Background Chlorinated perfluoroalkyl ether sulfonate Cl-PFAES, trade name F-53B, a novel per- and polyfluoroalkyl substance (PFAS), has been shown to induce multi-organ toxicity in humans and cross the blood-brain barrier. However, its toxic effects and underlying mechanisms on neural stem cells (NSCs) remain unclear. Objective To investigate the impact of F-53B on NSCs proliferation and differentiation through oxidative stress and explore its potential molecular mechanisms in associations with mitochondrial function damage and the expression of autophagy-related gene (PINK1/Parkin). Methods Primary NSCs isolated from neonatal C57BL/6 mice were used as a model and exposed to F-53B at concentrations of 0, 33, or 100 μmol·L⁻¹ for 24 h. Cell viability was assessed using the cell counting kit-8 (CCK-8) assay, while proliferation was evaluated by the 5-ethynyl-2’-deoxyuridine (EdU) incorporation assay. Immunofluorescence staining was performed to observe differentiation phenotypes. Intracellular and mitochondrial reactive oxygen species (ROS) levels were quantified using dihydroethidium (DHE) and MitoSOX probes, respectively. Mitochondrial morphology was observed using MitoTracker Green. ATP level was measured with a commercial kit. Additionally, real-time quantitative polymerase chain reaction (qPCR) was conducted to quantify the expression of PINK1 and Parkin genes. Results Exposure to 100 μmol·L⁻¹ F-53B significantly reduced cell viability to 93.6% of the control group (P<0.01), and decreased the proportion of EdU⁺ cells (P<0.01), indicating proliferation inhibition. The differentiation analysis showed a reduction in neuronal generation, axonal shortening, and an increase in astrocytes. The 100 μmol·L⁻¹ F-53B exposure elevated intracellular ROS to 122% (P<0.01) and mitochondrial ROS (MitoROS) to 135% (P<0.001) of the control levels, leading to mitochondrial fragmentation. The ATP levels after the F-53B exposure decreased to 62.4% relative to the control group (P<0.001). Furthermore, the mRNA expression levels of PINK1 and Par after the F-53B exposure were notably reduced (P<0.05). Conclusion F-53B may induce oxidative stress, thereby disrupting mitochondrial morphology and function while inhibiting the PINK1/Parkin-mediated mitophagy pathway, ultimately leading to impaired neural stem cell proliferation and abnormal differentiation. This study provides new insights into the neurotoxicity mechanisms of F-53B.

Objective To compare the safety and efficacy of vancomycin in obese patients guided by trough concentration and AUC24h/MIC,and to provide data for individualized administration of vancomycin in obese patients.Methods We retrospectively collected the data of obese adult patients(BMI 30 kg/m2)who had severe infection caused by gram-positive cocci and treated with vancomycin intravenously in two Grade A tertiary hospitals in Shanghai from 2012 to 2024.The patients were assigned to trough concentration monitoring group or AUC24h/MIC monitoring group according to the therapeutic drug monitoring(TDM)method at the time of admission.Nephrotoxicity and efficacy were compared between the two groups of patients.Results A total of 22 obese patients were included in this study,including 12 in the trough concentration monitoring group and 10 in the AUC24h/MIC monitoring group.No significant difference was found between the two groups in gender,age,BMI,creatinine clearance before treatment,underlying disease,site of infection,pathogen type,or concomitant medications.The proportion of ICU admission was higher in AUC24h/MIC monitoring group.The length of ICU stay,vancomycin treatment duration,bacterial clearance rate and comprehensive efficacy rate did not show significant difference between the two groups.The average daily dose of vancomycin in trough concentration monitoring group was significantly lower than that in A UC24h/MIC monitoring group[(1.63±0.59)g vs(2.29±0.72)g,P=0.026].The average treatment duration was not significantly different between the two groups[(15.33±10.28)d vs(14.90±6.92)d,P=0.911].Compared with the trough concentration monitoring group,the initial peak concentration[(30.99±16.22)mg/L vs(19.41±5.42)mg/L,P=0.025]and overall peak concentration[(33.67±16.53)mg/L vs(22.08±3.96)mg/L,P=0.045]of vancomycin were lower in theAUC24h/MIC monitoring group,but the initial trough concentration[(11.03±8.66)mg/L vs(6.33±4.45)mg/L,P=0.139]and overall trough concentration[(13.75±9.74)mg/L vs(9.74±4.24)mg/L,P=0.218]were similar in the two groups.Vancomycin-associated nephrotoxicity did not occur in any group,but 41.7％of the patients in the trough concentration monitoring group reached the threshold of renal toxicity,i.e.trough concentration ≥15 mg/L.Conclusions Vancomycin treatment with conventional dosing regimen still have good clinical efficacy in obese adult patients.Vancomycin therapy guided by A UC24h/MIC can achieve the target value at lower concentration or exposure,which is promising for reducing vancomycin-associated nephrotoxicity.

Objective To compare the safety and efficacy of vancomycin in obese patients guided by trough concentration and AUC24h/MIC,and to provide data for individualized administration of vancomycin in obese patients.Methods We retrospectively collected the data of obese adult patients(BMI 30 kg/m2)who had severe infection caused by gram-positive cocci and treated with vancomycin intravenously in two Grade A tertiary hospitals in Shanghai from 2012 to 2024.The patients were assigned to trough concentration monitoring group or AUC24h/MIC monitoring group according to the therapeutic drug monitoring(TDM)method at the time of admission.Nephrotoxicity and efficacy were compared between the two groups of patients.Results A total of 22 obese patients were included in this study,including 12 in the trough concentration monitoring group and 10 in the AUC24h/MIC monitoring group.No significant difference was found between the two groups in gender,age,BMI,creatinine clearance before treatment,underlying disease,site of infection,pathogen type,or concomitant medications.The proportion of ICU admission was higher in AUC24h/MIC monitoring group.The length of ICU stay,vancomycin treatment duration,bacterial clearance rate and comprehensive efficacy rate did not show significant difference between the two groups.The average daily dose of vancomycin in trough concentration monitoring group was significantly lower than that in A UC24h/MIC monitoring group[(1.63±0.59)g vs(2.29±0.72)g,P=0.026].The average treatment duration was not significantly different between the two groups[(15.33±10.28)d vs(14.90±6.92)d,P=0.911].Compared with the trough concentration monitoring group,the initial peak concentration[(30.99±16.22)mg/L vs(19.41±5.42)mg/L,P=0.025]and overall peak concentration[(33.67±16.53)mg/L vs(22.08±3.96)mg/L,P=0.045]of vancomycin were lower in theAUC24h/MIC monitoring group,but the initial trough concentration[(11.03±8.66)mg/L vs(6.33±4.45)mg/L,P=0.139]and overall trough concentration[(13.75±9.74)mg/L vs(9.74±4.24)mg/L,P=0.218]were similar in the two groups.Vancomycin-associated nephrotoxicity did not occur in any group,but 41.7％of the patients in the trough concentration monitoring group reached the threshold of renal toxicity,i.e.trough concentration ≥15 mg/L.Conclusions Vancomycin treatment with conventional dosing regimen still have good clinical efficacy in obese adult patients.Vancomycin therapy guided by A UC24h/MIC can achieve the target value at lower concentration or exposure,which is promising for reducing vancomycin-associated nephrotoxicity.

Objective:To explore the effectiveness and feasibility of strengthening inspiratory muscle training program matching the preoperative waiting time for patients with valvular heart disease in China with limited resources in preventing postoperative pulmonary complications(PPCs). Method:Patients undergoing elective heart valve surgery were randomly divided into control group and inter-vention group,with 65 patients in each group.All the enrolled patients received a routine physical therapy pro-gram before surgery,and the intervention group received an additional 3 days of enhanced inspiratory muscle training program before surgery.The incidence of postoperative complications was recorded for all patients with-in 14 days after surgery,respiratory function and motor capacity(6-minute walking test)were tested for all patients on the day of admission and discharge,and the length of postoperative hospital stay was counted. Result:Compared with the control group,the incidence of PPCs was lower in the intervention group(OR 2.18,95％CI 1.07-4.47,P-0.03),and the walking distance was longer(P=0.01).There was no statistical difference in lung function and length of hospital stay(P＞0.05),and no adverse events occurred during train-ing.There was no significant difference in general demographic characteristics between the two groups before treatment.The incidence of PPCs in the intervention group was lower than that in the control group(P＜0.05),and the 6-minute walking distance at discharge was higher than that in the control group(P＜0.05).There were no statistically significant differences in lung function and postoperative hospital stay between the intervention group and the control group(P＞0.05),and no adverse events occurred during training. Conclusion:Enhanced inspiratory muscle training 3 days before surgery is safe and feasible in patients with elective heart valves and can reduce postoperative pulmonary complications and improve the level of motor function at discharge.

Objective:To explore the diagnostic value of auditory verbal learning test-Huashan version(AVLT-H)of memo-ry impairment in patients with subjective cognitive decline(SCD)and mild cognitive impairment(MCI). Method:According to the inclusion criteria,the recruited elderly were screened and divided into three groups:normal cognition(NC),SCD and MCI group.The neuropsychological tests including mini-mental state exami-nation(MMSE),Montreal cognitive assessment-Beijing version(MOCA-BJ)and AVLT-H were completed af-ter inclusion.The scores of MMSE,MoCA-B,AVLT-N2,N3,N4,N5,N6 and N7 were recorded and analyzed. Result:There were significant differences in the scores of MMSE,MoCA and AVLT-H among the three groups(P＜0.0167).The adjusted Bonferroni test was used to detect significant differences in post-hoc comparison.There were significant difference in MMSE and MoCA scores between SCD and NC(P＜0.001)and between MCI and NC(P＜0.001).However,no significant difference between MCI and SCD was found.There were sig-nificant difference in N1 score between MCI and NC(P=0.013)and between MCI and SCD(P=0.001),but there was no significant difference between SCD and NC.There were significant difference in AVLT-N2,N3,N4,N5,N6 and N7 scores between MCI and NC(P＜0.001)and between MCI and SCD(P＜0.001),but there was no significant difference between SCD and NC.The area under the curve of MMSE,MoCA and AVLT-H scores were examined using NC group and SCD group as state variables,respectively.For differentiat-ing MCI and SCD,eAVLT-H scores had a larger area under the curve with higher sensitivity and specificity,N1 and N7 had the highest sensitivity.For distinguishing MCI from NC,AVLT-H and MoCA scores had a larger area under the curve with higher sensitivity and specificity,N4,N6 and N7 had the highest sensitivity. Conclusion:AVLT-H,combined with MMSE and MoCA,can improve the defining diagnostic sensitivity of MCI and SCD from normal cognition.It is recommended to routinely use AVLT-H in a routine assessment for MCI and SCD patients.

Chest CT manifestations of pulmonary tuberculosis(PTB)are characterized by multi-temporal and multi-morphological,which could guide clinical diagnosis of PTB and evaluating therapeutic efficiency.Radiomics has important clinical value for diagnosing and differentiating PTB,evaluating disease status,predicting drug resistance and assessing treatment efficacy.The status and prospects of clinical application of CT radiomics for diagnosis and treatment of PTB were reviewed in this article.

Chest CT manifestations of pulmonary tuberculosis(PTB)are characterized by multi-temporal and multi-morphological,which could guide clinical diagnosis of PTB and evaluating therapeutic efficiency.Radiomics has important clinical value for diagnosing and differentiating PTB,evaluating disease status,predicting drug resistance and assessing treatment efficacy.The status and prospects of clinical application of CT radiomics for diagnosis and treatment of PTB were reviewed in this article.

OBJECTIVE To establish the drug-induced liver injury （DILI） surveillance and assessment system （DILI-SAS）， and to improve the diagnostic efficiency of clinical DILI. METHODS The DILI-SAS was constructed by using natural language processing technology to mine and utilize all inpatient medical record data， and combined with Roussel Uclaf causality assessment method （RUCAM）. The medical records of 19 445 hospitalized patients from August 2022 to January 2023 were detected to verify the performance of the system and manually analyze the basic data of patients with DILI and the distribution of the first suspected drugs. RESULTS The overall accuracy rate of the DILI-SAS system was 91.95%， and the recall rate was 93.20%. Seventy-five DILI cases were detected， and the DILI incidence rate was 385.70/100 000 people. The efficiency of DILI monitoring by human- computer coupling was increased by about 60 times of manual monitoring； males （61.33%） and patients over 60 years old （56.00%） were the most common in the 75 cases of DILI. The clinical type of liver injury was hepatocyte injury （69.33%）， the incubation period was mainly 5-90 days after treatment （62.67%）， and the RUCAM score between 3 and 5 was the most common （66.67%）； pharmacological distribution of the first suspected drugs was mainly dihydropyridines， HMG CoA reductase inhibitors， proton pump inhibitors， etc. The specific drugs were atorvastatin， omeprazole， ceftriaxone， metronidazole and other drugs. CONCLUSIONS The establishment of DILI-SAS can improve the evaluation efficiency on the basis of ensuring the accuracy degree， and provide a solution for the early identification， diagnosis and evaluation of clinical DILI.

In the past two decades, adult cardiac surgery has developed by leaps and bounds in both anesthetic techniques and surgical methods, whereas the incidence of postoperative pulmonary complications (PPCs) has not changed. Until now PPCs are still the most common complications after cardiac surgery, resulting in poor prognosis, significantly prolonged hospital stays and increased medical costs. With the promotion of the concept of enhanced recovery after surgery (ERAS), pre-rehabilitation has been becoming a basic therapy to prevent postoperative complications. Among them, preoperative inspiratory muscle training as a very potential intervention method has been widely and deeply studied. However, there is still no consensus about the definition and diagnostic criteria of PPCs around the world; and there is significant heterogeneity in preoperative inspiratory muscle training in the prevention of pulmonary complications after cardiac surgery in adults, which impedes its clinical application. This paper reviewed the definition, mechanism, and evaluation tools of PPCs, as well as the role, implementation plan and challenges of preoperative inspiratory muscle training in the prevention of PPCs in patients undergoing cardiac surgery, to provide reference for clinical application.