ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

Objective To investigate the protective effects of paeonol(PAE)on autophagy in human neuroblastoma cells(SH-SY5Y)induced by overexpression of α-synuclein(α-Syn),and to explore its related mechanism.Methods SH-SY5Y cells served as control group,while those induced with A53T-α-Syn mutation were used as model group.Additional groups included PAE(150 μg/ml)group,3-MA(1 mmol/L)group,and PAE(150 μg/ml)+3-MA(1 mmol/L)group.Cell viability was assessed using CCK-8 method,cell morphology was observed under an optical microscope,and protein expressions of α-Syn,LC3-Ⅱ,p62,Beclin-1,phosphorylated c-Jun N-terminal kinase(p-JNK),and p-Bcl-2 were determined by Western blotting.Results Compared with control group,model control exhibited decreased cell survival(P＜0.01),increased α-Syn expression(P＜0.001),reduced expression of autophagy-related proteins LC3-Ⅱ and Beclin-1(P＜0.01,P＜0.05),elevated autophagy substrate protein p62(P＜0.05),and decreased expression of autophagy pathway-related proteins p-JNK and Bcl-2(P＜0.05,P＜0.01).Compared with model group,PAE group showed increased cell survival(P＜0.01),decreased α-Syn and p62 protein expression(P＜0.01,P＜0.05),and increased expression of LC3-Ⅱ,Beclin-1,p-JNK and Bcl-2(P＜0.05).Compared with PAE group,3-MA+PAE group demonstrated increased α-Syn expression(P＜0.05).Conclusions PAE could attenuate the injury of SH-SY5Y cells induced by A53T-α-Syn and eliminate over-expressed α-Syn by activating autophagy pathway,which may be associated with the upregulation of JNK/Bcl-2 mediated autophagy pathway.

Objective:To investigate the impact of different CT reconstruction kernels on the quantitative analysis of small pulmonary vessels in patients with chronic obstructive pulmonary disease (COPD) and high-risk patients.Methods:This study was a cross-sectional study. Clinical and imaging data of 73 COPD and high-risk patients visiting the China-Japan Friendship Hospital between March and April 2024 were retrospectively analyzed. All patients underwent high-resolution CT of the chest and pulmonary function tests, with the ratio of forced expiratory volume in one second to forced vital capacity (FEV 1/FVC) obtained. The raw CT data were reconstructed using different kernels: the FC86 group used the adaptive iterative dose reduction(AIDR) 3D standard lung sharp reconstruction algorithm, the FC18 group used the AIDR 3D standard Body standard reconstruction algorithm, the advanced intelligent clear-IQ engine(AiCE) Lung group used the AiCE deep learning reconstruction algorithm for lung, and the AiCE Body group used the AiCE deep learning reconstruction algorithm for body. Image signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and image noise were calculated. The pulmonary vessel segmentation & Measurement software was used to segment and extract pulmonary arteries and veins of four groups in thin-slice whole-lung CT imaging, obtaining the ratio of small pulmonary arteries (%V artery<5) and the ratio of small pulmonary veins (%V vein<5). The One-way repeated measures ANOVA or Friedman test was used to compare the differences in SNR, CNR, image noise, %V artery<5, and %V vein<5 among the four groups, followed by Bonferroni post hoc or Bonferroni-Dunn test with P-value correction to analysis differences between subgroups. The correlations between %V artery<5 and FEV 1/FVC, as well as between %V vein<5 and FEV 1/FVC were analyzed using Spearman rank correlation analysis in all four groups. Results:The overall differences in image noise, SNR, and CNR in the AiCE Lung, AiCE Body, FC18, and FC86 groups were statistically significant ( P<0.001). Except for the difference in CNR values between the AiCE Lung group and the FC18 group, which was not statistically significant ( P=0.192), all differences were statistically significant ( P<0.016 7). The overall differences in %V artery<5 values and %V vein<5 values in the AiCE Lung, AiCE Body, FC18, and FC86 groups were statistically significant ( P<0.001). The %V artery<5 and %V vein<5 values in the FC18 group were lower than those in the AiCE Lung, AiCE Body, and FC86 groups ( P<0.016 7), and the rest of the differences were not statistically significant ( P>0.016 7). %V artery<5 and %V vein<5 were positively correlated with FEV 1/FVC in all 4 groups ( P<0.05), with the highest correlation coefficient between %V vein<5 and FEV 1/FVC in the AiCE Body group ( r=0.501, P=0.001). Conclusions:DLR-AiCE-based kernel reconstruction optimizes image quality and significantly affects the results of quantitative parameters of small pulmonary vessels. The reconstruction kernel prioritized for quantitative analysis of small vessels within the lungs in COPD based on the CT scanner in this study is AiCE Body.

AIM To explore the clinical effects of Huayu Ditan Linao Decoction combined with Suhexiang Pills on elderly patients with cerebral hemorrhage in convalescent stage.METHODS One hundred and ten patients were randomly assigned into control group(55 cases)for 1-month intervention of both conventional treatment and rehabilitation training,and observation group(55 cases)for 1-month intervention of Huayu Ditan Linao Decoction,Suhexiang Pills,conventional treatment and rehabilitation training.The changes in clinical effects,TCM syndrome score,NIHSS score,FMA score,BI index,cerebrovascular function indices(dynamic resistance,average flow velocity,peripheral resistance,average flow rate),serum inflammatory indices(IL-6,hs-CPR,TNF-α)and serum oxidative stress indices(SOD,MDA)were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome score,NIHSS score,dynamic resistance,peripheral resistance,serum inflammatory indices,MDA(P＜0.05),and increased FMA score,BI index,average flow velocity,average flow rate,SOD(P＜0.05),especially for the observation group(P＜0.05).CONCLUSION For the elderly patients with cerebral hemorrhage in convalescent stage,Huayu Ditan Linao Decoction combined with Suhexiang Pills can enhance clinical effects,improve limb functions and nerve functions,regulate serum inflammatory and oxidative stress indice,and promote prognosis.

Phosgene is a highly reactive chemical substance and a prevalent chemical warfare agent,and it is vitally important for rapid and accurate detection of phosgene to counteract terrorist threats and industrial accidents.In this work,a phosgene probe,designated as SX-Pho,which incorporated benzimidazole and hydroxyl groups as recognition motifs,was prepared through Suzuki coupling and Debus-Radziszewski methodologies to incorporate an electron-donating carbazole moiety.This probe exhibited a large Stokes shift(Approximately 130 nm).Upon exposure to triphosgene/triethylamine conditions(in situ phosgene generation),the fluorescence emission of probe at 470 nm underwent significant quenching,with a 20-fold reduction in intensity,while the fluorescence lifetime decreased from 3.30 ns to 3.06 ns.Concentration titration experiments demonstrated that SX-Pho achieved a lower detection limit of 57.8 nmol/L with high specificity and interference resistance.Preton nuclear magnetic resonance spectroscopy(1H NMR),high-resolution mass spectrometry,and density functional theory(DFT)calculations confirmed the cyclization reaction between hydroxyl groups,imines,and phosgene.The extent of overlap between the highest occupied molecular orbital(HOMO)and the lowest unoccupied molecular orbital(LUMO)was notably decreased,leading to the suppression of radiative transitions.The energy gap underwent a reduction of 0.43 eV,while the non-radiative transition was augmented,resulting in fluorescence quenching and achieving rapid detection of phosgene.Based on this,probe-loaded test strips were prepared.The color change under 365 nm illumination allowed visual discrimination of phosgene at concentrations below 20 μL/L.Furthermore,using a smartphone's built-in RGB application to measure the intensity of the blue(B)channel after the test strips were exposed to phosgene enabled both qualitative and quantitative detection.The detection range was 1.82-50 μL/L,with a limit of detection(LOD)of 1.814 μL/L.

Clustered regularly interspaced short palindromic repeats-associated proteins(CRISPR-Cas)system has emerged as a next-generation nucleic acid detection tool due to its precise gene editing capabilities and exhibits high specificity and significant potential for application in the diagnosis of pathogen.However,the inherent shortcomings of CRISPR-Cas,including insufficient sensitivity of the traditional CRISPR-Cas system,complex operation of the CRISPR-Cas system combined with amplification,and limited capability for multi-target detection,have significantly constrained its practical applications in clinical settings.With the advantages of miniaturization,integration and automation,microfluidics has emerged as a promising tool for advancing the development of point-of-care testing(POCT)platforms.The integration of microfluidic technology with CRISPR-Cas system not only enhances the detection throughput and efficiency significantly,but also drives innovation in the development of portable POCT devices.In this paper,a comprehensive review of the research advancements of CRISPR-Cas nucleic acid detection platform facilitated by microfluidic technology was presented,with a focus on their application in detection of pathogens associated with clinical disease.This study aimed to explore emerging molecular diagnostic methodologies and offered novel insights for future research in clinical pathogen detection.

[Objective] To investigate the seroprevalence characteristics of hepatitis E virus (HEV) among blood donors with hepatitis B virus (HBV) infection, so as to provide data support for the monitoring, prevention and treatment of HEV. [Methods] From January to December 2022, 219 samples positive for hepatitis B surface antigen (HBsAg), 142 occult hepatitis B virus infection (OBI) samples (HBV group) and 873 samples tested negative (control group) were collected. 361 samples were further tested with viral load assay and serological testing for five serological markers (HBsAg, HBsAb, HBeAg, HBeAb and HBcAb), and the DNA load was measured using real time fluorescence quantitative PCR. Commercially available enzyme-linked immunosorbent assays (ELISA) were used for the detection of anti-HEV IgG, anti-HEV IgM and HEV antigen (Ag). The Chi-square test or Fisher's exact test was used to assess the differences in the reactivity rates of anti-HEV IgG and anti-HEV IgM among different blood donor populations and different variables. Multivariable logistic regression was used to examine potential risk factors associated with anti-HEV IgG seroprevalence. [Results] In the HBV group, HBsAg positive donors exhibited low expression of antigen. The HBV DNA load of OBI infected donors ranged from 1 to 131.43 IU/mL (median 11.24 IU/mL). The prevalence of anti-HEV IgG and IgM antibody in the HBV group were 34.63% and 1.11%, respectively. Among them, the prevalence of anti-HEV IgG and anti-HEV IgM in the HBV group was 34.63% and 0, respectively (P<0.05), while in the OBI donors, they were 41.55% and 2.82%, respectively. In the normal donors, the reactivity rates for anti-HEV IgG and anti-HEV IgM were 18.67% and 1.49%, respectively. Statistical analysis showed that there was a difference in the reactivity rate of anti-HEV IgG between the HBV-infected donors and the normal donors (34.63% vs 18.67%, P<0.05), but no difference in the reactivity rate of anti-HEV IgM (1.11% vs 1.49%, P>0.05). No HEV Ag was detected in either group of blood donors. Multivariate logistic regression analysis indicated that age was an independent risk factor for anti-HEV IgG reactivity in both groups of blood donors. [Conclusion] The reactivity rate of anti-HEV IgG among HBV-infected blood donors was significantly higher than that in the normal donors in Wuhan, with age being an independent risk factor. Therefore, for HBV-infected donors, it is essential to strengthen and prioritize the prevention and treatment of HEV to reduce the spread of HEV.

OBJECTIVE To screen the primary processing methods of Ligusticum sinense slice based on differential metabolites， and provide theoretical basis for the scientific processing of L. sinense. METHODS Using 13 groups of L. sinense slice processed by fresh-cutting or traditional methods as samples， UHPLC-QE-MS was employed for metabolite identification. Multivariate statistical analysis was applied to screen differential metabolites among the 13 sample groups， analyzing the effects of washing， soaking， drying methods， and drying cycles on both the relative expressions of differential metabolites and the contents of carboxylic acids and their derivatives in the samples （to reflect the total amino acid content）. RESULTS Principal component analysis and partial least squares-discriminant analysis both showed significant intergroup differences among the 13 sample groups. A total of 688 differential metabolites were screened from the 13 sample groups， with carboxylic acids and their derivatives showing the highest proportion. The relative expression levels of phosphatidylcholine significantly increased after washing treatment， while tryptophan expression significantly decreased after soaking treatment. Samples dried at 50-60 ℃ showed significantly increased expression of psoralen， whereas those dried at 40 ℃ showed significantly decreased expression of methyl -p- methoxycinnamate. Both washing and soaking treatments significantly reduced the total amino acid content in samples， while secondary drying significantly increased it. The three controlled-temperature drying methods maintained relatively stable total content of amino acids in samples. CONCLUSIONS The optimal processing protocol for L. sinense slice is as follows: fresh L. sinense slice should be freshly cut at the production site， undergo quick washing after soil removal， and be dried twice at 40 ℃ （before and after slicing）.

Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.