Objective To assess the impact of cytokines on pulmonary arterial hypertension using a bi-directional Mendelian randomization(MR)approach.Methods The data for 41 cytokines were derived from a genome-wide association study(GWAS)dataset consisting of 8,293 individuals of European descent,and the genetic data for pulmonary arterial hypertension were obtained from a GWAS dataset comprising 11,744 indi-viduals of European descent;the potential impact of cytokines on pulmonary arterial hypertension was ex-plored using MR analysis.Results The inverse variance weighted(IVW)analysis revealed a potential causal relationship between IL-9 and pulmonary arterial hypertension(OR=0.63,95%CI:0.50 to 0.78,P<0.001),and a potential causal relationship between β-NGF and pulmonary arterial hypertension(OR=1.34,95%CI:1.01 to 1.79,P=0.049).Multivariable MR analysis demonstrated an association between IL-9 and pulmonary arterial hypertension(OR=0.57,95%CI:0.44 to 0.72,P<0.001),as well as between β-NGF and pulmonary arterial hypertension(OR=1.47,95%CI:1.10 to 1.97,P=0.009).Conclusion Elevated IL-9 levels may be causally associated with a reduced risk of pulmonary arterial hypertension,while increased β-NGF levels may elevate the risk of pulmonary arterial hypertension.

Objective To investigate the transgenerational effects of paternal PM2.5 exposure on offspring growth and development,and to preliminarily elucidate the role of sperm DNA methylation modifications in mediating these effects.Methods Eight-week-old male C57BL/6 mice were randomly divided into filtered air(FA),unfiltered air(UA),and concentrated PM2.5(CAP)groups,with 10 animals in each group.The exposure was conducted from November 2019 to April 2020,and then,these male mice were mated with unexposed females to generate F1 offspring,which were bred successively to produce F2 and F3 generations.All the offspring were living in PM2.5-free environment.The birth body weight,birth number,and sex ratio of the offspring were recorded,body weight growth was monitored,and organ coefficients of the heart,liver,lung,and brain were calculated.Whole-genome methylation sequencing was performed on the sperm DNA of the CAP group,FA group,and their F1 generation offspring to screen for differentially methylated regions,and the genes and pathways associated with these regions were analyzed.Results When compared with the F1～F3 offspring of the FA group,the CAP group had significantly reduced birth body weight in the F1 generation(P<0.05),no statistical differences were observed in the birth body weight in the F2 and F3 generations(P>0.05),or either in the sex ratio and birth number among the F1,F2 and F3 generations.Compared with the FA group offspring,the F1～F3 offspring of CAP group exhibited delayed body weight gain,especially in the males(P<0.05),the CAP-F1 male generation had obviously elevated liver organ coefficient(P<0.01),but no statistical changes were observed in the heart,lung,or brain coefficients among the F1～F3 generations.Between the FA group and the CAP group,37 997 differentially methylated regions were detected,with a reduction of approximately 50%in the number of differentially methylated regions in the F1 generation.Differentially methylated genes in F0 and F1 sperm were potentially related to developmental processes,including imprinting genes(Gnas,Igf2)and metabolic genes(Ppard,Rps6kb1).Conclusion Paternal exposure to PM2.5 leads to reduced birth weight and intergenerational growth retardation in offspring.Its impact on phenotypic effects is gradually weakened during intergenerational transmission.Changes in the methylation of development-related genes in sperm may be one of the mechanisms mediating this intergenerational effect.

Additive manufacturing(3D printing)technology aligns with the direction of precision and customization in future medicine,presenting a significant opportunity for innovative development in high-end medical devices.Currently,research and industrialization of 3D printed medical devices mainly focus on nondegradable implants and degradable implants.Primary areas including metallic orthopaedic implants,polyether-ether-ketone(PEEK)bone implants,and biodegradable implants have been developed for clinical and industrial application.Recent research achievements in these areas are reviewed,with a discussion on the additive manufacturing technologies and applications for customized implants.Challenges faced by different types of implants are analyzed from technological,application,and regulatory perspectives.Furthermore,prospects and suggestions for future development are outlined.

Objective:To investigate the unqualified hepatitis C virus (HCV) detection result of blood donors from the served area of blood institutions.Methods:The data related to HCV markers detected of the first and repeat blood donors were collected from the system of practice comparison for the Chinese mainland blood institutions from 2017 to 2021. The anti-HCV reactive rate and the rates of anti-HCV negative but HCV-RNA reaction and all the relationship between rates and the annual, regional and different blood donors were statistically analyzed.Results:During 2017-2021, the number of anti-HCV reactive per 100 000 blood donors decreased from 444.3 to 250.44 in the served area of 22 blood institutions ( χ2=49.677, P<0.05). The number of HCV RNA detected positive per 100 000 anti-HCV negative increased from 0.69 to 2.05 year by year, but there was no statistical significance ( χ2=0.643, P>0.05). The anti-HCV unqualified rate was significantly different among regions ( χ2=3 260.283, P<0.05). The anti-HCV unqualified rate of the first blood donors was significantly higher than that of the repeated blood donors ( F=130.993, P < 0.05). The annual number of HCV RNA detected positive per 100 000 anti-HCV negative blood samples from donors ranged from 0 to 17.28. Conclusions:The anti-HCV unqualified rate of blood donors in the served area of 22 blood institutions decreased year by year. Compared with repeated blood donors, HCV infection should be emphasized in first-time blood donors. The implementation of HCV RNA test can detect out much more HCV infections and reduce the risk of transfusion transmitted infectious HCV.

Objective To investigate gene pathways associated with severe acne.Methods Kyoto encyclopedia of genes and genomes (KEGG)-based pathway analysis was conducted using the genome-wide association study (GWAS) data on 1 056 patients with severe acne and 1 056 healthy controls,and each testee was tested for 900 015 SNPs.A hypergeometric distribution test was used to analyze the relationship between each pathway and severe acne,and the false discovery rate (FDR) to correct for multiple testing.Any pathway with an adjusted P value of ＜ 0.05 was considered to be associated with severe acne.Results Twelve genes were identified to be associated with severe acne (P ＜ 0.001),including TMPRSS11E,DDB2,RIC1,CLLU1OS,IL3,PLA2G4B,SLC16A14,SOX17,FAHD2A,ENTPD7,MRPL50 and TXLNB.Pathway analysis revealed 5 pathways associated with severe acne (adjusted P ＜ 0.05),including the prolactin signaling pathway,hepatitis C,renal cell carcinoma,high affinity receptor for immunoglobulin E (Fc epsilon RI) signaling pathway,and tyrosine metabolism.Conclusion The 5 identified pathways are associated with severe acne,which affect the endocrine,immune and metabolic processes in the human body.

Objective To study the mechanism of RING finger protein 34 ( RNF34 ) involved in innate immunity . Methods Recombinant PCR was used and transient expression of the plasmid was achieved in HEK 293T cells.The cells were stimulated with Sendai virus ( SeV) or N-RIG-Ⅰfor the indicated time while luciferase activity was observed using the dual-luciferase reporter assay kit .Results We constructed the plasmid pcDNA 3-Flag-RNF34 and its three mutations .The study found that when stimulated by SeV , RNF34 could inhibit the activity of NF-κB and IFN-βmore significantly than RNF34-ΔFYVE, RNF34-ΔCID and RNF34-ΔRING.We also found that RNF 34 and its three mutants had similar inhibitory effect when the activation of NF-κB and IFN-βwas stimulated by the N-RIG-Ⅰ.Conclusion RNF34 negatively regulates innate immunity by acting on the RIG-Ⅰ-MAVS signaling pathway .

BACKGROUND:In recent years, many manufacturing techniques have been recently developed for soft tissue engineering scaffolds. Especialy additive manufacturing with a unique material accumulated forming principle can be feasible and reliable to manufacture the highly precise scaffolds with gradient structures and multi-materials for large soft tissue defect repairing.
OBJECTIVE:To summarize scaffolds manufacturing technologies in the soft tissue engineering applications developed in recent years and to predict the direction of development.
METHODS: A retrieval was performed for the literature about the manufacturing methods of soft tissue scaffolds using key words of “additive manufacturing, microfabrication, vascular tissue engineering, muscle tissue engineering, cartilage tissue engineering, stereolithography, 3D printing, biodegradable hydrogel” in English and Chinese, which were published between January 2010 and September 2013 in PubMed Database and China National Knowledge Infrastructure (CNKI) Database.
RESULTS AND CONCLUSION:For large soft tissue defects repairing, structure design of the scaffolds has been shifted from a simple planar structure to a more complex three-dimensional structure, and integration of scaffold structure, materials and cels, and growth factors during the manufacturing procedure can be used to obtain the resolution of vascularization. Additive manufacturings become one of the most promising approaches for the ideal soft tissue scaffolds with gradient and complex structure and multi-materials. In particular, the hydrogel/cellcomposite scaffolds fabrication, a hot but promising approach to develop the soft tissue engineering wil be made progress by the accurate principles and processes of the hydrogel additive manufacturing combined with the introduction of living cels and growth factors.

Objective To investigate the methods of diagnosis and treatment of pediatric and hebetic adrenocorticotropic hormone ( ACTH) secreting pituitary microadenoma. Methods The data of 10 patients with ACTH secreting pituitary microadenoma were retrospectively analysed. ACTH secreting pituitary microadenoma was diagnosed by clinical manifestations, biochemical and imaging findings, and 5 patients underwent bilateral inferior petrosal sinus sampling ( BIPSS). Transsphenoidal surgery was performed on all the patients under microscope, and the tumor specimens were detected by immunohistochemistry. Results Immunohistochemical examination revealed that ACTH was positive in 8 cases and negative in 2 cases. Patients were followed up for 12 to 63 months, 7 cases (70%) were cured, one (10%) achieved remission, and the other two (20%) experienced recurrence. Conclusion BIPSS is helpful in the diagnosis and localization of pediatric and hebetic ACTH pituitary microadenoma, and transsphenoidal surgery is the optimal choice of treatment.

Objective Due to the problem of individual matching, exclusivity and loose with pure mechanical fixation for artificial hemi-knee joints made by traditional method, a new manufacturing process based on rapid prototyping technique and custom-made concept is presented.MethodsRapid prototyping was processed to rapidly and accurately shape the prototype of an artificial implant almost with the same shape as the hemi-knee joint of the patient, and the process based on Titanium alloy centrifugal casting technology and biomaterial sintering molding technology was used to fabricate the artificial hemi-knee joint and bioactive proximal tibia artificial bone, respectively.Results and ConclusionThe custom-made knee joint prosthesis has been fabricated and put into clinical use successfully. In comparison with the traditional implants, this system can realize the well matching movement between the artificial hemi-knee joint and its opposite. Meanwhile,the design of functional holes and tibial nails realizes the combination of biological fixation with mechanical fixation for the artificial implant,and the use of bioactive artificial bone promotes bone growth and minimizes the exclusive reaction.