OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy （DN）. METHODS From the perspective of healthcare service providers， a Markov model was established to simulate the dynamic changes of each stage in DN patients who received finerenone combined with the standard treatment regimen or the standard treatment regimen alone based on the phase Ⅲ clinical trial study of finerenone for DN. Markov model was used to perform the cost-effectiveness of long-term effects and the costs of the two therapies with a simulation cycle of 4 months， a simulation period of 15 years and an annual discount rate of 5%. At the same time， one-way sensitivity analysis and probability sensitivity analysis were performed， and the stability of the results was validated. RESULTS Accumulative cost of the standard treatment regimen was 579 329.54 yuan， and the accumulative utility was 8.052 4 quality-adjusted life year （QALYs）； the accumulative cost of finerenone combined with the standard treatment regimen was 332 520.61 yuan， and the accumulative utility was 8.187 4 QALYs. Finerenone combined with the standard treatment regimen was more cost-effective. The results of one-way sensitivity analysis showed that dialysis status utility value， DN stage 3 utility value and DN stage 4 utility value had a great influence on the incremental cost-effectiveness ratio， but did not affect the robustness of the model. The results of probability sensitivity analysis showed that finerenone combined with the standard treatment regimen was more cost-effective with 100% probability. CONCLUSIONS For DN patients， finerenone combined with the standard treatment regimen is more cost-effective as an absolute advantage option.

BACKGROUND:Studies have shown that ischemia-induced cellular autophagy dysfunction is a key factor in brain injury.Autophagy related genes 6(ATG6),microtubule-associated protein 1 light chain(LC3),p62,and other autophagy key proteins are involved in the processes such as neuronal axonal degeneration,death,and intracellular homeostasis maintenance,playing an important role in the recovery of neural function. OBJECTIVE:To review the research progress in the role of cellular autophagy in cerebral ischemic injury and the regulatory mechanism of traditional Chinese medicine. METHODS:The first author used"ischemic stroke,brain tissue injury,cellular autophagy,signaling pathways,traditional Chinese medicine compounds,terpenoids,alkaloids,flavonoids,saponins,lignans,phthalates"as Chinese and English keywords respectively to search for literature on autophagy,cerebral ischemic injury,and the regulatory mechanisms of traditional Chinese medicine from China National Knowledge Infrastructure(CNKI)and PubMed databases from January 2016 to February 2024.Literature that is not highly relevant,repetitive,or outdated was excluded.A total of 1 746 relevant literature were retrieved,and 92 articles were ultimately included. RESULTS AND CONCLUSION:Numerous studies have confirmed that autophagy plays an important role in cerebral ischemic injury.Moderate autophagy can promote cell survival,while excessive autophagy exacerbates brain injury.Traditional Chinese medicine can regulate the expression of autophagy related proteins,inhibit neuronal necrosis and apoptosis,and exert neuroprotective effects at different stages of cerebral ischemia by regulating signaling pathways such as PI3K/Akt/mTOR,AMPK-mTOR,and mitogen activated protein kinase.

BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

ObjectiveTo observe the clinical efficacy and safety of Modified Guomin Decoction （加味过敏煎， MGD） in patients with mild to moderate atopic dermatitis （AD） of the traditional Chinese medicine （TCM） pattern of heart fire and spleen deficiency， and to explore its possible mechanisms. MethodsIn this randomized， double-blind， placebo-controlled study， 72 patients with mild to moderate AD and the TCM pattern of heart fire and spleen deficiency were randomly divided into a treatment group and a control group， with 36 cases in each group. The treatment group received oral MGD granules combined with topical vitamin E emulsion， while the control group received oral placebo granules combined with topical vitamin E treatment. Both groups were treated twice daily for 4 weeks. Clinical efficacy， TCM syndrome scores， Visual Analogue Scale （VAS） for pruritus， Dermatology Life Quality Index （DLQI） scores， Scoring Atopic Dermatitis （SCORAD） and serum biomarkers， including interleukin-33 （IL-33）， interleukin-1β （IL-1β）， immunoglobulin E （IgE）， and tumor necrosis factor-α （TNF-α） were compared before and after treatment. Safety indexes was also assessed. ResultsThe total clinical effective rates were 77.78% （28/36） in the treatment group and 38.89% （14/36） in the control group， with cure rates of 19.44% （7/36） and 2.78% （1/36）， respectively. The treatment group showed significantly better clinical outcomes compared to the control group （P＜0.05）. The treatment group exhibited significant reductions in total TCM syndrome scores， including erythema， edema， papules， scaling， lichenification， pruritus， irritability， insomnia， abdominal distension， and fatigue scores， as well as reductions in VAS， DLQI， SCORAD， and serum IgE and IL-33 levels （P＜0.05 or P＜0.01）. Compared to the control group， the treatment group had significantly better improvements in all indicators except for insomnia （P＜0.05）. No adverse events occurred in either group. ConclusionMGD is effective and safe in treating mild to moderate AD patients with heart fire and spleen deficiency pattern. It significantly alleviates pruritus， improves TCM syndromes and quality of life， and enhances clinical efficacy， possibly through modulation of immune responses.

Energy metabolism reconstruction is the new target of the treatment of heart failure. By combing the researches of Chinese medicinals for energy metabolism reconstruction of heart failure， it was found that Chinese medicinal compound formula and single Chinese medicinal have a certain role in regulating energy metabolism， mainly through three aspects， including the optimization of substrate utilization， improvement of mitochondrial structure， function， and homeostasis， and improvement of mitochondrial energy transport， so as to make the energy metabolism of the cardiomyocyte adjusted in the direction of beneficial to the organism， increasing the supply of energy， and improving the cardiac function.

BACKGROUND: The American Heart Association recently released a new cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the association between LE8 scores and the risk of chronic kidney disease (CKD) remains uncertain. We aimed to explore the association of LE8 scores with new-onset CKD and examine whether socioeconomic deprivation and genetic risk modify this association. METHODS: A total of 286,908 participants from UK Biobank and without prior CKD were included between 2006 and 2010. CVH was categorized using LE8 scores: low (LE8 scores <50), moderate (LE8 scores ≥50 but <80), and high (LE8 scores ≥80). The study outcome was new-onset CKD, ascertained by data linkage with primary care, hospital inpatient, and death data. Cox proportional hazard regression models were used to investigate the association between CVH categories and new-onset CKD. RESULTS: During a median follow-up of 12.5 years, 8857 (3.1%) participants developed new-onset CKD. Compared to the low CVH group, the moderate (adjusted hazards ratio [HR], 0.50; 95% confidence interval [CI]: 0.47-0.53) and high CVH (adjusted HR, 0.31; 95% CI: 0.27-0.34) groups had a significantly lower risk of developing new-onset CKD. The population-attributable risk associated with high vs. intermediate or low CVH scores was 40.3%. Participants who were least deprived ( vs.  most deprived; adjusted HR, 0.75; 95% CI: 0.71-0.79) and with low genetic risk of CKD ( vs.  high genetic risk; adjusted HR, 0.89; 95% CI: 0.85-0.94) had a significantly lower risk of developing new-onset CKD. However, socioeconomic deprivation and genetic risks of CKD did not significantly modify the relationship between LE8 scores and new-onset CKD (both P -interaction >0.05). CONCLUSION Achieving a higher LE8 score was associated with a lower risk of developing new-onset CKD, regardless of socioeconomic deprivation and genetic risks of CKD.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Male ; Female ; Middle Aged ; Genetic Predisposition to Disease/genetics* ; Aged ; Risk Factors ; Adult ; Proportional Hazards Models ; Socioeconomic Factors

Lateral organ boundaries (LOB) domain (LBD) genes encode a family of transcription factors ubiquitous in higher plants, playing crucial roles in the growth, development, and stress responses. Hippophae rhamnoides, known for its drought, cold, and saline-alkali tolerance, offers significant economic benefits and ecological values. Utilizing the whole genome data and bioinformatics approaches, this study identified and analyzed the LBD gene family in H. rhamnoides. Additionally, we examined the expression pattern of HrLBD genes by integrating the transcriptome data from male and female flower buds in development. Eleven LBD genes were identified in H. rhamnoides, and these genes were distributed on five chromosomes. The HrLBD proteins showed the lengths ranging from 159 aa to 302 aa, the molecular weights between 18 249.91 Da and 33 202.01 Da, and the subcellular localization in the nucleus or chloroplasts. LBD protein domains and gene structures were highly conserved, featuring similar motifs. The phylogenetic analysis of HrLBD genes and the LBD genes in Arabidopsis thaliana and Hordeum vulgare revealed that HrLBD genes falled into two major categories: Class Ⅰ and Class Ⅱ. The transcriptome data and RT-qPCR showed that HrLBD genes were highly expressed in male flower buds, with up-regulated expression levels throughout bud development, indicating a role in the specific stage of male flower bud development. This study lays a theoretical foundation for exploring the roles of HrLBD genes in the growth, development, and sex differentiation of H. rhamnoides flower buds.
Flowers/genetics* ; Hippophae/metabolism* ; Phylogeny ; Gene Expression Regulation, Plant ; Plant Proteins/genetics* ; Transcription Factors/genetics* ; Multigene Family ; Genes, Plant

Objective:To explore the correlation between IκB kinase-interacting protein(IKBIP)expression in tumor cells within cervical cancer tissues(TCCCT)and the clinical pathological characteristics and prognosis of patients,as well as its impact on the biological behaviors of cervical cancer(CC)cells HeLa and SiHa,and to elucidate its potential mechanism.Methods:GENT2 and Kaplan-Meier plotter databases were utilized to analyze the differential expression of IKBIP mRNA in CC and normal cervical tissues,as well as its correlation with the clinical prognosis of CC patients.The Hallmark reference gene set was chosen for pathway enrichment analysis using the Gene Set Enrichment Analysis(GSEA)software.Immunohistochemistry method was used to detect the IKBIP protein expression in TCCCT and epithelial cells in normal cervical tissue(ECNCT),and analyze the correlations between its expression level and clinicopathological characteristics and prognosis of CC patients.Furthermore,univariate and multivariate Cox regression analyses were performed to identify the risk factors impacting the prognosis of CC patients.The stably transfected cells of CC(HeLa cells and SiHa cells)with IKBIP knockdown were established for the experiment,which were divided into sh-NC group and sh-IKBIP group.The expression of IKBIP protein in various groups was assessed using Western blotting method.The cell proliferation activity and the percentage of 5-ethynyl-2'-deoxyuridine(EdU)positive cells were measured using cell counting kit-8(CCK-8)and EdU methods,while Transwell chamber assay was employed to determine the numbers of migration and invasion cells in various groups.Additionally,the expression levels of E-cadherin,N-cadherin,and Snail proteins in the cells in various groups were analyzed by Western blotting method.Results:The GENT2 database analysis revealed that the expression level of IKBIP mRNA in CC tissue was higher than that in normal cervical tissue(P＜0.001).The GSEA enrichment analysis identified the epithelial-mesenchymal transition(EMT)pathway as the top-ranked pathway in IKBIP high-expression group.The immunohistochemistry results indicated the positive expression rate of IKBIP protein in TCCCT was higher than that in ECNCT(50.5％vs 8.0％),and its over-expression was associated with FIGO stage(2018)and differentiation grade of tumor(P＜0.05).The univariate and multivariate Cox regression analyses suggested that lymph node metastasis(LNM)and high expression of IKBIP were the risk factors affecting the overall survival(OS)and progression-free survival(PFS)of CC patients(P＜0.05).The Western blotting method results showed that compared with sh-NC group,the expression level of IKBIP protein in the cells in sh-IKBIP group was decreased(P＜0.05).The CCK-8 and EdU assay results showed that compared with sh-NC group,the proliferation activity and the percentage of EdU positive cells in sh-IKBIP group were decreased(P＜0.05).The Transwell chamber assay results showed that compared with sh-NC group,the numbers of migration and invasion cells in sh-IKBIP group were significantly decreased(P＜0.05).Additionally,the Western blotting method results indicated that compared with sh-NC group,the expression level of E-cadherin protein in sh-IKBIP group in CC cells was increased(P＜0.05),while the expression levels of N-cadherin and Snail protein were decreased(P＜0.05).Conclusion:The expression of IKBIP protein is significantly up-regulated in HeLa and SiHa cells derived from CC,and it is closely correlated with poor prognosis in CC patients.Suppression of IKBIP protein expression can effectively inhibit the proliferation,invasion and migration capabilities as well as EMT process of CC cells.

Objective To explore correlations of expression levels of microRNA-147(miR-147),Ki-67 and carcinoembryonic antigen(CEA)with lymph node metastasis of invasive lung adenocarci-noma.Methods A total of 160 patients with invasive pulmonary adenocarcinoma were selected as study subjects.Based on presence of lymph node metastasis,patients were divided into lymph node metastasis group(n=74)and non-lymph node metastasis group(n=86).Immunohistochemistry was employed to detect the expression levels of miR-147 and Ki-67 in cancer tissues.The serum CEA level was measured using the chemiluminescence method.The correlations of the expression levels of miR-147,Ki-67 and serum CEA with the clinicopathological characteristics of patients were analyzed.The value of miR-147,Ki-67 and CEA in predicting lymph node metastasis was evaluated using the receiver operating characteristic(ROC)curve.Results The expression level of miR-147 in the lymph node metastasis group was significantly lower than that in the non-lymph node metastasis group,while the expression levels of Ki-67 and serum CEA were significantly higher in the lymph node me-tastasis group than in the non-lymph node metastasis group(P＜0.05).Patients with a tumor diameter≥3 cm or TNM stage Ⅲ to Ⅳ had significantly lower miR-147 expression levels in cancer tissues compared to those with a tumor diameter＜3 cm or TNM stage Ⅰ to Ⅱ(P＜0.05).The Ki-67 ex-pression level in cancer tissues was significantly higher in patients with a tumor diameter ≥3 cm than in those with a tumor diameter＜3 cm(P＜0.05).The serum CEA level was significantly higher in patients with TNM stage Ⅲ to Ⅳ than in those with TNM stage Ⅰ to Ⅱ(P＜0.05).The expres-sion level of miR-147 was negatively correlated with Ki-67,serum CEA and lymph node metastasis(P＜0.05);Ki-67 and serum CEA were positively correlated with lymph node metastasis(P＜0.05);Ki-67 was positively correlated with serum CEA(P＜0.05).The areas under the ROC curves for miR-147,Ki-67 and CEA in predicting lymph node metastasis were 0.785,0.835 and 0.798,respectively(P＜0.05).Conclusion The expression levels of miR-147 and Ki-67 in cancer tissues and the serum CEA level are correlated with lymph node metastasis in invasive pulmo-nary adenocarcinoma.

The special natural environment of the plateau brings about great difficulties and challenges to the field medical support.The serious injury treatment group of the field medical team is responsible for the early treatment of the critically injured,which is highly demanding and is more likely to be adversely affected by the plateau environment.Based on the real experiences and current reality,this paper outlines the priorities of work done by the serious injury treatment group on the plateau in terms of personnel selection,professional training,material preparation,site construction,treatment regimens and combat readiness in the hope of providing references for the medical support for China's the military on the plateau.