OBJECTIVE To conduct a comprehensive clinical evaluation of phosphate-lowering drugs in the treatment of chronic kidney disease （CKD） with hyperphosphatemia， and to provide evidence-based support for clinical drug decision-making. METHODS Relevant studies meeting the inclusion and exclusion criteria were retrieved， a comprehensive evaluation of efficacy， safety and economics was conducted based on existing study results. Innovation was analyzed from three aspects including filling the clinical gap， and suitability was assessed from two aspects including technical suitability. Accessibility was evaluated based on the survey data from 37 medical institutions in Kunming， combined with information from the National Reimbursement Drug List and national centralized drug procurement. RESULTS A total of 10 meta-analyses and 2 pharmacoeconomic studies were included. In terms of efficacy， all three categories of phosphate-lowering drugs （calcium-based phosphate binders， non-calcium-based phosphate binders， sodium-hydrogen exchanger 3 inhibitors） effectively reduced serum phosphorus levels. Calcium-based phosphate binders elevated serum calcium levels more significantly； sevelamer was superior to calcium-based phosphate binders in reducing intact parathyroid hormone levels； iron-based phosphate binders improved iron metabolism and anemia-related indicators. In terms of safety， iron-based phosphate binders had the highest incidence of gastrointestinal adverse reactions， followed by lanthanum carbonate. In terms of economics， sevelamer demonstrated economic advantages over calcium-based phosphate binders and lanthanum carbonate. In terms of innovation， non-ca lcium-based phosphate binders addressed the clinical limitation of hypercalcemia associated with calcium-based phosphate binders； iron-based phosphate binders met the treatment needs of patients with comorbid iron deficiency anemia； tenapanor exhibited an innovative phosphorus-lowering mechanism. In terms of suitability， all three categories showed good suitability in various aspects. In terms of accessibility， sevelamer had the highest availability rate， while tenapanor was not yet available in medical institutions. All three categories have been included in the National Reimbursement Drug List ； the prices of lanthanum carbonate and sevelamer decreased substantially following centralized procurement with improved affordability. CONCLUSIONS For CKD patients with hyperphosphatemia， non-calcium-based phosphate binders are preferred， among which sevelamer is recommended as the first-line choice. Lanthanum carbonate may be considered for patients with gastrointestinal intolerance； iron-based phosphate binders are preferred for patients with comorbid iron deficiency anemia； tenapanor may be considered for patients with poor response to or intolerance of conventional regimens； calcium-based phosphate binders are not recommended as long-term first-line therapy.

Objective:To explore the association of blood and urinary cadmium levels with lipid profile levels and dyslipidemia in Chinese adults aged 18 to 79 years.Methods:Based on the China National Human Biomonitoring (CNHBM) program, a cross-sectional survey was conducted from 2017 to 2018 using a multi-stage stratified random sampling method, including a total of 10 713 adults aged 18 to 79 years. Data was obtained through questionnaires, physical examinations, biological sample collection, and laboratory testing. Multiple linear mixed effect model (MLMM) and generalized linear mixed effect model (GLMM) were used to analyze the association of blood and creatinine-corrected urinary cadmium levels with lipid profile levels as well as dyslipidemia among adults.Results:The age of 10 713 participants was (47.23±0.24) years, with 5 372 males accounting for 61.3% of the national population. The weighted mean±standard error (SE) of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was (5.21±0.03), (1.86±0.03), (2.96±0.03), and (1.43±0.01) mmol/L, respectively. The prevalence rate of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, low HDL-C, and high LDL-C was 16.0%, 21.6%, 6.6%, 13.5%, and 10.0%, respectively. MLMM showed that, after adjusting for relevant confounders, log-transformed blood cadmium levels were positively associated with increased levels of TC, TG and LDL-C ( P<0.05). When blood cadmium levels were categorized into quartiles, compared to the lowest exposure group ( Q1), participants in the highest blood cadmium exposure group ( Q4) had increases of 0.19 (95% CI: 0.06, 0.32) mmol/L in TC and 0.25 (95% CI: 0.08, 0.43) mmol/L in TG. GLMM indicated that, after adjusting for confounders, higher blood cadmium exposure levels were associated with increased risks of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, and high LDL-C ( P<0.05). Further analysis by quartiles showed that, compared to the blood cadmium Q1 exposure group, the OR value (95% CI) for the Q4 group was 1.53 (1.12, 2.08) for hypercholesterolemia, 1.54 (1.09, 2.17) for hypertriglyceridemia, 2.24 (1.47, 3.40) for mixed hyperlipidemia, and 1.49 (1.07, 2.09) for high LDL-C. Conclusion:The cadmium internal exposure levels are associated with blood lipid profile levels as well as the incidence of dyslipidemia in Chinese adults aged 18 to 79.

Objective·To comprehensively evaluate the efficiency of different kits and methods for DNA and RNA extraction from blood samples.Methods·A total of 145 blood samples were collected,including those from patients with Alzheimer's disease(20 cases),fibrosis(5 cases),colorectal cancer(108 cases),and healthy individuals(12 cases).A column-based kit(Kit A)and a nucleic acid extraction instrument were used to extract genomic DNA(gDNA)from leukocytes in the blood.Cell-free DNA(cfDNA)and cell-free RNA(cfRNA)in plasma were extracted using five different kits(Kit B?F),which employed either column-based(Kit B,E)or magnetic bead-based methods(Kit C,D,F).The extraction process of Kit B was optimized by increasing the plasma sample volume and extending the elution incubation time.Furthermore,this protocol was applied to extracting cfDNA from plasma samples of 100 colorectal cancer patients.Quantitative real-time PCR(qPCR)was used to quantify the extracted DNA and RNA,and the molecular yields were compared to evaluate the extraction efficiency.A comprehensive assessment was conducted,considering factors such as cost and operation time.Results·In gDNA extraction,although the the operation time was shortened by using the nucleic acid extraction instrument,the median number of DNA molecules extracted using Kit A(column-based method)was 25.36-fold higher than that obtained with the instrument(P<0.05).For cfDNA extraction,while the overall efficiency of the three kits(Kit B?D)was similar,Kit B(column-based method)showed superior performance in low-concentration samples,with average DNA yields 4.24-fold and 1.18-fold higher than those of Kit D and Kit C(both magnetic bead-based).Optimization of Kit B's extraction protocol further improved cfDNA yield.When comparing three samples,the cfDNA yields from larger plasma input volumes was 3.98-fold,2.38-fold,and 3.82-fold higher than those from smaller input volumes,respectively.The results of cfDNA extraction from 100 colorectal cancer patients indicated that this extraction protocol reliably extracted sufficient amounts of cfDNA from clinical samples.For cfRNA extraction,Kit E(column-based method)was widely recommended due to its high efficiency,convenience,and cost-effectiveness.The median RNA content extracted using Kit E was 5.01-fold higher than that of Kit F(magnetic bead-based method).Lastly,a comparison of the copy numbers of cfDNA and cfRNA in plasma revealed that the average copy number of cfRNA per milliliter of plasma was 27.65-fold higher than that of cfDNA.Conclusion·Kit A,Kit B,and Kit E show outstanding performance in leukocyte gDNA extraction,plasma cfDNA extraction,and plasma cfRNA extraction,respectively.However,although Kit E has advantages in extraction efficiency and cost,its safety requires further evaluation.

Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity, expanding antibacterial spectra, and reducing required dosages. Previously, compound 15 was identified as a potential adjuvant for Polymyxin B (PB) against multidrug-resistant (MDR) Pseudomonas aeruginosa DK2; however, its clinical utility was hindered by high cytotoxicity, uncertain in vivo efficacy, and an unclear synergetic mechanism. To address these challenges, we synthesized and evaluated a series of novel benzamide derivatives, with A22 emerging as a particularly promising candidate. A22 demonstrated potent synergistic activity to PB, minimal cytotoxicity, improved water solubility, and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains. In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22. Moreover, A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2. Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production, reducing ATP levels, increasing NOX activity, and inhibiting biofilm formation, leading to bacterial death. These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants, offering a robust approach to combating MDR Gram-negative bacterial infections.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

Objective:To analyze and validate the reliability and validity of the social skills improvement system-rating scales Chinese version (parent version) (SSIS-RS-C) in middle school students.Method:A total of 1 486 parents of middle school students were recruited according to the cluster sampling method.The social responsiveness scale and strengths and difficulties questionnaire were used as criterion validity tools.A retest was conducted one month later.SPSS 27.0 was used for descriptive statistics, item analysis, internal consistency test, test-retest reliability test and criterion validity test. AMOS 24.0 was used to perform confirmatory factor analysis .Results:Item analysis indicated significant positive correlations between each item and the subscales ( r=0.293-0.782, all P<0.01), with significant differences in scores between high and low groups ( t=10.079-37.038, all P<0.01).Confirmatory factor analysis supported a seven-factor structure for the social skills subscale(communication, cooperation, assertion, responsibility, empathy, engagement and self control) and a five-factor structure for the problem behavior subscale (externalizing, bullying, hyperactivity/inattention, internalizing and autism spectrum) of the SSIS-RS-C.There was a positive correlation between the social skills subscale and prosocial behavior ( r=0.637, P<0.001), and between the problem behavior subscale and social impairments and difficult behaviors ( r=0.765, 0.688, both P<0.001).The Cronbach's α coefficients for the total scale, social skills subscale and problem behavior subscale were 0.934, 0.972 and 0.963, respectively.The test-retest correlation coefficients for the total score and the two subscales were 0.665, 0.871 and 0.598, respectively (all P<0.001). Conclusion:The SSIS-RS-C demonstrated good reliability and validity in the Chinese adolescent population.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

Objective:To determine the epidemiological characteristics of human bocavirus (HBoV) in children with acute respiratory infections (ARI) in Bengbu City, Anhui Province, in 2024.Methods:Nasopharyngeal swab samples were collected from 269 children with ARI in Bengbu City, Anhui Province, in 2024. Seventeen respiratory pathogens were screened using quantitative fluorescence PCR. For HBoV-positive samples, the VP1/VP2 structural gene fragments of HBoV were amplified and sequenced for genetic evolutionary analysis.Results:Among the 269 nasopharyngeal swab samples from children with ARI, the overall detection rate of respiratory pathogens was 48.33% (103/269). The top three pathogens with the highest detection rates were: Influenza A virus (FluA): 10.04% (27/269), Respiratory syncytial virus (RSV): 8.18% (22/269), Human bocavirus (HBoV): 7.43% (20/269). The age distribution of HBoV-infected children showed that the detection rate was highest in the 0-2 years age group (50%, 10/20), followed by the 3-5 years age group (25%, 5/20) and the over 6 years age group (25%, 5/20). However, there was no statistically significant difference in viral detection rates among the age groups. Genetic evolutionary analysis based on VP1/VP2 revealed that all 13 HBoV strains were of the HBoV-1 genotype.Conclusions:HBoV is one of the major pathogens causing ARI in children in Bengbu City, Anhui Province, in 2024, with HBoV-1 being the predominant genotype. Additionally, infants aged 0-2 years are the most susceptible population to HBoV infection.

Objective·To comprehensively evaluate the efficiency of different kits and methods for DNA and RNA extraction from blood samples.Methods·A total of 145 blood samples were collected,including those from patients with Alzheimer's disease(20 cases),fibrosis(5 cases),colorectal cancer(108 cases),and healthy individuals(12 cases).A column-based kit(Kit A)and a nucleic acid extraction instrument were used to extract genomic DNA(gDNA)from leukocytes in the blood.Cell-free DNA(cfDNA)and cell-free RNA(cfRNA)in plasma were extracted using five different kits(Kit B?F),which employed either column-based(Kit B,E)or magnetic bead-based methods(Kit C,D,F).The extraction process of Kit B was optimized by increasing the plasma sample volume and extending the elution incubation time.Furthermore,this protocol was applied to extracting cfDNA from plasma samples of 100 colorectal cancer patients.Quantitative real-time PCR(qPCR)was used to quantify the extracted DNA and RNA,and the molecular yields were compared to evaluate the extraction efficiency.A comprehensive assessment was conducted,considering factors such as cost and operation time.Results·In gDNA extraction,although the the operation time was shortened by using the nucleic acid extraction instrument,the median number of DNA molecules extracted using Kit A(column-based method)was 25.36-fold higher than that obtained with the instrument(P<0.05).For cfDNA extraction,while the overall efficiency of the three kits(Kit B?D)was similar,Kit B(column-based method)showed superior performance in low-concentration samples,with average DNA yields 4.24-fold and 1.18-fold higher than those of Kit D and Kit C(both magnetic bead-based).Optimization of Kit B's extraction protocol further improved cfDNA yield.When comparing three samples,the cfDNA yields from larger plasma input volumes was 3.98-fold,2.38-fold,and 3.82-fold higher than those from smaller input volumes,respectively.The results of cfDNA extraction from 100 colorectal cancer patients indicated that this extraction protocol reliably extracted sufficient amounts of cfDNA from clinical samples.For cfRNA extraction,Kit E(column-based method)was widely recommended due to its high efficiency,convenience,and cost-effectiveness.The median RNA content extracted using Kit E was 5.01-fold higher than that of Kit F(magnetic bead-based method).Lastly,a comparison of the copy numbers of cfDNA and cfRNA in plasma revealed that the average copy number of cfRNA per milliliter of plasma was 27.65-fold higher than that of cfDNA.Conclusion·Kit A,Kit B,and Kit E show outstanding performance in leukocyte gDNA extraction,plasma cfDNA extraction,and plasma cfRNA extraction,respectively.However,although Kit E has advantages in extraction efficiency and cost,its safety requires further evaluation.