Objective To analyze the PLCβ4 gene mRNA expression and its clinical significance in hepatocellular carcinoma (HCC) based on TCGA database. Methods Based on the data on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumor liver tissues) in the TCGA database, Kaplan–Meier method, Cox regression analysis, and immune infiltration analysis were performed to evaluate the relationship between PLCβ4 gene and the clinical characteristics and survival prognosis of HCC patients. Correlation analysis between PLCβ4 gene and 24 types of immune cells was applied to investigate the relationship between PLCβ4 gene and immune cell infiltration and mRNA expression level of TP53 gene, a high-frequency mutation gene in HCC. In addition, paraffin sections of highly, moderately, and poorly differentiated tumor tissues and normal liver tissues from HCC patients were collected. The histopathological observation was carried out via HE staining method, and the expression levels of PLCβ4 and Ki-67 proteins in each clinical sample were verified through the immunohistochemical method. Results The expression level of PLCβ4 gene in HCC was significantly higher than that in normal tissues (P<0.01), and all patients in the PLCβ4 high-expression group had a significantly longer overall survival than those in the low-expression group (P<0.05), which suggested that PLCβ4 substantially affected the prognosis of HCC patients. Correlation analysis showed that the expression level of PLCβ4 gene was highly correlated with immune cell infiltration and the expression level of TP53 gene. As verified by clinical sample experiments, HE staining experiments and immunohistochemical results revealed that PLCβ4 gene expression in HCC tissue samples was significantly higher than that in normal tissues (P<0.001), and it was negatively correlated with the degree of differentiation. Conclusion PLCβ4 may serve as an independent prognostic factor in HCC and is expected to be a novel molecular target for HCC treatment.

AIM: To identify the primary active components and underlying mechanisms of Yijing Decoction(YJD)in treating early diabetic retinopathy(DR)based on liquid chromatography-mass spectrometry and network pharmacology.METHODS: Active components of YJD were characterized through LC-MS. Components with optimal ADME(absorption, distribution, metabolism, excretion)properties were selected as key bioactive candidates. Network pharmacology approaches were employed to predict YJD-DR therapeutic targets. Protein-protein interaction(PPI)networks, gene ontology(GO)enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were subsequently conducted to predict core targets and networks. Critical targets and pathways were experimentally validated through Western blot.RESULTS: Ten core therapeutic targets were identified, including TNF, Alb, EGFR, STAT3, PTGS2, ESR1, PPAR, MMP9, TLR4, and MAPK. YJD was related to cancer-related signaling, fluid shear stress and atherosclerosis, and neurodegenerative diseases, encompassing key biological processes such as inflammatory response regulation, programmed cell death activation, and enhanced cell migration. Furthermore, Western blot analysis confirmed that YJD significantly inhibited high glucose-induced phosphorylation of STAT3(P-STAT3/STAT3)and ERK(P-ERK/ERK)in rat retinal microvascular endothelial cells.CONCLUSION: This study revealed YJD's pharmacodynamical basis and its multi-component, multi-target, and multi-paths pharmacology. YJD exerts therapeutic effects on DR by coordinately regulating critical signaling pathways and alleviating intraocular inflammation, thus preserving retinal vascular endothelial cells, maintaining blood-retinal barrier integrity, and facilitating retinal neurovascular repair.

Objective To Explore the effect of expression of peroxidase reductase 4(PRDX4)on cervi-cal lymph node metastasis in oral squamous cell carcinomas(OSCC)and its relationship with prognosis.Methods Using bioinformatics databases to explore the expression,prognosis analysis,and related pathway prediction of PRDX4 gene in head and neck squamous cell carcinoma.At the same time,clinical and pathologi-cal data including cervical lymph node metastasis were collected from 124 OSCC patients,the expression of PRDX4 was detected in 124 OSCC tissues using immunohistochemical experimental methods.Results Analy-sis of online bioinformatics databases showed that PRDX4 was highly expressed in head and neck squamous cell carcinoma and significantly correlated with tumor grade.The immunohistochemical results showed that the occurrence of cervical lymph node metastasis was significantly correlated with the intensity of PRDX4 stai-ning in 124 OSCC cases studied,and high expression of PRDX4 was an independent risk factor for cervical lymph node metastasis in OSCC(P=0.010).The staining intensity of PRDX4 was significantly correlated with the presence of multiple lymph node metastasis(P=0.020)and the the maximum diameter of lymph node metastasis(P=0.031),but not related to the invasion of lymph nodes outside the membrane.Survival a-nalysis showed that strong PRDX4 positivity was significantly correlated with poor disease-free survival(DFS)rate and overall survival(OS)rate in OSCC patients.Conclusion OSCC patients with strong expres-sion of PRDX4 have a higher incidence of cervical lymph node metastasis and a poorer prognosis.

Objective To investigate the correlation of sarcoplasmic/endoplasmic reticulum Ca2+ATPase 2a(SERCA2a)and blood urea nitrogen(BUN)to albumin(ALB)ratio(BAR)with cardiac function and prognosis in patients with chronic heart failure(CHF).Methods A total of 200 CHF patients admitted to this hospital from January 2021 to January 2023 were selected as the CHF group and 100 healthy people un-dergoing physical examination as the control group.CHF patients were divided into class Ⅰ group(38 cases),class Ⅱ group(40 cases),class Ⅲ group(54 cases)and class Ⅳ group(68 cases)according to the New York Heart Association(NYHA)cardiac function classification after admission.According to the prognosis,they were divided into poor prognosis group(60 cases)and good prognosis group(140 cases).Serum SERCA2a BUN,ALB levels were measured and BAR was calculated.Spearman rank correlation coefficient was used to analyze the correlation between serum SERCA2a,BAR and NYHA cardiac function classification in CHF pa-tients.Taking the prognosis of CHF patients as the dependent variable,a multivariate unconditional Logistic regression model was established to determine its influencing factors.Receiver operating characteristic curve was drawn to evaluate the predictive value of serum SERCA2a and BAR for poor prognosis of CHF patients.Results Compared with the control group,the serum SERCA2a level was decreased and BAR was increased in the CHF group(P＜0.05).The level of SERCA2a in class Ⅰ group,class Ⅱ group,class Ⅲ group and classⅣ group decreased and BAR increased successively(P＜0.05).The NYHA classification was negatively cor-related with serum SERCA2a level(rs=-0.756,P＜0.05),and positively correlated with BAR(rs=0.722,P＜0.05).After 1-year follow-up,the incidence of poor prognosis in 200 CHF patients was 30.00％(60/200).Increased NYHA class(OR=1.936,95％CI:1.115-3.364),atrial fibrillation(OR=3.269,95％CI:1.078-9.913),N-terminal pro-B-type natriuretic peptide(OR=1.002,95％CI:1.001-1.009)and BAR(OR=1.169,95％CI:1.082-1.263)were independent risk factors for poor prognosis in patients with CHF(P＜0.05),increased left ventricular ejection fraction(OR=0.810,95％CI:0.716-0.916)and SERCA2a(OR=0.964,95％CI:0.947-0.981)were independent protective factors(P＜0.05).The area under the curve of serum SERCA2a combined with BAR to predict the poor prognosis of CHF patients was 0.865(95％CI:0.810-0.910),which was larger than 0.784(95％CI:0.720-0.839)and 0.777(95％CI:0.713-0.833)predicted by serum SERCA2a and BAR levels alone,and the difference was statistically significant(Z=2.944,3.250,P＜0.05).Conclusion The decrease of SERCA2a and the increase of BAR are closely re-lated to cardiac function and prognosis in patients with CHF.Serum SERCA2a combined with BAR has a higher value in predicting poor prognosis in patients with CHF.

Objective To analyze the predictive value of serum levels of procalcitonin(PCT)and cytokines on the prognosis of patients with COVID-19 at admission.Methods From November 2022 to February 2023,patients diagnosed with COVID-19 who were admitted to Beijing Chest Hospital were enrolled.Chemiluminescence was used to detect serum PCT levels,and flow microsphere array was used to detect serum cytokines IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17A,IL-17F,IL-22,TNF-α,TNF-β,IFN-γ level.ICU admission,mechanical ventilation and in-hospital death were defined as poor prognosis.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.Results A total of 176 patients with complete data were included,including 134 in the PCT-normal group and 42 in the PCT-elevated group,with a median age of 71.50 years and 71.59%males.Patients in the PCT elevated-group had significantly higher rates of ICU admission(38.41%vs.13.11%,P<0.05),mechanical ventilation(76.92%vs.24.59%,P<0.001)and in-hospital mortality(38.46%vs.6.56%,P<0.001)were significantly higher than those in the PCT-normal group.Serum levels of cytokines IL-6(7.40 pg/mL vs.4.78 pg/mL,P = 0.033 4)and IL-8(10.97 pg/mL vs.5.92 pg/mL,P<0.001)were significantly higher in patients with poor prognosis than in those with good prognosis.The area under the curve for PCT,IL-6,and IL-8 to predict poor prognosis in COVID-19 patients was 0.687,0.660,and 0.746,respectively;sensitivity was 52.78%,55.17%,and 72.41%,respectively;and specificity was 81.58%,74.19%,and 74.19%,respectively,as calculated from the ROC curve.When PCT,IL-6 and IL-8 jointly predict the prognosis of COVID-19 patients,the area under the curve is 0.764,the sensitivity is 70.00%,and the specificity is 80.00%.Conclusion Serum PCT and cytokines IL-6 and IL-8 could be used as predictive markers for poor prognosis in patients with COVID-19.

Objective To establish a safe disposal management program for home used sharps waste of insulin injection so as to provide a reference for the standardised management of sharps waste after insulin.injection.Methods Based on the model of information-motivation-behavioural skills,the safe disposal management program for insulin needles used at home was developed by literature reviews and semi-structured interviews to investigate the perceptions and requirements of patients.The program was then modified and refined by two rounds of expert consultation with Delphi method.Results The effective retrieval rates of questionnaire for two rounds of expert consultations were 88.89%and 93.75%,with an expert authority coefficient at 0.93.In the second round,the mean importance scores of the items were 4.40 to 5.00,with a coefficient of variation ranged from 0 to 0.168.The established program consisted of three primary items,six secondary items,and 20 tertiary items.Conclusion The safe disposal management program for home used sharps waste of insulin injection established from the perspectives of information,motivation and behavioural skills was scientific and practical,which offered a guidance to healthcare professionals in the clinical practices.

Objective:To investigate the intelligence status of children aged 10 - 12 in rural areas of Linxia Hui Autonomous Prefecture (referred to as Linxia) in Gansu Province.Methods:From September to November 2019, a cross-sectional study was carried out to investigate the intelligence status of children aged 10 to 12 in 8 counties (cities) of Linxia. Chinese Raven's Progressive Matrices (rural version) was used for intelligence test and children's intelligence quotient (IQ) was calculated by regular mold to evaluate children's intelligence level.Results:A total of 1 721 children in Linxia were tested for intelligence, with an average IQ of 103.2. Among them, low intelligence (≤69) accounted for 1.0% (18/1 721), borderline (70 - 79) accounted for 3.0% (52/1 721), middle and lower (80 - 89) accounted for 8.4% (144/1 721), moderate (90 - 109) accounted for 56.6% (974/1 721), middle and upper (110 - 119) accounted for 21.9% (377/1 721), excellent (120 - 129) accounted for 7.8% (135/1 721), extremely excellent (≥130) accounted for 1.2% (21/1 721). There were 635, 598 and 488 children aged 10, 11 and 12, respectively, with an average IQ of 106.1, 103.3 and 99.2. There were 919 males and 802 females, with an average IQ of 102.9 and 103.4, respectively.Conclusion:In 2019, the intelligence of children aged 10 to 12 in rural areas of Linxia has reached the moderate level.

Objective To investigate the effect of Danshen Baoxin Cha (DBC) on a rat model of coronary heart disease combined with cognitive impairment. Methods Male Sprague-Dawley(SD) rats were randomly assigned to two groups:normal group and model group. Streptozotocin was injected into the bilateral ventricles of rats in the model group to establish cognitive impairment model,then isoproterenol hydrochloride was injected subcutaneously to model myocardial ischemia. Behavioral experiments were conducted to verify the success of the model of cognitive dysfunction. The rats of the model group were randomly divided into five groups:model control group,Tongxinluo Capsule group (TXL group,1.6 g·kg-1),and low-(4 g·kg-1),medium-(8 g·kg-1),and high-(16 g·kg-1) dose DBC groups. These groups were received the respective treatments continuously for two weeks. Subsequently,the Y-maze,novel object recognition and Morris water maze experiment were employed to assess the learning and memory abilities of rats. A kit was utilized to quantify the level of oxidative stress in the brain and the adenosine triphosphate (ATP) content in the brain and mitochondria. Hematoxylin-eosin (HE) staining and Nissl staining were employed to observe the pathological changes of neurons in hippocampus CA1 region. Electron microscopy was utilized to observe the pathological changes of mitochondria in hippocampal CA1 region. The expression levels of peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),glucose transporter type 4(GLUT4),and optic atrophy 1(OPA1) were quantified by real-time fluorescence quantitative polymerase chain reaction (PCR),and the expression of proteins related to the AMPK/OPA1 signaling pathway was determined by Western Blot analysis. Results Compared with the normal group,the spontaneous alternating reaction rate,the novel object recognition index,number of crossing the original platform,and distance ratio in the model group were obviously decreased (P<0.01). Neuronal density in the CA1 region of the hippocampus was decreased,Nissl bodies were decreased,and nucleus consolidation was increased. The ATP level in mitochondria,and the levels of ATP,SOD,and GSH-PX in brain were significantly decreased(P<0.05,P<0.01),as well as the content of ROS and MDA were significantly increased (P<0.05,P<0.01). The mitochondria of hippocampus in CA1 region were swollen,with sparse and vacuolated cristae. The mRNA expression levels of GLUT4,PGC-1α,and OPA1 were significantly decreased (P<0.01). The protein expression levels of GLUT4,SIRT1,PGC-1α and OPA1,and p-AMPK/AMPK ratio were significantly decreased (P<0.05,P<0.01). Compared with the model group,the behavioral indexes of rats in the DBC groups were significantly improved (P<0.05,P<0.01),the number of neurons in the hippocampal CA1 area,Nissl bodies and nucleus consolidation were improved. The ATP level in mitochondria and the levels of ATP,SOD,and GSH-PX in brain were significantly increased (P<0.05,P<0.01). The levels of ROS and MDA were significantly decreased (P<0.05,P<0.01). The structure of mitochondrial cristae in hippocampal CA1 region were relatively intact. The mRNA expression levels of GLUT4,PGC-1α and OPA1 were increased (P<0.05,P<0.01),and the expression of proteins related to the AMPK/OPA1 signaling pathway was significantly increased(P<0.05,P<0.01). Conclusion DBC can enhance learning and memory abilities,reduce neuronal damage in a rat model of coronary heart disease combined with cognitive impairment. The mechanism may be related to the reduction of oxidative stress damage in the brain,the activation of the AMPK/OPA1 signaling pathway,and the restoration of energy levels.

Objective To explore the mechanism of action of Danshen Baoxin Cha(DBC) on depressed mice with coronary heart disease (CHD) based on network pharmacology and NLRP3 inflammatory pathway. Methods (1) TCMSP and BATMAN-TICAM databases were used to screen the DBC active ingredients and targets. The targets of CHD with depression were screened using the OMIM and Genecards databases. The targets of DBC active ingredients and related targets of CHD with depression were imported into Venny 2.1 online platform to obtain the intersection targets,which was the potential target of DBC in the treatment of CHD with depression. Protein-protein interaction (PPI) analysis was performed on the intersection targets using the STRING platform to screen the key targets. A "drug-active ingredients-disease-targets" network was created to select the main active ingredients and core targets of DBC for the treatment of CHD with depression. Thereafter,the primary targets were examined by GO function and KEGG pathway enrichment using the Metascape database.(2)Kunming mice were split into six groups of eight mice each at random:the control group,the model group,the positive control group (metoprolol tartrate 5.14 mg·kg-1+sertraline hydrochloride 10.3 mg·kg-1),and the DBC high-,middle-,and low-dose groups (30.8,15.4 and 7.7 g·kg-1·d-1). Chronic unpredictable mild stimulation (CUMS)and subcutaneous injection of isoprenaline hydrochloride (ISO) were used to induce a mice model of CHD with depression. Mice were treated orally with the corresponding drug once a day for 18 consecutive days. Behavioral experiments involving forced swimming test,tail suspension test,and open-field test were applied to detect depression levels of mice. Histopathological alterations in hippocampus tissues were noted using HE and Nissl staining. qPCR was used to determine the mRNA expression levels of IL-6,TNF-α,NLRP3,IL-1β,IL-10,and Caspase-1 in hippocampus tissues. Results(1) Sixty-five active components in Salvia and seven active components in green tea were screened out. A total of 1042 potential targets and 2116 CHD complicated with depression-related targets were obtained. The intersection of the targets of active components and disease-related targets was performed by Venny 2.1.0 platform to obtain 299 potential targets (common targets) of DBC in the treatment of CHD with depression. The core targets including IL-1β,AKT1,TNF-α,IL-6,VEGFA,CASP3 and IL-10 were screened through PPI network analysis of potential targets. Key active ingredients including vitamin B,luteolin,salvianolic acid,tanshinone ⅡA and catechin,as well as key targets,such as PTGS2、IL-1β、IL-6、TNF-α and IL-10,were obtained by network analysis of "drugs-active ingredients-disease-targets". The potential targets were correlated with biological processes such as inflammation response,regulation of tumour necrosis factor (TNF),glucocorticoid regulation,regulation of nuclear factor kappa B(NF-κB) transcription factor,as well as major pathways including PI3K-Akt signaling pathway,TNF signaling pathway,apoptosis signaling pathway,and NF-κB signaling pathway.(2) Compared with the control group,mice in the model group showed a significant decrease in the total and center distance of the open field (P<0.01) and a significant increase in the time of forced swimming and immobility time of tail suspension test (P<0.01). The mRNA expression of IL-6,TNF-α,NLRP3,IL-1β,and Caspase-1 was significantly up-regulated(P<0.01) in the hippocampus tissues,but IL-10 mRNA expression was down-regulated (P<0.05). Compared with the model group,the total and center distance in DBC high-,middle-,and low-dose groups were significantly up-regulated(P<0.05,P<0.01),and the time of forced swimming and immobility time of tail suspension test were significantly down-regulated (P<0.01). The mRNA expression of IL-6,TNF-α,NLRP3,IL-1β and Caspase-1 of the DBC high-,middle-,and low-dose groups were significantly down-regulated(P<0.01),IL-10 mRNA expression in mice hippocampus tissue of DBC high-and middle-dose groups was up-regulated (P<0.01). Conclusion The intervention effect of DBC on depressed mice with CHD may be achieved by active ingredients including luteolin,tanshinone,salvianolic acid and catechin acting on the key targets,such as IL-6,TNF-α,IL-1β and IL-10,to regulate the NLRP3 inflammatory signaling pathway.

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).