Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control* ; Animals ; Hypericum/chemistry* ; Phloroglucinol/administration & dosage* ; Mice ; Humans ; Male ; Liver/blood supply* ; Apoptosis/drug effects* ; Molecular Structure ; Protective Agents/pharmacology* ; Hepatocytes/drug effects* ; Mice, Inbred C57BL ; Liver Diseases/drug therapy*

Objective:To analyze the pregnancy outcomes in patients with positive anti-centromere antibodies(ACA)receiving in vitro fertilization(IVF)-embryo transfer(ET)and natural conception.Methods:A case-control study was used to retrospectively analyze the clinical data of 3955 patients who received IVF-ET therapy and had the results of antinuclear antibody(ANA)spectrum at Zhejiang Provincial People's Hospital from June 2016 to June 2023.Patients with positive ACA and negative ACA were matched at a ratio of 1∶3 using propensity score matching.Embryo outcomes of IVF were compared between the two groups,and the impact of different fertilization methods and the use of immunosuppressants on pregnancy outcomes were analyzed using self-matching.The natural conception and disease progress were followed up for ACA-positive patients after IVF failure.Results:The ACA-positive patients accounted for 0.86%of all IVF patients(34/3955)and 2.51%of total ANA-positive IVF patients.Regardless of whether patients received conventional IVF(c-IVF)or intracytoplasmic sperm injection(ICSI),the ACA-positive group exhibited significant differences in oocyte maturity and fertilization compared to the ACA-negative group(both P＜0.01).Moreover,the ACA-positive group had a decreased number of D3 suboptimal embryos and D3 optimal embryos(both P＜0.05).In 5 cases of ACA-positive patients who underwent ICSI cycles,the two pronucleus(2PN)rate did not increase compared to c-IVF cycles(P＞0.05),and there was a decrease in the number of D3 high-quality embryos and D3 suboptimal embryos(both P＜0.05).After 1-2 months of immuno-suppressant treatment,12 ACA-positive patients underwent c-IVF/ICSI again,and there were no changes in egg retrieval and fertilization before and after medication(both P＞0.05),but there was an improvement in the 2PN embryo cleavage rate(P＜0.05).The number of embryos transferred was similar between the ACA-positive and negative groups,but the ACA-positive group had significantly lower embryo implantation rate and clinical pregnancy rate compared to the ACA-negative group(both P＜0.05),with no significant differences in the miscarriage rate between the two groups(P＞0.05).Twenty-seven ACA-positive patients attempted natural conception or artificial insemination after IVF failure,resulting in a total of 7 cases of clinical pregnancy.Conclusions:Serum ACA positivity may disrupt oocyte maturation and normal fertilization processes,with no improvement observed with ICSI and immunosuppressant use.However,ACA-positive patients may still achieve natural pregnancy.

Objective:To evaluate the relationship between lung injury induced by cardiopulmonary bypass (CPB) and acetyltransferase p300 (p300) in rats.Methods:Eighteen SPF healthy adult male Sprague-Dawley rats, aged 12-16 weeks, weighing 350-450 g, were divided into 3 groups ( n=6 each) using a random number table method: sham operation group (S group), CPB group, and CPB+ left lung ischemia-reperfusion (I/R) group (CPB+ IR group). CPB group was connected to CPB pipeline for cardiopulmonary bypass. The lung I/R injury model was prepared by clamping the left lung hilum for 45 min followed by opening during CPB, 30 min later CPB was terminated, and mechanical ventilation was continuously performed for 1.5 h before ending the experiment in CPB+ IR group. Arterial blood gas analysis was performed and oxygenation index (OI) and respiratory index (RI) were calculated before CPB, at 10 min after opening the lung hilum, and immediately after the end of experiment. The bronchoalveolar lavage fluid (BALF) and left lung tissues were collected immediately after the end of experiment for determination of the concentrations of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in BALF and total protein in BALF and concentrations of IL-17 in lung tissues (by enzyme-linked immunosorbent assay), expression of p300, phosphorylated p300 (p-p300), and acetylated histone H3 (AC-H3) in lung tissues (by Western blot) and expression of p-p300 (using immunohistochemical staining) and for microscopic examination of the pathological changes of lung tissues (under the light microscope) which were scored. Results:Compared with S group, OI was significantly decreased and RI was increased at 10 min after opening the lung hilum and immediately after the end of experiment, the lung injury score and levels of IL-6, TNF-α and total protein in BALF and IL-17 in lung tissues were increased, and the expression of p300, p-p300 and AC-H3 was up-regulated in CPB and CPB+ IR groups ( P<0.05). Compared with CPB group, OI was significantly decreased and RI was increased at 10 min after opening the lung hilum and immediately after the end of experiment, the lung injury score and levels of IL-6, TNF-α and total protein in BALF and IL-17 in lung tissues were increased, and the expression of p300, p-p300 and AC-H3 was up-regulated in CPB+ IR group ( P<0.05). Conclusions:The mechanism by which CPB induces lung injury may be related to up-regulation of the expression of p300 and enhancement of activity of p300 in lung tissues and increased release of inflammatory factors in rats.

Atherosclerosis(AS)is a common cardiovascular disease,and its treatment and prevention have been the focus of medical research.AS an emerging technology,nanotechnology has unique advantages and plays an important role in the prevention,diagnosis and treatment of AS.This paper reviews the latest research on the application of nanotechnology in AS diseases,systematically discusses the role of nanotechnology in the diag-nosis and treatment of AS,and comprehensively analyzes the effects of nano-drug carriers based on different sur-face trimmers,loading diagnostic and therapeutic drugs so as to monitordisease progression of AS and its targeted treatment.The aim is to provide new thought for the clinical treatment of AS.

Objective To explore the effect of chemotherapeutic drugs doxorubicin or cisplatin on lipid metabolism of macrophages and its regulatory mechanism.Methods Macrophage RAW264.7 was treated with doxorubicin or cisplatin,and intracellular lipid level was detected by oil red O and ELISA;RNA sequence screen-ing and Western blot were used to confirm the changes of gene expression after chemotherapeutic drug treatment;The effects of silencing ROBO3 on cellular lipid metabolism were explored,and changes in key target genes of lipid metabolism were detected by Q-PCR and western blot.Results Adriamycin or cisplatin induced disturbances in macrophage cholesterol metabolism and exacerbated macrophage foaminess.Further studies showed that the expression of the axon guidance factor receptor,ROBO3,increased and then decreased during the chemotherapeutic drug-induced macrophage foaming process.Further intervention with ROBO3 exacerbates oxldl-induced cholesterol accumulation and foam formation in macrophages.Mechanistically,ROBO3 deficiency promotes the expression of cholesterol synthesis-related gene DHCR24 and inhibits the expression of cholesterol elimination-related gene ABCG1,resulting in cholesterol accumulation in macrophages.Conclusion This study found that ROBO3 plays an important regulatory role in the disruption of cholesterol metabolism and its foaming process in macrophages induced by chemotherapeutic drugs,which may provide new targets and ideas for the prevention and treatment of chemotherapy-related atherosclerosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic debilitating lung disease with unknown etiology, complex syndromes and prolonged illness, which is difficult to cure. Based on the theory of "spleen is the envoy" in Huang Di Nei Jing, this article explained the TCM meaning of "spleen is the envoy" and the relationship between spleen and other four organs, especially the relationship between spleen and lung. It is believed that the onset of IPF is due to deficiency of lung and spleen qi, loss of solid defense and evil invasion of the nutritive and defensive levels; qi deficiency and depression lead to heat damage to yin, while long-term blood damage to collaterals involves yang. The pathological process shows the changes from qi entering blood and from meridian to collateral, which eventually leads to the imbalance of qi and blood, yin and yang, the stagnation of phlegm and blood stasis, the obstruction of lung collateral, the mixture of excess and deficiency, and the lingering is difficult to heal. In the treatment, the "spleen is the envoy" is the center, the lung and spleen are treated together, the qi of lung and spleen is strengthened, the yin of lung and stomach is nourished, and finally the root is protected. The treatment is based on syndrome differentiation, modified with syndromes, and the methods of promoting blood circulation, resolving phlegm, warming yang and dredging collaterals are supplemented in time, which provides a new idea for enriching the differentiation and treatment of IPF in TCM.

Objective:To explore the attitude of kidney transplant (KT) recipients towards xenotransplantation and explore its related influencing factors to provide auxiliary references for the clinical research of xenotransplantation in China.Methods:The questionnaire data of "Attitude survey of KT recipients towards xenotransplantation" were collected from 194 KT recipients followed up at Organ Transplant Center of Affiliated Tongji Hospital. Nonparametric tests were utilized for comparing score differences and χ2 tests for comparing responses to specific questions. Variables with statistical significance in non-parametric test were included into multifactor linear regression analysis for exploring the influencing factors of recipients' attitudes towards xenotransplantation. Results:KT recipients had a higher score (75 points) on attitude scale of xenotransplantation. "Cognitive preference" dimension scored the highest (85 points); "Fear of risk" dimension scored lowest (50 points). The results of univariate analysis indicated that gender ( P=0.020), medical background ( P=0.006) and knowledge of clinical trial cases ( P<0.001) were the influencing factors of score of cognitive preference. Educational background ( P=0.029) was the factor affecting the score of "risk concern" dimension. Age ( P=0.028) and knowledge of clinical trial cases ( P=0.001) were the factors influencing the score of "psychosocial" dimension. Whether medical background ( P=0.018) and knowledge of clinical trial cases ( P=0.008) were the factors influencing the score of "efficacy expectation" dimension; Gender ( P=0.010), medical background ( P=0.018) and knowledge of clinical trial cases ( P=0.008) were the factors influencing total score. The results of multi-factor analysis revealed that gender ( B=-0.821, 95% CI: -1.419~0.223, P=0.007), medical background ( B=0.938, 95% CI: 0.097~1.779, P=0.029) and knowledge of clinical trials of xenotransplantation in the United States ( B=1.498, 95% CI: 0.887~2.110, P<0.001) was the influencing factor of cognitive preference. Educational background (B=-0.693, 95% CI: -1.353~-0.034, P=0.040) was the influencing factor of score on "risk concern" dimension. Knowledge of clinical trials of xenotransplantation in the United States ( B=1.075, 95% CI: 0.418~1.731, P=0.001) was an influencing factor of score on "social psychological" dimension; Knowledge of clinical trials of xenotransplantation in the United States ( B=0.710, 95% CI: 0.063~1.358, P=0.032) was an influencing factor of score on "efficacy expectation" dimension; Gender ( B=-2.259, 95% CI: -4.094~-0.423, P=0.016), medical background ( B=2.799, 95% CI: 0.219~5.378, P=0.034) and knowledge of clinical trials of xenotransplantation in the United States ( B=3.237, 95% CI: 1.360~5.114, P=0.001) were the influencing factors of total score. Conclusions:KT recipients have a higher awareness rate of xenotransplantation and a better acceptance of xenotransplantation in general. Those males with medical background and knowing clinical cases of xenotransplantation demonstrate a better attitude towards xenotransplantation. More concerned about the risk of infection, respondents expect heterologous pig kidneys to achieve the same long-term survival as allogeneic kidneys.

AIM:To determine the link between infliximab,adalimumab,vedolizumab,ustekinumab and risk of lymphoma in order to provide reference for the safety of clinical application.METHODS:Dis-proportionality analysis and Bayesian analysis were used in data mining to screen the suspected lym-phoma after the use of four biological agents based on the FAERS data from October 2012 to June 2023.The fatality and hospitalization rates of this four biological agents associated lymphoma were also investigated.RESULTS:Totally 705 cases of four biological agents associated lymphoma were collected.Four biological agents associated lymphoma appeared to influent more young pa-tients and middle-aged patients than elderly pa-tients(25.11％vs.22.41％vs.12.2％).There were slightly more male than females(42.84％vs.35.60％).Infliximab has the highest reporting odds ratio[ROR3.40,95％CI=(3.03,3.82)],proportional ratio[PRR3.38,95％CI=(3.01,3.79)],information component(IC1.14,IC-2SD=1.02)and empirical Bayes geometric mean(EBGM2.21,EBGM05=2.01).Significant difference in the fatality rate and hospi-talization rate among four biological agents were not found.CONCLUSION:Infliximab showed a strongest lymphoma association than the other three biological agents.Lymphoma risk should be vigilant when using infliximab.

Objective:To explore health utility value, evaluate health-related quality-of-life(QOL)of pediatric liver transplantation(LT)recipients and examine its influencing factors to provide rationales for related health economic evaluations.Methods:This cross-sectional QOL was conducted through a questionnaire in pediatric LT recipients aged 5-17 years.The interviewees undergoing initial LT from June 2013 to September 2021 were reviewed regularly.Those children and their parents unwilling to participate or failing to understand the contents of questionnaire were excluded.The questionnaire was designed on the basis of Child Health Utility 9D Instrument(CHU9D)and answered online by one of primary caregiver.Chinese score system of CHU9D was employed for converting the responses into health utility values and the influencing factors were analyzed.Univariate analysis was performed by nonparametric tests and multivariate analysis by multiple linear regression model. P<0.05 was deemed as statistically significant. Results:A total of 140 valid questionnaires were obtained.Mean age of pediatric LT recipients was(7.95±2.74)years and mean postoperative time(4.90±2.17)years.Among them, 19 cases had experienced acute rejection and 101(72.1%)cases were living-related LT recipients.CHU9D scale indicated that average health utility value was(0.85±0.14)points.Univariate analysis revealed that age( P=0.008), education level( P<0.001)and primary disease( P=0.010)influenced the postoperative level of QOL.Multivariate analysis indicated that QOL was correlated with education level(behind schedule: 95% CI: -0.146, -0.034, P=0.002; leave of absence: 95% CI: -0.251, -0.068, P=0.001). Conclusions:Health utility of pediatric LT recipients is high with an excellent QOL.Poor QOL is associated with absence from school or dropping out of school.