exert preventive and therapeutic effects,rescuing mice infected with lethal doses and reducing viral ti-ters in lungs of mice.This article provides a review of the currently reported human monoclonal antibodies targe-ting NA of Influenza A and Influenza B viruses,providing new ideas and prospects for the subsequent development of anti-influenza drugs.

Objective:To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and 24-h urinary calcium excretion (24-h UCaE) and hypercalciuria in Chinese adults.Methods:This cross-sectional study was conducted from March 2022 to March 2023 in nine cities in China and included 1 239 residents. Demographic characteristics were collected through questionnaires and physical examinations, fasting blood samples were assessed for bone metabolism indicators, and 24-h urine samples were used to determine the 24-h UCaE. Multiple linear regression analysis was used to explore the relationship between serum 25(OH)D and 24-h UCaE and bone metabolism indexes. The relationship between serum 25(OH)D and hypercalciuria was analyzed using a multiple logistic regression model combined with restricted cubic spline modeling.Results:The mean participant age was (47.9±18.1) years, of which 453 (36.6%) were male. The percentages of vitamin D sufficiency, insufficiency, and deficiency were 7.6% (94/1 239), 29.0% (359/1 239), and 63.4% (786/1 239), respectively. The multiple linear regression model showed that after adjusting for the covariates the 24-h UCaE gradually increased with higher levels of 25(OH)D ( P overall <0.001, P nonlinear <0.001). The logistic regression analysis revealed that compared with the vitamin D deficient group, the OR for the prevalence of hypercalciuria in the vitamin D sufficient and vitamin D insufficient groups were 3.290 (95% CI 1.745 to 6.202) and 3.742 (95% CI 2.458 to 5.697), respectively. The results of the restricted cubic spline modeling showed a positive nonlinear relationship between 25(OH)D and the prevalence of hypercalciuria ( P overall <0.001, P nonlinear <0.001). The prevalence of hypercalciuria increased when 25(OH)D was >17.00 μg/L and peaked at 26.71 μg/L, after which there was a decreasing trend in the prevalence of hypercalciuria with increasing 25(OH)D. Conclusion:Associations between serum 25(OH)D levels and urinary calcium excretion and the prevalence of hypercalciuria were observed in the Chinese adult population.

Objective To investigate the serum micro-ribonucleic acid-15a(miR-15a)and macrophage mi-gration inhibitory factor(MIF)levels and their relationship with adverse maternal and infant outcomes in pa-tients with gestational diabetes mellitus(GDM).Methods From January 2020 to December 2022,106 patients with GDM who underwent prenatal examination and gave birth in the Hengshui Fourth People's Hospital were selected as the experimental group.Another 106 healthy women who underwent pregnancy examination and delivered in a hospital during the same period were selected as the control group.Detection of serum miR-15a level by real-time fluorescent quantitative polymerase chain reaction and serum MIF levels were detected by enzyme-linked immunosorbent assay.Serum MIF and miR-15a levels were compared between the two groups,and the relationship between miR-15a and MIF levels and adverse maternal and infant outcomes in GDM patients was analyzed by multivariate Logistic regression.Results The serum levels of miR-15a and MIF in the experimental group were higher than those in the control group,the difference was statistically sig-nificant(P＜0.05).The age of patients with adverse maternal and infant outcomes in the experimental group was＞35 years old,the pre-pregnancy body mass index was＞24 kg/m2,the proportion of patients with ad-verse pregnancy history,poor blood glucose control and serum MIF and miR-15a levels were higher than those with good maternal and infant outcomes in the experimental group,and the differences were statistically sig-nificant(P＜0.05).Multivariate Logistic regression analysis showed that age＞35 years old,pre-pregnancy body mass index＞24 kg/m2,adverse pregnancy history,poor blood glucose control and serum miR-15a and MIF were all risk factors for adverse maternal and infant outcomes in the experimental group(P＜0.05).Conclusion Serum miR-15a and MIF levels are abnormally elevated in GDM patients,and serum miR-15a and MIF levels are closely related to adverse maternal and infant outcomes.

Objective Prior studies have established a connection between albuminuria and various inflammatory reactions,highlighting that an increase in C-reactive protein by 1 mg/L increases the likelihood of albuminuria by 2%.Recent investigations indicate a positive correlation between the systemic immune-inflammation index(SII)and increased urinary protein excretion.In addition,elevated levels of the systemic inflammatory response index(SIRI)also correlate with a higher prevalence of albuminuria.The aggregate index of systemic inflammation(AISI)offers a more comprehensive indicator of inflammation,providing an extensive assessment of systemic inflammatory status compared to SII and SIRI.Yet,the specific relationship between AISI and albuminuria remains unclear.This study aims to explore this association in U.S.adults.Methods We analyzed data from the National Health and Nutrition Examination Survey(NHANES)for 2007-2018,excluding pregnant women and individuals under 18.Cases with missing data on AISI,urinary albumin concentration,and other covariates were also excluded.AISI was computed using the formula:AISI=(platelet count×neutrophil count×monocyte count)/lymphocyte count.Albuminuria was defined as the urinary albumin-to-creatinine ratio exceeding 30 mg/g.Continuous variables were presented in the form of the mean±standard error,and categorical variables in percentages.We utilized weighted t-tests and chi-square tests for baseline comparisons.We applied weighted multivariable logistic regression and generalized additive models(GAM)to explore the association between AISI and albuminuria and to assess potential nonlinear relationships.Results The study included 32 273 participants,with an average age of(46.75±0.24)years old.The cohort comprised 48.73% males and 51.27% females.The prevalence of albuminuria was 9.64%.The average logarithmic value of log2AISI was 7.95±0.01,and were categorized into tertiles as follows:Quartile 1(Q1)(4.94 to 7.49),Q2(7.49 to 8.29),and Q3(8.29 to 10.85).As log2AISI increased,so did the prevalence of hypertension,diabetes,congestive heart failure,and albuminuria,all showing statistically significant increases(P<0.001).Similarly,the use of antihypertensive,lipid-lowering,and hypoglycemic drugs was also more prevalent(P<0.001).Statistically significant differences were observed across the three groups concerning age,race and ethnicity,formal education,alcohol consumption,smoking status,systolic and diastolic blood pressures,body mass index,estimated glomerular filtration rate,HbA1c,alanine aminotransferase,aspartate aminotransferase,albumin,creatinine,uric acid,and high-density lipoprotein cholesterol(P<0.05).However,no significant differences were noted in the total cholesterol or the sex ratios among the groups.The association between log2AISI and albuminuria was assessed using weighted multivariable logistic regression,and the detailed results are presented in Table 2.In model 1,without adjusting for covariates,each unit increase in log2AISI was associated with a 32% increase in the risk of albuminuria(odds ratio[OR]=1.32,95% confidence interval[CI]:1.27-1.38,P<0.001).Model 2 was adjusted for age,gender,race,and education level,and showed a similar trend,with each unit increase in log2AISI associated with a 31% increased risk(OR=1.31,95% CI:1.26-1.37,P<0.001).Model 3,which was further adjusted for all covariates,revealed that each unit increase in log2AISI was associated with a 20% increase in the risk of albuminuria(OR=1.20,95% CI:1.15-1.26,P<0.001).The study also transformed log2AISI from a continuous to a categorical variable for analysis.Compared with Q1,the risk of albuminuria in Q3,after adjusting for all covariates,significantly increased(OR=1.37,95% CI:1.22-1.55,P<0.001).Q2 also demonstrated a higher risk compared with Q1(OR=1.13,95% CI:1.06-1.36,P=0.004).The trend test indicated a dose-effect relationship between increasing log2AISI and the rising risk of albuminuria.GAM revealed a nonlinear relationship between log2AISI and albuminuria,with distinct trends noted between sexes.Segmented regression based on turning points showed significant effects among women,although the slope difference between the segments was not significant.In men,a significant threshold effect was observed;below the log2AISI of 7.25,increases in log2AISI did not enhance the risk of albuminuria,but above this threshold,the risk significantly increased.As part of a sensitivity analysis,weighted multivariable logistic regression was performed by changing the outcome variable to macroalbuminuria and adjusting for all covariates.The analysis showed that for every unit increase in log2AISI,the risk of developing macroalbuminuria increased by 31% (OR=1.31,95% CI:1.15-1.49,P<0.001).Compared with Q1,the risk of albuminuria in Q3 increased by 69% (OR=1.69,95% CI:1.27-2.25,P<0.001),and in Q2,it increased by 40% (OR=1.40,95% CI:1.03-1.92,P=0.030).Subgroup analysis and interaction results showed that the positive association between AISI and proteinuria risk was stronger in men than in women.Similarly,the association was stronger in people with hypertension compared with those with normal blood pressure,and higher in overweight people compared with those of normal weight.Furthermore,smokers and drinkers showed a stronger positive association between AISI and the risk of proteinuria than non-smokers and non-drinkers do.These results suggest that sex,blood pressure,body mass index,smoking,and alcohol consumption interact with AISI to influence the risk of proteinuria.Conclusion There is a robust positive association between AISI and increased risks of albuminuria in US adults.As log2AISI increases,so does the risk of albuminuria.However,further validation of this conclusion through large-scale prospective studies is warranted.

RNA therapeutics inhibit the expression of specific proteins/RNAs by targeting complementary sequences of corresponding genes or encode proteins for the synthesis desired genes to treat genetic diseases. RNA-based therapeutics are categorized as oligonucleotide drugs (antisense oligonucleotides, small interfering RNA, RNA aptamers), and mRNA drugs. The antisense oligonucleotides and small interfering RNA for treatment of genetic diseases have been approved by the FDA in the United States, while RNA aptamers and mRNA drugs are still in clinical trials. Chemical modifications can be applied to RNA drugs, such as pseudouridine modification of mRNA, to reduce immunogenicity and improve the efficacy. The secure and effective delivery systems such as lipid-based nanoparticles, extracellular vesicles, and virus-like particles are under development to address stability, specificity, and safety issues of RNA drugs. This article provides an overview of the specific molecular mechanisms of eleven RNA drugs currently used for treating genetic diseases, and discusses the research progress of chemical modifications and delivery systems of RNA drugs.
Aptamers, Nucleotide ; RNA, Small Interfering/therapeutic use* ; RNA, Messenger ; Oligonucleotides, Antisense/therapeutic use*

RNA therapeutics inhibit the expression of specific proteins/RNAs by targeting complementary sequences of corresponding genes, or synthesize proteins encoded by the desired genes to treat genetic diseases. RNA-based therapeutics are categorized as oligonucleotide drugs (antisense oligonucleotides, small interfering RNA, RNA aptamers), and mRNA drugs. The antisense oligonucleotides and small interfering RNA for treatment of genetic diseases have been approved by the FDA in the United State, while RNA aptamers and mRNA drugs are still in clinical trials. Chemical modifications are applied to RNA drugs, such as pseudouridine modification of mRNA, to reduce immunogenicity and improve the efficacy. The secure and effective delivery systems like lipid-based nanoparticles, extracellular vesicles, and virus-like particles are under development to address stability, specificity, and safety issues of RNA drugs. This article provides an overview of the specific molecular mechanisms of 11 RNA drugs currently used for treating genetic diseases, and discusses the research progress of chemical modifications and delivery systems of RNA drugs.