OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

OBJECTIVE: To analyze the distribution characteristics of glucose-6-phosphate-dehydrogenase (G6PD) mutations and their enzyme activity in newborns patients with G6PD deficiency in Guilin region. METHODS: From July 2022 to July 2024, umbilical cord blood samples from 4 554 newborns in Guilin were analyzed for G6PD mutations using fluorescence PCR melting curve analysis. Enzyme activity was detected in 4 467 cases using the rate assay. RESULTS: Among 4 467 newborns who underwent G6PD activity testing, 162 newborns (3.63%) were identified as G6PD-deficient, including 142 males (6.04%) and 20 females (0.94%), the prevalence of G6PD deficiency was significantly higher in males than in females (P < 0.001). Genetic analysis of 4 554 newborns detected G6PD mutations in 410 cases (9%), including 171 males (7.13%) and 239 females (11.09%), with a significantly higher mutation detection rate in females than in males (P < 0.001). A total of nine single mutations and four compound heterozygous mutations were identified. The most common mutations were c.1388G>A (33.66%), c.1376G>T (23.66%) and c.95A>G (16.34%). Among newborns who underwent both enzyme activity and genetic mutation testing, males with G6PD mutations had significantly lower enzyme activity than that of females with G6PD mutations(P < 0.001). Specifically, among newborns carrying the mutations c.1388G>A, c.1376G>T, c.95A>G, c.1024C>T or c.871G>A, males consistently exhibited lower enzymatic activity than females with the same mutations (P < 0.001). Furthermore, in male G6PD-deficient newborns, the enzyme activity levels in those carrying c.1388G>A, c.1376G>T, c.95A>G, c.1024C>T, or c.871G>A were lower than those in both the control group and the c.519C>T group (P < 0.05). CONCLUSION This study provides a comprehensive profile of G6PD deficiency incidence and mutation spectrum in the Guilin region. By analyzing enzyme activity and genetic mutation results, this study provides insights into potential intervention strategies and personalized management approaches for the prevention and treatment of neonatal G6PD deficiency in the region.
Humans ; Infant, Newborn ; Glucosephosphate Dehydrogenase Deficiency/epidemiology* ; Glucosephosphate Dehydrogenase/genetics* ; Female ; Male ; Mutation ; China/epidemiology*

OBJECTIVE: To investigate the effect of chrysophanol, a phytochemical derived from Radix et Rhizoma Rhei on HepG2 liver cancer cells. METHODS: HepG2 cell line was treated with different concentrations chrysophanol (0-100 μmol/L) for 24 h. The cell counting kit 8 assay was employed to assess cell viability. Intracellular calcium levels were examined using Fluo-4 AM and Mag-fluo-4 AM staining, followed by flow cytometry analysis. Mitochondrial membrane potential was measured with JC-1 assay kit. Additionally, the expressions of key proteins such as p-JNK, Bax, cytochrome c (Cyt C), cleaved caspase-3 (cCaspase-3), and caspase-8 were analyzed by Western blot. The inhibitory effects of chrysophanol on the invasion of cells were determined using a Transwell assay. Analysis of invasiveness was conducted by wound healing assay. RESULTS: Chrysophanol significantly reduced the proliferation of HepG2 liver cancer cells by affecting intracellular calcium distribution, diminishing mitochondrial membrane potential, and enhancing the expressions of p-JNK, Bax, Cyt C, cCaspase-3, and caspase-8 in the groups treated with 75 or 100 μmol/L chrysophanol compared to the control group (P<0.05). Additionally, 75 and 100 μmol/L chrysophanol exhibited inhibitory effects on cell migration and wound healing. CONCLUSION Chrysophanol demonstrates potential against HepG2 liver cancer cells, suggesting its potential use as a therapeutic agent for liver cancer treatment.
Humans ; Calcium/metabolism* ; Hep G2 Cells ; Liver Neoplasms/metabolism* ; Neoplasm Invasiveness ; Membrane Potential, Mitochondrial/drug effects* ; Anthraquinones/pharmacology* ; Cell Proliferation/drug effects* ; Cell Death/drug effects* ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Cell Survival/drug effects*

OBJECTIVE: To explore the anti-photoaging properties of salvianolic acid B (Sal B). METHODS: The optimal photoaging model of human immortalized keratinocytes (HaCaT cells) were constructed by expose to ultraviolet B (UVB) radiation. The cells were divided into control, model and different concentrations of Sal B groups. Cell viability was measured via cell counting kit-8. Subsequently, the levels of oxidative stress, including reactive oxygen species (ROS), hydroxyproline (Hyp), catalase (CAT), and glutathione peroxidase (GSH-Px) were detected using the relevant kits. Silent information regulator 1 (SIRT1) protein level was detected using Western blot. The binding pattern of Sal B and SIRT1 was determined via molecular docking. RESULTS: Sal B significantly increased the viability of UVB-irradiated HaCaT cells (P<0.05 or P<0.01). Sal B effectively scavenged the accumulation of ROS induced by UVB (P<0.05 or P<0.01). In addition, Sal B modulated oxidative stress by increasing the intracellular concentrations of Hyp and CAT and the activity of GSH-Px (P<0.05 or P<0.01). The Western blot results revealed a substantial increase in SIRT1 protein levels following Sal B administration (P<0.05). Moreover, Sal B exhibited good binding affinity toward SIRT1, with a docking energy of -7.5 kCal/mol. CONCLUSION Sal B could improve the repair of photodamaged cells by alleviating cellular oxidative stress and regulating the expression of SIRT1 protein.
Humans ; Sirtuin 1/metabolism* ; Ultraviolet Rays ; Oxidative Stress/radiation effects* ; Keratinocytes/metabolism* ; Molecular Docking Simulation ; Benzofurans/pharmacology* ; Skin Aging/radiation effects* ; Reactive Oxygen Species/metabolism* ; Cell Survival/radiation effects* ; HaCaT Cells ; Hydroxyproline/metabolism* ; Glutathione Peroxidase/metabolism* ; Catalase/metabolism* ; Depsides

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

Objective:To compare the differences in the evaluation of hemolysis performance of cellulose hemostatic materials using different detection methods and test media,and to explore a m ore reasonable testing plan for such products.Methods:Hemolysis tests were conducted on cellulose hemostatic materials using the absorbance measurement hemolysis method and hemoglobin concentration measurement hemolysis method in accordance with YY/T 1651.1-2019 standard.We compared the changes in hemolysis rate,pH value,and osmotic pressure under different experimental media.Results:Under the same experimental method,compared to SC,the hemolysis results using PBS as the extraction medium are smaller,and the changes in pH and osmotic pressure are closer to the normal range of human body changes.Conclusions:The changes in pH and osmotic pressure may be one of the reasons for the high hemolysis rate of cellulose hemostatic materials.Choosing PBS with buffering effect as the leaching medium may be more suitable for evaluating the hemolysis performance of cellulose hemostatic materials.

BACKGROUND:Osteoporosis is a high-risk factor for dental implant treatment.The preparation of tissue engineering scaffolds with sustained-release Alendronate and its application in oral implant surgery for osteoporosis patients is a current hot topic in oral bone tissue engineering research.OBJECTIVE:To prepare alendronate/chitosan/polyvinyl alcohol composite hydrogel film and characterize its sustained release properties.METHODS:(1)Chitosan/polyvinyl alcohol composite hydrogel films with varying mass ratios(mass ratios of chitosan and polyvinyl alcohol were 3:7,5:5,and 7:3,respectively),chitosan and polyvinyl alcohol hydrogel films were prepared using a physical crosslinking method.By characterizing the morphology,water contact angle,mechanical properties,swelling rate,and cell compatibility of the hydrogel film,a suitable hydrogel film was screened as a carrier of alendronate.(2)Chitosan/polyvinyl alcohol composite hydrogel films containing 0,0.4,1.2,and 2.0 mg/L alendronate were prepared,and rat bone marrow mesenchymal stem cells were co-cultured with the four groups of hydrogel films.The cytocompatibility of the hydrogel films was detected by CCK-8 assay and CD44 immunofluorescence staining.The drug-loaded chitosan/polyvinyl alcohol composite hydrogel films were immersed in PBS.The drug release performance of the composite hydrogel films was detected by ultraviolet-visible spectroscopy.RESULTS AND CONCLUSION:(1)The characterization results showed that with the increase of the mass of polyvinyl alcohol in the hydrogel film,the structural density of the hydrogel film increased,the porosity decreased,the water contact angle(all within 90°),the elongation at break and the compressive strength increased,and the equilibrium swelling rate decreased.It had no effect on the proliferation of rat bone marrow mesenchymal stem cells.Chitosan hydrogel film could promote the adhesion of rat bone marrow mesenchymal stem cells.The 3:7 and 5:5 ratio composite hydrogel films did not affect the adhesion of rat bone marrow mesenchymal stem cells.Polyvinyl alcohol hydrogel film and 7:3 ratio composite hydrogel film inhibited the adhesion of rat bone marrow mesenchymal stem cells.Based on the above results,the 5:5 composite hydrogel film was selected as the carrier of alendronate.(2)CCK-8 assay results showed that the composite hydrogel film containing 0.4 and 1.2 mg/L alendronate had no cytotoxicity.CD44 immunofluorescence staining results showed that the composite hydrogel film containing 0.4 mg/L alendronate did not affect the adhesion of rat bone marrow mesenchymal stem cells,while the composite hydrogel film containing 1.2 and 2.0 mg/L alendronate inhibited the adhesion of rat bone marrow mesenchymal stem cells.Chitosan/polyvinyl alcohol composite hydrogel film containing 0.4,1.2,and 2.0 mg/L alendronate released alendronate in the first 6 hours,and then released alendronate evenly and stably,with a release time of more than 96 hours.(3)The results showed that the chitosan/polyvinyl alcohol composite hydrogel film with a ratio of 5:5 had good physical and chemical properties and cytocompatibility,and could be used as a sustained-release carrier of alendronate.

Objective To construct a machine learning prediction model for diabetic kidney disease(DKD)in type 2 diabetes mellitus(T2DM)patients in the plain-sand and loess hilly areas of Gansu Province,and analyze the interpretability of the model.Methods A multi-stage stratified random sampling method was used to collect the data of T2DM patients in the two areas.After key feature screening,eight ML prediction models were constructed for the risk of DKD in the two areas.The receiver operating characteristic(ROC)curve,accuracy and F1 index were used to evaluate the model,and Shapley additive explanation(SHAP)algorithm was used for model interpretation.Results A total of 1599 patients with T2DM were enrolled in this study.After feature screening,ten variables were selected for model construction in the plain-sand areas.Among the eight models,the gradient boosting decision tree(GBDT)model had the highest prediction efficiency.The area under the curve(AUC)of the test dataset was 0.972,the accuracy was 0.949,and the F1 index was 0.884.In the loess hilly region,12 variables were included in the model,and the best model was the random forest(RF).The AUC of the test set was 0.966,the accuracy was 0.951,and the F1 index was 0.861.SHAP analysis showed that in addition to serum creatinine,age,LDL-C,HbA1c,DM duration,serum uric acid and urinary microalbumin were also closely related to the high risk of DKD.Conclusions The GBDT and RF models have good predictive efficiency for the occurrence of DKD in the two areas,which can be used for the screening of DKD high-risk populations and the in-depth exploration of potential risk factors in the two areas.

Objective:To investigate the relationship between the severity of pharyngolaryngeal sensory impairment and swallowing biomechanics as well as the risk of penetration-aspiration in patients with dysphagia following infratentorial stroke.Methods:This retrospective cross-sectional study enrolled 51 patients with dysphagia following infratentorial stroke hospitalized in the Department of Rehabilitation Medicine of The Third Affiliated Hospital of Sun Yat-sen University between January 2022 and December 2023. Participants were categorized into three groups: normal sensation group [15 males, 2 females; age range 29-76 (56.0±13.3)years], diminished sensation group[16 males, 3 females; age range 38-80(62.0±11.8)years], and absent sensation group [14 males, 1 female; age range 44-75 (60.0±9.7)years]. All patients underwent laryngoscopy and videofluoroscopic swallowing study, which included pharyngolaryngeal sensory testing and Penetration-Aspiration Scale assessment. Swallowing temporal parameters were quantitatively analyzed. Group comparisons for different variable types were conducted using the Chi-square test, one-way ANOVA, and the Kruskal-Wallis test. The correlation between sensory groups and Penetration-Aspiration Scale scores was assessed using Spearman′s correlation analysis. Logistic regression was employed to analyze the impact of pharyngolaryngeal sensory function on penetration-aspiration events.Results:Among the 51 patients, 33.33% (17/51) had normal pharyngolaryngeal sensation, while, 66.67% (34/51) exhibited sensory impairment. The normal sensation group exhibited a significantly longer laryngeal vestibule closure (LVC) time [792 (643, 1 205) ms] compared to the diminished [528 (380, 776) ms] and absent sensation groups [380 (322, 404) ms] ( H=6.502, P=0.039). Additionally, the upper esophageal sphincter opening time was longer in the normal sensation group than in the absent sensation group [528 (371, 710) ms vs 182 (0, 710) ms, H=6.003, P=0.049]. Correlation analysis indicated a significant negative correlation between the severity of sensory impairment and Penetration-Aspiration Scale scores ( r=-0.366, P=0.008). Logistic regression analysis demonstrated that greater sensory impairment was an independent risk factor for penetration-aspiration ( OR=9.29, 95%CI=1.57-54.77, P=0.014). Conclusion:Pharyngolaryngeal sensory deficits are common after infratentorial stroke dysphagia and are significantly associated with impaired swallowing biomechanics and increased aspiration risk. The severity of sensory deficit is a key determinant of penetration-aspiration risk, highlighting its value in risk stratification and therapeutic decision-making for dysphagia.