Allergic conjunctivitis is a common ocular inflammatory disease, with intense itching being the most typical and distressing symptom for patients. In recent years, with the in-depth study of the interaction between the nervous and immune systems, significant progress has been made in understanding the mechanism of itching in allergic conjunctivitis. This review elaborates on the neurobiological basis of itching in allergic conjunctivitis, with a focus on the complex dialogue between immune cells and sensory neurons, particularly the core role of the IL-33-ST2-CGRP signaling axis in mediating itching. Additionally, this article introduces new findings in genetic susceptibility research, including the identification of susceptibility genes for allergic conjunctivitis through transcriptome-wide association studies. The sensory nervous system not only transmits itch signals but also actively participates in the formation of antigen channels related to conjunctival goblet cells, thereby regulating the local uptake of allergens and the initiation of the immune response. Moreover, targeted novel therapeutic strategies offer hope for patients with refractory allergic conjunctivitis. Exploring the molecular and cellular mechanisms of itching in allergic conjunctivitis will provide a theoretical basis for the development of more effective treatment methods.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

The codon was optimized for the bovine nebovirus(BNeV)VP1 gene and the recombi-nant plasmid pFastBac-Dual-VP1 was constructed,and BNeV-VP1 virus-like particles(VLPs)were prepared using a baculovirus expression system,and identified by Western blot,indirect im-munofluorescence and electron microscopy.Successfully validated VLPs were mixed with MF59 adjuvant and CpG-ODG,and mice were immunised by intramuscular injection and evaluated for immunity effects.The results showed that the optimized CAI(codon adaptation index)of VP1 gene was 0.93 and the GC content was 60.4％.The constructed recombinant plasmid was trans-formed into DH10Bac for blue-white spot screening,and after successful verification,it was trans-fected into SF9 cells to obtain recombinant baculovirus Baculo-BNeV-VP1.BNeV virus-like parti-cles with diameters ranging from 35 to 40 nm were observed under the electron microscope,and both IFA and Western blot experiments proved that the target proteins were successfully ex-pressed and biologically active,and protein optimisation revealed that the highest protein expres-sion was found at the infectious dose MOI=0.5.Mice were immunized by intramuscular injection after 50 μg of VLPs were mixed with MF59 adjuvant and CpG-ODN.The results showed that the VLPs immunization group produced IgG antibodies 7 days after the first dose,and the antibody ti-ter increased gradually,reaching a maximum of 1∶102 400,and declined at 35 d,but still main-tained a high level;The blocking titer BT50 is up to 640,which can induce the production of BNeV VP1-specific blocking antibody in mice.In this study,the baculovirus expression system was used to express the VP1 protein of BNeV,and BNeV VLPs were successfully constructed,which could induce humoral immune response in mice,which provided a reference for the follow-up research of BNeV vaccine.

Objective To investigate the nutritional quality characteristics of vitamin D3-fortified yogurt and explore its improving effect on vitamin D metabolism in the body under simulated weightlessness,thereby providing a theoretical basis for the development of functional foods.Methods Using reconstituted milk as the matrix and Vitamin D3(VD3)microcapsule powder as the fortifier,VD3-fortified yogurt was prepared.A systematic study was conducted to investigate the effects of different gradients(1.25 μg/100 mL,2.50 μg/100 mL,3.75 μg/100 mL,5.00 μg/100 mL,6.25 μg/100 mL)of VD3 microcapsule addition on its quality characteristics(titratable acidity,solid content,water-holding capacity,syneresis).In vivo assessments were conducted using a Sprague-Dawley(SD)rat tail-suspension model to simulate weightlessness.Levels in serum 25(OH)D3,1,25-(OH)2D3,calcium(Ca),and phosphorus(P)were detected using the enzyme-linked immunosorbent assay(ELISA)to evaluate its metabolic capacity.Results During fermentation(3 h),titratable acidity of VD?-fortified yogurt initially increased,then decreased,and eventually stabilized with rising microcapsule dosage,while total solid content remained consistent.WHC exhibited an initial increase followed by a decline,whereas syneresis showed an inverse trend.At an optimal dosage of 3.75 μg/100 mL,the yogurt displayed a dense and uniform network structure,characterized by non-Newtonian fluid behavior with shear-thinning properties.This formulation demonstrated robust structural stability under high-frequency mechanical stress,alongside desirable textural,flavor,and sensory attributes.Animal experiments revealed that the serum concentrations of 25(OH)D3,1,25-(OH)2D3,calcium,and phosphorus in the vitamin D?-fortified yogurt intervention group were significantly higher than those in the tail-suspended control group(P<0.05).Conclusion VD? microencapsulation technology effectively preserves and enhances the nutritional quality characteristics of yogurt and mitigates vitamin D metabolic dysregulation under simulated weightlessness.

Objective To investigate the protective effects of paeonol(PAE)on autophagy in human neuroblastoma cells(SH-SY5Y)induced by overexpression of α-synuclein(α-Syn),and to explore its related mechanism.Methods SH-SY5Y cells served as control group,while those induced with A53T-α-Syn mutation were used as model group.Additional groups included PAE(150 μg/ml)group,3-MA(1 mmol/L)group,and PAE(150 μg/ml)+3-MA(1 mmol/L)group.Cell viability was assessed using CCK-8 method,cell morphology was observed under an optical microscope,and protein expressions of α-Syn,LC3-Ⅱ,p62,Beclin-1,phosphorylated c-Jun N-terminal kinase(p-JNK),and p-Bcl-2 were determined by Western blotting.Results Compared with control group,model control exhibited decreased cell survival(P＜0.01),increased α-Syn expression(P＜0.001),reduced expression of autophagy-related proteins LC3-Ⅱ and Beclin-1(P＜0.01,P＜0.05),elevated autophagy substrate protein p62(P＜0.05),and decreased expression of autophagy pathway-related proteins p-JNK and Bcl-2(P＜0.05,P＜0.01).Compared with model group,PAE group showed increased cell survival(P＜0.01),decreased α-Syn and p62 protein expression(P＜0.01,P＜0.05),and increased expression of LC3-Ⅱ,Beclin-1,p-JNK and Bcl-2(P＜0.05).Compared with PAE group,3-MA+PAE group demonstrated increased α-Syn expression(P＜0.05).Conclusions PAE could attenuate the injury of SH-SY5Y cells induced by A53T-α-Syn and eliminate over-expressed α-Syn by activating autophagy pathway,which may be associated with the upregulation of JNK/Bcl-2 mediated autophagy pathway.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To compare the cumulative live birth rate (CLBR) per oocyte retrieval cycle between gonadotropin-releasing hormone agonist (GnRH-a) long protocol and GnRH antagonist (GnRH-A) protocol in overweight and obese women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Methods:A retrospective cohort study was conducted to analyze the clinical characteristics of overweight and obese patients who underwent IVF/ICSI at the Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University between January 2013 and December 2019. A total of 3 707 cycles were executed in overweight and obese patients who fulfilled the prescribed inclusion criteria, comprising 1 555 GnRH-a long protocol cycles and 2 152 GnRH-A protocol cycles. To mitigate confounding factors, post hoc randomization and propensity score matching (PSM) at a 1∶1 ratio were applied to match female age, anti-Müllerian hormone levels, and antral follicle count. The primary outcome observation indicator was the CLBR of the oocyte retrieval cycle. Analysis of subgroups of the population was conducted by the women's body mass index, age, and polycystic ovarian syndrome (PCOS) status.Results:After PSM, a total of 2 496 cycles were included comprising 1 248 GnRH-a long protocol cycles and 1 248 GnRH-A protocol cycles. GnRH-a long protocol had a higher CLBR [71.88% (897/1 248)] than that in GnRH-A protocol [62.98% (786/1 248), P<0.001]. No statistically significant difference was observed in the interval from gonadotropin initiation to live birth delivery day between the GnRH-a long protocol and GnRH-A protocol ( P>0.05). Subgroup analysis revealed that after PSM, the CLBR of GnRH-a long protocol in the patients with a body mass index of 25.0-29.9 kg/m 2 [71.36% (856/1 195)] and ≥30.0 kg/m 2 [77.36% (41/53)] were higher than those of the GnRH-A protocol patients [63.30% (759/1 199), P<0.001; 55.10% (27/49), P=0.017]. The CLBR of GnRH-a long protocol in women aged 20-34 [73.32% (805/1 098)] and ≥35 years [61.33% (92/150)] were higher than those of the GnRH-A protocol patients [67.18% (696/1 036), P=0.002; 42.45% (90/212), P<0.001]; among patients without PCOS, the CLBR with the GnRH-a long protocol [71.55% (850/1 188)] was significantly higher than that with GnRH-A protocol [60.95% (654/1 073), P<0.001]. However, in overweight and obese patients with PCOS, there was no statistically significant difference in CLBR between the two protocols ( P>0.05). The incidence of moderate-severe ovarian hyperstimulation syndrome (OHSS) was significantly lower in the overweight and obese population using GnRH-A protocol [0.64% (8/1 248)] compared with GnRH-a long protocol [1.76% (22/1 248), P=0.016]. Conclusion:For overweight and obese patients, GnRH-a long protocol demonstrates higher CLBR compared with GnRH-A protocol, indicating superior efficacy. For those with PCOS, both protocols show comparable CLBR, while the incidence of severe OHSS is lower in the GnRH-A.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.