ObjectiveTo investigate the protective effect of Qiju Dihuang Wan on diabetic retinopathy （DR） and its regulatory mechanism on the NOD-like receptor protein 3/Cysteinyl aspartate-specific proteinase-1/Gasdermin D （NLRP3/Caspase-1/GSDMD） signaling pathway. MethodsHuman retinal microvascular endothelial cells （HRMEC） were divided into the blank group， model group， and Qiju Dihuang Wan low- and high-dose groups. Except for the blank group， all groups were induced with 40 mmol·L^-1 high glucose， and the treatment groups were supplemented with 6% and 12% Qiju Dihuang Wan-containing serum， respectively， based on the induction. After 24 h of culture， the levels of interleukin （IL）-1β and IL-18 were measured by enzyme-linked immunosorbent assay （ELISA）， pyroptosis-related protein expression was detected by immunofluorescence and Western blot， and the mRNA levels of NLRP3/Caspase-1/GSDMD signaling pathway-related molecules were determined by real-time polymerase chain reaction （Real-time PCR）. The mice were randomly divided into the blank group， model group， Qiju Dihuang Wan low-， medium-， and high-dose groups （11， 22， 44 g·kg^-1·d^-1）， and calcium dobesilate group （0.13 g·kg^-1·d^-1）. Except for the blank group， all groups were intraperitoneally injected with streptozotocin to establish the DR model. After successful modeling， the treatment groups received corresponding doses of Qiju Dihuang Wan crude drug or calcium dobesilate suspension by gavage once daily， while the blank group and model group received an equal volume of normal saline， for 8 consecutive weeks. Fundus changes were examined by optical coherence tomography， optical coherence tomography angiography， and fundus fluorescein angiography. Retinal pathological morphology was observed by hematoxylin-eosin staining. Real-time PCR was used to detect the mRNA levels of NLRP3， Caspase‑1， GSDMD， IL‑1β， and IL‑18 in retinal tissue， and Western blot was used to detect the protein expression of NLRP3， ASC， cleaved Caspase‑1， and GSDMD‑N. ResultsCell experiments showed that compared with the blank group， the model group showed significantly decreased HRMEC viability （P<0.01）， and significantly increased levels of IL-1β， IL-18， as well as increased protein expression of NLRP3， cleaved Caspase-1， and GSDMD-N （P<0.01）. Compared with the model group， the above indicators were significantly reduced in the high-dose Qiju Dihuang Wan groups （P<0.05， P<0.01）. Animal experiments showed that compared with the blank group， the model group had elevated blood glucose （P<0.01）， decreased retinal thickness and vascular density （P<0.01）， up‑regulated mRNA expression of NLRP3， Caspase‑1， GSDMD， IL‑1β and IL‑18 in retinal tissue （P<0.01）， and up‑regulated protein expression of NLRP3， ASC， cleaved Caspase‑1 and GSDMD‑N （P<0.01）. Compared with the model group， the Qiju Dihuang Wan medium- and high‑dose groups showed decreased blood glucose （P<0.01）， increased retinal thickness and vascular density （P<0.01）， alleviated retinal pathological damage， and down‑regulated mRNA expression of NLRP3， Caspase‑1， GSDMD， IL‑1β， IL‑18， as well as protein expression of NLRP3， ASC， cleaved Caspase‑1， and GSDMD‑N （P<0.05， P<0.01）. ConclusionQiju Dihuang Wan may exert protective effects against diabetic retinopathy by inhibiting the activation of the NLRP3/Caspase-1/GSDMD signaling pathway and alleviating high glucose-induced retinal pyroptosis.

ObjectiveTo investigate the protective effect of Qiju Dihuang Wan on diabetic retinopathy （DR） and its regulatory mechanism on the NOD-like receptor protein 3/Cysteinyl aspartate-specific proteinase-1/Gasdermin D （NLRP3/Caspase-1/GSDMD） signaling pathway. MethodsHuman retinal microvascular endothelial cells （HRMEC） were divided into the blank group， model group， and Qiju Dihuang Wan low- and high-dose groups. Except for the blank group， all groups were induced with 40 mmol·L^-1 high glucose， and the treatment groups were supplemented with 6% and 12% Qiju Dihuang Wan-containing serum， respectively， based on the induction. After 24 h of culture， the levels of interleukin （IL）-1β and IL-18 were measured by enzyme-linked immunosorbent assay （ELISA）， pyroptosis-related protein expression was detected by immunofluorescence and Western blot， and the mRNA levels of NLRP3/Caspase-1/GSDMD signaling pathway-related molecules were determined by real-time polymerase chain reaction （Real-time PCR）. The mice were randomly divided into the blank group， model group， Qiju Dihuang Wan low-， medium-， and high-dose groups （11， 22， 44 g·kg^-1·d^-1）， and calcium dobesilate group （0.13 g·kg^-1·d^-1）. Except for the blank group， all groups were intraperitoneally injected with streptozotocin to establish the DR model. After successful modeling， the treatment groups received corresponding doses of Qiju Dihuang Wan crude drug or calcium dobesilate suspension by gavage once daily， while the blank group and model group received an equal volume of normal saline， for 8 consecutive weeks. Fundus changes were examined by optical coherence tomography， optical coherence tomography angiography， and fundus fluorescein angiography. Retinal pathological morphology was observed by hematoxylin-eosin staining. Real-time PCR was used to detect the mRNA levels of NLRP3， Caspase‑1， GSDMD， IL‑1β， and IL‑18 in retinal tissue， and Western blot was used to detect the protein expression of NLRP3， ASC， cleaved Caspase‑1， and GSDMD‑N. ResultsCell experiments showed that compared with the blank group， the model group showed significantly decreased HRMEC viability （P<0.01）， and significantly increased levels of IL-1β， IL-18， as well as increased protein expression of NLRP3， cleaved Caspase-1， and GSDMD-N （P<0.01）. Compared with the model group， the above indicators were significantly reduced in the high-dose Qiju Dihuang Wan groups （P<0.05， P<0.01）. Animal experiments showed that compared with the blank group， the model group had elevated blood glucose （P<0.01）， decreased retinal thickness and vascular density （P<0.01）， up‑regulated mRNA expression of NLRP3， Caspase‑1， GSDMD， IL‑1β and IL‑18 in retinal tissue （P<0.01）， and up‑regulated protein expression of NLRP3， ASC， cleaved Caspase‑1 and GSDMD‑N （P<0.01）. Compared with the model group， the Qiju Dihuang Wan medium- and high‑dose groups showed decreased blood glucose （P<0.01）， increased retinal thickness and vascular density （P<0.01）， alleviated retinal pathological damage， and down‑regulated mRNA expression of NLRP3， Caspase‑1， GSDMD， IL‑1β， IL‑18， as well as protein expression of NLRP3， ASC， cleaved Caspase‑1， and GSDMD‑N （P<0.05， P<0.01）. ConclusionQiju Dihuang Wan may exert protective effects against diabetic retinopathy by inhibiting the activation of the NLRP3/Caspase-1/GSDMD signaling pathway and alleviating high glucose-induced retinal pyroptosis.

Objective To establish and verify a mature and stable glioblastoma(GBM)organoid model,so as to provide an accurate and personalized preclinical model for the research and treatment of GBM.Methods Fresh GBM tissues obtained through surgical procedures were initially processed,and then GBM stem cells(GSCs)were isolated using stem cell culture medium and were identified.Subsequently,GSCs were cultured in organoid culture medium for 3D cultivation,and GBM organoids were successfully obtained.The histological morphology of GBM organoids was observed by hematoxylin-eosin(H-E)staining;the stemness and similarity to the parental tumor were identified by immunofluorescence staining;and the in vivo tumorigenic ability of GBM organoids was identified by orthotopic tumorigenesis experiments in nude mice.Results A total of 7 GBM organoids were constructed from 9 human GBM samples,with a morphology resembling"neurosphere",and the average duration for organoid formation was 1 week.H-E staining results showed that the histological morphology of GBM organoids under high-power microscope was very similar to that of GBM tumor tissues;immunofluorescence staining results indicated that the GBM organoids possessed stemness characteristics and histological cellular similarity;and GBM organoids had a stronger tumorigenic ability compared to ordinary GBM cells in nude mice.Conclusion This study presents a stable and reliable method for constructing GBM organoids retaining the histological characteristics of the original GBM tissue,which providing new insights for future GBM research and clinical practice.

Objective:The components of Rubus parvifolius L. were analyzed based on UPLC-MS/MS technology and combined with network pharmacology analysis to explore the mechanism of action of Rubi Parvifolii Radix in treating inflammation, cough, fever, influenza and sore throat. Method:The chemical constituents of Rubi Parvifolii Radix were identified according to the information of mass spectrometry. The network pharmacology was used to analyze the corresponding targets and related pathways of its chemical components, and the "component-target-pathway" interaction diagram was drawn. PyMOL 2.5.7 software wasused to perform molecular docking between active components and key targets.Results:Twenty chemical components were identified by UPLC-MS/MS, and 15 components were screened out by network pharmacology, which can be used as quality markers of Rubi Parvifolii Radix, namely Azelaic acid, Procyanidol B3, Caprolactam, Bis (2-ethylhexyl) adipate, Cryptochlorogenic acid, 3-O-Feruloylquinic, Ellagic acid, Aurantiamide acetate, 2 α,3 β,19 α,23-Tetrahydroxyurs-12-en-28-oic acid, L-Epicatechin, (E)-3-Indoleacrylic acid, Euscaphic acid, Suberic acid, Diisononyl phthalate and Prodelphinidin T4. Molecular docking showed that 5 compounds compared with the reference substance could bind to the target proteins of disease well. Conclusions:The 15 active ingredients in Rubi Parvifolii Radix, including Caprolactam and (E)-3-Indoleacrylic acid, may play a therapeutic role in treating colds, high fever, sore throat, and inflammation by acting on targets such as AKT1 and TNF. This provides a certain reference for the clinical application of Rubi Parvifolii Radix.

Objective:To investigate the prevalence and risk factors of overweight and obesity among Chinese children aged 3-18 years from 11 provinces, antonomous regions, or municipalities.Methods:This national cross-sectional community health survey utilized a multistage stratified cluster-random sampling method to recruit 193 997 nationally representative participants from 11 provinces, autonomous regions, or municipalities between January 2017 and December 2019. All participants underwent physical examinations, and their caregivers completed questionnaires assessing participants′ dietary, lifestyle, familial, and perinatal information. Multilevel multinomial logistic regression models were employed to identify the potential risk factors.Results:The cohort comprised 193 997 children (102 178 boys, 91 819 girls),aged (10±4) years. Overall prevalence rates were 30 574(15.8%)overweight children and 17 217(8.9%) obesity children. Boys exhibited higher overweight and obesity rates than girls (17.0% (17 368/102 178) vs. 14.4% (13 206/102 178), 11.3% (11 553/91 819) vs. 6.2% (5 664/91 819), χ2=249.12,1 578.69,both P<0.001). The detection rates of obesity in Tanner stage 2 and 3 were the highest in boys and girls, with 13.4%(2 231/16 665) and 8.6%(880/10 221) respectively. Risk factors for obesity included parental overweight (paternal OR=2.34 and maternal OR=2.29), annual household income of 100 000-200 000 yuan (compared with<100 000 yuan, OR=1.04), higher paternal education (compared with below high school,high school and a college education OR=1.09,1.14), birth weight >4.0 kg (≤5 and>5 years old OR=1.74, 1.44,respectively), and western food consumption≥1 time/month (compared with<1, 1-2, 3-4,>4 times/month OR=1.36, 1.30, 1.67(≤5 years), 1.19, 1.16, 1.15 (>5 years), respectively) (all P<0.05). Conversely, coarse grain intake≥1 times/week (compared with<1 times/week, every day, 3-4, 1-2 times/week OR=0.74, 0.80, 0.71 (≤5 years), 0.75, 0.87, 0.90(>5 years), respectively, all P<0.05) was associated with reduced obesity risk. Conclusions:Obesity epidemiology in children demonstrates significant heterogeneity across age, gender, geographic regions, and pubertal stages. It is necessary to establish a personalized prevention and control strategy.

Hand degloving injury represents one of the most severe forms of hand trauma, characterised by challenging treatment and a complex prognostic outcome. It is crucial to effectively utilise the degloved tissues in emergency or primary repair of a hand degloving injury. This consensus provides a comprehensive review of the existing literature on definition, classification, emergency assessment, debridement, judgment of skin viability, in situ repair of the degloved skin, and adjunctive treatment for degloving injury of hand. Based on conclusion of both domestic and international experiences, this expert consensus on the classification of hand degloving injury and the emergency repair with the avulsed skin is established, aiming to provide a guidance to surgeons on standardised treatment strategy and improve the management of hand degloving injury.

Objective This study aims to explore the efficacy and complication rates of the transcranial approach(TCA)and extended endoscopic endonasal approach(EEEA)for the treatment of craniopharyngiomas based on the QST classification,providing a scientific reference for clinical decision-making on surgical approach.Methods A total of 151 patients who underwent craniopharyngioma surgery at our center from January 2018 to December 2023 were enrolled.The patients were categorized into Q-CP(suprasellar type),S-CP(infundibular type),and T-CP(tuberal type)according to the QST classification.Systematic collection and analysis were performed on the outcomes of TCA and EEEA treatments,respectively.The differences in effectiveness between the two approaches were evaluated based on the QST classification.Results The improvement rate of visual symptoms was overall higher in the EEEA group than in the TCA group(59.1%vs.36.5%,P=0.006),and the visual deterioration rate was lower(3.0%vs.14.1%,P=0.006).However,the incidence of cerebrospinal fluid leakage was higher in the EEEA group(15.2%vs.3.5%,χ2=4.986,P=0.026).The incidence of postoperative seizures(8.2%vs.0,P=0.019),brain contusions(10.6%vs.0,P=0.005),and subdural hematoma(9.4%vs.0%,P=0.01)was higher in the TCA group.For patients with Q-CP type,the EEEA group had a higher rate of total tumor resection(92.9%vs.65.2%,P=0.025)and a lower recurrence rate(3.6%vs.21.7%,P=0.047),with shorter hospital stays and lower postoperative costs.The TCA group had higher intraoperative blood loss in this type(300 mL vs.200 mL,Z=-2.261,P=0.024).For S-CP type patients,the EEEA group showed a higher rate of total tumor resection(91.3%vs.74.2%)and a lower recurrence rate(0 vs.12.9%,P=0.031),with lower postoperative hospital costs.In T-CP type,due to the deeper location,EEEA showed limitations in protecting hypothalamic function and the TCA group had a better postoperative hypothalamic function score(P=0.035).Conclusion Based on QST classification,EEEA has advantages in Q-CP and S-CP types and is recommended as the preferred surgical procedure;In the T-CP type,TCA surgery is more helpful in protecting hypothalamic function.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

BackgroundPreventing and intervening in adolescent gaming disorder is of significant practical importance. Gaming motivation is strongly linked to gaming addiction and serves a key function in comprehending and addressing addictive gaming behaviors. However， the relationship between components of gaming motivation and symptoms of gaming disorder remains unclear. ObjectiveTo explore the relationship between components of gaming motivation and symptoms of gaming disorder among adolescents， so as to provide references for the prevention and intervention of gaming disorder in this population. MethodsFrom January to February 2024， a cluster sampling method was employed to select 1 414 adolescents from four middle schools in Sichuan Province and Chongqing Municipality as participants in the study. Online Game Motivation Scale （OGMS） and Gaming Disorder Scale for Adolescents （GADIS-A） were administered. Network analysis methods were utilized to investigate the relationships between components of gaming motivation and symptoms of gaming disorder. ResultsThe network edge weights revealed that achievement motivation was positively correlated with impaired game control ability， continued gaming despite negative consequences and the frequency of symptom occurrence （r=0.115， 0.050， 0.076， P<0.05）. Social motivation was negatively correlated with negative consequences （r=-0.054， P<0.05），while immersion motivation was positively correlated with continued gaming despite negative consequences （r=0.032， P<0.05）. Achievement motivation exhibited the highest strength centrality （1.157） among the three components of gaming motivation. ConclusionThe connections between components of gaming motivation and symptoms of gaming disorder exhibit distinct patterns， with each motivational component influencing gaming disorder through specific symptom pathway. Among these components， achievement motivation plays the most critical role in the interplay between gaming motivation and symptoms of gaming disorder. ［Funded by Chongqing Science and Health Joint Medical Science and Technology Innovation Projects General Projects （number， 2023MSXM133）］

Objective To establish a cellular model of Parkinson disease by treating retinoic acid(RA)-differentiated SH-SY5Y cells with α-synuclein preformed fibrils(α-Syn PFF).Methods SH-SY5Y cells were divided into undifferentiated and RA-differentiated groups.The expression levels of tyrosine hydroxylase(TH),dopamine transporter(DAT),lymphocyte activation gene 3(LAG3),and Nestin proteins in the cells were detected using Western blotting,whereas those of microtubule-associated protein 2(MAP2)and neu-ronal nuclei(NeuN)were detected using immunofluorescence staining.Furthermore,RA-treated SH-SY5Y cells were divided into control and α-Syn PFF groups,and their levels of chromatin condensation were detected using Hoechst 33342 staining.Nitric oxide(NO)levels were measured using a NO assay kit.Additionally,the protein levels of TH,poly(ADP-ribose)(PAR),and poly(ADP-ribose)poly-merase(PARP)in these cells were detected using Western blotting,whereas their expression levels of phosphorylated α-Syn(pS129-α-Syn)and phosphorylated histone H2AX(γH2AX)were detected using immunofluorescence staining.Results Treatment with RA resulted in a reduction in cell body size and the elongation of protrusions in SH-SY5Y cells.The results of Western blotting showed that RA treatment could increase the TH,DAT,and LAG3 levels and decrease the Nestin level in SH-SY5Y cells(P＜0.05).α-Syn PFF treat-ment decreased the TH protein level and increased the PAR,PARP-l,and cleaved PARP-1 levels in differentiated SH-SY5Y cells(P＜0.05).According to the immunofluorescence results,RA treatment increased the expression levels of MAP2 and NeuN in SH-SY5Y cells(P＜0.001).The α-Syn PFF treatment increased the expression levels of γH2AX and pS129-α-Syn in RA-differentiated SH-SY5Y cells(P＜0.01).The Hoechst 33342 staining results showed that α-Syn PFF treatment led to chromatin condensation in the differentiated SH-SY5Y cells(P＜0.001)and increased the NO levels(P＜0.01).Conclusion A cellular model of Parkinson disease can be established by treating RA-differentiated SH-SY5Y cells with α-Syn PFF.