ObjectiveTo clarify the anti-inflammatory and lung-protective effects of Yantiao prescription on lipopolysaccharide （LPS）-induced acute lung injury （ALI）， and to explore the impact of Yantiao prescription on the metabolic pathways of arachidonic acid （AA） in vivo. MethodsThirty male C57BL/6J mice were randomly divided into the following groups based on body weight： normal group， model group， dexamethasone group （2 mg·kg^-1）， low-dose Yantiao prescription group （18 g·kg^-1）， and high-dose Yantiao prescription group （36 g·kg^-1）， with 6 mice in each group. The ALI mouse model was established by intraperitoneal injection of LPS. The treatment groups received oral gavage once a day for 7 consecutive days， and serum and lung tissue were collected at the end of the experiment. The content of pro-inflammatory cytokines tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to assess lung tissue pathology. The wet/dry weight ratio （W/D） and myeloperoxidase （MPO） activity in lung tissue were measured. The content of AA metabolites in serum and lung tissue was measured by liquid chromatography triple quadrupole-mass spectrometry （LC-MS/MS）. ResultsCompared with the conditions in the normal group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the model group was significantly increased （P<0.01）. The alveolar structure in mice was severely damaged， with markedly thickened alveolar walls and extensive inflammatory cell infiltration. The W/D ratio and MPO activity in lung tissue were significantly increased （P<0.01）. The content of AA metabolites， including prostaglandin D₂ （PGD₂）， prostaglandin E₂ （PGE₂）， 11（S）-hydroxy-eicosatetraenoic acid ［11（S）-HETE］， and 5-hydroxy-eicosatetraenoic acid （5-HETE） in serum and lung tissue was significantly increased （P<0.05）， while the content of 11，12-epoxyeicosatrienoic acid （11，12-EET） and 14，15-epoxyeicosatrienoic acid （14，15-EET） in serum was significantly decreased （P<0.01）. Compared with the results in the model group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the dexamethasone group， low-dose Yantiao prescription group， and high-dose Yantiao prescription group was significantly reduced （P<0.05）. Mild thickening of alveolar walls， scattered inflammatory cell infiltration， and relatively intact tissue structure with improved alveolar architecture were observed. The W/D ratio and MPO activity in lung tissue were significantly reduced （P<0.01）. The content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum from the dexamethasone group was significantly decreased （P<0.05）， while the content of 14，15-EET in serum significantly increased （P<0.01）， and the content of 5-HETE in lung tissue significantly decreased （P<0.01）. In the low-dose and high-dose Yantiao prescription groups， the content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum and lung tissue was significantly decreased （P<0.05）， while the content of 11，12-EET in both serum and lung tissue was significantly increased （P<0.05）. ConclusionYantiao prescription has significant protective effects against LPS-induced ALI， which are related to its regulation of AA metabolic pathways in vivo.

Arginine methylation is a critical post-translational modification that plays multifaceted biological functions. However, the manipulation of protein arginine methylation largely depends on genetic or pharmaceutic inhibition of the regulatory enzymes, protein arginine methyltransferases (PRMTs), or non-methylation substitution of corresponding arginine residue to lysine or alanine of protein of interest (POI), which inevitably affects other substrates, or disrupts the structure of POI. Thus, it urges an approach to specifically modulate the arginine methylation of a POI under physiological conditions. To this end, we report the discovery of a methylation tagging system (MeTAG), that enables targeted modification of protein arginine methylation. Through bridging the methyltransferase PRMT5 proximity to a POI, MeTAG facilitates the arginine methylation of POIs, including known arginine methylated proteins, androgen receptor (AR) and protein kinase B (AKT), as well as a neo-substrate E1A binding protein (p300), in a reversible and PRMT5-dependent manner. Moreover, MeTAG can regulate downstream signaling in a methylation dependent manner, leading to downregulation of PSMA mRNA level and activation of AKT. Therefore, MeTAG represents a feasible approach to modulate protein methylation and thereby perturbs protein function in biological and therapeutic contexts.

Objective:A C57/BL6 mouse model of traumatic temporomandibular joint ankylosis (TTMJA) was established through composite trauma to lay the foundation for studying the pathophysiology of TTMJA.Methods:This study was conducted from January 2024 to February 2025. Forty-two 4-weeks old C57/BL6 mice, numbered 1 to 42, are randomly assigned to a control group ( n=21) and an experimental group ( n=21) using a computer-generated random number sequence. The experimental group undergoes modeling surgery on the left temporomandibular joint (TMJ), while the control group is routinely raised without special treatment. At 12 weeks post-surgery, the TMJ complex of both groups is assessed via body weight and mouth opening measurements, gross observation, micro-CT, and histological staining to evaluate model establishment. Results:At 12 weeks post-operation, in the experimental group, the body weight of mice [(27.75±1.08) g] did not show a significant difference compared with that of the control group [(30.80±0.29) g]( t=0.54, P=0.610). The maximum vertical passive mouth opening [(1.70±0.26) mm] in the experimental group was significantly lower than that in the control group [(3.43±0.21) mm]( t=8.92, P<0.001). Gross observation indicated that the right TMJ structure of the experimental-group mice was normal, while irregular hyperplasia occurred in the left TMJ complex. Micro-CT revealed that at 12 weeks post-operation, the right joint structure of the experimental-group mice was normal, with regular condyles and glenoid fossae. On the left side, a large amount of bone hyperplasia occurred on the lateral side of the joint in the condyles and glenoid fossae, forming two irregular bone masses, and there was an uncalcified radiolucent zone between the bone masses. In histological staining, no new cartilage or bone tissue was observed in the left joint space of the control-group mice, and the articular disc structure was normal. In the experimental-group mice, obvious new cartilage and calcified bone tissue were visible on the lateral side of the left joint space. A bone bridge was formed between the condyles and glenoid fossae, the articular disc structure disappeared, and bony ankylosis occurred. Conclusions:In this experiment, a TTMJA model of C57/BL6 mice was initially established by removing the articular disc and damaging part of the fibrous cartilage of the glenoid fossae and condyles, providing an experimental platform for further research on the pathogenesis of TTMJA.

Objective To explore the causal association between immune cells and allergic rhi-nitis using Mendelian randomization(MR)approach.Methods GWAS data for 731 types of im-mune cells and allergic rhinitis were obtained from genome-wide association study(GWAS)databas-es.A two-sample bidirectional MR analysis was conducted,with the inverse-variance weighted(IVW)method as the primary analytical approach,and the weighted median method,MR-Egger re-gression,simple mode method,and weighted mode method as supplementary approaches.Sensitivity analyses,including heterogeneity tests,pleiotropy tests,and the leave-one-out method,were per-formed.Bonferroni correction was applied to the preliminary results to enhance their reliability and rigor.Results The two-sample forward MR analysis revealed correlations between 67 immune cell phenotypes and allergic rhinitis.After Bonferroni correction,four immune cell phenotypes were finally identified.Among them,the expression of CD3 on CD39-positive activated CD4 regulatory T cells(OR=0.953,95％CI,0.931 to 0.978,P＜0.001,Padj=0.007),the expression of herpesvirus entry mediator(HVEM)on CD45RA-negative CD4+T cells(OR=0.965,95％CI,0.948 to 0.983,P＜0.001,Padj=0.008),and the percentage of human leukocyte antigen class DR(HLA-DR)-high-expressing monocytes among leukocytes(OR=0.929,95％CI,0.885 to 0.974,P=0.002,Padj=0.157)were protective factors for allergic rhinitis.In contrast,the percentage of transitional B cells among B cells(OR=1.094,95％CI,1.032 to 1.161,P=0.003,Padj=0.183)was a risk factor for allergic rhinitis.The reverse MR analysis showed no causal relationship between allergic rhinitis and the four immune cell phenotypes.Conclusion The two-sample forward MR analysis confirms a caus-al link between immune cells and allergic rhinitis.MR analysis has the advantages of reducing con-founding factor interference and avoiding reverse causation,providing a theoretical basis for in-depth research on immune mechanisms,sensitive biomarkers,and drug treatment targets of allergic rhinitis.

Objective:To investigate the effect of brinzolamide-timolol maleate eye drops on the metabolism of intravitreally injected vancomycin hydrochloride (VH) in rabbit eyes.Methods:Nine healthy male New Zealand white rabbits were selected.Among them, three were used to extract blank aqueous humor and the right eyes of the remaining six were set as experimental eyes.The experimental eye was topically administered 30 μl of brinzolamide-timolol maleate eye drops twice a day.The fellow eyes were set as control eyes.The intraocular pressure of both eyes was measured before the initial application of the eye drops and 1 hour after application of the eye drops next day.Both eyes of each rabbit were intravitreally injected with 0.5 mg of VH (10 mg/ml) solution.The aqueous humor was drawn at 2 hours and 1, 2, 4, 6, 8, 10 and 12 days after intravitreal injection.VH concentrations in aqueous humor were measured by high performance liquid chromatography.The time of peak concentrations ( tmax), peak concentration ( Cmax), elimination half-life ( t1/2) and the area under the concentration-time curve ( AUC) of VH in rabbit eyes were calculated by the average concentrations.This study was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECA-2023-01). Results:The intraocular pressure after eye drop was significantly lower than that before eye drop in experimental eyes ( P<0.01).The tmax of VH in experimental eyes and control eyes were both 1 day.The Cmax of VH in experimental eyes and control eyes were (61.40±13.48) and (51.56±5.07)μg/ml, respectively.The VH aqueous concentrations in the experimental eyes on days 4, 6 and 8 after injection were all significantly higher than those in the control eye ( t=2.378, 3.150, 2.694; all P<0.05).The t1/2 of VH in the aqueous humor of the experimental eyes was 2.69 days, which was 31% longer than 2.05 days of the control eyes.The AUC0-10 d of experimental eyes increased by 24.3% relative to the control eyes. Conclusions:Brinzolamide-timolol maleate eye drops can significantly extend the ocular residence time of intravitreally injected VH.

Objective:To compare the effects of brinzolamide-timolol (B&T) eye drops and dipivefrine hydrochloride (DH) eye drops on the intraocular metabolism of ranibizumab after intravitreal injection in rabbit.Methods:Eighteen New Zealand white rabbits were randomly and equally divided into DH group, B&T group, and control group.The right eye was selected as the experimental eye.The B&T and DH groups received DH and B&T eye drops, respectively, twice daily, 30 μl each time.The control group did not receive any treatment.Intraocular pressure (IOP) was measured in both eyes before the first administration and 1 hour after the first administration on the second day.After IOP measurement, the experimental eye received an intravitreal injection of 0.25 mg ranibizumab (10 mg/ml).Aqueous humor samples were collected 1, 3, 7, 10, 14, 21 and 28 days after injection.Ranibizumab concentration in the aqueous humor was measured by ELISA kit.Pharmacokinetic parameters including time to peak concentration ( tmax), peak concentration ( Cmax), elimination half-life ( t1/2) and area under the concentration-time curve (AUC) of ranibizumab were calculated.This experiment was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECA-2023-03). Results:The tmax of ranibizumab in the aqueous humor was 1 day in all three groups.The Cmax values in the control, B&T and DH groups were (8.122±2.445), (13.079±3.140) and (8.299±0.899)μg/ml, respectively.Except for day 3 in the control group, the ranibizumab concentrations in aqueous humor of the B&T group were higher than that of the DH group and the control group at all time points after injection, with statistically significant significances (all P<0.05).The t1/2 of ranibizumab in aqueous humor in the control group, B&T group, and DH group were (2.90±0.29), (3.36±0.35) and (2.80±0.29) days, respectively, and the AUC0-t values were (52.697±10.178), (80.244±11.249) and (51.985±8.734)μg/ml·d, respectively.The t1/2 and AUC0-t of ranibizumab in aqueous humor of the B&T group were significantly higher than those of the DH group and the control group, and the differences were statistically significant (all P<0.05).The mean bioavailability in the B&T group was increased by 52.3% compared to the control group. Conclusions:B&T eye drops prolong the half-life and enhance the intraocular bioavailability of ranibizumab after intravitreal injection in rabbits, whereas DH has no significant effect on its intraocular metabolism.

In recent years, the third medical education reform characterized by competency-based medical education (CBME) is being carried out around the world; however, there are still challenges in bridging competency framework with clinical practice during implementation. With reference to the three-step method for constructing a CBME curriculum system based on entrustable professional activities (EPAs) and related policies and studies in China in recent years, this article constructs a framework of EPAs with the features of orthopedics by detailing the EPAs of specified clinical operation. On this basis, this article proposes a competency-oriented standardized training system for orthopedic residents, with the help of teaching evaluation methods to ensure the successful implementation of courses, so as to provide a reference for establishing a training system for surgery based on EPAs.

Objective:To investigate the effect of brinzolamide-timolol maleate eye drops on the metabolism of intravitreally injected vancomycin hydrochloride (VH) in rabbit eyes.Methods:Nine healthy male New Zealand white rabbits were selected.Among them, three were used to extract blank aqueous humor and the right eyes of the remaining six were set as experimental eyes.The experimental eye was topically administered 30 μl of brinzolamide-timolol maleate eye drops twice a day.The fellow eyes were set as control eyes.The intraocular pressure of both eyes was measured before the initial application of the eye drops and 1 hour after application of the eye drops next day.Both eyes of each rabbit were intravitreally injected with 0.5 mg of VH (10 mg/ml) solution.The aqueous humor was drawn at 2 hours and 1, 2, 4, 6, 8, 10 and 12 days after intravitreal injection.VH concentrations in aqueous humor were measured by high performance liquid chromatography.The time of peak concentrations ( tmax), peak concentration ( Cmax), elimination half-life ( t1/2) and the area under the concentration-time curve ( AUC) of VH in rabbit eyes were calculated by the average concentrations.This study was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECA-2023-01). Results:The intraocular pressure after eye drop was significantly lower than that before eye drop in experimental eyes ( P<0.01).The tmax of VH in experimental eyes and control eyes were both 1 day.The Cmax of VH in experimental eyes and control eyes were (61.40±13.48) and (51.56±5.07)μg/ml, respectively.The VH aqueous concentrations in the experimental eyes on days 4, 6 and 8 after injection were all significantly higher than those in the control eye ( t=2.378, 3.150, 2.694; all P<0.05).The t1/2 of VH in the aqueous humor of the experimental eyes was 2.69 days, which was 31% longer than 2.05 days of the control eyes.The AUC0-10 d of experimental eyes increased by 24.3% relative to the control eyes. Conclusions:Brinzolamide-timolol maleate eye drops can significantly extend the ocular residence time of intravitreally injected VH.

Objective:To compare the effects of brinzolamide-timolol (B&T) eye drops and dipivefrine hydrochloride (DH) eye drops on the intraocular metabolism of ranibizumab after intravitreal injection in rabbit.Methods:Eighteen New Zealand white rabbits were randomly and equally divided into DH group, B&T group, and control group.The right eye was selected as the experimental eye.The B&T and DH groups received DH and B&T eye drops, respectively, twice daily, 30 μl each time.The control group did not receive any treatment.Intraocular pressure (IOP) was measured in both eyes before the first administration and 1 hour after the first administration on the second day.After IOP measurement, the experimental eye received an intravitreal injection of 0.25 mg ranibizumab (10 mg/ml).Aqueous humor samples were collected 1, 3, 7, 10, 14, 21 and 28 days after injection.Ranibizumab concentration in the aqueous humor was measured by ELISA kit.Pharmacokinetic parameters including time to peak concentration ( tmax), peak concentration ( Cmax), elimination half-life ( t1/2) and area under the concentration-time curve (AUC) of ranibizumab were calculated.This experiment was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECA-2023-03). Results:The tmax of ranibizumab in the aqueous humor was 1 day in all three groups.The Cmax values in the control, B&T and DH groups were (8.122±2.445), (13.079±3.140) and (8.299±0.899)μg/ml, respectively.Except for day 3 in the control group, the ranibizumab concentrations in aqueous humor of the B&T group were higher than that of the DH group and the control group at all time points after injection, with statistically significant significances (all P<0.05).The t1/2 of ranibizumab in aqueous humor in the control group, B&T group, and DH group were (2.90±0.29), (3.36±0.35) and (2.80±0.29) days, respectively, and the AUC0-t values were (52.697±10.178), (80.244±11.249) and (51.985±8.734)μg/ml·d, respectively.The t1/2 and AUC0-t of ranibizumab in aqueous humor of the B&T group were significantly higher than those of the DH group and the control group, and the differences were statistically significant (all P<0.05).The mean bioavailability in the B&T group was increased by 52.3% compared to the control group. Conclusions:B&T eye drops prolong the half-life and enhance the intraocular bioavailability of ranibizumab after intravitreal injection in rabbits, whereas DH has no significant effect on its intraocular metabolism.

Objective:A C57/BL6 mouse model of traumatic temporomandibular joint ankylosis (TTMJA) was established through composite trauma to lay the foundation for studying the pathophysiology of TTMJA.Methods:This study was conducted from January 2024 to February 2025. Forty-two 4-weeks old C57/BL6 mice, numbered 1 to 42, are randomly assigned to a control group ( n=21) and an experimental group ( n=21) using a computer-generated random number sequence. The experimental group undergoes modeling surgery on the left temporomandibular joint (TMJ), while the control group is routinely raised without special treatment. At 12 weeks post-surgery, the TMJ complex of both groups is assessed via body weight and mouth opening measurements, gross observation, micro-CT, and histological staining to evaluate model establishment. Results:At 12 weeks post-operation, in the experimental group, the body weight of mice [(27.75±1.08) g] did not show a significant difference compared with that of the control group [(30.80±0.29) g]( t=0.54, P=0.610). The maximum vertical passive mouth opening [(1.70±0.26) mm] in the experimental group was significantly lower than that in the control group [(3.43±0.21) mm]( t=8.92, P<0.001). Gross observation indicated that the right TMJ structure of the experimental-group mice was normal, while irregular hyperplasia occurred in the left TMJ complex. Micro-CT revealed that at 12 weeks post-operation, the right joint structure of the experimental-group mice was normal, with regular condyles and glenoid fossae. On the left side, a large amount of bone hyperplasia occurred on the lateral side of the joint in the condyles and glenoid fossae, forming two irregular bone masses, and there was an uncalcified radiolucent zone between the bone masses. In histological staining, no new cartilage or bone tissue was observed in the left joint space of the control-group mice, and the articular disc structure was normal. In the experimental-group mice, obvious new cartilage and calcified bone tissue were visible on the lateral side of the left joint space. A bone bridge was formed between the condyles and glenoid fossae, the articular disc structure disappeared, and bony ankylosis occurred. Conclusions:In this experiment, a TTMJA model of C57/BL6 mice was initially established by removing the articular disc and damaging part of the fibrous cartilage of the glenoid fossae and condyles, providing an experimental platform for further research on the pathogenesis of TTMJA.