This study investigates the neuroprotective potential of extracellular vesicles (EVs) delivering quercetin-3-O-β-d-glucuronic acid (QG-EVs) in cerebral ischemia-reperfusion injury (CIRI). Targeted brain delivery of QG-EVs was confirmed, with neuron cells identified as pivotal in modulating CIRI through single-cell RNA sequencing (scRNA-seq). Activating transcription factor 4 (Atf4) was highlighted as a critical regulatory factor, and in vitro studies revealed that silencing Atf4 diminished the neuroprotective effects of QG-EVs, increasing oxidative stress levels and neuronal apoptosis. In a CIRI mouse model, the knockdown of Atf4 attenuated the protective outcomes provided by QG-EVs, further affirming the role of Atf4 in mediating neuroprotection. Behavioral assessments and protein analysis showed that QG-EVs significantly reduced neuronal damage and pro-apoptotic markers, while improving neurological function via Atf4 upregulation. The outcomes hint at the potential of QG-EVs as a beneficial therapeutic modality to mitigate neuronal damage in CIRI by enhancing Atf4 expression, highlighting its potential for improving ischemic stroke outcomes.

Objective:To analyze the changing trend of incidence and prevalence of pneumoconiosis globally, and provide scientific basis for the formulation of health policy.Methods:In June 2022, through the Global Health Data exchange (GHDx) query tool (http: //ghdx.healthdata.org/gbd-results-tool) , the pneumoconiosis incidence and prevalence data was downloaded and organized. Estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trends of pneumoconiosis from 1990 to 2019. EAPC was estimated by linear regression model based on ASR.Results:The overall ASR of the incidence and prevalence of pneumoconiosis decreased from 1990 to 2019, and their EAPCs were-0.85% (95% CI: -1.11%--0.60%) and -0.78% (95% CI: -1.08%--0.49%) . Over the past 30 years, the incidence and prevalence of pneumoconiosis in all SDI areas showed decreasing trends, especially in high SDI areas, their EAPCs were -1.46% (95% CI: -1.76%--1.15%) and -1.99% (95% CI: -2.44%--1.53%) . 110 countries/areas showed increasing trends in age standardized incidence rate (ASIR) , with Iran and Georgia showing the most pronounced upward trend, their EAPCs were 5.32% (95% CI: 4.43%-6.22%) and 4.39% (95% CI: 3.81%-4.97%) . 125 countries/areas showed anincreasing trends in prevalence ASR, with Iran had the fastest rise in prevalence (EAPC=6.40%, 95% CI: 5.33%-7.49%) . Conclusion:Although decreasing trends in the burden of pneumoconiosis are observed globally from 1990 to 2019, but the burden of pneumoconiosis in low-and middle-income countries or regions are still heavy. We need more effective strategies to prevent and reduce the burden of pneumoconiosis.

Objective:To analyze the disease burden of Noise-Induced Hearing Loss (NIHL) in China from 1990 to 2019, forecast the disease burden of NIHL from 2020 to 2030, and provide data support for the prevention and control of NIHL.Methods:In July 2022, the disease burden data of NIHL in different age groups and genders in China during 1990-2019 were selected from the GBD database. The Jointpoint regression model was established to analyze the trend of the disease burden of NIHL in China. An age-period-cohort model was constructed to analyze the changing trend of NIHL in terms of age, period, and cohort, and a Bayesian age-period-cohort model was developed to predict the disease burden of NIHL in China from 2020 to 2030.Results:From 1990 to 2019, the disability adjusted life year (DALY) of China's NIHL increased from 1361600 to 2327700 years. The coarse rate of DALY increased from 115.03/100000 to 163.65/100000 (AAPC=1.23, P<0.001), and the normalization rate of DALY decreased from 127.67/100000 to 119.83/100000 (AAPC=-0.21, P<0.001). It is predicted that from 2020 to 2030, the DALYs of China's NIHL will increase from 2412900 in 2020 to 2655000 in 2030, and the DALY normalization rate will decrease from 241.29/100000 in 2020 to 125.71/100000 in 2030. Conclusion:The burden of noise-induced hearing loss (NIHL) in China is significant and should not be overlooked. To reduce this burden, we need to focus on strengthening source management, process control, personal protection, and comprehensive prevention and treatment through various methods.

Clinical trials are an important method for evaluating the safety and efficacy of in vitro diagnostic reagents, and are a key basis for product registration review and approval. In order to strengthen the management of clinical trials of in vitro diagnostic reagents, the National Medical Products Administration and relevant departments have formulated a series of regulations at the regulatory level, and require applicants and clinical trial institutions to establish a quality management system for clinical trials of in vitro diagnostic reagents. Medical laboratory is the main department and implementer of in vitro diagnostic reagent clinical trials in medical institutions. In recent years, with the rapid development of the in vitro diagnostic industry, the clinical trial projects of in vitro diagnostic reagents conducted by medical laboratory have been increasing day by day. However, there are currently few discussions on the clinical trial of in vitro diagnostic reagents from the perspective of researchers. Therefore, this article summarizes the characteristics of clinical trials of in vitro diagnostic reagents, analyzes the problems and difficulties in conducting clinical trials of in vitro diagnostic reagents in current medical laboratories, and introduces the laboratory′s experience in management; to provide reference for medical testing laboratories that have not yet conducted or have already conducted clinical trials of in vitro diagnostic reagents, in order to improve the quality and efficiency of clinical trials.

Objective To investigate correlation between the expression level of multiple cytokine levels in neonatal umbilical cord plasma and early-onset sepsis for screening out the cytokines with good diagnostic value for early-onset neonatal sepsis(EONS).Methods Full-term neonates and preterm neonates(Gestational age ≥ 32 weeks)of 310 cases between September 2021 and June 2023 were selected as study subjects.According to clinical signs,laboratory results and blood culture,these subjects were divided into 3 groups:control group without sepsis,EONS blood culture positive group and EONS blood culture negative group.Umbilical cord blood plasma of all subjects was collected within 72 hours after birth.The expression levels of cytokines IL-2,IL-4,IL-6,IL-9,IL-10,IL-21,IFN-γ and TNF-α were determined,and cytokines with high expression levels(high correlation)were screened out.Receiver operating characteristic(ROC)curve was used to analyze the specificity and sensitivity of the selected cytokines in the diagnosis of neonatal early-onset sepsis.Results Among the 8 cytokines mentioned above,the concentrations of IL-6,IL-9 and IL-21 in cord blood plasma of neonatal early-onset sepsis positive blood culture patients(392.6±258.7pg/ml,11.9±7.5pg/ml,29.1±16.8 pg/ml)and negative blood culture patients(353.8±244.5pg/ml,10.4±6.3pg/ml,27.7±19.2pg/ml)were higher than those of the control group(34.9±25.1pg/ml,5.9±4.5pg/ml,10.8±10.1 pg/ml),with significant differences(t=23.961,20.732;15.174,17.824;22.466,21.193,all P＜0.01),and the increase of IL-6 concentration was the most obvious.ROC curve analysis(the cut-off values of IL-6,IL-9 and IL-21:123.0 pg/ml,3.60 pg/ml,6.00 pg/ml,respectively)showed that the areas under the ROC curve for IL-6,IL-9 and IL-21 alone detection were 0.876(95％CI:0.786～0.955),0.782(95％CI:0.667～0.875)and 0.825(95％CI:0.737～0.913),respectively.The area under the ROC curve for the combined detection of IL-6,IL-9 and IL-21 was 0.930(95％CI:0.875～0.997).The combined detection of IL-6,IL-9 and IL-21 improved the specificity and sensitivity of the test than IL-6,IL-9 and IL-21 alone detection,and the differences were statistically significant(Z=2.137,2.391,2.257,all P＜0.05).There was no significant difference in cytokine expression between positive blood culture and negative blood culture neonates with early-onset sepsis(t=0.276～3.377,all P＞0.05).Conclusion The cytokines expression of IL-6,IL-9 and IL-21 in neonatal umbilical cord plasma of neonatal early-onset sepsis were increased.Combined detection of IL-6,IL-9 and IL-21 has good diagnostic value for early-onset neonatal sepsis.

Clinical trials are an important method for evaluating the safety and efficacy of in vitro diagnostic reagents, and are a key basis for product registration review and approval. In order to strengthen the management of clinical trials of in vitro diagnostic reagents, the National Medical Products Administration and relevant departments have formulated a series of regulations at the regulatory level, and require applicants and clinical trial institutions to establish a quality management system for clinical trials of in vitro diagnostic reagents. Medical laboratory is the main department and implementer of in vitro diagnostic reagent clinical trials in medical institutions. In recent years, with the rapid development of the in vitro diagnostic industry, the clinical trial projects of in vitro diagnostic reagents conducted by medical laboratory have been increasing day by day. However, there are currently few discussions on the clinical trial of in vitro diagnostic reagents from the perspective of researchers. Therefore, this article summarizes the characteristics of clinical trials of in vitro diagnostic reagents, analyzes the problems and difficulties in conducting clinical trials of in vitro diagnostic reagents in current medical laboratories, and introduces the laboratory′s experience in management; to provide reference for medical testing laboratories that have not yet conducted or have already conducted clinical trials of in vitro diagnostic reagents, in order to improve the quality and efficiency of clinical trials.

Tumor cells use glycolysis to provide material and energy under hypoxic conditions to meet the energy requirements for rapid growth and proliferation， namely the Warburg effect. Even under aerobic conditions， tumor cells mainly rely on glycolysis to provide energy. Therefore， glucose transporter protein 1（GLUT1）， which is involved in the process of glucose metabolism， plays an important role in tumorigenesis， development and drug resistance， and is considered to be one of the important targets in the treatment of malignant tumors. In recent years， research on tumor glucose metabolism has gradually become a hot spot. It has been shown that various factors are involved in the regulation of tumor energy metabolism， among which the role of GLUT1 is the most critical. In this paper， the authors reviewed the latest research progress of GLUT1-targeted traditional Chinese medicine（TCM） active ingredient nano-delivery system in tumor therapy， aiming to reveal the feasibility and effectiveness of this system in the delivery of chemotherapeutic drugs. The GLUT1-targeted TCM active ingredient nano-delivery system can overcome the bottleneck of the traditional targeting strategy as well as the high-permeability long retention（EPR） effect. In summary， the authors believe that the GLUT1-targeted TCM active ingredient nano-delivery system provides a new strategy for targeted treatment of tumors and has a broad application prospect in tumor prevention and treatment.

Objective To establish the theories and methods for the compatibility of Chinese patent medicines in pre-scription review.Methods Based on the prescription combination theory and the classics literatures of traditional Chinese med-icine,the methods of prescription suitability review for the compatibility of Chinese patent medicines were discussed.Results Based on the examples of the compatibility of Chinese patent medicines,five basic principles of combined Chinese patent medi-cines and the key points for reviewing the combined Chinese patent medicines dosage form were discussed in detail.Conclusion The methods for the compatibility of Chinese patent medicines prescription review have been established,which can provide a theoretical reference for the review of combined Chinese patent medicines prescriptions.

Objective To observe the value of drug-eluting bead TACE(D-TACE)combined with apatinib and camrelizumab for treating massive hepatocellular carcinoma(HCC).Methods Data of 35 patients with massive HCC who underwent D-TACE sequential apatinib and camrelizumab were retrospectively analyzed.The overall survival(OS)and progression free survival(PFS)were recorded,and the objective response rate(ORR),disease control rate(DCR)and treatment-related adverse event(TRAE)were evaluated.Results Combination treatment were all successfully performed in all 35 cases.At the last follow-up,the median PFS was 8.09 months,and the median OS was 20.00 months.One,3,6,and 12 months after treatments,ORR was 65.71%(23/35),71.43%(25/35),65.71%(23/35)and 60.71%(17/28),respectively,DCR was 94.29%(33/35),88.57%(31/35),80.00%(28/35)and 67.86%(19/28),respectively.TRAE of combination treatment mainly ranged from grade 1 to 2,and all relieved after symptomatic treatments.Conclusion D-TACE combined with apatinib and camrelizumab was effective and safe for treating massive HCC,with controllable adverse reactions.

Objective:To analyze the changing trend of incidence and prevalence of pneumoconiosis globally, and provide scientific basis for the formulation of health policy.Methods:In June 2022, through the Global Health Data exchange (GHDx) query tool (http: //ghdx.healthdata.org/gbd-results-tool) , the pneumoconiosis incidence and prevalence data was downloaded and organized. Estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trends of pneumoconiosis from 1990 to 2019. EAPC was estimated by linear regression model based on ASR.Results:The overall ASR of the incidence and prevalence of pneumoconiosis decreased from 1990 to 2019, and their EAPCs were-0.85% (95% CI: -1.11%--0.60%) and -0.78% (95% CI: -1.08%--0.49%) . Over the past 30 years, the incidence and prevalence of pneumoconiosis in all SDI areas showed decreasing trends, especially in high SDI areas, their EAPCs were -1.46% (95% CI: -1.76%--1.15%) and -1.99% (95% CI: -2.44%--1.53%) . 110 countries/areas showed increasing trends in age standardized incidence rate (ASIR) , with Iran and Georgia showing the most pronounced upward trend, their EAPCs were 5.32% (95% CI: 4.43%-6.22%) and 4.39% (95% CI: 3.81%-4.97%) . 125 countries/areas showed anincreasing trends in prevalence ASR, with Iran had the fastest rise in prevalence (EAPC=6.40%, 95% CI: 5.33%-7.49%) . Conclusion:Although decreasing trends in the burden of pneumoconiosis are observed globally from 1990 to 2019, but the burden of pneumoconiosis in low-and middle-income countries or regions are still heavy. We need more effective strategies to prevent and reduce the burden of pneumoconiosis.