OBJECTIVE To investigate the mechanism of Xihuang pill （XHP） against diffuse large B-cell lymphoma （DLBCL）. METHODS The active ingredients of XHP and potential therapeutic targets for DLBCL were identified using TCMSP， GeneCards and DisGeNET databases. Protein-protein interaction networks were constructed using the String database and Cytoscape software to screen core components and core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were then performed. The clinical relevance of core targets was analyzed using the GEPIA and PanCanSurvPlot databases. Molecular docking and molecular dynamics （MD） simulation were conducted to verify the interactions between core components and core targets， and the binding free energy was calculated using the molecular mechanics Poisson-Boltzmann surface area （MM-PBSA） method. The effects of XHP on DLBCL and the related molecular mechanisms were validated using CCK-8 assay， flow cytometry and Western blot. RESULTS Network pharmacology analysis identified 108 active ingredients of XHP and 410 potential therapeutic targets for DLBCL. Six core components （e.g.， 17 beta-estradiol， quercetin） and ten core targets [e.g.， tumor protein 53 （TP53）， proto-oncogene tyrosine-protein kinase Src （SRC）] were obtained. Enrichment analysis indicated that the anti-DLBCL effects of XHP were primarily associated with the apoptotic signaling pathway， the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and so on. Clinical correlation analysis revealed that TP53 and SRC expression were significantly up-regulated in DLBCL tissues and associated with poor patient prognosis （P＜0.05）. Molecular docking， MD simulations and MM-PBSA calculations confirmed that the SRC-quercetin complex had a mail：stronger and more stable binding affinity. In vitro experiments demonstrated that XHP concentration-dependently inhibited the proliferation of DLBCL cells； compared with control group， XHP medium- and high-dose groups could significantly induce the apoptosis of SU-DHL2 and SU-DHL4 cells， and significantly down- regulated the expressions of SRC protein， phosphorylated （p）-PI3K/PI3K and p-Akt/Akt in SU-DHL4 cells （P＜0.05）. CONCLUSIONS XHP may inhibit the proliferation and induce the apoptosis of DLBCL cells by regulating the SRC/PI3K/Akt signaling pathway.

The welfare and ethics of laboratory animals are the ethical principles and behavioral norms that need to be followed in conducting animal-based scientific research, breeding and managing laboratory animals, and supervising and regulating such activities. The level of protection of laboratory animal welfare and ethics is closely related to the development of science and technology, which has become a widely recognized international consensus. At present, Guangdong Province is accelerating the construction of a high-level science and technology innovation province and the Guangdong-Hong Kong-Macao Greater Bay Area International Science and Technology Innovation Center. Guangdong Province should rely on its advanced governance capacity in the field of laboratory animal science and technology ethics to promote the high-quality development of its laboratory animal science and technology sector. Based on the management laws, regulations, and institutional mechanisms of laboratory animals in China, this paper explores the optimization of the laboratory animal science and technology ethics governance system, which includes the institutional guarantees, responsibility systems, ethical review and supervision mechanisms, and education and outreach. Through methods such as literature research, questionnaire surveys, and interview investigations, an empirical study of the laboratory animal science and technology ethics governance system in Guangdong Province has been conducted. Analysis of literature and research results shows that Guangdong Province has basically established a laboratory animal management system, collaboration mechanism, supervision mechanism, and education and training system that meet the current requirements of the laboratory animal science and technology ethics governance system in China. However, there are still problems such as an incomplete laboratory animal science and technology ethics supervision mechanism, an underdeveloped operation mechanism of review institutions, insufficient attention paid by laboratory animal units to the ethical review of animal experiments, inconsistent ethical review standards, and a lack of professional ethical education and training for ethics review personnel. Therefore, optimization measures such as improving the laboratory animal science and technology ethics review system, strengthening supervision and inspection, further strengthening the accountability of responsible entities, formulating review norms, and enhancing hierarchical and classified education and training are proposed, to provide a theoretical basis for promoting the normalized and long-term governance of laboratory animal science and technology ethics in Guangdong Province.

Objective To investigate the mechanism of Astragali Complanati Semen in the prevention and treatment of hyperlipidemia;To provide theoretical basis for its clinical application.Methods The active components of Astragali Complanati Semen were retrieved and screened through TCMSP,TCMID and TDT databases to obtain the action targets of the active components.Hyperlipidemia targets were obtained through GeneCards,DisGeNET,and TTD databases,and the drug active component targets were intersected with hyperlipidemia targets.Cytoscape 3.9.1 software and STRING database were used to construct active component-target network and protein-protein interaction network,screening for major active components and core targets.GO and KEGG pathway enrichment analysis was performed using the DAVID database,and the CB-Dock platform was used for molecular docking.HepG2 cells were induced to construct a high-fat cell model using oleic acid and palmitic acid,and intervened with Astragali Complanati Semen freeze-dried powder solution.The mRNA expression of the core target was detected by RT-qPCR.Results A total of 10 active components of Astragali Complanati Semen and 67 potential action targets of hyperlipidemia were identified,involving signaling pathways such as AGE-RAGE,lipid metabolism,HIF-1,etc.Experimental results showed that intervention with Astragali Complanati Semen could reduce lipid accumulation in the high-lipid cell model,with an optimal intervention concentration of 500 μg/mL;RT-qPCR revealed significant down-regulation of TNFα,IL6,AKT1,PPARG,and other genes after intervention with Astragali Complanati Semen.Conclusion Astragali Complanati Semen exerts lipid-regulating effects through multiple targets and pathways,providing a basis for its application in the prevention and treatment of hyperlipidemia.

Objective To observe and compare the therapeutic effects of aflibercept biosimilar and originator afliber-cept through intravitreal injection in patients with age-related wet macular degeneration(AMD).Methods This retro-spective study enrolled 60 AMD patients(60 eyes)who were diagnosed and treated at the Department of Ophthalmology,Zibo Central Hospital,from January 2024 to May 2024.These patients were divided into two groups.Specifically,30 pa-tients(30 eyes)(the originator group)received the intravitreal injection of originator aflibercept,while another 30 patients(30 eyes)(the biosimilar group)received the intravitreal injection of aflibercept biosimilar.All patients followed a 3+PRN treatment regimen with a follow-up period of at least 6 months.Relevant examinations including best-corrected visual acui-ty(BCVA),optical coherence tomography,corneal endothelial microscopy,and multifocal electroretinogram(mfERG)were performed before and after treatment.Moreover,the BCVA,central retinal thickness(CRT),pigment epithelial de-tachment(PED)height,corneal endothelial cell density,hexagonal cell ratio,coefficient of variation(CV)of corneal en-dothelial cells,P1 wave amplitude density of the first ring,number of intravitreal injections,and incidence of complications were compared between both groups.Results No statistically significant differences were observed in the age,sex ratio,or disease duration between both groups(all P＞0.05).After treatment,the BCVA,CRT,and PED height of patients in both groups decreased,and the P1 wave amplitude density of the first ring increased in both groups,with statistically sig-nificant differences compared with baseline values(all P＜0.05).In the originator group,the corneal endothelial cell den-sity,hexagonal cell ratio,and CV of corneal endothelial cells of patients in both groups increased after treatment,while the biosimilar group showed a decrease in the corneal endothelial cell density and hexagonal cell ratio,alongside an increase in the CV of corneal endothelial cells;however,these changes were not statistically significant compared with baseline values(all P＞0.05).No significant difference was observed in the number of intravitreal injections between both groups(P＞0.05).The correlation analysis results revealed positive associations between disease duration and post-treatment BCVA(logMAR)in both groups(r=0.901 and 0.905,respectively;both P＜0.000 1).No severe ocular complications or cardio-vascular/cerebrovascular events occurred in all patients.Conclusion There is no significant difference in the short-term efficacy between originator aflibercept and aflibercept biosimilar in the treatment of patients with wet AMD.

Objective To explore the effect of low-frequency repetitive transcranial magnetic stimulation(rTMS)combined with unilateral upper limb mirror training on contralateral limb strength in patients with hemiplegia after ischemic stroke.Methods A total of 196 patients with hemiplegia after ischemic stroke were selected.All patients were divided into study group and control group via a random number table method,with 98 patients in each group.The control group received mirror training,while the study group received low-frequency rTMS treatment in addition to the control group.The neuroelectrophysiology,neurological function,limb motor function,and clinical efficacy of all patients were observed before and after treatment,and all patients were performed the resting-state functional MRI examination.A generalized estimating equation(GEE)model were used to analyze the improvement of contralateral limb strength.Results After treatment,the seed points in the study group showed a significant enhancement in connectivity with the whole brain function.The overall efficiency of the study group was significantly better than that of the control group.After treatment,the central motor conduction time(CMCT),neuron specific enolase(NSE),cortical latency(CL),and S100β of the two groups of patients were significantly reduced compared with before treatment,while the neurotrophin-3(NT-3),nerve growth factor(NGF),Fugl-Meyer assessment upper extremities(FMA-UE),Wolf motor function test(WMFT),modified Barthel index(MBI),and Berg balance scale(BBS)scores were significantly increased.Moreover,the study group showed a more significant improvement compared to the control group(P＜0.05).The GEE model analysis results showed that the improvement of contralateral limb strength in the study group was significantly better than that in the control group.Conclusion Low-frequency rTMS combined with unilateral upper limb mirror training can improve cortical excitability and upper limb motor function in hemiplegic patients after ischemic stroke,with good therapeutic effects.

Objective:To explore the value of quantitative parameters of diffusion weighted imaging (DWI) combined with dynamic enhanced magnetic resonance imaging (DCE-MRI) in predicting the efficacy of neoadjuvant chemotherapy for locally advanced breast cancer (LABC) .Methods:A total of 97 patients with LABC admitted to the hospital from Mar. 2020 to Mar. 2023 were studied and received neoadjuvant chemotherapy to evaluate the therapeutic effect, and DWI and DCE-MRI scans were performed before and after treatment. The difference of DWI and DCE-MRI quantitative parameters before treatment in patients with different therapeutic effects was compared, and the correlation between the difference of DWI and DCE-MRI quantitative parameters and therapeutic effect was analyzed. The predictive value of quantitative parameters of DWI and DCE-MRI before treatment was analyzed. The quantitative parameters of DWI and DCE-MRI in patients with different pathological reactions were compared before treatment, and the quantitative parameters of DWI and DCE-MRI were compared before and after treatment.Results:The apparent diffusion coefficient (ADC) of patients with effective chemotherapy before treatment was higher, but transport constant (Ktrans) , extracellular space volume percentage (Ve) and rate constant (Kep) were lower ( t=5.0, 3.27, 3.55, 3.89, P < 0.05) ; Spearman correlation analysis showed that ADC was positively correlated with chemotherapy efficacy before treatment (r=0.66; P < 0.05) , while Kep, Ve, Ktrans were negatively correlated with it (r=-0.58, -0.47, -0.60; P < 0.05) ; ROC curves showed that the area under the curve (AUC) values of ADC, Kep, Ve and Ktrans in predicting chemotherapy efficacy before treatment were 0.771, 0.797, 0.664 and 0.715, respectively, while the combined AUC value of each indicator was 0.832; Compared with patients with non-significant pathological response, ADC before treatment was higher in patients with significant pathological response, Kep, Ve and Ktrans were lower ( t=4.46, 3.32, 3.60, 3.95, P < 0.05) ; Compared with before treatment, ADC value increased after treatment, while Kep, Ve and Ktrans decreased ( t=8.77, 6.22, 9.34, 10.26, P < 0.05) . Conclusion:Quantitative parameters of DWI and DCE-MRI can reflect the changes in the condition of patients with locally advanced neoadjuvant chemotherapy, and the combination of the two can help to improve the predictive value of chemotherapy efficacy in patients.

Phospholipid pharmaceutical excipients are primarily composed of a glycerol backbone,fatty acid chains,and phosphate groups.Due to their amphiphilic structure and unique physicochemical properties,they are commonly used as emulsifiers and carrier materials in pharmaceutical formulations.The pharmacopoeias of various countries have included phospholipid based pharmaceutical excipients and specified the testing methods and limits for their critical quality attributes.This article focuses on the current inclusion status,characteristic indicators,component content determination indicators,and functionality-related indicators determination methods and limits of phospholipid pharmaceutical excipients of various countries,in order to provide references and a basis for the rational applicatione of phospholipid pharmaceutical excipients.

A 66-year-old female patient with multiple chronic diseases was on long-term treatment with digoxin, spironolactone, metoprolol, atorvastatin, dapagliflozin, and entecavir, with no abnormality platelet count (PLT). Due to hypertrophic obstructive cardiomyopathy and atrial fibrillation, digoxin was discontinued, and rivaroxaban 15 mg once daily orally was added to prevent thrombosis. Concurrently, furosemide, sacubitril valsartan, meglumine adenosine cyclophosphate, and silibinin was given for cardiac load reducement, blood pressure control and heart failure improvement, myocardial nutrition, and liver function improvement, respectively. After the initiation of this regimen, the patient′s PLT gradually decreased and was 51×10 9/L on day 13. Drug-induced thrombocytopenia was considered, with rivaroxaban being the likely causative agent. Rivaroxaban was then switched to warfarin, methylprednisolone 40 mg was administered intravenously once, and the remaining medications were continued. The patient′s PLT gradually increased. On day 11 after discontinuing rivaroxaban, the PLT was 155×10 9/L. At a 2-week follow-up, PLT of the patient was 169×10 9/L.

Objective:To explore the predictive value of dual-energy CT lumbar quantitative measurement combined with serum bone alkaline phosphatase (BALP), osteocalcin (BGP), and β-type I collagen carboxy-terminal peptide ( β-CTx) for the risk of fractures in patients with osteoporosis. Methods:A total of 90 patients with osteoporosis who underwent dual-energy CT lumbar quantitative detection at the First People’s Hospital of Shangqiu from Jan. 2020 to Jan. 2023 were selected as the research subjects. According to the occurrence of fractures within one year of follow-up, the patients were divided into the fracture group ( n=36) and the non-fracture group ( n=54). The clinical data, dual-energy CT lumbar quantitative parameters, and serum BALP, BGP, and β-CTx levels of the two groups were compared. Logistic multivariate regression analysis was used to analyze the risk factors for fractures in patients with osteoporosis, and the receiver operating characteristic (ROC) curve was used to analyze the predictive value of dual-energy CT lumbar quantitative parameters combined with serum BALP, BGP, and β-CTx for fractures in patients with osteoporosis. Results:There were no statistically significant differences in gender, age, body mass index (BMI), smoking history, drinking history, or bone marrow CT value parameters between the fracture group and the non-fracture group ( χ2=0.66, t=1.86, t=1.59, χ2=0.19, χ2=0.98, t=0.40, all P > 0.05). However, there were statistically significant differences in the history of fragility fractures, regular calcium supplementation, lumbar bone mineral density (BMD), calcium CT value, mixed energy image CT value, calcium concentration, fat fraction, BALP, BGP, and β-CTx ( χ2=9.73, χ2=4.17, t=3.14, t=7.06, t=7.92, t=6.50, t=3.26, t=8.12, t=12.66, t=11.37, all P < 0.05). Logistic multivariate regression analysis showed that the history of fragility fractures ( OR=1.863, P=0.023), regular calcium supplementation ( OR=1.728, P=0.031), fat fraction ( OR=1.685, P=0.009), BALP ( OR=1.815, P=0.002), BGP ( OR=1.605, P=0.003), and β-CTx ( OR=1.636, P < 0.001) were risk factors for fractures in patients with osteoporosis, while lumbar bone BMD ( OR=0.456, P=0.025), calcium CT value ( OR=0.486, P=0.005), mixed energy image CT value ( OR=0.490, P < 0.001), and calcium concentration ( OR=0.509, P=0.010) were protective factors. The ROC curve showed that the sensitivity of dual-energy CT lumbar quantitative measurement parameters combined with serum BALP, BGP, and β-CTx in predicting fractures in patients with osteoporosis was 94.68%, the specificity was 92.16%, the Youden index was 0.868, the area under the curve (AUC) was 0.947, and the 95% confidence interval ( CI) was 0.905 to 0.982. Conclusion:Dual-energy CT lumbar quantitative parameters and serum BALP, BGP, and β-CTx levels have certain predictive value for the risk of fractures in patients with osteoporosis, and the combined prediction value is higher.

Objective:To analyze differences in the expression of routine laboratory parameters and cerebrospinal fluid (CSF) examination indicators between patients with non-neurosyphilis (syphilis without nervous system involvement) and those with neurosyphilis, to screen for key predictive factors, and to construct a predictive model for neurosyphilis.Methods:A retrospective analysis was conducted on the clinical data from patients with syphilis at the Fifth People's Hospital of Suzhou from 2019 to 2024. Patients with neurosyphilis and non-neurosyphilis who were hospitalized from November 2019 to June 2022 were included in the model cohort, and those hospitalized from January 2024 to October 2024 were included in the validation cohort. The patients' basic information and laboratory test indicators (including routine blood tests, CSF biochemical analysis, and syphilitic antibody tests) were collected. Statistical analysis was performed using the GraphPad software. The receiver operating characteristic (ROC) curve and the binary logistic regression method were used to analyze the predictive performance of key indicators in patients from the model cohort with SPSS software, and a predictive model for neurosyphilis was constructed. The performance of the neurosyphilis predictive model for neurosyphilis was validated based on relevant indicators from the validation cohort.Results:The model cohort included 99 patients with non-neurosyphilis (including 49 males and 50 females), and they were aged between 19 and 85 years, with an average age of 47 years; 69 patients with neurosyphilis were also included in the model cohort, including 58 males and 11 females, and they were aged between 26 and 73 years, with an average age of 51 years. The neurosyphilis group showed a significant increase in the median levels of CSF adenosine deaminase (1 U/L) and microprotein (711 mg/L), white blood cell counts (0.009 × 10?/L), as well as in the proportion of positive Pandy tests (35/69, 50.7%) compared with the non-neurosyphilis group (0 U/L, 309 mg/L, 0.002 × 10?/L, 2 /99 [2.0%], respectively, all P < 0.001). Based on the ROC curve analysis, the CSF microprotein and white blood cell count had relatively high discriminative ability (area under the ROC curve [AUC] > 0.85), while adenosine deaminase and the Pandy test showed moderate discriminative ability (0.7 < AUC < 0.85). According to the above four indicators, the logistic regression analysis showed that CSF microprotein combined with CSF white blood cell counts could construct the best predictive model for neurosyphilis, with a prediction accuracy rate of 0.980, a sensitivity of 98.5%, and a specificity of 89.9%. The prediction formula was logit (p) = -9.926 + 0.015 × microprotein + 362.33 × CSF white blood cell count, with a cutoff value of ≥ -0.867. The validation cohort enrolled 72 patients with non-neurosyphilis and 51 with neurosyphilis, and there were significant differences in CSF microprotein levels and white blood cell counts between the two groups (both P < 0.001). In the validation cohort, the predictive model demonstrated an accuracy of 86.2%, with a sensitivity of 83.6% and a specificity of 91.1% for predicting neurosyphilis. Conclusion:The predictive model for neurosyphilis constructed by combining CSF microprotein and CSF white blood cell count may contribute to the early differential diagnosis of neurosyphilis.