ObjectiveTo determine the optimal combination of the effective monomer components "quercetin-kaempferol-abietic acid-boswellic acid" in Fujin Shengjisan for promoting diabetic ulcer （DU） wound healing through uniform design， thereby achieving the modern application of the ancient formula. MethodsFollowing the principle of "uniform design-pharmacodynamic experiment-mathematical modeling and model verification"， the U₁₄（14⁵） uniform design table was adopted.The four monomer components of Chinese medicine were considered as the independent variables， and the proliferation rate of human umbilical vein endothelial cells （HUVECs） induced by glucose was used as the pharmacodynamic indicator. A mathematical model was constructed using DPS software to correlate the effective monomer components with the pharmacodynamic indicator. The results of uniform design were verified through CCK-8 assay， cell scratch healing， tube formation， Western blot， and Real-time PCR. ResultsAmong the 14 compatibility groups， compared with the high-glucose model group， compound compatibility group 6 showed the strongest proliferation effect and statistical significance （P<0.05）. Four quadratic polynomial regression equations （Y₁-Y₄） were obtained through DPS modeling. Considering the model's fit， stability， and practical application， equations Y₁-Y₃ were selected for the follow-up verification. To ensure experiment reproducibility， group 6 was used for validation. Group 6 and equations Y₁-Y₃ were renamed as compound prescription ① to compound prescription④， respectively， to represent the modern application of the ancient FJSJ Powder through compatibility of monomer components. Verification experiments showed that in the CCK-8， scratch healing， and tube formation assays， the cell viability， wound healing rate， and tube formation number of HUVECs stimulated with 50 mmol·L^-1 glucose were significantly reduced compared with the blank group. Moreover， the expression levels of angiogenesis-related cytokines， vascular endothelial growth factor （VEGF） and fibroblast growth factor 2 （FGF2）， and CD31 secretion were significantly down-regulated. However， after intervention with compound prescriptions ① to ④， compound prescriptions ① and ③ significantly improved the biological functions of HUVECs induced by 50 mmol·L^-1 glucose. Further analysis of the regression coefficients of compound prescriptions ① and ③， and the relative dose ratios of each monomer component， indicated that abietic acid， quercetin， and boswellic acid promoted angiogenesis of HUVECs in the high glucose environment， with a major effect （positive partial correlation coefficients， all > 0.9）. Abietic acid and boswellic acid， as well as kaempferol and boswellic acid， promoted angiogenesis in HUVECs through interaction （positive partial correlation coefficients）. ConclusionCompound prescriptions ① and ③ are the optimal combinations. They can reverse the inhibitory effects of high glucose， stimulate the proliferation， migration， and tube formation abilities of HUVECs in a high glucose environment， and promote the expression of vascular endothelial growth factorA（VEGFA）， FGF2， and CD31， thereby promoting angiogenesis and facilitating DU wound healing. This finding not only confirms the good reproducibility and feasibility of compound prescriptions ① and ③ but also provides new insights and methods for the rational construction of mathematical models to further study the compatibility theory of Chinese medicine.

Avian coccidiosis, an acute parasitic disease that mainly harms chicks, is widely prevalent across the world, which poses a serious threat to poultry industry. Because of the single prophylactic formulations, veterinary clinical treatment of coccidiosis mainly relies on chemically synthesized agents, polyether ionophores and Chinese herbal medicines. The introduction of novel anticoccidial drugs is slow for a long period of time, and there is an increasing problem of anticoccidial drug resistance following long-term use, which has become an urgent problem to be solved in poultry industry. This review summarizes the levels of anticoccidial drug resistance across China from 2018 to 2023, and analyzes the resistance to various anticoccidial agents in coccidia. It is indicated that the overall prevalence of anticoccidial drug resistance is high in coccidia, and development of novel anticoccidial agents and products with reduced antibiotics use and alternatives of antibiotics is of an urgent need.

Background and aims:Hepatocellular carcinoma(HCC)is a malignant tumor with a high mortality rate,but there are still no effective treatments.The aim of this study was to investigate the anticancer po-tential of the combined use of brefeldin A(BFA)and tunicamycin(TM)in HepG2 cells,as well as the underlying mechanisms.Methods:HepG2 cells were treated with different concentrations of BFA(0.1-2.5 mg/L)and TM(1-5 mg/L)for 24 h.DMSO(0.1％,v/v)was used as a vehicle control.Cell viability and cell migration were measured using MTT assay and scratch wound assay,respectively.Apoptosis was detected using flow cytometry and acridine orange(AO)staining.The protein and mRNA levels of various factors involved in apoptosis(poly(ADP-ribose)polymerase-1(PARP-1),caspase-12,caspase-3,and stearoyl-CoA desaturase 1)and endoplasmic reticulum(ER)stress(binding immunoglobulin protein(BiP),protein kinase R-like endoplasmic reticulum kinase(PERK),p-PERK,phosphorylation of eukaryotic translation initiation factor 2alpha(p-eIF2α),activating transcription factor(ATF)4,and C/EBP homologous protein(CHOP))were measured using Western blotting and qRT-PCR,respectively.Results:Both BFA and TM alone significantly reduced the viability of HepG2 cells in a dose-dependent way.The co-incubation with TM(1 mg/L)further significantly reduced the viability of HepG2 cells treated with BFA(0.25 mg/L)alone(P＜0.05).BFA significantly increased the protein and mRNA levels of caspase-3 and PARP-1(P＜0.05)compared to control and DMSO-treated cells,indicating that BFA induced apoptosis in HepG2 cells by increasing the expression of caspase-3 and PARP-1.The induction of apoptosis by BFA could be further significantly enhanced by co-incubation with TM.In addition,BFA significantly increased the mRNA levels of BiP,PERK and ATF4(P＜0.05)compared to control and DMSO-treated cells.After co-incubation of BFA and TM,the protein levels of BiP,p-PERK,p-eIF2α and CHOP were significantly increased,indicating that TM could enhance BFA-induced ER stress in HepG2 cells through the PERK-eIF2α-ATF4-CHOP pathway.Conclusions:BFA could induce apoptosis and ER stress,and TM could enhance the ability of BFA to induce apoptosis and ER stress in HepG2 cells through the PERK-eIF2α-ATF4-CHOP pathway.The findings highlight the therapeutic potential of the combined use of BFA and TM in treating HCC.

Objective To statistically analyze the allergen-specific IgE test results for allergic patients and observe the distribution of allergens and their prevalence trends.Methods Allergen-specific IgE test results were collected from 12 486 patients with suspected allergic diseases who attended the outpatient clinic of the Department of Dermatology of the Second Affiliated Hospital of Air Force Medical University from January 2018 to December 2023,and the distribution of the positivity rate of various allergens and their differences among different age,gender and seasonal subgroups were statistically analyzed.Results Allergen-specific IgE positive results were found in 5 109 cases out of 12 486 patients with suspected allergic diseases,with a positive rate of 40.92%.Between different gender groups,the allergen positivity rate were 45.41%(2 371/5 221)in males and 37.69%(2 738/7 265)in females,respectively,and the difference in positivity rate between males and females was statistically significant(x2=74.99,P<0.001).The allergen positivity rate among different age groups was highest in the 3～<6 years group(60.00%),followed by the 6～<18 years group(54.92%),and lowest in the≥60 years group(29.18%),with statistically significant differences in allergen positivity rates among different age groups(x2=344.97,P<0.001).The top three overall allergen positivity rates were milk(11.73%),dwarf ragweed/artemisia/rudolfia/quinoa(11.43%)and house dust mite(10.82%),and the positivity rates of milk and house dust mite had a tendency to increase year by year.The highest allergen positivity rate among groups in different seasons was in summer(42.28%),followed by fall(41.32%)and lowest in winter(38.31%),and the difference in allergen positivity rates among the four seasons was statistically significant(x2=9.09,P=0.028).Dwarf ragweed/artemisia/rutabaga/quinoa had the highest positivity rate in the fall(15.75%),while milk(14.59%)and egg white(2.58%)had the highest positivity rates in the summer,and the differences in the positivity rates of dwarf ragweed/artemisia/rutabaga/quinoa,milk and egg white between the four seasons were statistically significant(x2=92.50,70.45,8.10,all P<0.05).Multiple positives were present for allergen-specific IgE,with 22.18%single positives and 18.92%double and more than double positives.Positive test results for ingestion were mainly distributed in the lower levels,while positive test results for inhalation were more distributed in the higher levels,especially for dwarf ragweed/artemisia/rutabaga/quinoa,which were most distributed in level 6.Conclusion Different types of allergens have different distribution characteristics among different genders,ages and seasons,the distribution levels of positive results are different,and there are multiple positive results.Based on the distribution characteristics of allergens in the region,rational arrangement of the dietary and living shoule be mode to avoid the risks and to reduce the probability of the occurrence of allergic diseases.

ObjectiveTo evaluate the effectiveness and safety of neck seven-line method combined with periauricular acupuncture as salvage treatment for sudden hearing loss in non-acute stage. MethodsSixty-six patients with non-acute stage of sudden hearing loss with a disease duration of 15-90 days were randomly divided into 33 cases each in treatment group and control group. The treatment group was given neck seven-line method combined with acupuncture at periauricular points； the control group used sham acupuncture and sham electroacupuncture at the same points. Both groups were treated 3 times a week for 6 weeks. The pure tone average hearing threshold of impaired frequencies were examined before treatment， after treatment finish and at follow-up （week 10）， and the difference between pure tone average hearing threshold of impaired frequencies before and after treatment was calculated； calculate the proportion of patients with ≥10 dB improvement in pure tone average hearing threshold of impaired frequency after treatment and at follow-up； compare the patients' Tinnitus Evaluation Scale （TEQ） scores， Chinese Medicine Quality of Life Assessment Scale （CQ-11D） health utility values and the difference between before and after treatment， and record the occurrence of adverse events. ResultsThe pure tone average of impaired frequency in the treatment group were （50.57±18.07） dB and （47.70±17.42） dB at post-treatment and follow-up respectively， and （54.38±21.77） dB and （53.36±20.99） dB in the control group at post-treatment and follow-up. Compared with the pre-treatment period， the pure tone average hearing threshold of impaired frequency in the two groups significantly decreased （P＜0.05） at post-treatment and follow-up. The difference of pure tone average hearing threshold of impaired frequency in the treatment group after treatment and at the follow-up visit compared to that before treatment was lower than those in the control group （P＜0.05）. After treatment， 13 patients （39.39%） in the treatment group and 10 patients （30.30%） in the control group showed improvement of ≥10 dB in pure tone average hearing threshold of impaired frequency； at the follow-up visit， 18 patients （54.55%） in the treatment group and 10 patients （30.30%） in the control group showed improvement of ≥10 dB in the pure tone average hearing threshold of impaired frequency， and there was no statistical significance for comparison between groups at the time of post-treatment and follow-up （P＞0.05）. The TEQ score of the treatment group significantly lower than that before treatment （P＜0.05）； the TEQ score of the treatment group and the difference between before and after treatment significantly lower than that of the control group （P＜0.05）. The difference in CQ-11D health utility values and the difference between before and after treatment were not statistically significant between the two groups （P＞0.05）. Eight cases of acupuncture-related adverse events occurred among 66 patients， including subcutaneous haematomas after needling， severe pain during needling and needle fainting， which disappeared after symptomatic treatment and did not affect the following treatment. ConclusionNeck seven-line method combined with periauricular acupuncture could be used as salvage treatment for sudden hearing loss in non-acute stage to improve the pure tone average hearing threshold of impaired frequency， alleviate tinnitus， with safety.

Introduction::Observational studies have revealed an association between waist circumference (WC) and atrial fibrillation (AF). However, it is difficult to infer a causal relationship from observational studies because the observed associations could be confounded by unknown risk factors. Therefore, the causal role of WC in AF is unclear. This study was designed to investigate the causal association between WC and AF using a two-sample Mendelian randomization (MR) analysis.Methods::In our two-sample MR analysis, the genetic variation used as an instrumental variable for MR was acquired from a genome-wide association study (GWAS) of WC (42 single nucleotide polymorphisms with a genetic significance of P <5 × 10 –8). The data of WC (from the Genetic Investigation of ANthropometric Traits consortium, containing 232,101 participants) and the data of AF (from the European Bioinformatics Institute database, containing 55,114 AF cases and 482,295 controls) were used to assess the causal role of WC on AF. Three different approaches (inverse variance weighted [IVW], MR–Egger, and weighted median regression) were used to ensure that our results more reliable. Results::All three MR analyses provided evidence of a positive causal association between high WC and AF. High WC was suggested to increase the risk of AF based on the IVW method (odds ratio [OR] = 1.43, 95% confidence interval [CI], 1.30–1.58, P = 2.51 × 10 -13). The results of MR–Egger and weighted median regression exhibited similar trends (MR–Egger OR = 1.40 [95% CI, 1.08–1.81], P = 1.61 × 10 -2; weighted median OR = 1.39 [95% CI, 1.21–1.61], P = 1.62 × 10 -6). MR–Egger intercepts and funnel plots showed no directional pleiotropic effects between high WC and AF. Conclusions::Our findings suggest that greater WC is associated with an increased risk of AF. Taking measures to reduce WC may help prevent the occurrence of AF.

Acupuncture has a certain effect for the patients with post-stroke depression. In clinics, acupuncture treat this disease from the brain, liver and kidney, heart and spleen, and phlegm and blood stasis. Acupuncture plays a role in nourishing the bone of marrow, regulating the liver and kidney, nourishing the heart and mind, and invigorating the spleen and stomach. Acupuncture plays an antidepressant role by regulating neurotransmitters and receptors, promoting nerve function repair, inhibiting the secretion of inflammatory factors, reducing inflammatory response, inhibiting the hyperfunction of hypothalamic-pituitary-adrenal axis, and regulating the brain-gut axis.

Objective:To understand the current status and analyze the factors of demoralization of patients with chronic heart failure (CHF), providing references for targeted psychological interventions of nursing staff.Methods:Using the cross-sectional survey method, from August 2022 to January 2023, 282 CHF patients who were followed up in the Cardiovascular Department of the First Affiliated Hospital of Zhengzhou University were selected as the study subjects. They were investigated using the General Information Questionnaire, Demoralization Scale Revised Mandarin Version, Brief Illness Perception Questionnaire (BIPQ), Fear of Progression Questionnaire-Short Form (FoP-Q-SF), and the factors influencing the demoralization of CHF patients were analyzed using univariate analysis and multiple linear regression.Results:Among 282 cases, male 172 cases, female 110 cases, aged (62.29±10.05) years old. The Demoralization Scale Revised Mandarin Version′s score of CHF patients was (30.30 ± 10.37) points; the score of BIPQ was (42.18 ± 13.94) points; the score of FoP-Q-SF was (35.41 ± 7.29)points, which were at high level. The results of multiple linear regression analysis showed that patient disease duration, disease stages, New York heart association cardiac function classification, the score of BIPQ, and the score of FoP-Q-SF were factors influencing the demoralization of CHF patients ( t values were 3.08 to 12.50, all P<0.05). Conclusions:There is an urgent need to focus on the current status of the demoralization of CHF patients. It is necessary to develop a systematic and effective intervention strategy for demoralization, to take into account patient disease duration, disease stages, illness perception, and fear of progression in a comprehensive manner.

Objective:To explore the mediating role of disease progression′s fear and positive affect in the relationship between disease perception and demoralization in patients with chronic heart failure. It provided a theoretical basis for targeted interventions for healthcare workers.Methods:From October 2022 to March 2023, 320 patients with chronic heart failure in the First Affiliated Hospital of Zhengzhou University were selected as the research objects by convenience sampling. The General Information Questionnaire, Demoralization Scale Redacted Mandarin Version, Brief Illness Perception Questionnaire, Fear of Progression Questionnaire-Short Form, Positive and Negative Affect Schedule (Positive Affect Schedule) were used to conduct the questionnaire survey exploring the mediating effects of fear of disease progression and positive emotions between disease perception and disorientation by construction structural equation model.Results:There were 268 valid questionnaires. Of the 268 patients, 168 were male and 100 were female, 3.36% (9/268) were ≤40 years old, 55.22% (148/268) were 41-65 years old, and 41.42% (111/268) were >65 years old. Correlation analysis showed that disease perception was positively correlated with disease progression ′s fear, and every dimension of demoralization ( r values were 0.300-0.586, all P<0.01), and negatively correlated with positive affect ( r=-0.374, P<0.01); disease progression′s fear was negatively correlated with positive affect ( r=-0.318, P<0.01), and positively correlated with every dimension of demoralization ( r values were 0.339-0.464, all P<0.01); positive affect was negatively correlated with every dimension of demoralization ( r values were -0.430--0.334, all P<0.01). Structural equation model analysis showed that the direct effect of disease perception on demoralization was significant ( β=0.407, P<0.01), and both mediating effects of disease progression ′s fear and positive affect between disease perception and demoralization in patients with chronic heart failure were significant ( β=0.074, 0.079, both P<0.01). The chain mediating effect of disease progression ′s fear and positive effect was also significant ( β=0.019, P<0.01). Conclusions:Disease perception could directly predict the demoralization of patients with chronic heart failure and indirectly predict the demoralization of patients with chronic heart failure through the mediating effect of disease progression ′s fear, positive affect, and the chain mediating effect of disease progression ′s fear and positive affect.

Objective To investigate whether BPA and its substitutes BPAF,BPB,and BPS can induce lipid accumulation in hepato-cytes.Methods HL-7702 cells were treated with BPA,BPAF,BPB,or BPS for 24 h.Lipid droplet accumulation in cells was observed via oil red O staining,and triglyceride content was determined through the GPO-PAP chemical-enzymatic method.In addition,qRT-PCR was used to detect the expression of triglyceride synthesis-related genes.Results Red lipid droplets of different sizes could be observed in the BPA,BPAF,BPB,and BPS groups.The intracellular triglyceride content increased significantly under 1 and 50 μmol/L BPA,10 and 50μmol/L BPAF,1,10,and 50μmol/L BPB,and 50μmol/L BPS.LIPIN2 mRNA expression level increased significantly under 10μmol/L BPAF,10μmol/L BPB,and 1 and 10μmol/L BPS.DGAT2 mRNA expression increased significantly under 50μmol/L BPA,10μmol/L BPAF,10 and 50μmol/L BPB,and 1μmol/L BPS.Conclusion BPAF,BPB,and BPS can increase intracellular triglyceride synthesis by upregulating LIPIN2 and DGAT2 mRNA expression,leading to intracellular fat accumulation and increased triglyceride con-tent in HL-7702 cells.