Antibody-based therapies are one of the crucial tumor-targeted therapies,enabling pre-cise elimination of tumor cells by specifically binding to antigens on the tumor cell surface.However,their wide applications in solid tumor therapy are often limited by on-target toxicity.Recent advance-ments in antibody engineering have led to the development of novel tumor-targeted masking antibod-ies,which are specifically designed to address these limitations.Masking antibodies typically consist of an antibody domain,a masking domain and a linker.These antibodies are characterized by selective activation and other functional properties.Currently,various masking antibody technologies with distinct characteristics have been developed and have demonstrated favorable safety profiles in animal studies.This review summarizes the structure and characteristics of tumor-targeted masking antibodies outlines common masking technologies and their drug development in order to offer new lines of thought for the design and development of next-generation tumor-targeted therapeutics.

Antibody-based therapies are one of the crucial tumor-targeted therapies,enabling pre-cise elimination of tumor cells by specifically binding to antigens on the tumor cell surface.However,their wide applications in solid tumor therapy are often limited by on-target toxicity.Recent advance-ments in antibody engineering have led to the development of novel tumor-targeted masking antibod-ies,which are specifically designed to address these limitations.Masking antibodies typically consist of an antibody domain,a masking domain and a linker.These antibodies are characterized by selective activation and other functional properties.Currently,various masking antibody technologies with distinct characteristics have been developed and have demonstrated favorable safety profiles in animal studies.This review summarizes the structure and characteristics of tumor-targeted masking antibodies outlines common masking technologies and their drug development in order to offer new lines of thought for the design and development of next-generation tumor-targeted therapeutics.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Hepatocellular carcinoma (HCC) is characterized by high postoperative recurrence and mortality rates. In recent years, researchers have identified a significant correlation between microvascular invasion (MVI) and early postoperative recurrence and metastasis of HCC, making it a focal point of HCC research. Accurate preoperative prediction of MVI occurrence and the implementation of relevant interventions (such as expanded resection) could provide substantial benefits to patients. This study analyzes global research over the past decade on MVI predictive indicators based on tumor biological characteristics, genetic measurements, imaging examinations, and tumor markers. The aim is to use these predictive indicators to objectively forecast the occurrence of MVI, thereby aiding in preoperative individual assessments and enhancing treatment plans.

Objective To analyze the outcomes of catheter ablation for persistent atrial fibrillation(AF)and the independent risk factors for its recurrence in the elderly.Methods A total of 194 patients with persistent AF who underwent catheter ablation at our department from January 2019 to December 2021 were enrolled in this study.They were divided into elderly group(≥60 years old,99 cases)and non-elderly group(＜60 years old,95 cases).Their surgical characteris-tics,postoperative complications and recurrence were compared between the two groups,and the independent risk factors for postoperative recurrence were analyzed in the elderly group.Results Advanced age,higher B-type natriuretic peptide,larger proportions of hypertension and coronary heart disease,and increased CHA2DS2-VASc and HAS-BLED scores,while lower male ratio and estimated glomerular filtration rate were observed in the elderly group than the non-elderly group(P＜0.05,P＜0.01).The elderly group had a higher proportion of left atrial fibrosis than the non-elderly group(30.3％vs 8.4％,P=0.001).Postoperative complications in the elderly group in-cluded 1 case of pericardial effusion and 2 cases of hematoma at the puncture site,and all of these were improved after treatment.There were no significant differences in the 1-year success rate(71.7％vs 69.5％,P=0.763)or recurrence rate during blanking period(21.2％vs 21.1％,P=0.981)between the elderly and non-elderly groups.AF duration(HR=1.020,95％CI:1.007-1.032,P=0.002)and recurrence during blanking period(HR=6.781,95％CI:3.078-14.935,P=0.001)were independent risk factors for postoperative recurrence in the elderly group.Conclu-sion Catheter ablation is safe and effective in the treatment of persistent AF in the elderly.The elderly patients with long duration of AF and recurrences during blanking period are more likely to experience recurrences within 1 year after ablation.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective:To investigate the relationship of urinary 8-oxoguanosine(8-oxoGsn)with muscle mass, muscle strength, advanced glycation end products(AGEs), trace elements, heavy metals and other health-related indictors in different age groups of the Beijing area.Methods:A cross-sectional research was conducted.Healthy adults aged 25 to 93 years who sought health examination in the Health Examination Center of Beijing Hospital were recruited.Participants were divided into the young and middle-aged group and the elderly group with age 60 as the cutoff.Urinary 8-oxoGsn levels were detected by mass spectrometry and adjusted using urine creatinine values.Body composition was measured by multifrequency bioelectrical impedance analysis(BIA). Grip strength, 6-meter walking speed and 5-times sit to stand test were conducted by experienced team members.Skin autofluorescence was used to detect skin AGEs.A portable optical scanner was used to detect heavy metals and trace elements using reference points of the palm.Levels of fasting blood glucose, glycosylated hemoglobin, high-density lipoprotein and other common blood biochemical indicators were measured.Results:A total of 106 subjects were enrolled, including 68 in the young and middle-aged group and 38 in the elderly group.The proportion of patients with hypertension(14 ases or 36.8% vs.7 ases or 10.3%), systolic blood pressure[130(120, 140) vs.120(110, 126)mmHg], fasting blood glucose[5.7(5.2, 5.9)mmol/L vs.5.2(4.9, 5.5)mmol/L], glycosylated hemoglobin[6.0(5.7, 6.2)% vs.5.7(5.4, 5.9)%], 8-oxoGsn/Cre[1.9(1.4, 2.6) vs.1.3(1.0, 1.6)], AGEs(2.44±0.46 vs.2.01±0.29), 5-times sit to stand test scores[7.8(6.9, 9.8)s vs.6.0(5.0, 6.8)s], magnesium(31.4±7.2 vs.27.7±6.4), mercury(0.013±0.003 vs.0.008±0.003)and silver[0.011(0.010, 0.012) vs.0.010(0.009, 0.011)]were higher in the elderly group than in the young and middle-aged group, while grip strength[28.0(22.0, 35.1)kg vs.36.6(28.5, 49.1)kg], fat-free mass[44.9(37.5, 51.1)kg vs.53.3(42.4, 58.5)kg], trunk muscle mass[21.0(17.5, 23.9)kg vs.25(19.8, 27.4)kg], appendicular skeletal muscle mass[20.9(17.6, 23.9)kg vs.24.9(19.8, 27.3)kg], calcium[273.3(219.1, 480.0) vs.457.8(428.5, 489.1)], cobalt[0.029(0.027, 0.031) vs.0.031(0.028, 0.034)], selenium[1.44(0.93, 1.71) vs.1.61(1.53, 1.68)]and nickel[3.5(3.3, 4.0)*10 -3vs.3.8(3.6, 4.1)*10 -3]were lower in the elderly group than in the young and middle-aged group( P<0.05). Urinary 8-oxoGsn/Cre levels were positively correlated with age, time of 5-times sit to stand test, AGEs, fasting blood glucose, mercury and aluminum( rs=0.443, 0.292, 0.357, 0.205, 0.316 and 0.214, P<0.05), and negatively correlated with trunk muscle mass, appendicular skeletal muscle mass, fat-free mass, grip strength, silicon and manganese( rs=-0.334, -0.333, -0.332, -0.366, -0.246 and -0.234, P<0.05), with statistical significance. Conclusions:Increased urinary 8-oxoGsn/Cre levels are correlated with decreased muscle mass, poor physical function, accumulation of AGEs, decreased trace element levels and increased heavy metal levels.Therefore, 8-oxoGsn has the potential to be a broadly representative and sensitive indicator for health assessment.

ObjectiveTo investigate the effect of intraoperative Viatorr stent implantation for shunting of blood flow in the left or right branch of the portal vein on the clinical outcome of patients with cirrhotic portal hypertension undergoing transjugular intrahepatic portosystemic shunt (TIPS). MethodsA retrospective analysis was performed for the clinical data of 120 patients with cirrhotic portal hypertension who underwent TIPS in The General Hospital of Western Theater Command from March 2016 to December 2019, and according to the target position of portal vein puncture determined by intraoperative angiography, the patients were divided into left branch group and right branch group. The two groups were compared in terms of the incidence rates of postoperative recurrence and bleeding, stent dysfunction, and hepatic encephalopathy (HE) and survival. The t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier curve was used to calculate rebleeding rate, stent patency rate, incidence rate of HE, and survival rate. ResultsThe surgical success rate was 100% for all 120 patients, with a short-term hemostasis rate of 100%. Among the 120 patients, 52 underwent shunting of the left branch of the portal vein and 68 underwent shunting of the right branch. There was a significant reduction in portal venous pressure after surgery (9.98±2.84 mm Hg vs 24.72±5.11 mm Hg, t=37.76, P＜0.01). The cumulative rebleeding rates at 12 and 24 months after surgery were 3.2% and 11.0%, respectively, and the cumulative incidence rates of HE at 3, 6, 12, and 24 months after surgery were 10.8%, 13.6%, 21.2%, and 24.5%, respectively. Among the 29 patients who experienced HE, 23 had grade Ⅰ-Ⅱ HE and 6 had grade Ⅲ HE. The cumulative incidence rates of stent dysfunction at 12 and 24 months after surgery were 7.1% and 21.4%, respectively. The cumulative survival rates at 12 and 24 months after surgery were 92.0% and 86.5%, respectively. As for comparison of the left branch group and the right branch group, there were no significant differences in postoperative stent patency rate, rebleeding rate, incidence rate of HE, and survival rate(all P＜0.05). ConclusionTIPS is a safe and effective method for the treatment of cirrhotic portal hypertension, and intraoperative Viatorr stent implantation, no matter for establishing the shunt of the left or right branch of the portal vein, will not affect the clinical outcome of patients.

Objective:To explore the association between blood pressure control and risk of ischemic stroke (IS) in patients with hypertension.Methods:A total of 5 488 patients with hypertension from 60 communities were randomly selected from 101 communities in 8 streets of Nanshan District in Shenzhen City by using two-stage sampling method. The social demographic characteristics, behavior and life style, coronary heart disease and diabetes were collected and the physical condition, blood pressure and blood biochemical indexes were measured. From April 1, 2010 to August 31, 2017 as the follow-up period, the incidence of IS was annually collected by using telephone survey. Cox proportional hazard regression model was used to analyze the relationship between blood pressure control, systolic blood pressure (SBP), diastolic blood pressure (DBP) and the risk of IS.Results:The age of all patients was (58.50±12.14) years old, including 2 712 males (49.42%) and 3 112 patients with well-controlled blood pressure (56.71%). During the follow-up period, 358 new cases of IS were confirmed, and the incidence density was 1 346.27/100 000 person-years. Cox proportional hazard regression model analysis showed after adjusting for confounding factors, unstable blood pressure control, SBP≥150 mmHg (1 mmHg=0.133 kPa; compared with SBP<120 mmHg), and DBP≥95 mmHg (compared with DBP<80 mmHg) were associated with risk of IS. The HR (95% CI) was 1.29 (1.04, 1.59), 2.00 (1.26, 3.17) and 1.52 (1.01, 2.64), respectively. Subgroup analyses showed these associations only existed in female patients with hypertension. The HR (95% CI) was 1.39 (1.05, 1.85), 2.53 (1.41, 4.56) and 1.73 (1.00, 3.36), respectively. Conclusion:Unstable blood pressure control increases the risk of IS in female patients with hypertension.

Objective:To explore the association between blood pressure control and risk of ischemic stroke (IS) in patients with hypertension.Methods:A total of 5 488 patients with hypertension from 60 communities were randomly selected from 101 communities in 8 streets of Nanshan District in Shenzhen City by using two-stage sampling method. The social demographic characteristics, behavior and life style, coronary heart disease and diabetes were collected and the physical condition, blood pressure and blood biochemical indexes were measured. From April 1, 2010 to August 31, 2017 as the follow-up period, the incidence of IS was annually collected by using telephone survey. Cox proportional hazard regression model was used to analyze the relationship between blood pressure control, systolic blood pressure (SBP), diastolic blood pressure (DBP) and the risk of IS.Results:The age of all patients was (58.50±12.14) years old, including 2 712 males (49.42%) and 3 112 patients with well-controlled blood pressure (56.71%). During the follow-up period, 358 new cases of IS were confirmed, and the incidence density was 1 346.27/100 000 person-years. Cox proportional hazard regression model analysis showed after adjusting for confounding factors, unstable blood pressure control, SBP≥150 mmHg (1 mmHg=0.133 kPa; compared with SBP<120 mmHg), and DBP≥95 mmHg (compared with DBP<80 mmHg) were associated with risk of IS. The HR (95% CI) was 1.29 (1.04, 1.59), 2.00 (1.26, 3.17) and 1.52 (1.01, 2.64), respectively. Subgroup analyses showed these associations only existed in female patients with hypertension. The HR (95% CI) was 1.39 (1.05, 1.85), 2.53 (1.41, 4.56) and 1.73 (1.00, 3.36), respectively. Conclusion:Unstable blood pressure control increases the risk of IS in female patients with hypertension.