Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver injury of unknown etiology. The onset of this disease involves the activation and recruitment of diverse immune and non-immune cells, which in turn trigger hepatic damage. Immune checkpoint molecules (ICM) are expressed on the surface of multiple cell types. By regulating cellular functional states, they help limit the intensity and duration of immune responses, thereby preventing excessive inflammation and tissue damage, and maintaining immune homeostasis. In AIH, however, this natural "braking" mechanism is impaired, leading to aberrant activation of both immune and non-immune cells and the breakdown of immune homeostasis. Consequently, ICM are likely to play a critical role in the pathogenesis of AIH. A deeper understanding of the function of ICM in AIH not onlyadvances our insight into the disease mechanism, but also suggests that targeting these molecules may represent a promising therapeutic strategy for the treatment of AIH.

Objective To investigate the causal relationship between metabolic syndrome and breast cancer by using a bidirectional two-sample Mendelian randomization (MR) approach. Methods Genome-wide association study (GWAS) summary statistics for metabolic syndrome and breast cancer were acquired from the Integrative Epidemiology Unit GWAS database and the GWAS Catalog, with populations encompassing the United States and East Asia. A bidirectional causal design was employed: a forward analysis with metabolic syndrome as the exposure and breast cancer as the outcome, followed by a reverse analysis wherein their roles were interchanged. The inverse-variance weighting (IVW) method was primarily used for effect estimation, supplemented by MR-Egger regression, the weighted median method, the simple mode method, and the weighted mode method. Instrument variable strength was screened using the F-statistic (F>10). Robustness of the results was assessed through heterogeneity tests, horizontal pleiotropy tests, forest plots, and leave-one-out sensitivity analyses. Results The IVW analysis indicated no significant causal relationship between metabolic syndrome and breast cancer (OR=1.00, 95%CI: 0.97-1.03), P>0.05). Sensitivity analyses yielded consistent results, suggesting the good robustness of the study findings. Conclusion This study found no evidence to support a causal relationship, either positive or negative, between metabolic syndrome and breast cancer.

BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.

BACKGROUND:LncRNA-TNFRSF13C,an important factor in B cell development and function,is expressed in periodontal tissues of patients with periodontitis,but the specific mechanism is still unclear. OBJECTIVE:To investigate the mechanism of lncRNA-TNFRSF13C regulating miR-1246 on hypoxia-inducible factor 1α in periodontal cells. METHODS:Human periodontal ligament cells(hPDLCs)were treated with lipopolysaccharide and divided into group A(hPDLCs cell lines without transfection),group B(hPDLCs cell lines transfected with TNFRSF13C NC-siRNA),group C(hPDLCs cell lines transfected with TNFRSF13C-siRNA),group D(hPDLCs cell line transfected with miR-1246 mimics),group E(hPDLCs cell line transfected with miR-1246 siRNA),group F(hPDLCs cell line transfected with TNFRSF13C-siRNA+miR-1246 mimics),and group G(hPDLCs cell line transfected with TNFRSF13C-siRNA+miR-1246 siRNA).The relative expression of lncRNA-TNFRSF13C and miR-1246 in each group was detected by qRT-PCR.Cell counting kit-8 assay was used to detect cell viability.Apoptosis was detected by flow cytometry.Expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins was detected by western blot.The correlation between lncRNA-TNFRSF13C and miR-1246 was analyzed by Pearson,and the targeting relationship was analyzed by dual-luciferase reporter assay. RESULTS AND CONCLUSION:There was no significant difference in human periodontal ligament cell activity,apoptosis rate and protein indexes between groups A and B(P>0.05).Compared with group B,hPDLCS cell activity in group C was increased,and apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins were decreased(P<0.05).Compared with group C,hPDLCS cell activity in group D was decreased,and apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor proteins were increased(P<0.05).Compared with group D,the cell activity of group E was increased(P<0.05).The cell activity in group F was lower than that in group E,and the apoptosis rate was reduced in both groups E and F(P<0.05).Compared with group F,the cell activity of group G was increased,and the apoptosis rate and the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor were decreased(P<0.05).LncRNA-TNFRSF13C was positively correlated with miR-1246(P<0.05).Compared with the TNFRSF13C-siRNA group,the fluorescence activity of miR-1246-wt in the TNFRSF13C-NC group was reduced(P>0.05);compared with the miR-1246-NC group,the fluorescence activities of hypoxia-inducible factor 1α-wt and vascular endothelial growth factor-wt in the miR-1246 mimics group were increased(P<0.05).To conclude,down-regulation of lncRNA-TNFRSF13C can promote the activity of periodontal cells treated with lipopolysaccharide,reduce apoptosis,and inhibit hypoxia-inducible factor 1α and vascular endothelial growth factor.The mechanism is related to the regulation of miR-1246 activity.

ObjectiveTo observe the clinical efficacy of acupuncture combined with bloodletting and cupping in the treatment of chronic spontaneous urticaria（CSU） and to explore its potential mechanisms of action. MethodsSeventy CSU patients were randomly divided into loratadine group and acupuncture + bloodletting group， with 35 patients in each group. The loratadine group received oral loratadine tablets， 10 mg once daily in the evening. The acupuncture + bloodletting group received acupuncture at Zhongwan （CV 12）， Guanyuan （CV 4）， Tianshu （ST 25）， Zusanli （ST 36）， Sanyinjiao （SP 6）， Xuehai （SP 10）， Quchi （LI 11）， Hegu （LI 4）， Taichong （LR 3）， Baihui （GV 20）， and Shenting （GV 24）， once daily，along with bloodletting and cupping at Dazhui （GV 14） and Geshu （BL 17）， every other day. Both groups were treated for 4 weeks. The 7-day urticaria activity score（UAS7） was assessed before and after the treatment， and levels of serum immunoglobulin E （IgE）， interleukin-4 （IL-4）， interleukin-5 （IL-5）， eosinophil cationic protein （ECP）， plasma tissue factor （TF）， activated factor Ⅶ （FⅦa）， prothrombin fragment 1+2 （F1+2）， D-dimer （D-D） and complement component 5a （C5a） were detected. ResultsA total of 65 patients were included in the final analysis， 32 in the loratadine group and 33 in the acupuncture + bloodletting group. Before treatment， there was no significant difference in UAS7 score， serum IgE， IL-4， IL-5， ECP levels， or plasma TF， FⅦa， F1+2， D-D， C5a levels between groups （P＞ 0.05）. After treatment， both groups showed significant reductions in UAS7 score， serum IgE， IL-4， IL-5， and plasma TF， FⅦa， F1+2， D-D， and C5a levels compared to those before treatment （P＜0.01）. However， after treatment， there was no significant difference in UAS7 score and serum ECP， IgE， IL-4， IL-5 levels between groups （P＞0.05）. The acupuncture + bloodletting group showed lower plasma TF， FⅦa， F1+2， D-D and C5a levels compared to the loratadine group （P＜0.05 or P＜0.01）. ConclusionAcupuncture combined with bloodletting and cupping can effectively improve the skin symptoms of CSU patients and reduce the levels of inflammatory factors. The potential mechanism of action may involve the regulation of the coagulation-complement-mast cell activation axis， thereby inhibiting mast cell degranulation.

AIM: To investigate the abnormal conditions and change patterns of accommodative facility in patients with different refractive states before and after small incision lenticule extraction(SMILE)surgery.METHODS:A prospective clinical cohort study was conducted. A total of 59 patients(118 eyes)who underwent SMILE surgery and had visual function files established in our hospital from June to December 2023 were randomly selected, including 37 males and 22 females, aged 18-35 years(with an average age of 25.19±5.65 years). According to the preoperative spherical equivalent(SE), they were divided into two groups: the low-to-moderate myopia group(SE≥-6.00 DS)with 40 patients(80 eyes), and the high myopia group(SE<-6.00 DS)with 19 patients(38 eyes). The monocular and binocular accommodative facility before surgery and at 1 wk and 1 mo after surgery were compared, and the changes in accommodative facility before and after SMILE surgery in the two groups of patients were analyzed.RESULTS:All surgeries were completed successfully. In the low-to-moderate myopia group, 33 cases(66 eyes)completed the 1-month follow-up after surgery, with a loss to follow-up rate of 17.5%(7/40). In the high myopia group, 15 patients(30 eyes)completed the 1-month follow-up after surgery, with a loss to follow-up rate of 21.1%(4/19). After SMILE surgery, the uncorrected visual acuity and SE of both low-to-moderate myopia and high myopia were significantly improved(all P<0.05). The accommodative facility of the right eyes in all the patients at 1 mo after surgery was better than that before surgery and at 1 wk after surgery(P=0.002, 0.006), the accommodative facility of the left eyes was significantly increased at 1 mo after surgery than that at 1 wk after surgery(P=0.005), and the binocular accommodative facility at 1 mo after surgery was significantly increased compared with that before surgery(P<0.017). Furthermore, there were statistical significance in accommodative facility of the right eyes in the low-to-moderate group at 1 mo compared with that before surgery and at 1 wk after surgery(P=0.011, 0.004); it was significantly increased in the left eyes at 1 mo after surgery compared with that at 1 wk after surgery(P=0.001), and binocular accommodative facility at 1 mo after surgery was significantly better than that before surgery(P<0.001). Furthermore, there was no statistical significance in the right, left and binocular accommodative facility of patients in the high myopia group(all P>0.017).CONCLUSION: After SMILE surgery, the monocular accommodative facility shows a transient decrease and then exceeds the preoperative level at 1 mo after surgery, and the binocular accommodative facility gradually improves after surgery. SMILE surgery has a positive impact on the monocular and binocular accommodative facility in patients with low-to-moderate myopia, but has no significant impact on the accommodative facility in patients with high myopia. It is of clinical significance to strengthen the detection of monocular and binocular accommodative facility before and after SMILE surgery.

OBJECTIVE To analyze the characteristics of pediatric medicines with priority review and approval for marketing in China， providing a reference for promoting enterprise R&D and production， as well as improving the supply guarantee mechanism for pediatric medicines. METHODS Based on publicly available data sources such as List of Approved Information for Pediatric Medications Subject to Priority Review and Approval， Pharnexcloud biomedical database， and National Medical Insurance Drug Directory， this study conducted a comprehensive analysis of the main characteristics of pediatric medicines with priority review and approval for marketing. RESULTS As of June 30， 2024， a total of 68 pediatric medicines had been approved through the priority review and approval process， covering 12 therapeutic areas， with oral dosage forms accounting for 64.71%. The median time from application to inclusion in priority review was 35.50 days， with an average of 41.69 days. The median time from inclusion in priority review to market approval was 1.24 years， with an average of 1.42 years. This included 12 domestic new medicines， 21 domestic generic medicines， 35 imported medicines， as well as 29 pediatric-specific medicines and 21 orphan medicines. Additionally， 31 of these medicines had been included in the medical insurance catalog， representing a proportion of 45.59%. CONCLUSIONS Currently， a trend of differentiated competition is emerging between domestic and imported pediatric medicines. The therapeutic areas for pediatric medicines are continuously expanding， and the dosage forms are becoming more tailored to children’s needs. However， there are still issues such as slow progress in new medicine development， insufficient stability in the medicine review and approval process， and a need to increase the proportion of medicines included in medical insurance.

Objective: To reveal the molecular biological mechanism of a rare Dc-variant individual using PacBio third-generation sequencing technology. Methods: ABO and Rh blood type identification, DAT, unexpected antibody screening and D antigen enhancement test were conducted by serological testing. The absorption-elution test was used to detect the e antigen. RHCE gene typing was performed by PCR-SSP, and the 1-10 exons of RHCE were sequenced by Sanger sequencing. The full-length sequences of RHCE, RHD and RHAG were detected by PacBio third-generation sequencing technology. Results: Serological findings: Blood type O, Dc-phenotype, DAT negative, unexpected antibody screening negative; enhanced D antigen expression; no detection of e antigen in the absorption-elution test. PCR-SSP genotyping indicated the presence of only the RHCE c allele. Sanger sequencing results: Exons 5-9 of RHCE were deleted, exon 1 had a heterozygous mutation at c. 48G/C, and exon 2 had five heterozygous mutations at c. 150C/T, c. 178C/A, c. 201A/G, c. 203A/G and c. 307C/T. Third-generation sequencing results: RHCE genotype was RHCE 02N. 08/RHCE-D(5-9)-CE; RHD genotype was RHD 01/RHD 01; RHAG genotype was RHAG 01/RHAG 01 (c. 808G>A and c. 861G>A). Conclusion: This Dc-individual carries the allele RHCE 02N. 08 and the novel allele RHCE-D(5-9)-CE. The findings of this study provide data support and a theoretical basis for elucidating the molecular mechanisms underlying RhCE deficiency phenotypes.

AIM: To discuss the impacts of pterygium excision combined with low-temperature plasma radiofrequency ablation and autologous conjunctival flap transplantation on tear film function, visual function, and recurrence rate in patients with pterygium.METHODS: A retrospective study was conducted on patients with pterygium who underwent surgery at Jiangyin Hospital of Traditional Chinese Medicine from March 2021 to January 2024. The patients were divided into two groups based on the surgical methods: the excision group with 50 cases(50 eyes)and the combined group with 51 cases(51 eyes). The excision group underwent pterygium excision, while the combined group received low-temperature plasma radiofrequency ablation and autologous conjunctival flap transplantation in addition to the excision. The tear film function [Schirmer's test(SⅠt), tear film break-up time(BUT)], visual quality, therapeutic effect, incidence of complications within 1 a, and recurrence rate were compared between the two groups before and after treatment.RESULTS: The general data of the two groups were comparable(P>0.05). After treatment, the SⅠt and BUT in the combined group were greater than those in the excision group(both P<0.001), while the corneal astigmatism and uncorrected visual acuity were lower than those in the excision group(both P<0.001). The initial treatment efficiency in the combined group(92%)was higher than that in the excision group(76%). Within 1 a, the recurrence rate(8% vs 22%)and complication rate(6% vs 24%)in the combined group were both lower than those in the excision group(both P< 0.05).CONCLUSION: The union of pterygium excision, low-temperature plasma radiofrequency ablation, and autologous conjunctival flap transplantation is beneficial for improving the efficacy, visual acuity, tear film function, and reducing recurrence rate in patients with pterygium.