OBJECTIVE To investigate the ameliorative effect and mechanism of Euphorbia hirta L.-derived exosome-like nanovesicles（Eh-ENVs） on acetaminophen （APAP）-induced liver injury based on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H：quinone oxidoreductase 1 （NQO1） pathway. METHODS The safety of Eh-ENVs was evaluated by examining their effects on the viability of RAW264.7 and AML12 cells， as well as serum liver and kidney function indicators and histopathology of liver， lung， and other tissues in normal mice. A lipopolysaccharide （1 μg/mL）-induced RAW264.7 cell inflammation model was constructed to investigate the effects of 10 and 20 μg/mL Eh-ENVs on the mRNA expression of inflammatory factors and reactive oxygen species （ROS） level in model cells， and the uptake efficiency of Eh-ENVs by RAW264.7 cells was also examined. An APAP-induced liver injury mouse model was established to investigate the effects of 4 mg/kg Eh-ENVs on serum liver function indicators， liver histopathology， mRNA expression of inflammatory factors， malondialdehyde （MDA） level， superoxide dismutase （SOD） level， and mRNA and protein expressions related to the Nrf2/HO-1/NQO1 pathway in liver tissue of model mice. RESULTS In vitro results showed that Eh-ENVs had no inhibitory effect on the proliferation of RAW264.7 and AML12 cells；Eh-ENVs could be efficiently taken up by RAW264.7 cells and significantly reduced the mRNA expression of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and ROS level in cells （ P ＜0.05）. In vivo results showed that 4 mg/kg Eh-ENVs had no obvious toxic side effects on normal mice，could significantly decrease the serum alanine transaminase （ALT） and aspartate transaminase （AST） levels in model mice （ P ＜0.05），upregulated/increased the mRNA expressions of IL-10， as well as the mRNA and protein expressions of Nrf2， HO-1， and NQO1， and SOD level in liver tissue （ P ＜0.05）， and down-regulated/decreased the mRNA expression of TNF-α， IL-1β and MDA level in liver tissue （ P ＜0.05）. CONCLUSIONS Eh-ENVs may activate the Nrf2/HO-1/NQO1 pathway to inhibit inflammatory response and alleviate oxidative stress， thereby improving APAP-induced liver injury.

ObjectiveTo construct and validate a clinical prediction model for inflammatory remission outcomes in rheumatoid arthritis （RA） patients with liver and kidney deficiency syndrome treated with Bushen Zhiwang Decoction （补肾治尪汤， BZD） based on metabolomics. MethodsA prospective cohort study was conducted， enrol-ling 60 RA patients with liver and kidney deficiency syndrome. All patients were treated with BZD and conventional-dose oral conventional synthetic disease-modifying antirheumatic drugs （csDMARDs） for 12 months. Clinical data were collected， and the change in disease activity score in 28 joints （DAS28） after treatment compared with baseline （△DAS28） was used as the primary outcome and grouping criterion. Peripheral blood samples were collected before treatment to analyze plasma metabolites. Differential analysis and least absolute shrinkage and selection operator （LASSO） regression were used to preliminarily screen differential metabolites， followed by machine learning algorithms to further identify a core metabolite combination. Based on the expression levels of the core metabolite combination， a novel metabolite index， namely the metabolomics-based inflammatory remission score （Met-IRS）， was calculated using standar-dized metabolite values， and its clinical applicability was evaluated. A clinical prediction model was constructed by integrating clinical characteristics and Met-IRS， and the model performance was assessed. ResultsAmong the 60 patients， those with △DAS28 ≥ 0.27 were assigned to the high inflammatory remission group， while those with △DAS28 ＜ 0.27 were assigned to the low inflammatory remission group， with 30 cases in each group. Compared to the low inflammatory remission group， the high inflammatory remission group showed a higher frequency of methotrexate use and a lower positive rate of rheumatoid factor （RF） （P＜0.05）. Seven core metabolites were identified as the optimal combination， including mangiferic acid， fatty acid-hydroxy fatty acid ester 40∶6， fatty acid-hydroxy fatty acid ester 18∶0， fatty acid-hydroxy fatty acid ester 36∶1， glucosylceramide， lysophosphatidylcholine 22∶5， and pregnanetriol ketone. The calculated Met-IRS comprehensively reflected the characteristics of differential metabolites and demonstrated clinical applicability. Met-IRS was significantly higher in the high inflammatory remission group than in the low inflammatory remission group， and was positively correlated with high inflammatory remission outcomes （P＜0.05）. Based on the variables Met-IRS， methotrexate use， leflunomide use， and RF positivity， a clinical prediction model for inflammatory remission in RA treatment （Cj-RTRM） was constructed. Model performance evaluation demonstrated that the model had good clinical predictive ability， with an area under the receiver operating characteristic curve （AUC） of 0.880， sensitivity 0.967， specificity 0.700 and Youden's index 0.667. ConclusionThe clinical prediction model Cj-RTRM constructed based on the metabolomics-based inflammatory remission score Met-IRS can effectively predict clinical inflammatory remission outcomes in RA patients treated with BZD and accurately identify the advantageous population for this treatment. This model provides guiding evidence for dynamic inflammation monitoring， targeted management， and identification of populations with advantages in traditional Chinese medicine.

ObjectiveTo study the clinical characteristics and influencing factors of rheumatoid arthritis （RA） in the patients with cold dampness obstruction syndrome. MethodsThe RA patients treated in the Department of Traditional Chinese Medicine and Rheumatology of the China-Japan Friendship Hospital from August 2022 to June 2024 were selected. The demographic information， clinical data， laboratory test results， and traditional Chinese medicine （TCM） symptom information were collected for syndrome differentiation， on the basis of which the characteristics and influencing factors of cold dampness obstruction syndrome were analyzed. ResultsA total of 258 RA patients were selected in this study， including 88 （34.1%） patients with cold dampness obstruction syndrome， 53 （20.5%） patients with dampness and heat obstruction syndrome， 31 （12.0%） patients with wind dampness obstruction syndrome， 29 （11.2%） patients with liver-kidney deficiency syndrome， 19 （7.4%） patients with Qi-blood deficiency syndrome， 14 （5.4%） patients with phlegm-stasis obstruction syndrome， 15 （5.8%） patients with stasis obstructing collateral syndrome and 9 （3.5%） patients with Qi-Yin deficiency syndrome. The patients were assigned into two groups of cold dampness obstruction syndrome and other syndromes. The group of cold dampness obstruction syndrome had lower joint fever， 28-tender joint count （TJC28）， and 28-joint disease activity score （DAS28）-C-reactive protein （CRP） and higher central sensitization， cold feeling of joints， fear of wind and cold， cold limbs， and abdominal distention than the group of other syndromes （P<0.05）. The binary logistic regression analysis showed that central sensitization （OR 5.749， 95%CI 2.116-15.616， P<0.001） and DAS28-CRP （OR 0.600， 95% CI 0.418-0.862， P=0.006） were the independent factors influencing cold dampness obstruction syndrome in RA. ConclusionCold dampness obstruction syndrome is a common syndrome in RA patients. It is associated with central sensitization， cold feeling of joints， abdominal distension and may be a clinical syndrome associated with central sensitization.

Objective:To explore the phenotypic heterogeneity among patients harboring identical pathogenic variants in the dystrophin ( DMD) gene by analyzing clinical and imaging data from 7 pairs of male twins with dystrophinopathy. Methods:Clinical and laboratory data of 14 (7 pairs) male twins diagnosed with dystrophinopathy through genetic testing among 1 767 patients at Peking University First Hospital from January 2017 to October 2024 were collected. Eleven patients underwent thigh muscle magnetic resonance imaging (MRI), and muscle biopsies were performed in at least 1 case of each pair.Results:Among the 7 pairs of twin patients, 2 pairs had Duchenne muscular dystrophy, and 5 pairs had Becker muscular dystrophy. In terms of variant types, 4 pairs had in-frame deletions, while the remaining 3 pairs had duplication variants, frameshift variants, and nonsense variants, respectively. Clinically, 6 individuals had asymptomatic hypercreatine kinasemia, and 8 had varying degrees of limb weakness. Among the 5 pairs of symptomatic twins, there were differences in the degree of limb weakness. Four individuals showed no significant abnormalities in thigh muscle MRI, 7 showed fat infiltration mainly in the bilateral gluteus maximus and adductor magnus muscles, and 2 pairs of twins had obvious differences in the degree of fat infiltration in muscle MRI. Muscle biopsies revealed dystrophic or mild myopathic pathological changes, with 2 individuals showing severe loss of dystrophin, while the others had partial loss.Conclusions:Dystrophinopathy exhibits significant individual differences. Even among individuals with highly similar genetic background, clinical and imaging manifestations caused by the same pathogenic variant also vary.

Objective To construct a nursing consultation information system based on consultation process and information interaction needs and explore its application effect.Methods The nursing consultation process and information interaction needs were analyzed;the information process,content modules and information interaction interface were designed;the structured records for nursing consultation were developed.The system was officially applied in January 2024.The application effect was evaluated by comparing the completion time of nursing consultations,nursing consultation record quality score,nursing consultation evaluation completion rate,and satisfaction rate before(August 2023 to October 2023)and after(January 2024 to March 2024)the application of the information system.Results After the application of the nursing consultation information system,the implementation rate of nursing consultation for inpatients increased from 1.27％ before the application of the system to 1.47％(P=0.019).The completion time of nursing consultation in the whole hospital reduced from 351(225,421)minutes before the application of the system to 310(156,402)minutes(P＜0.001),and there was a statistically significant difference in the completion time of nursing consultation among the 3 specialties of intravenous therapy,blood purification,and diabetes nursing(P＜0.05).The quality score of nursing consultation records increased from 90.5(82.0,100)points to 95.5(92.0,100)points(P＜0.001).The completion rate of nursing consultation evaluation was higher than those before the system application,with statistical significance(21.6％ vs 78.4％,P＜0.001).Conclusion Nursing consultation information system based on information interaction needs can improve the implementation of nursing consultation for inpatients,shorten the completion time of nursing consultations,improve the writing quality of nursing consultation records and the completion rate of nursing consultation evaluation,and it succeeded in real-time quality monitoring.

Childhood cataract is a disease that affects the development of children's vision. It is divided into infants and adolescents according to the age of onset. Surgery is the main treatment, but the vision after surgery is difficult to reach the level of healthy children. Macular dysplasia is an important factor affecting postoperative visual acuity. In recent years, with the development of optical coherence tomography and optical coherence tomography angiography, more and more research has been done on macular development of children's cataract. The retinal structure in the macular area of children with cataract is abnormal, and the early inflammatory reaction after surgery can also lead to structural changes. In addition, insufficient blood supply to the macular area may affect retinal structure and function. The mechanism by which childhood cataract affects macular structure is still unclear and needs further study. Understanding the relationship between macular structure and vision prognosis is helpful to develop more effective treatment and improve the vision prognosis of children.

[Purpose]To analyze the incidence,mortality and disease burden of malignant tumors in the cancer registration areas of Hebei Province in 2020.[Methods]The incidence and mortality data of cancer in 2020 were collected from the cancer registries of Hebei Province,and the quality of data was evaluated.The crude incidence(mortality)rate,age-specific incidence(mortality)rates and age-standardized incidence(mortality)rates by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW)were calculated and analyzed.The disability-ad-justed life years(DALY)were calculated and analyzed according to the Excel disease burden cal-culation template recommended by the World Health Organization(WHO).[Results]In 2020,the crude incidence rate,ASIRC,ASIRW of malignant tumors in the cancer registration areas of Hebei Province were 229.36/105,147.06/105 and 143.74/105,respectively.The incidence rate in men was higher than that in women.The incidence rates in urban and rural areas were 230.26/105 and 228.84/105,and the age-standardized incidence rates reached a peak in the age group of 80～84 years old.The crude mortality rate,ASMRC,ASMRW were 146.38/105,85.33/105 and 84.79/105,respectively.The mortality rate in men was higher than that in women.The age-standardized mor-tality rate rose with age,reaching a peak in the age group of 85+years old,and the crude mortality rates in urban and rural areas were 143.82/105 and 147.84/105,respectively.The DALY of ma-lignant tumors in the cancer registration areas of Hebei Province were 345 030 person-years,reaching a maximum in the age group of 45～59 years old,with a DALY rate of 15.00/103,and the highest in the age group of 70～79 years old.Lung cancer had the heaviest disease burden,with DALY of 83 684 person-years,accounting for 24.25％of all malignant tumors,followed by stomach,liver,female breast,and colorectal cancers.The DALY in urban and rural areas were 122 062 and 222 993 person-years,respectively,and the trends in DALY rates were basically stable.[Conclusion]The disease burden of malignant tumors in Hebei Province is relatively heavy,cancer prevention and control should be further strengthened and focused on urban men and the elderly to reduce disease burden of malignant tumors in the future.

Objective To observe the effects of Huosha Oral Liquid on irritable bowel syndrome with diarrhea(IBS-D)rats with cold and dampness syndrome based on Notch1/Hes-1/Math-1 signaling pathway;To elucidate its mechanism of repair of intestinal mucosal barrier.Methods An IBS-D cold and dampness syndrome rat model was established by using restraint stress combined with bitter-cold cathartic method and cold and dampness environmental method.After modeling,the rats were randomly divided into model group,Western medicine group and Huosha Oral Liquid low-,medium-and high-dosage groups,with 6 rats in each group.An additional 6 rats were set as the normal group.The Western medicine group was given mebeverine(13.5 mg/kg)by gavage,while the Huosha Oral Liquid low-,medium-and high-dosage groups were given Huosha Oral Liquid(3.15,6.3,12.6 g/kg)by gavage,the normal group and model group were given distilled water by gavage,for 4 weeks.The general status of rats were ovserved,the body mass,loose stool rate,fecal water rate and abdominal withdrawal reflex(AWR)score were measured,the morphalogy of colon tissue were observed by HE staining,the mRNA expression of Occludin,ZO-1,Notch1,Hes-1 and Math-1 in colon tissue were detected by RT-PCR,the protein expression of Notch1 was detected by Western blot.Results Compared with the normal group,the model group had a reduced body mass(P<0.05)and increased loose stool rate,fecal water rate and AWR score(P<0.05),inflammatory cell infiltration was observed in colon tissue and the expressions of Occludin,ZO-1,Math-1 mRNA decreased(P<0.05),the expressions of Notch1,Hes-1 mRNA increased(P<0.05),and the expression of Notch1 protein increased(P<0.05).Compared with the model group,the body mass of rats in Western medicine group and Huosha Oral Liquid low-,medium-and high-dosage groups increased(P<0.05),loose stool rate,fecal water rate and AWR scores decreased(P<0.05),a small amount of neutrophils was visible in the colon tissue,the expressions of Occludin,ZO-1,Math-1 mRNA in colon tissue increased in Huosha Oral Liquid medium-and high-dosage groups(P<0.05)and the expressions of Notch1 and Hes-1 mRNA decreased(P<0.05),the expression of Notch1 protein decreased in Western medicine group and Huosha Oral Liquid groups(P<0.05).Conclusion Huosha Oral Liquid may regulate the expressions of tight junction proteins by inhibiting excessive activation of the Notch/Hes-1/Math-1 signaling pathway,thereby protecting the intestinal mucosal barrier function,improving diarrhea symptoms in IBS-D rats with cold and dampness syndrome,and reducing visceral sensitivity and colonic tissue inflammation.

[Purpose]To analyze the prevalence characteristics and disease burden of lung cancer in Hebei cancer registration areas from 2012 to 2020.[Methods]Lung cancer data were collected from the Hebei Provincial Cancer Registry from 2012 to 2020.The crude incidence/mortality rates,age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)and by world standard population(ASIRW/ASMRW)were calculated.The Joinpoint model was used to calculate the annual percentage change(APC)and average annual percentage change(AAPC).Years of life lost(YLL)and years lived with disability(YLD)and the disability-adjusted life years(DALY)were calculated.[Results]From 2012 to 2020,the ASIRW of lung cancer in Hebei can-cer registration areas was 33.13/105,44.56/105 for men and 22.54/105 for women,respectively;the incidence rates of urban and rural areas were 29.05/105 and 33.52/105,respectively.The incidence rates increased with ages,reaching a peak in the age group of 80～84 years old.There was a de-creasing trend in the ASIRW of lung cancer(AAPC=-3.99％,P＜0.05).From 2012 to 2020,the ASMRW of lung cancer was 25.80/105,36.56/105 for men and 15.96/105 for women,respectively;the mortality rates of urban and rural areas were 25.14/105 and 26.12/105,respectively.The mor-tality rates increase with ages,reaching a peak in the age group of 85 and above years old.There was a decreasing trend in the mortality of lung cancer(AAPC=-4.65％,P＜0.001)from 2012 to 2020.The DALY of lung cancer in Hebei Province from 2012 to 2020 was 484 194 person-years,with male accounting for 66.77％,female accounted for 33.23％,the DALY rate of lung cancer was 3.31‰,of which 35.57％in urban areas and 64.43％in rural areas.[Conclusion]Lung can-cer incidence and mortality rate in Hebei cancer registration areas from 2012 to 2020 showed a decreasing trend.The disease burden is gradually increasing with age in middle-aged and el-derly population.

Aim To explore the impact and mechanism of proprotein convertase subtilisin kexin 9(PCSK9)on the progression of abdominal aortic aneurysm(AAA).Methods 6～8 week old ApoE-/-mice were selected to estab-lish the AAA model.Angiotensin Ⅱ(Ang Ⅱ)was continuously infused through subcutaneous implantation of a micro-os-motic pump.The mice were fed with high-fat diet and killed after 28 days.The expression of PCSK9 in abdominal aor-tic smooth muscle cells was detected by immunohistochemistry and immunofluorescence in normal abdominal aortic blood vessels and AAA samples in human and mice.Primary cultured murine vascular smooth muscle cells(mVSMC)of C57BL/6 mice were treated with different concentrations of AngⅡ for 24 h,and the expression of PCSK9 mRNA and pro-tein was detected.PCSK9 overexpression and knockdown cell models were established,and mitochondrial reactive oxygen species(mtROS),mitochondrial membrane potential(MMP),mitochondrial permeability transition pore(MPTP)open-ing,and Z-DNA binding protein 1(ZBP1)protein expression were detected.Bioinformatics was used to analyze the dif-ferential expression of multiple single-cell sequencing datasets to obtain the key differentially expressed genes,and to study their expression and role in AAA.Results Immunohistochemistry and immunofluorescence results showed that PCSK9 expression in human and mouse AAA increased(P＜0.01),and co-localized with smooth muscle.Ang Ⅱ promoted PCSK9 expression in mVSMC in a concentration-dependent manner,the 2.0 μmol/L Ang Ⅱ group showed a 2.9-fold and 1.1-fold increase in the expression of PCSK9 mRNA and protein,respectively(P＜0.01),with the most significant effect observed.After successfully constructing PCSK9 overexpression and PCSK9 interference mVSMC models,PCSK9 overex-pression led to an increase in intracellular mtROS,a decrease in MMP,an increase in MPTP opening,and a decrease in cellular activity(P＜0.01);PCSK9 knockdown could reduce Ang Ⅱ induced increase in mtROS,decrease in MMP and MPTP opening;compared with the siNC+Ang Ⅱ group,the siPCSK9+Ang Ⅱ group showed a decrease in mtROS and an in-crease in the fluorescence brightness of MMP and MPTP(P＜0.05).Bioinformatics analysis revealed that ZBP1 was a core differentially expressed gene in AAA.Immunohistochemistry and immunofluorescence results showed that ZBP1 ex-pression in human and mouse AAA tissues increased,and co-localized with smooth muscle.Western blot results showed that PCSK9 overexpression or treatment with 2.0 μmol/L Ang Ⅱ could increase ZBP1 protein expression(P＜0.01),while PCSK9 knockdown could alleviate the increased ZBP1 expression caused by AngⅡ(P＜0.05).Conclusion PCSK9 may induce mitochondrial damage in smooth muscle cells,activate downstream molecule ZBP1 to cause cell damage,and promote the development of AAA.