Objective To evaluate the feasibility of the porous titanium/chitosan/hydroxyapatite (Ti/Ch/HA) composite scaffold as a bone repair substitute.Methods Additive manufacturing (3D printing) technology was used to fabricate porous Ti scaffolds as supporting structures.Chitosan/hydroxyapatite (Ch/HA) sponge was prepared within the macro-pores of Ti scaffolds using freeze drying technology.Thus,a kind of composite porous Ti/Ch/HA scaffold with good cell affinity was obtained.Osteoblastic cells were seeded and cultured in pure porous Ti scaffolds and composite Ti/Ch/HA scaffolds for 7 days.The cellular morphology,seeding efficiency and proliferation were examined and compared between the 2 kinds of scaffolds using scanning electron microscopy (SEM) and MTT assay.Results The SEM examination showed that the macro-pores of Ti/Ch/HA scaffolds were full of the composite sponge structure of Ch/HA,with a micropore size of 50 to 200 μm.Like the pure porous Ti scaffolds,composite Ti/Ch/HA ones have a compressive strength of 168.2 to 192.6 MPa,a yielding strength of 137.1 to 154.1 MPa,and a Young's modulus of 3.21 to 4.51 GPa.After culture for 7 days,a large number of flat cells adhered onto the surface of Ti scaffolds while the cells adhering onto the Ti/Ch/HA composite scaffolds were fusiform.The seeding efficiency of osteoblastic cells in the composite Ti/Ch/HA scaffolds (73.218％ ± 3.748％) was significantly higher than that in the pure porous Ti scaffolds (21.352％ ±4.365％) (P ＜0.05);the OD value of the composite Ti/Ch/HA scaffolds (0.783 ±0.043) was significantly higher than that of the pure porous Ti scaffolds (0.382 ± 0.036) (P ＜ 0.05).Conclusions Ti/Ch/HA composite scaffolds can match human bone in mechanical properties.Compared with pure porous Ti scaffolds,the Ti/Ch/HA composite ones are more suitable for adhesion and proliferation of osteoblasts,making them an ideal kind of bone repair substitute.

ObjectiveTo evaluate the association between Pro12Ala polymorphism in peroxisome proliferator activated receptorγ2 (PPARγ2) gene and gestational diabetes mellitus(GDM).Methods Publications on genetic association studies of PPARγ2 and GDM were searched using the PubMed database, The HuGE Navigator, China National Knowledge Infrastructure (CNKI), Wanfang database and VIP Science from the inception of the databases to December 1, 2014. Two reviewers independently selected literature according to the inclusion and exclusion criteria, extracted data and assessed the quality of the data using the Newcastle-Ottawa Scale (NOS) standard. Meta-analysis was performed using RevMan 5.3 software.ResultsOverall, 13 eligible articles were identified, including seven in English and six in Chinese, with a total of 2 787 GDM cases and 5 408 healthy controls. Quality assessment showed that the quality of the 13 articles was all good, with NOS≥5. (1) Pro12Ala polymorphism in PPARγ2 (allele Ala or genotype Ala/Ala or Pro/Ala) was shown to be highly associated with GDM occurrence on general evaluation, with anOR(95%CI) of 0.74(0.60-0.93) in the allele model and 0.79(0.65-0.96) in the dominant genetic model (P<0.05, respectively). (2) Pro12Ala polymorphism in PPARγ2 was shown to be highly associated with GDM occurrence in Asians in a stratification analysis of ethnicity in the populations included in the studies, with anOR(95%CI) of 0.61(0.48-0.79) in the allele model and 0.64(0.50-0.82) in the dominant genetic model (P<0.01, respectively). No correlation was found between the Pro12Ala polymorphism in PPARγ2 and GDM in the Caucasian population. (3) A meta-analysis of six Chinese studies showed that the Pro12Ala polymorphism in PPARγ2 was associated with the risk of GDM in the Chinese population, with anOR(95%CI) of 0.52 (0.36-0.73) in the allele model and 0.55(0.39-0.80) in the dominant genetic model (P<0.01, respectively). (4) No significant association was observed in the TaqMan allelic discrimination assay with anOR(95%CI) of 0.96(0.83-1.10) in the allele model and 0.95(0.81-1.11) in the dominant genetic model (P>0.05, respectively), although there was still a significant correlation in polymerase chain reaction-restriction fragment length polymorphism with anOR(95%CI) of 0.58(0.43-0.79) in the allele model and 0.62(0.45-0.85) in the dominant genetic model (P<0.01, respectively).ConclusionsThe Ala allele and the Ala/Ala or Pro/Ala genotypes of the Pro12Ala polymorphism in PPARγ2 can decrease the risk of GDM. However, there are differences in the results which are affected by the genotype analysis method or races.

Objective To evaluate the efficacy and safety of fluorouracil and leucovorin and oxaliplatin(FOLFOX)regimen hepatic artery infusion chemotherapy(HAIC)combined with lenvatinib(LEN)and immune checkpoint inhibitors(ICIs)in treating patients with hepatocellular carcinoma(HCC)after the occurrence of transcatheter arterial chemoembolization(TACE)refractoriness.Methods The clinical data of 54 HCC patients who developed TACE refractoriness,were admitted to the Jiangsu Provincial Cancer Hospital of China to receive FOLFOX-HAIC combined with LEN and ICIs therapy between January 2019 and December 2022,were retrospectively analyzed.The modified Response Evaluation Criteria in Solid Tumors(mRECIST)was used to statistically analyze the clinical efficacy,the Common Terminology Criteria For Adverse Events version 5.0(CTCAE 5.0)was adopted to record and evaluate the treatment-related adverse events(TRAEs).The primary endpoints were progression-free survival(PFS)and overall survival(OS),the secondary endpoints were objective response rate(ORR),disease control rate(DCR),and safety.Results The median PFS was 11.7 months(95％CI:8.124-15.276 months),the median OS was 23.1 months(95％CI:19.508-26.692 months),the ORR was 46.3％,and the DCR was 87.0％.The most common TRAE at all levels was elevated alanine aminotransferase(51.9％),and the most common TRAE of grade 3/4 was hypertension(9.3％).No treatment-related death occurred.Conclusion For the treatment of HCC patients who developed TACE refractoriness,FOLFOX-HAIC combined LEN and ICIs is clinically safe and effective.(J Intervent Radiol,2024,33:610-615)

BACKGROUND: AND PURPOSE: Previous studies have explored the association between retinal vascular changes and cognitive impairment. The retinal vasculature shares some characteristics with the cerebral vasculature, and quantitative changes in it could indicate cognitive impairment. Hence, a comprehensive meta-analysis was performed to clarify the potential relationship between retinal vascular geometric changes and cognitive impairment. METHODS: Relevant databases were scrupulously and systematically searched for retinal vascular geometric changes including caliber, tortuosity, and fractal dimension (FD), and for cognitive impairment. The Newcastle-Ottawa Scale was used to evaluate the methodological quality of included studies. RevMan was used to perform the meta-analysis and detect publication bias. Sensitivity analyses were also performed. RESULTS: Five studies that involved 2,343 subjects were finally included in the meta-analysis. The results showed that there was no significant association between central retinal artery equivalents (Z=1.17) or central retinal venular equivalents (Z=1.74) and cognitive impairment (both p>0.05). Similarly, no significant difference was detected in retinal arteriolar tortuosity (Z=0.91) and venular tortuosity (Z=1.31) (both p>0.05). However, the retinal arteriolar FD (mean difference: −0.03, 95% CI: −0.05, −0.01) and venular FD (mean difference: −0.03, 95% CI: −0.05, −0.02) were associated with cognitive impairment. CONCLUSIONS A smaller retinal microvascular FD might be associated with cognitive impairment. Further large-sample and well-controlled original studies are required to confirm the present findings.

Objective To observe the changes of serum clara cell protein?16 ( CC?16 ) and monocyte chemotaxis protein?1 (MCP?1) level in patients with acute respiratory distress syndrome (ARDS) and to explore their relationship with the disease severity and prognosis of ARDS??Methods One hundred and fourteen patients with ARDS who were admitted to Changzhi People′s hospital from January 2017 to March 2018 were selected as the subjects??They were divided into mild group ( n＝37),moderate group (n＝41) and severe group ( n＝36) according to the severity of ARDS??Sixty healthy persons in out?patient examination were selected as control group??The survival situation of patients in 4 weeks were recorded,the patients were divided into survival group ( n＝65) and death group ( n＝49) according to their survival situation??The age,gender,body mass index (BMI),smoking history,acute physiology and acute physiology and chronic health evaluation II ( APACHE II) score,sequential organ failure assessment ( SOFA) score, serum CC?16 and MCP?1 level were analyzed in each group??The relationship between serum CC?16,MCP?1 level and disease and prognosis of patients with ARDS were analyzed??Results With the increase of disease severity,APACHE II score, SOFA score and serum CC?16, MCP?1 level in patients with ARDS were significantly increased??The differences were statistically significant ( F＝1 216??886,1 339??247,290??879, 417??262; all P＝0??000)??The APACHE II score,SOFA score and serum CC?16,MCP?1 levels in the death group were (22??13± 2??47) scores,( 15??09 ± 1??97) scores,( 23??85 ± 4??27) μg／L, ( 36??64 ± 5??21) ng／L respectively,which were significantly higher than those in the survival group (18??25±2??35) scores,(13??23 ±2??03) scores,(17??34±4??13) μg／L,(27??93±4??88) ng／L,the differences were statistically significant (t＝8??538,4??905,8??211,9??146;all P＝0??000)??Pearson correlation analysis showed that there was a positive correlation between serum CC?16 level and MCP?1 level in patients with ARDS ( r＝0??589, P ＝0??000)??Meanwhile,the CC?16,MCP?1 were positive correlation with APACHE II score,SOFA score and mortality (CC?16:r＝0??504,0??549,0??472;P＝0??000,0??000,0??012;MCP?1:r＝0??493,0??528,0??435;P＝0??006, 0??000,0??025)??APACHE II score ( OR＝3??083,95%CI:0??025－1??364,P＜0??05),CC?16 ( OR＝5??403, 95%CI:0??011－6??561, P＜0??05) and MCP?1 ( OR＝2??892, 95%CI: 0??034－1??619, P＜0??05) were all closely related to ARDS death??CC?16 independent detection, MCP?1 independent detection and the two combined detection predicted the under?curve area, sensitivity and specificity of ARDS patients with in 4 weeks were 0??830, 82??35% and 72??16%; 0??719, 79??25% and 72??19%; 0??866, 85??06% and 80??72%respectively??Conclusion CC?16,MCP?1 are abnormally high expression in serum of patients with ARDS, and its levels are closely related to the severity and prognosis of patients with ARDS??CC?16 combined with MCP?1 detection has high diagnostic value for patients with ARDS,which can be used as an effective index to judge the disease and prognosis of patients with ARDS??

Objective:To investigate the effect of glabridin on neutrophil extracellular traps (NETs) formation and pyroptosis in rats with sepsis-induced lung injury.Methods:Twenty-four male Wistar rats were divided into three groups according to the random number table method. The sepsis group was established by cecal ligation and puncture (CLP). The Glabridin group underwent CLP and glabridin gavage (30 mg/kg)(CLP+GLA). The sham operation group underwent cecal exploration, and only the abdomen was closed after cecal turning(Sham). After 12 hours, plasma、alveolar lavage fluid and lung tissue samples were taken for detection . Then, protein content of the alveolar lavage fluid was determined; The wet/dry weight(W/D) ratio of the lung tissue was determined; The pathological changes in lung tissue were observed after hematoxylin-eosin (HE) staining. The levels of NETs marker MPO-DNA complex and related inflammatory factors IL-18 and IL-1β in plasma were detected by enzyme-linked immunosorbent assay. The changes of Caspase-1and Cleaved-caspase-1 protein in lung tissue were detected by Western blot.Results:The total protein concentration of alveolar lavage fluid was significantly higher in the sepsis group compared with the Sham group ( P<0.01), and it decreased in the glabridin group compared with the sepsis group ( P<0. 05). Significant aggravation of pulmonary edema in the sepsis group, and the glabridin group reduced pulmonary edema compared with the sepsis group.The pathological results of lung tissue under the light microscope showed: The structure of lung tissue in the Sham group was normal, and the alveoli were clear; In the sepsis group, the alveolar wall was thickened widely and inflammatory cells infiltrated obviously; Compared with the sepsis group, the lung tissue injury was significantly reduced in the light licorice group. The enzyme-linked immunosorbent assay results showed that the levels of NETs marker MPO-DNA complex and inflammatory factors IL-18 and IL-1β in the plasma of the sepsis group were significantly higher than those in the Sham group ( P<0.001). The levels of NETs marker MPO-DNA complex and inflammatory factors IL-18 and IL-1β in the glabridin group were significantly lower than those in the sepsis group (MPO-DNA: P<0. 01; IL-18、IL-1β: P<0.05) . Western blot Technical results showed that the expression of Caspase-1 and Cleaved-caspase-1 protein positive signal was significantly enhanced in the lung tissue of the rats in the sepsis group compared with the Sham group; the distribution of Caspase-1 positive cells in the lung tissue of the sepsis + glabridin group was similar to that of the Sham group, and the expression of Cleaved-caspase-1 positive signal was higher than that of the Sham group. Conclusions:Glabridin can effectively reduce lung inflammation and play a protective role in lung injury in septic rats by inhibiting NETs production and pyroptosis.

OBJECTIVE：To put forward some suggestions for the implementation of OTC monograph in China. METHODS ： Literature research was used to comprehensively review the concept ，emergence and development ，function of OTC monograph in USA；referring to experience in USA ，the necessity and feasibility of monograph system for OTC registration and evaluation in China were explored ，and some suggestions were put forward to the implementation of OTC monograph in China. RESULTS & CONCLUSIONS：OTC monograph in USA refers to the regulatory standards that should be followed when selling OTC products not included in new drug applications. The monograph originates from the re-evaluation project of the effectiveness of OTC drugs ， which plays a special role in accelerating the drug marketing and promoting product innovation. The OTC monograph system is necessary to help to optimize the OTC registration and evaluation ，but at present ，the conditions to establish and implement OTC monograph are not yet ripe in China. Based on the optimization of resource allocation and infrastructure construction ，national OTC drug management experience ，OTC monograph can play a full part in OTC registration and evaluation ，in terms of carrying out in-depth research ，taking pilot test ，improving risk management system and enhancing drug review resource allocation ability.

Objective To elucidate the causal relationship between high-density lipoprotein cholesterol(HDL-C)and colorectal cancer(CRC)through Mendelian randomization.Methods Mendelian randomi-zation analysis was conducted using genetic instrumental variables selected from a genome-wide association study dataset.The main methods included inverse variance weighted,MR-Egger,weighted median,simple mode,and weighted mode method;among which,inverse variance weighted method served as the primary analytical approach.Sensitivity analyses were performed to verify the robustness of results.Results A total of 41 genetic instrumental variables associated with HDL-C were identified.Inverse variance weighted method(OR=0.84,95% CI:0.73-0.96,P=0.01)and weighted median method(OR=0.82,95% CI:0.67-0.99,P=0.04)indicated a negative correlation between genetically-determined HDL-C and CRC risk.Sensitivity analyses confirmed the absence of heterogeneity and horizontal pleiotropy(P>0.05).Conclusion A causal relationship exists between HDL-C and CRC risk,with rs1077834 as a potential key determinant in the influence of HDL-C on CRC risk.

Metastasis is the leading cause of death in breast cancer patients. However, the mechanisms underlying metastasis are not well understood and there is no effective treatment in the clinic. Here, we demonstrate that in MMTV-PyMT, a highly malignant spontaneous breast tumor model, IL-25 (also called IL-17E) was expressed by tumor-infiltrating CD4 T cells and macrophages. An IL-25 neutralization antibody, while not affecting primary tumor growth, substantially reduced lung metastasis. Inhibition of IL-25 resulted in decreased type 2 T cells and macrophages in the primary tumor microenvironments, both reported to enhance breast tumor invasion and subsequent metastasis to the lung. Taken together, our data suggest IL-25 blockade as a novel treatment for metastatic breast tumor.
Animals ; Antibodies, Neoplasm ; pharmacology ; Antibodies, Neutralizing ; pharmacology ; Breast Neoplasms ; drug therapy ; genetics ; immunology ; CD4-Positive T-Lymphocytes ; immunology ; pathology ; Female ; Humans ; Interleukin-17 ; antagonists & inhibitors ; genetics ; immunology ; Interleukins ; antagonists & inhibitors ; genetics ; immunology ; Macrophages ; immunology ; pathology ; Mammary Neoplasms, Animal ; drug therapy ; genetics ; immunology ; Mice ; Neoplasm Metastasis ; Tumor Microenvironment ; drug effects ; genetics ; immunology