ObjectiveTo investigate the therapeutic effects and mechanism of decoctions from four kinds of processed products of Aconiti Radix Lateralis Praeparata（ARLP） in deficiency-cold syndrome. MethodsA total of 36 SD rats were randomly divided into the control group， model group， Shengfupian（SFP） group， Paofuzi（PFZ） group， Heishunpian（HSP） group and Paofupian（PFP） group with 6 rats in each group. Except for the control group， rats in other groups were administered hydrocortisone sodium succinate via intramuscular injection to induce a cold deficiency syndrome model. After 14 consecutive days， each ARLP decoction pieces was administered via continuous gastric lavage at a dose of 12 g·kg^-1·d^-1 for 7 d， while the control and model groups received an equivalent volume of physiological saline. After the end of administration， body weight， spleen weight and thymus weight were measured for calculating the spleen and thymus indexes. Hematoxylin-eosin（HE） staining was used to observe the pathological morphology of adrenal tissue. The fully automatic biochemistry analyzer was used to measure the total cholesterol（TC）， triglyceride（TG）， lactic dehydrogenase（LDH） and lactate（LAC） levels in serum. Enzyme-linked immunosorbent assay（ELISA） was employed to measure the contents of 17-hydroxycorticosteroid（17-OHCS）， cortisol（CORT）， triiodothyronine（T₃）， thyroxine（T₄）， thyrotropin（TSH）， immunoglobulin（Ig） M， IgG， cyclic adenosine monophosphate（cAMP） and cyclic guanosine monophosphate（cGMP）. Western blot was used to measure the protein expression levels of protein kinase A（PKA）， cAMP response element-binding protein（CREB）， silent information regulator 1（Sirt1） and peroxisome proliferator-activated receptor γ coactivator-1α（PGC-1α）. And high performance liquid chromatography（HPLC） was used to determine the content of major alkaloids， followed by Pearson correlation analysis with pharmacodynamic indicators. ResultsAfter modeling， compare with the control group， the model rats exhibited symptoms such as lethargy and loose stools， mild abnormalities were observed in adrenal tissue structure， and both spleen and thymus indices were significantly reduced（P<0.01）. Thyroid， adrenal and immune system functions were suppressed， with decreased serum cAMP level and significantly elevated cGMP level（P<0.01）. Compared with the model group， the adrenal injury by hydrocortisone sodium succinate were repaired and the spleen index were increased significantly in all four ARLP groups（P<0.05， P<0.01）. The thymus index in SFP and PFZ groups were increased significantly（P<0.05）. The contents of T₃， TSH， 17-OHCS and CORT were increased significantly in SFP and PFZ groups（P<0.05）. In addition， the content of IgG in SFP， PFZ and PFP groups were increased significantly（P<0.01）， while the content of IgM in PFZ and HSP groups were also increased significantly（P<0.05）. Regarding the cyclic nucleotide system， PFZ significantly elevated cAMP level while reducing cGMP level（P<0.05）， exhibiting the most pronounced effect among the four decoction pieces. For energy metabolism indicators， PFZ significantly improved abnormal markers including TC， TG， LDH， and LAC（P<0.05）. HSP showed marked improvement effects on TG， LDH， and LAC（P<0.05）. Both PFZ and SFP significantly elevated the expression levels of PKA， CREB， Sirt1， and PGC-1α proteins（P<0.01）. Additionally， the diester alkaloids in ARLP showed a strong positive correlation with TG， IgG， and CORT， a strong negative correlation with LAC， a moderate positive correlation with T₄， and moderate negative correlations with cAMP and spleen index. Monomeric alkaloids showed strong positive correlations with TG and IgG， strong negative correlations with LAC， moderate positive correlations with CORT and T₄， and moderate negative correlations with cAMP and spleen index. However， the content of water-soluble alkaloids showed strong positive correlations with TC， LDH， 17-OHCS， T₃， TSH， and thymus index， moderate positive correlations with cAMP， CORT， T₄， and spleen index， and moderate negative correlation with cGMP. ConclusionAmong different processed ARLP decoction pieces， PFZ processed according to ZHANG Zhongjing's method exhibits the most potent warming and cold-dispelling effects. Its pharmacological actions are mediated through regulating the thyroid， adrenal， immune， cyclic nucleotide systems， and material-energy metabolism pathways. Among these， water-soluble alkaloids show strong or moderate correlations with more indicators of deficiency-cold syndrome and exhibit the highest content in PFZ. Therefore， PFZ processed according to ZHANG Zhongjing's method may exert its warming and cold-dispelling effects through water-soluble alkaloids.

OBJECTIVES: To investigate the effect of orexin-A-mediated regulation of ionotropic glutamate receptors for promoting motor function recovery in rats with spinal cord injury (SCI). METHODS: Thirty-six newborn SD rats (aged 7-14 days) were randomized into 6 groups (n=6), including a normal control group, a sham-operated group, and 4 SCI groups with daily intrathecal injection of saline, DNQX, orexin-A, or orexin-A+DNQX for 3 consecutive days after PCI. Motor function of the rats were evaluated using blood-brain barrier (BBB) score and inclined plane test 1 day before and at 1, 3, and 7 days after SCI. For patch-clamp experiment, spinal cord slices from newborn rats in the control, sham-operated, SCI, and SCI+orexin groups were prepared, and ventral horn neurons were acutely isolated to determine the reversal potential and dynamic indicators of glutamate receptor-mediated currents under glutamate perfusion. RESULTS: At 3 and 7 days after SCI, the orexin-A-treated rats showed significantly higher BBB scores and grip tilt angles than those with other interventions. Compared with those treated with DNQX alone, the rats receiving the combined treatment with orexin and DNQX had significantly higher BBB scores and grip tilt angles on day 7 after PCI. In the patch-clamp experiment, the ventral horn neurons from SCI rat models exhibited obviously higher reversal potential and greater rise slope of glutamate current with shorter decay time than those from sham-operated and orexin-treated rats. CONCLUSIONS Orexin-A promotes motor function recovery in rats after SCI possibly by improving the function of the ionotropic glutamate receptors.
Animals ; Spinal Cord Injuries/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Receptors, Ionotropic Glutamate/metabolism* ; Recovery of Function/drug effects* ; Orexins/pharmacology* ; Male ; Female ; Animals, Newborn ; Neuropeptides/pharmacology* ; Intracellular Signaling Peptides and Proteins/pharmacology*

Purpose To investigate the value of radiomics nomogram for the prediction of p53 abnormal in patient with endometrial carcinoma based on intratumoral and peritumoral MRI.Materials and Methods A total of 145 female patients were pathologically confirmed endometrial carcinoma who underwent pelvic MRI before treatment in Baoding First Central Hospital from January 2020 to April 2024,including 96 patients with p53 wild type and 49 with p53 abnormal.Radiomics features were extracted from both intratumoral and peritumoral regions(2 mm)in diffusion weighted imaging and equilibrium phase of dynamic contrast enhanced MRI,which were selected using least absolute shrinkage and selection operator.Three machine learning algorithms of random forest,K-nearest neighbors and extra trees were conducted to develop the intratumoral,peritumoral and intratumoral combined peritumoral radiomics models.Multivariate Logistic regression was used to constitute the clinical model and nomogram.The performance of these models was evaluated using receiver operating characteristic curve,decision curve analysis and calibration curve.Results The K-nearest neighbors model of the intratumoral combined peritumoral regions performed the best in all radiomics models,the area under the curve were 0.921 and 0.773 in the training cohorts and test cohorts.The radiomics nomogram,which was composed of age,apparent diffusion coefficient and radiomics signatures,achieved the best performance with area under the curve of 0.970 and 0.777 in the training cohorts and test cohorts,respectively.Calibration curve analysis and decision curve analysis demonstrated favorable calibration and clinical utility of the nomogram model.Conclusion The nomogram based on intratumoral and peritumoral MRI radiomics yields a favorable diagnostic value for predicting p53 abnormal in patient with endometrial carcinoma.

Objective:To comprehensively assess the nutritional literacy among family caregivers of elderly patients with chronic heart failure (CHF), so as to provide reference for developing clinical nutrition management strategies for elderly CHF patients.Methods:This study was a descriptive qualitative research. From February to March 2025, purposive sampling was used to select 17 family caregivers of elderly CHF patients at Affiliated Hospital of Yangzhou University as research subjects for semi-structured interviews. The data was analysed using a directed content analysis approach.Results:Three themes and nine subthemes were identified, including functional nutrition literacy (lack of disease-related nutrition knowledge, difficulty in knowledge transformation and utilization, and barriers to voluntary nutritional adherence), interactive functional literacy (limited channels for accessing nutrition information, broken healthcare services, insufficient motivation for proactive communication, and demand for professional dietary guidance), and critical nutrition literacy (challenges in distinguishing information authenticity, reliance on inherent cognition for evaluation) .Conclusions:Family caregivers of elderly patients with CHF commonly lack relevant nutritional knowledge. Healthcare providers should attach importance to the education of nutrition knowledge and skills for family caregivers, establish a multidimensional nutrition education system, develop personalized nutrition guidance plans, and integrate the family-community-medical collaborative support network to systematically strengthen caregivers' understanding of disease nutrition management for elderly CHF patients and enhance their compliance with nutrition care practices.

Objective To establish an optimized diagnostic model for hepatocellular carcinoma(HCC),designated as G-GADA,in chronic hepatitis B(CHB)patients based on the parameters of age,sex,alpha-fetoprotein(AFP),des-γ-carboxy prothrombin(DCP),and Golgi protein 73(GP73),to address the problems of low sensitivity and specificity in the early diagnosis of hepatitis B virus(HBV)-related liver cancer,and to assess the value of this model in the diagnosis of HCC.Methods A retrospective analysis was performed for 201 CHB patients(CHB group),137 patients with HBV-related liver cirrhosis(LC group),and 111 treatment-na?ve patients with newly diagnosed HCC(HCC group)who were admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from June 2015 to June 2020.Serological markers(AFP,DCP,alpha-fetoprotein L3%[AFP-L3%],and GP73)were compared between groups and were analyzed in terms of their differences from the clinical and tumor characteristics of HCC patients,and the Spearman correlation analysis was used to assess the correlation between different markers.A Logistic regression analysis was used to establish a diagnostic model for liver cancer,and the receiver operating characteristic(ROC)curve was used to assess the diagnostic performance of each marker.Results Comparison of clinical features between CHB,LC,and HCC patients showed that HCC patients had significantly higher age,proportion of male patients,and serum levels of DCP,AFP,GP73,and AFP-L3%(all P<0.05).In HCC patients,DCP levels are associated with tumor size and microvascular invasion;AFP levels are related to patient age,tumor size,tumor number,distant metastasis,and microvascular invasion;AFP-L3%levels are associated with patient age,tumor size,tumor number,distant metastasis,Milan staging,and microvascular invasion;GP73 levels are linked to tumor number,distant metastasis,and microvascular invasion(all P<0.05).The correlation analysis of the serum markers showed a strong positive correlation between AFP and AFP-L3%(r=0.71,P<0.05)and a moderate positive correlation between AFP and GP73(r=0.33,P<0.05)and between AFP-L3%and GP73(r=0.41,P<0.05).Based on the features of age,sex,DCP,AFP,and GP73,the multivariate Logistic regression analysis was used to establish a G-GADA diagnostic model for HCC,and for all patients,the G-GADA model had an area under the ROC curve(AUC)of 0.915(95%confidence interval[CI]:0.875-0.945)in the derivation cohort and 0.913(95%CI:0.862-0.950)in the validation cohort for the diagnosis of HCC.In the AFP-negative patients,the G-GADA model achieved an AUC of 0.884(95%CI:0.833-0.924)in the derivation cohort and 0.851(95%CI:0.779-0.907)in the validation cohort,and in the patients with liver cirrhosis,the G-GADA model achieved an AUC of 0.901(95%CI:0.841-0.944)in the derivation cohort and 0.885(95%CI:0.806-0.940)in the validation cohort.Conclusion The G-GADA diagnostic model based on multiple variables significantly improves the detection rate of HCC,and demonstrates superior diagnostic performance in patients with low AFP expression and those with liver cirrhosis.The G-GADA model has a better clinical application value in the noninvasive diagnosis of HCC.

Conducting ethical review of investigator-initiated trials （IIT） is one of the important links to ensure the quality of research projects. Currently， the quality of ethical review for IIT projects is greatly influenced by the personal factors of committee members， which to some extent affects the ethical review committee’s judgments of research risks and benefits. Based on the previously developed Risk-Benefit Assessment Scale for Clinical Research， this paper established an ethical review decision-making pathway based on risk-benefit assessment， that is， proposed the “four-step method” for ethical review risk-benefit assessment， including evaluating the research benefits， assessing the research risks， constructing a risk-benefit matrix， and establishing an ethical review pathway. The “four-step method” helps to reduce the impact of committee members’ subjective/intuitive judgments on the quality of ethical review， assists in promoting the implementation of multi-center ethical review policy， narrows the gap in the quality of ethical review among different medical institutions， and provides clearer guidance for the risk judgments of scientific research management and ethical review departments.

OBJECTIVE: To observe the clinical efficacy of acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux for gastroesophageal reflux cough (GERC). METHODS: A total of 120 GERC patients were randomly assigned to an observation group (60 cases, 1 case dropped out) and a control group (60 cases, 1 case was eliminated). The observation group received acupoint thread-embedding treatment at positive response points of governor vessel. If no such points were detected, the following acupoints were used: Dazhui (GV14), Fenghu (Extra), Shendao (GV11), Lingtai (GV10), and Zhiyang (GV9). Treatment was administered once every two weeks. The control group received oral rabeprazole enteric capsules at 20 mg twice daily. All the treatment was given for 6 weeks. Clinical outcomes were assessed using cough symptom score, reflux disease questionnaire (RDQ) score, and Leicester cough questionnaire (LCQ) score before and after treatment in the two groups. Clinical efficacy was also compared between the two groups. RESULTS: After treatment, both groups showed decreased cough symptom scores and the each item scores and total scores of RDQ (P<0.001), and increased LCQ scores (P<0.001) compare with those before treatment. The observation group exhibited lower cough symptom score and chest pain, reflux and total score of RDQ, and higher LCQ score compared to those in the control group (P<0.05). The total effective rate in the observation group was 94.9% (56/59), which was higher than 84.7% (50/59) in the control group (P<0.05). CONCLUSION Acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux could effectively alleviate cough and reflux symptoms in patients with GERC and improve their quality of life.
Humans ; Acupuncture Points ; Gastroesophageal Reflux/physiopathology* ; Male ; Female ; Cough/physiopathology* ; Middle Aged ; Aged ; Acupuncture Therapy ; Adult ; Treatment Outcome ; Lung/physiopathology* ; Meridians

BACKGROUND: The correlation between the morphological structure of the patellofemoral joint (PFJ) and the severity of knee joint osteoarthritis (KOA) remains uncertain. This study aims to investigate the correlation between the severity of knee joint osteoarthritis and the alignment of patellofemoral and patellar height on radiographs. METHODS: This multi-center, retrospective study analyzed the magnetic resonance imaging (MRI) scans and anteroposterior radiographs of 534 adult outpatients with KOA. To evaluate the radiographic severity of KOA, anteroposterior radiographs of the knee and the Kellgren-Lawrence (K-L) grade were used. Knee MRI scans were used to measure the patellar length ratio (PLR), sulcus angle (SA), lateral patellar tilt angle (LPTA), and the distance between tibial tuberosity and trochlear groove (TT-TG). We examined the association between the configuration of the PFJ, arrangement, and harshness of the KOA. Information on participants' demographics, such as age, sex, side, height, and weight, was collected. A chi-squared test was used for the correlation of radiographic severity of KOA with sex and the affected side. Spearman correlation was used for patellofemoral alignment or morphology and the radiographic severity of lateral KOA. Multiple linear regression models were used for the association between LPTA, SA, TT-TG, and severity of KOA after accounting for demographic variables. RESULTS: The study comprised of 534 patients; of these, 339 (63%) were female. A total of 586 knees were evaluated in this study. Age showed a strong positive correlation with KOA severity ( r  = 0.516, P <0.01), whereas LPTA showed a strong negative correlation ( r  = -0.662, P <0.01). Additionally, SA ( r  = 0.616, P <0.05), and TT-TG showed a strong positive correlation ( r  = 0.770, P <0.01) with tibiofemoral osteoarthritis (TFOA) severity. Multiple linear regression analysis indicated that knee osteoarthritis severity (β = -2.946, P <0.001) and side (β = -0.839, P  = 0.001) was associated with LPTA; knee osteoarthritis severity (β = 5.032, P <0.001) and age (β = -0.095, P <0.001) was associated with SA; knee osteoarthritis severity (β = 2.445, P <0.001), sex (β = -0.326, P  = 0.041), body mass index (β = -0.061, P  = 0.017) and age (β = -0.025, P <0.001) was associated with TT-TG. CONCLUSION Radiographic severity of KOA was positively associated with age, SA, and TT-TG but negatively associated with LPTA.
Humans ; Female ; Male ; Osteoarthritis, Knee/pathology* ; Middle Aged ; Retrospective Studies ; Aged ; Patellofemoral Joint/pathology* ; Magnetic Resonance Imaging ; Adult ; Patella/pathology* ; Radiography

Objective To identify candidate compounds that activate thermogenesis during cold exposure by integrating the Library of Integrated Network-Based Cellular Signatures(LINCS)with RNA expression profiles specific to cold-induced thermogenesis.Methods Gene expression profiles of interscapular brown adipose tissue(BAT)and inguinal white adipose tissue(iWAT)were generated from 8-week-old C57BL/6J mice which were housed at 5 ℃ or room temperature(23 ℃)for 7 days.The gene expression signatures of the cold-induced BAT and iWAT were compared to the LINCS dataset to predict potential candidates for testing in a cold challenge model that was intended to assess thermogenesis activation.The pharmacological potential of the identified compounds was evaluated in a cold-exposed mouse model.The core body temperature and infrared thermal imaging were collected to monitor physiological responses during cold exposure.Additionally,hematoxylin and eosin(HE)staining was used to assess morphological changes of fat cells of BAT,iWAT,and epididymal white adipose tissue(eWAT).Results The transcriptomic signatures related to cold-induced thermogenesis were obtained and the top 20 candidate compounds were identified by comparison with the LINCS dataset.Mice treated with withaferin A(WA)during the cold challenge exhibited elevated rectal temperatures and smaller adipocyte sizes compared to controls.Conclusion Our drug repurposing strategy,which connects transcriptional profiles with LINCS data,identifies potential compounds.WA enhances thermogenesis and metabolic activity in adipose tissue,which helps maintain body temperature,and improves cold tolerance during exposure to low temperatures.

Both cold stress and ischemia-reperfusion injury significantly contribute to poor prognosis after liver transplantation(LT).However,limited animal models incorporating both stimuli hinder the advance-ment of transplant-related research.Here,a simplified and reproducible isolated perfused liver model is established to simulate the stresses experienced by livers maximally during transplantation.We provide a detailed protocol for a straightforward technique that requires 20-30 min for harvesting,24-48 h for static cold storage(SCS),and 2 h for normothermic machine perfusion(NMP)to induce LT-like stresses in the liver.Hepatic injury from SCS and NMP(LT-like stresses)is evaluated using three types of parameters.The pH values and hepatic enzyme levels of cold preservation solutions and perfusate serve as dynamic indicators of hepatic injury.Bile production and portal venous resistance directly reflect liver function,whereas pathological analysis visually illustrates the location and extent of injury.This animal model eliminates the influence of hemodynamic and immune factors,yielding highly reproducible results,and is strongly recommended as a standardized animal model for inducing LT-like stresses.