ObjectiveTo investigate the mechanism by which Sini San （SNS） treats liver fibrosis through regulating the polarization of intrahepatic Kupffer cells. MethodsSixty SPF-grade male Balb/c mice were randomized into blank control， model， silymarin （0.2 g·kg^-1）， and low-， medium-， and high-dose （2.93， 5.85， 11.70 g·kg^-1， respectively） SNS groups. A mouse model of liver fibrosis was induced by intraperitoneal injection of CCl₄. After 5 weeks of administration， the body mass， liver pathological changes ［Hematoxylin and Eosin （HE）， Masson， and Sirius red staining］， serum biochemical indicators ［alkaline phosphatase （ALP）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT）］， liver fibrosis markers ［procollagen type Ⅲ （PCⅢ）， laminin （LN）， and hyaluronic acid （HA）］， inflammatory cytokines ［interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and interleukin-10 （IL-10）］， and fibrosis-related proteins ［α-smooth muscle actin （α-SMA）， collagen type Ⅰ （Col Ⅰ）， and collagen type Ⅲ （Col Ⅲ）］ were assessed. A co-culture system of THP-1 cells （M1 macrophages） and human hepatic stellate cells （LX-2） was established. The cell experiment was designed with blank control （LX-2 alone）， model （LX-2 + M1 macrophages）， and low-， medium-， and high-dose SNS （co-culture with 5%， 10%， or 20% SNS-containing serum， respectively） groups. Cell viability， inflammatory cytokines， and macrophage phenotype were examined. Human primary hepatic Kupffer cells were allocated into blank control， M1 （LPS 100 μg·L^-1+IFN-γ 20 μg·L^-1）， M2 （IL-4 20 μg·L^-1+IL-13 20 μg·L^-1）， M1+M2， M1+SNS （supplemented with 10% SNS-containing serum for 2 h after culture under M1 conditions for 24 h）， M2+SNS （supplemented with 10% SNS-containing serum for 2 h after culture under M2 conditions for 24 h）， and M1+M2+SNS groups （supplemented with 10% SNS-containing serum for 2 h after culture under M1+M2 conditions for 24 h）， and the expression of nuclear factor-κB （NF-κB） p65 and signal transducer and activator of transcription 3 （STAT3） at protein and mRNA levels was determined. ResultsCompared with the blank group， the model group exhibited increased serum levels of ALT， AST， ALP， PCⅢ， LN， HA， IL-6， and TNF-α， upregulated protein and mRNA levels of α-SMA， Col Ⅰ， and Col Ⅲ in the liver tissue （P<0.05， P<0.01）， and decreased IL-10 level and STAT3 mRNA level （P<0.05， P<0.01）， accompanied by marked collagen deposition and inflammatory infiltration in the liver. Compared with the model group， all doses of Sini San reversed these alterations （P<0.05， P<0.01）， with the high-dose group showing the most pronounced effects. Cell experiments demonstrated that， compared with the blank control group， the model group had elevated levels of pro-inflammatory cytokines （IL-1β， IL-6， and TNF-α） and upregulated protein and mRNA levels of M1 markers ［cluster of differentiation 86 （CD86， inducible nitric oxide synthase （iNOS）， and monocyte chemoattractant protein-1 （MCP-1）］ （P<0.01）， along with declined level of IL-10 and downregulated expression of M2 markers ［（CD163， CD206， and arginase-1 （Arg-1）］ （P<0.05，P<0.01）. Compared with the model group， treatment with Sini San-containing serum at various concentrations lowered the levels of pro-inflammatory cytokines and expression of M1 markers （P<0.05， P<0.01）， while increasing the IL-10 level and M2 marker expression （P<0.05， P<0.01）. Additionally， Sini San downregulated the mRNA level of NF-κB and upregulated the mRNA level of STAT （P<0.05， P<0.01）. In the experiment with human primary Kupffer cells， compared with the blank group， the M1 group showed increased NF-κB p65 expression （P<0.01） and decreased STAT3 expression （P<0.05）， whereas the M2 group exhibited increased STAT3 expression （P<0.01）. Compared with the respective model groups， Sini San-containing serum reversed the M1-induced overexpression of NF-κB p65 （P<0.05， P<0.01） and further enhanced the M2-induced STAT3 expression （P<0.05， P<0.01）. ConclusionSini San can inhibit the NF-κB p65/STAT3 signaling pathway and repolarize intrahepatic Kupffer cells from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype to attenuate inflammation and suppress hepatic stellate cell activation and collagen deposition， thereby exerting anti-fibrotic effect.

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.

Objectives:To evaluate the accuracy and safety of cervical pedicle screw implantation in chil-dren with O-arm navigation assistance.Methods:This study retrospectively analyzed 27 pediatric patients with cervical spine disease who underwent cervical pedicle screw implantation with O-arm navigation assis-tance between January 2015 and December 2021.The patients aged 4-15(8.2±3.2)years,among which,there were 7 cases of atlantoaxial dislocation,12 cases of congenital cervical-thoracic deformity,4 cases of neurofi-bromatosis with cervicothoracic atrophic scoliosis,2 cases of Gorham's disease,and 2 cases of neoplasms.All the patients were treated with O-arm navigation-assisted posterior cervical pedicle screw internal fixation.Pre-operatively,the pedicle width of each segment was measured on the widest cross-sectional image of cervical CT scans,and pedicles＜3.5mm in width were defined as high-risk pedicles,and during operation,cervical pedicle screws(CPS)were inserted under O-arm navigation guidance.The accuracy of CPS implantation was e-valuated immediate postoperatively by CT scans(grade 0:no breach;grade 1:breach＜25％screw diameter;grade 2:breach by 25％-50％the screw diameter and invading the internal or lower wall;grade 3:breach by 25％-50％the screw diameter and invading the external or upper wall;grade 4:breach＞50％screw diameter).The CPS breach numbers and grades of different levels,as well as complications were recorded.Results:A total of 109 CPSs were implanted,the mean preoperative pedicle diameter was 3.49±0.58mm(C3-6),including 36 high-risk screws.And the screw distributions by segments were C1 13(11.9％),C2 25(22.9％),C3 8(7.3％),C4 17(15.6％),C5 14(12.8％),C6 17(15.6％),and C7 15(13.8％).Postoperative CT scan showed that 100(91.7％)CPSs were well positioned(≤grade 2),5(4.6％)CPSs were of grade 3,and 4(3.7％)CPSs were of grade 4.No surgical complications such as vertebral artery or nerve root injury were found.The C4 vertebra was relatively more likely to undergo wall breakage due to positional influence and navigational excursions.Breach of grade 4 was due to extremely thin preoperative pedicles(mean 2.78mm),which did not require immediate secondary surgical adjustment or removal in the absence of significant neurologic complications.Conclusions:O-arm navigation-assisted CPS placement has a high accuracy in different cervical diseases in children,and therefore is endowed with high safety.

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.

Objective:To conduct a Meta-synthesis on the characteristics of symptom help-seeking behavior in adult cancer patients, so as to provide evidence-based guidance for early intervention of symptom help-seeking behavior in cancer patients in China.Methods:Qualitative studies on symptom help-seeking behavioral characteristics of cancer patients were systematically searched in PubMed, Cochrane Library, Web of Science, ProQuest, Nature, ScienceDirect, China National Knowledge Infrastructure, WanFang Data, China Biology Medicine disc, and VIP. The search period was from database establishment to December 31, 2024. Included literature was independently evaluated using the Australian Joanna Briggs Institute Center for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research. The results were integrated through the Meta-synthesis method.Results:A total of 15 papers were included, and 30 findings were distilled and grouped into nine categories, resulting in three integrated findings of low symptom perception and interpretation bias, coping styles of symptom disclosure, and factors influencing symptom help-seeking behaviors.Conclusions:Symptom help-seeking behaviors of cancer patients are influenced by a variety of factors, and understanding their behavioral characteristics is useful in informing the development of intervention strategies.

Objective To analyze the mechanisms of meaning in life and living arrangements impacting the effect of activities of dai-ly living(ADL)on depression for older adults.Methods From September to November,2024,community-dwelling older adults from Weifang,Shandong,were investi-gated with questionnaire using Basic Activities of Daily Living Scale(BADL),Meaning in Life Questionnaire(MLQ),Geriatric Depression Scale(GDS),and a general information questionnaire including living arrange-ments.Results A total of 256 questionnaires were distributed,and 245 valid questionnaires were returned.There were signifi-cant differences in GDS scores among older adults with different personal monthly incomes and living arrange-ments(F>3.744,P<0.05).BADL scores were positively correlated with GDS scores(r=0.490,P<0.001)and negatively correlated with MLQ scores(r=-0.370,P<0.001),and MLQ scores were negatively correlated with GDS scores(r=-0.369,P<0.001).There was significant direct effect of BADL scores on GDS scores(effect=1.128,95%CI 0.829～1.427),and mediating effect of MLQ scores on the relationship between BADL and GDS scores(effect=0.171,95%CI 0.028～0.337).The moderating effect of living alone was significant(|B|=0.127,|t|=2.103,P<0.05)on the association between MLQ and GDS,compared with intergenerational coresidence.Conclusion Meaning in life partially mediates the association between ADL and depression in older adults,especially for those living alone.

Objective To investigate the effects of cinnamic aldehyde(CA)on Bcl-2-associated X protein(Bax)and Bcl-2 homologous antagonist/killer(Bak)in vascular endothelial cells of diabetic ulcer wound tissues,as well as on cell apoptosis.Methods ① Forty-eight healthy SPF-grade male SD rats(5 weeks old,weighing 180～220 g)were randomly assigned to a control group(12 rats)and a diabetes group(36 rats).The diabetic model was established with an intraperitoneal injection of 50 mg/kg STZ-citrate sodium solution and high-fat diet feeding.The diabetes group was further randomly divided into Model group,CA group,and the rb-bFGF group,with 12 animals in each group.Wounds in the Con and Model groups were disinfected and topically treated with normal saline,CA group received topical application of 4 μmol/L CA in PEG 400 gel,and those of the rb-bFGF group were treated with bevacizumab gel.The wound healing rate of each group was calculated at 3,7 and 14 d after intervention.At 14 d after intervention,pathological changes in the wounds were observed with HE staining,and the expression levels of Bax and Bak were detected by Western blotting.② Human umbilical vein endothelial cell line EA.hy926 was treated with 175 mmol/L glucose for 48 h to establish a cell model of high glucose injury.The experimental cells were divided into control group,model group and CA treatment group.Cell scratch test and tube formation test were performed respectively to determine the migration ability and angiogenesis of the cells.The expression levels of Bax and Bak was detected with immunofluorescence assay,and cell apoptosis was detected by TUNEL staining.Results ①The diabetic rats in the Model group exhibited significantly higher blood glucose level(P<0.05),declined wound healing rate at 7 and 14 d after intervention(P<0.05),and enhanced expression levels of Bax and Bak(P<0.05)when compared with the control group.Pathological observation revealed that,at 14 d after intervention,accompanied with inflammatory reactions,dense infiltration of inflammatory cells,fewer new blood vessels,and continuous fluid exudation in the wound were observed in the Model group,but the control group presented complete epithelialization in full-thickness skin.Compared with the conditions in the Model group,both CA and rb-bFGF treatment improved the epithelialization process,with mature granulation tissues,showing good healing condition,promoted wound healing rate(P<0.05),and decreased the expression levels of Bax and Bak(P<0.05).② The results of cell experiments showed that the cells of the model group showed significantly reduced migration ability and tube formation ability(P<0.05),reduced protein levels of Bax and Bak(P<0.05),and lower apoptotic rate(P<0.05)when compared with the cells in the model group.Conclusion CA can inhibit the expression of apoptosis-related proteins Bax and Bak,promote the migration and tube formation of vascular endothelial cells,and inhibit the cell apoptosis under high glucose condition,which may be an important reason for its promoting wound healing in diabetic ulcer rats.

Necrotizing enterocolitis（NEC）is a gastrointestinal emergency commonly seen in premature infants，and its etiology and high-risk factors have not been fully elucidated.Premature infants who receive blood component transfusions are at significantly increased risk of developing NEC，with a higher incidence and mortality rate.This review focuses on a comprehensive analysis of the association between multiple blood component transfusions and NEC，the pathogenesis，prevention measures，and the threshold of blood component transfusions，aiming to provide a reference for the safe and rational use of blood component transfusions in clinical practice，and to guide fulture research directions.

[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.

[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.