OBJECTIVE To establish a multi-index quantitative detection method， and to evaluate the quality difference of Gleditsia sinensis from different producing areas. METHODS The contents of protocatechuic acid， vanillic acid， isoscopoletin， scoparone， isovitexin， fustin， taxifolin， fisetin， quercetin， kaempferol， echinocystic acid， betulinic acid， β -sitosterol and stigmasterol were detected by high performance liquid chromatography-quantitative analysis of multi-components by single marker （HPLC-QAMS）. The chromatographic column was Kromasil C18， the mobile phase was 0.2% phosphoric acid-acetonitrile solution （gradient elution）， the detection wavelengths were 254， 360， 210 nm for different index components， the column temperature was 30 ℃ ， the flow rate was 1.0 mL/min， and the sample injection volume was 10 μL. The contents of extract and total ash were detected according to the method of Chinese Pharmacopoeia. The quality differences of 30 batches of G. sinensis （No. S1-S30） from different producing areas were evaluated by chemometrics， weighted technique for order preference by similarity to an ideal solution （TOPSIS） analysis and Logistic regression model. RESULTS The linear ranges of 14 components were 1.55-77.50， 0.71- 35.50， 0.28-14.00， 0.96-48.00， 1.77-88.50， 0.09-4.50， 4.65-232.50， 1.49-74.50， 0.37-18.50， 1.18-59.00， 7.35-367.50， 3.58- 179.00， 0.49-24.50 and 0.21-10.50 μg/mL， respectively （all r＞0.999）. The RSDs of precision， stability （24 h） and repeatability were less than 2.00%； the average recoveries were 96.99%-100.13% （all RSDs＜2.00%）， and the relative correction factor had good repeatability. The contents of extract and total ash were Δ 基金项目 湖北省中医药科研立项青年人才项目 （No. 4.2%-12.5% and 0.5%-2.3%， respectively. There was no ZY2019Q014） significant difference in the content of 14 components measured by QAMS method and external standard method （P＞0.05）. The results of chemometrics showed that 30 batches of samples were clustered into 3 categories： S1 to S11 form one category， S12 to S20 form another category， and S21 to S30 constitute the third category. Echinocystic acid， betulinic acid， taxifolin， kaempferol， isovitexin， scoparone and protocatechuic acid may be the differential components affecting the quality of G. sinensis from different producing areas. The analysis results of the weighted TOPSIS method revealed that relative closeness （Jb） for 30 batches of G. sinensis ranged from 0.144 5 to 0.721 8， with S27 achieving the highest value （Jb） of 0.721 8. The analysis results of the Logistic regression model showed that S21-S30 batches of samples were of superior grade， S1-S11 were of intermediate grade， and S12-S20 were of inferior grade. CONCLUSIONS The established HPLC-QAMS method is simple and accurate. The comprehensive evaluation method is objective and comprehensive， and can be used to evaluate the quality difference of G. sinensis from different producing areas.

The European Society of Cardiology (ESC) released the "2024 ESC guidelines for the management of elevated blood pressure and hypertension" on August 30, 2024. This guideline updates the 2018 "Guidelines for the management of arterial hypertension." One notable update is the introduction of the concept of "elevated blood pressure" (120-139/70-89 mm Hg). Additionally, a new systolic blood pressure target range of 120-129 mm Hg has been proposed for most patients receiving antihypertensive treatment. The guideline also includes numerous additions or revisions in areas such as non-pharmacological interventions and device-based treatments for hypertension. This article interprets the guideline's recommendations on definition and classification of elevated blood pressure and hypertension, and cardiovascular disease risk assessment, diagnosing hypertension and investigating underlying causes, preventing and treating elevated blood pressure and hypertension. We provide a comparison interpretation with the 2018 "Guidelines for the management of arterial hypertension" and the "2017 ACC/AHA guideline on the prevention, detection, evaluation, and management of high blood pressure in adults."

Pinellia ternata， belonging to the Pinellia genus within the Araceae family， is a medicinal plant due to its tubers. There are severe issues with unclear germplasm and mixed varieties in its cultivation， necessitating urgent new variety protection efforts. The distinctness， uniformity， and stability （DUS） testing of the plant variety is the basis for protecting new plant varieties， and the DUS test guidelines are the technical basis for DUS testing. To develop the DUS test guidelines for P. ternata， agronomic traits of 229 germplasm of P. ternata were observed and measured during its two growth stages over the years， and each character was graded and described. A total of 38 traits were selected as the test traits of the DUS test guideline for P. ternata. There were three plant traits， 19 leaf traits， six flower traits， two fruit traits， two tuber traits， five bulbil traits， and one ploidy trait. These traits could be divided into 22 quality characters， 12 quantitative characters， and four pseudo-quantitative characters， as well as seven groups， including plants， leaves， flowers， fruit， tubers， bulbils， and ploidy. By searching for standard traits， 10 standard varieties were ultimately determined. Preparing these guidelines will have great significance for reviewing and protecting P. ternata varieties， safeguarding breeders' rights， and promoting the development of the P. ternata industry.

[Objective] To retrospectively analyze the detection results of alanine aminotransferase (ALT) unqualified repeat blood donors in Guangzhou, so as to provide evidence for further expanding the repeat blood donor pool, reducing the rate of blood discarding and improving the qualified rate of blood test. [Methods] Blood donors with unqualified ALT in Guangzhou Blood Center from January 2018 to April 2024 were selected as the research objects. The past blood donation and population characteristics were analyzed according to the number of blood donations and ALT unqualified times. [Results] Among repeat blood donors with previous ALT disqualification, 99.5% to 99.7% did not have reactive markers for transfusion-transmitted diseases (TTD), which was higher than the rate among first-time blood donors with unqualified ALT (95.8%) (P<0.05). The rate of single-item ALT disqualification in repeat blood donors was higher in males than in females (P<0.05); it also varied by age (18-25 years > 26-35 years > 36-45 years > over 45 years) (P<0.05); and by quarter (third and fourth quarters > first and second quarters) (P<0.05). The ALT unqualified rate was significantly higher whole blood donors than that of platelet donors and returning blood donors (P<0.05). The overall ALT level (51.0 U/L), individual ALT level (56.0 U/L) and individual ALT unqualified rate (66.7%) of repeat blood donors with multiple ALT disqualifications were higher than those of repeat blood donors with single-item ALT disqualifications (26.0 U/L, 38.5 U/L, and 33.3%, respectively) (P<0.05). Moreover, as the number of ALT disqualifications increased, the overall level of ALT in repeat blood donors also increased (P<0.05), and the average level of individual ALT and individual ALT unqualified ratio tended to increase. Repeat blood donors with frequent ALT disqualifications had higher ALT levels (69.0 U/L). [Conclusion] The ALT unqualified rates of repeat blood donors were mostly non-specific elevation without TTD. Repeat blood donors with multiple ALT disqualifications tend to have continuous high ALT. Moreover, and with the increase of ALT disqualifications times, the overall ALT levels the average individual ALT levels and individual ALT unqualified rates showed an increasing trend.

OBJECTIVES: To investigate the antioxidative mechanism of snake venom-derived protein C activator (PCA) in mitigating vascular endothelial cell injury. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured in DMEM containing 1.0 g/L D-glucose and exposed to hypoxia (1% O₂) for 6 h followed by reoxygenation for 2 h to establish a cell model of oxygen-glucose deprivation/reoxygenation (OGD/R). The cell model was treated with 2 μg/mL PCA alone or in combination with 2-ME2 (a HIF-1α inhibitor) or DMOG (a HIF-1α stabilizer), and intracellular production of reactive oxygen species (ROS) and protein expression levels of HIF-1α, BNIP3, and Beclin-1 were detected using DCFH-DA fluorescence probe, flow cytometry, and Western blotting. The OGD/R cell model was transfected with a BNIP3-specific siRNA or a scrambled control sequence prior to PCA treatment, and the changes in protein expressions of HIF-1α, BNIP3 and Beclin-1 and intracellular ROS production were examined. RESULTS: In the OGD/R cell model, PCA treatment significantly upregulated HIF-1α, BNIP3 and Beclin-1 expressions and reduced ROS production. The effects of PCA were obviously attenuated by co-treatment with 2-ME2 but augmented by treatment with DMOG (a HIF-1α stabilizer). In the cell model with BNIP3 knockdown, PCA treatment increased BNIP3 expression and decreased ROS production without causing significant changes in HIF-1α expression. Compared with HUVECs with PCA treatment only, the cells with BNIP3 knockdown prior to PCA treatment showed significantly lower Beclin-1 expression and higher ROS levels. CONCLUSIONS Snake venom PCA alleviates OGD/R-induced endothelial cell injury by upregulating HIF-1α/BNIP3 signaling to suppress ROS generation, suggesting its potential as a therapeutic agent against oxidative stress in vascular pathologies.
Humans ; Reactive Oxygen Species/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Human Umbilical Vein Endothelial Cells/drug effects* ; Membrane Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Up-Regulation ; Cell Hypoxia ; Cells, Cultured ; Snake Venoms/chemistry* ; Beclin-1

Objective: To investigate the association between edentulism and the risk of social isolation in middle-aged and elderly populations, provide empirical evidence for formulating social isolation prevention and intervention policies targeting edentulous middle-aged and elderly populations. Methods: Data were derived from the baseline survey (2011) and three follow-ups (2013, 2015, 2018) of the China Health and Retirement Longitudinal Study (CHARLS). Participants were enrolled in the follow-up from the baseline. Those identified as socially isolated in any of the follow-up surveys conducted in 2013, 2015, or 2018 were considered to have reached the endpoint; otherwise, the follow-up was continued until the end of the 2018 survey; 9 870 individuals were ultimately included. Subjects were grouped by edentulism status. Chi-square test and multivariate Cox regression analysis were performed using Stata 17.0. Results: During a median follow-up of 6.54 years, 1 800 cases of social isolation occurred, with an incidence rate of 18.23%（17.47%~18.99%）. Multivariate Cox regression showed that edentulism was associated with an increased risk of social isolation (HR=1.21, 95% CI: 1.03-1.42) after adjusting for confounders. Subgroup analysis revealed population heterogeneity. Sensitivity analyses confirmed the stability of the results. Conclusion Edentulism is associated with an increased risk of social isolation in middle-aged and elderly adults.

Background: Intradermal microdroplet injections of botulinum toxin type-A (BoNT/A) effectively ameliorate rosacea-related angiogenesis, but the mechanism remains unclear. Objective: To explore the anti-angiogenesis of BoNT/A in the rosacea-like mouse model and to measure the secretion of vascular endothelial growth factor (VEGF) by mast cells. Methods: A rosacea-like mouse model was induced by LL37 in both Mas-related G-proteincoupled receptor B2 conditional knockout (MrgprB2 −/− ) mice and wild-type (WT) mice, then treated with BoNT/A and/or Apatinib. The abundance of endothelial cells and mast cells in mouse skin was determined using dual immunofluorescence staining. The VEGF levels in supernatants and cell lysates of laboratory of allergic disease 2 (LAD2) mast cells were assessed using reverse transcription quantitative polymerase chain reaction, western blots, and enzyme-linked immunosorbent assay. The effect of conditioned medium (CM) collected from LAD2 on human umbilical vein endothelial cells (HUVECs) was determined using tube formation assays. The number of proliferative cells was confirmed using the 5-ethynyl-2’-deoxyuridine incorporation assays.The effect of BoNT/A on the internalization of Mas-related G-protein-coupled receptor X2 (MRGPRX2) was detected using flow cytometry and immunofluorescence staining. Results: LL37-induced rosacea-like skin manifestations were significantly alleviated in MrgprB2 −/− mice compared to WT controls. BoNT/A mitigated the LL37-induced secretion of VEGF by LAD2. The CM from BoNT/A-treated LAD2 inhibited HUVEC proliferation and tube formation. The LAD2 cells co-treated with LL37 and BoNT/A exhibited dramatically enhanced MRGPRX2 internalization. Conclusion BoNT/A enhances LL37-mediated MRGPRX2 internalization in mast cells, thereby reducing VEGF secretion and neovascularization and improving facial flushing symptom in rosacea.

Objective:To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL).Methods:This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children′s Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors.Results:Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×10 9/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively ( χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant ( χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively ( χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%, χ2=4.13, P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%, χ2=4.06, P=0.044;(58.3±18.6)% vs. (85.7±3.2)%, χ2=9.44, P=0.002). Multivariate analysis showed that age ( OR=0.58, 95% CI 0.35-0.97) and white blood cell count at first diagnosis ( OR=0.43, 95% CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 ( OR=0.55,95% CI 0.31-0.97), ETV6-RUNX1 fusion gene ( OR=0.13,95% CI 0.03-0.54), MLL gene rearrangement ( OR=2.55,95% CI 1.18-5.53) and white blood cell count at initial diagnosis ( OR=0.52,95% CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions:The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

Objective:To summarize the clinical and genetic characteristics of children with β-ketothiolase deficiency (BKTD).Methods:The clinical characteristics, biochemical, markers detected by tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS), as well as the variants in ACAT1 gene among 5 children with BKTD in Children′s Hospital of Chongqing Medical University between October 2018 and December 2022 were retrospectively analyzed.Results:The onset age of the disease in 5 patients (4 males and 1 female) ranged from 9.7 to 28.0 months. During the acute phase, severe metabolic acidosis was observed with a pH of 6.9-7.1, as well as hypoglycaemia (2.3-3.4 mmol/L) and positive urinary ketone bodies (+-++++). Blood levels of methylcrotonyl carnitine, methylmalonyl carnitine and malonyl carnitine were 0.03-0.42, 0.34-1.43 and 0.83-3.53 μmol/L respectively and were significantly elevated. Urinary 2-methyl-3-hydroxybutyric acid was 22-202 and 3-hydroxybutyric acid was 4-6 066, both were higher than the normal levels. Methylcrotonylglycine was mild elevated (0-29). The metabolites detected by MS/MS and GC/MS were significantly reduced after treatment. Analysis of ACAT1 gene mutation was performed in 5 children. Most variants were missense (8/9). Four previously unreported variants were identified: c.678G>T (p.Trp226Cys), c.302A>G (p.Gln101Arg), c.627_629dupTGA (p.Asn209_Glu210insAsp) and c.316C>T (p.Gln106Ter), the first 2 variants were predicted to be damaging by SIFT, PolyPhen-2 and Mutation Taster software. c.316C>T (p.Gln106Ter) is a nonsense variant.Conclusions:β-ketothiolase deficiency is relatively rare, lacks specific clinical manifestations, however severe metabolic acidosis, hypoglycemia, and ketosis during the acute onset were consistent findings. Missense mutations in the ACAT1 gene are common genetic causes of β-ketothiolase deficiency.

BACKGROUND:Traditional scoliosis orthosis has some disadvantages,such as complex manufacturing process,long processing cycle,poor fit and so on.Three-dimensional printed scoliosis orthosis has the advantages of high manufacturing precision and personalization. OBJECTIVE:To evaluate the efficacy of three-dimensional printed scoliosis orthosis for scoliosis based on multi-criteria decision model. METHODS:Clinical data of 72 patients with scoliosis admitted to Chen Xinghai Hospital of Integrated Traditional Chinese and Western Medicine from January 2019 to October 2022 were retrospectively collected and divided into two groups according to the treatment of orthosis.Study group(n=23)received three-dimensional printed scoliosis orthosis.Traditional group(n=49)received the traditional polypropylene spine brace treatment.The clinical efficacy and complications were compared between the two groups.A multi-criteria decision model for the treatment of scoliosis with three-dimensional printed scoliosis orthosis was established,and the stability of the benefit value,risk value and decision model of the two groups were evaluated. RESULTS AND CONCLUSION:(1)Compared with the traditional group,there were significant differences in the top vertebral offset distance,Cobb angle,top vertebral rotation,Functional Movement Screen score,visual analog scale score and total effective rate in the study group at 6 months after surgery(P<0.05).(2)Among the benefit indexes,Cobb angle had the greatest impact on the condition of patients,while the risk indexes had the greatest impact on dyspnea.(3)The benefit values of the study group and the traditional group for scoliosis were 79 and 64,and the risk values were 74 and 57,respectively.The combined benefit and risk values found that the benefit-risk value of the study group was 16 higher than that of the traditional group.(4)In the range of 0-100%relative risk weight,the benefit-risk value of the study group was always higher than that of the traditional group,which proved that the multi-criteria decision-making model had good stability.(5)It is indicated that three-dimensional printed scoliosis orthosis can better restore the physiological curvature of scoliosis and improve the efficiency of treatment.