AIM:Study on the bioequivalence of rivaroxaban tablets from two different manufactur-ers in healthy subjects under fasting and postpran-dial conditions.METHODS:Adopting a single cen-ter,randomized,open,fasting and postprandial,four cycle,fully repeated crossover trial design.28 healthy male and female subjects were given oral administration of either the test or reference for-mulation(10 mg)on an empty stomach or in a post-prandial state,with a cleaning period of 7 days be-tween cycles.The concentration of rivaroxaban in the plasma(heparin sodium)of the subjects was measured using liquid chromatography tandem mass spectrometry(LC-MS/MS),and pharmacoki-netic(PK)parameters were calculated using Phoe-nix WinNonlin 7.0 software to evaluate the bio-equivalence of the test and reference formulations.RESULTS:Fasting group:After oral administration of the investigational drug,the Cmax of the test formula-tion and reference formulation were(200.96±68.99)ng/mL and(196.96±50.97)ng/mL,respec-tively,and the AUC0-t were(1 439.93±493.94)h·ng·mL-1 and(1 395.90±411.49)h·ng·mL-1,respectively,the AUC0-∞ were(1 506.56±511.47)h·ng·mL-1 and(1 451.94±417.89)h·ng·mL-1,respectively,the 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ were 91.87％-103.37％,95.00％-105.07％,95.33％-105.57％,respectively,the 90％CI of the intra-individual standard devia-tion ratio(SWT/SWR)for Cmax,AUC0-t,AUC0-∞were 0.88-1.73,0.74-1.45 and 0.72-1.41,respectively.Post-prandial group:After oral administration of the ex-perimental drug,the Cmax of the test and reference formulations were(241.23±54.44)ng/mL and(226.54±48.04)ng/mL,respectively,and the AUC0-t were(1 383.26±437.05)h·ng·mL-1 and(1 333.54±372.53)h·ng·mL-1,respectively,the AUC0-∞ were(1 404.01±439.89)h·ng·mL-1 and(1 352.31±374.45)h·ng·mL-1,respectively,the 90％confi-dence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ were 100.92％-110.50％,98.30％-108.31％,and 98.46％-108.39％,respective-ly,the 90％CI of the intra-individual standard devia-tion ratio(SWT/SWR)for Cmax,AUC0-t and AUC0-∞ were 0.63-1.29,0.78-1.61 and 0.79-1.61,respectively.CONCLUSION:Bioequivalence of the two prepara-tions in fasting and postprandial state in healthy subjects.

BACKGROUND:Research has shown that vanillic acid has anti-inflammatory and anti-oxidative stress effects,but it is unclear whether it has a protective effect on endplate chondrocytes.OBJECTIVE:To explore the effect and mechanism of vanillic acid on endplate chondrocytes under inflammatory microenvironment.METHODS:(1)Primary endplate chondrocytes were isolated from the intervertebral disc of SD rats and identified by toluidine blue staining and collagenⅡ immunofluorescence.(2)The CCK-8 assay was employed to detect the effects of interleukin-1β and vanillic acid on the proliferation activity of endplate chondrocytes,in order to determine the concentration of vanillic acid for subsequent cell treatment.(3)An inflammatory microenvironment was simulated by adding 10 ng/mL interleukin-1β to the culture medium,and the endplate chondrocytes were treated with low,medium,and high mass concentrations of vanillic acid.The expression levels of inflammatory markers and extracellular matrix proteins were detected by western blot assay and immunofluorescence.(4)The expression of nuclear factor κB signaling pathway-related proteins was detected by western blot assay.RESULTS AND CONCLUSION:(1)The morphology of endplate chondrocytes in adherent culture was pike or triangular in shape,positive for toluidine blue staining and immunofluorescence for collagen Ⅱ,indicating that the experimentally extracted cells were endplate chondrocytes.(2)The CCK-8 assay results showed that treatment with 2.5,5,10,and 20 μg/mL vanillic acid for 24 hours did not significantly inhibit the proliferation of endplate chondrocytes.Compared with the interleukin-1β group,the viability of endplate chondrocytes treated with 5,10,and 20 μg/mL vanillic acid for 24 hours was significantly increased(P＜0.05).Therefore,5,10,and 20 μg/mL vanillic acid was selected as the low,medium,and high dose groups for subsequent treatment of endplate chondrocytes.(3)Compared with the model group(complete medium containing 10 ng/mL interleukin-1β),the expression of NOD-like receptor thermal domain associated protein 3(NLRP3),matrix metalloproteinase 13,matrix metalloproteinase 3,and tumor necrosis factor alpha protein in the endplate chondrocytes of the low,medium,and high doses of vanillic acid groups were significantly reduced(P＜0.05).(4)Compared with the model group,the protein expression of aggrecan and collagen Ⅱ in the endplate chondrocytes of the low,medium,and high dose groups of vanillic acid significantly increased(P＜0.05).(5)Compared with the model group,the protein expression of phospho-nuclear factor κB and phospho-inhibitor of nuclear factor κB in the endplate chondrocytes of the low,medium,and high dose groups of vanillic acid was significantly reduced(P＜0.05).(6)The above results indicate that vanillic acid may alleviate the inflammatory response and extracellular matrix degradation induced by interleukin-1β in rat endplate chondrocytes by inhibiting the activation of the nuclear factor κB signaling pathway.

Objective To investigate the expression of forkhead box P3(Foxp3)in peripheral blood of children with bronchial asthma and its relationship with airway hyper-responsiveness and body allergy.Methods A total of 80 children with bronchial asthma treated in the Affiliated Hospital of Yangzhou University from July 2024 to June 2025 were selected as experimental group,and 47 health-y children with physical examinations in the same period were selected as control group.Airway hy-per-responsiveness indicators(respiratory resistance,bronchial stimulant reaction threshold,and re-sistance increase slope),body allergy indicators[serum immunoglobulin E(IgE),eosinophil cationic protein(ECP),and eosinophil count(EOS)],pulmonary function indicators[peak expiratory flow(PEF),forced expiratory volume in the first second(FEV,),forced vital capacity(FVC),and the ratio of forced expiratory volume in the first second to forced vital capacity(FEV1/FVC)],and the expression level of Foxp3 in peripheral blood were compared between the two groups.Pearson corre-lation analysis was used to explore the correlations of Foxp3 with airway hyper-responsiveness and body allergy.Results The respiratory resistance and resistance increase slope in the control group were significantly lower than those in the experimental group,while the reaction threshold was signif-icantly higher than that in the experimental group(P＜0.05).The levels of IgE,ECP and EOS in the experimental group were significantly higher than those in the control group(P＜0.05).The FEV1,FVC,PEF,and FEV1/FVC in the experimental group were significantly lower than those in the control group(P＜0.05).The expression level of Foxp3 in the experimental group was(3.04±0.22),which was significantly lower than(4.22±0.41)in the control group(P＜0.05).Foxp3 was significantly correlated with respiratory resistance(r=-0.700,P＜0.001),reaction thresh-old(r=0.704,P＜0.001),resistance increase slope(r=-0.842,P＜0.001),IgE(r=0.864,P＜0.001),ECP(r=-0.684,P＜0.001),and EOS(r=-0.854,P＜0.001).Con-clusion The decreased Foxp3 in peripheral blood in children with bronchial asthma is associated with aggravated airway hyper-responsiveness and body allergy,suggesting that Foxp3 may be in-volved in the pathogenesis of bronchial asthma.

A scientific and efficient comprehensive operation system for the transformation of clinical research achievements is an important guarantee to fully release the capability of public hospitals of the achievement transformation. A public hospital, focusing on the bottleneck problems faced in the process of transforming scientific and technological achievements, began to explore the construction of a comprehensive operation system for the transformation of clinical research achievements and implemented it throughout the hospital from October 2023. By improving the organizational structure and setting up full-time management positions; formulating supporting policies and perfecting the incentive mechanism; drawing a systematic portrait and creating a standard pathway; expanding the transformation platform and promoting coordinated development; innovating management services and strengthening digital empowerment; and highlighting publicity and education to enhance the capability of transformation, the hospital has effectively promoted the transformation of clinical research achievements. This practice can provide a reference for other hospitals to improve the management of clinical research achievements transformation and promote high-quality hospital development.

BACKGROUND:Research has shown that vanillic acid has anti-inflammatory and anti-oxidative stress effects,but it is unclear whether it has a protective effect on endplate chondrocytes.OBJECTIVE:To explore the effect and mechanism of vanillic acid on endplate chondrocytes under inflammatory microenvironment.METHODS:(1)Primary endplate chondrocytes were isolated from the intervertebral disc of SD rats and identified by toluidine blue staining and collagenⅡ immunofluorescence.(2)The CCK-8 assay was employed to detect the effects of interleukin-1β and vanillic acid on the proliferation activity of endplate chondrocytes,in order to determine the concentration of vanillic acid for subsequent cell treatment.(3)An inflammatory microenvironment was simulated by adding 10 ng/mL interleukin-1β to the culture medium,and the endplate chondrocytes were treated with low,medium,and high mass concentrations of vanillic acid.The expression levels of inflammatory markers and extracellular matrix proteins were detected by western blot assay and immunofluorescence.(4)The expression of nuclear factor κB signaling pathway-related proteins was detected by western blot assay.RESULTS AND CONCLUSION:(1)The morphology of endplate chondrocytes in adherent culture was pike or triangular in shape,positive for toluidine blue staining and immunofluorescence for collagen Ⅱ,indicating that the experimentally extracted cells were endplate chondrocytes.(2)The CCK-8 assay results showed that treatment with 2.5,5,10,and 20 μg/mL vanillic acid for 24 hours did not significantly inhibit the proliferation of endplate chondrocytes.Compared with the interleukin-1β group,the viability of endplate chondrocytes treated with 5,10,and 20 μg/mL vanillic acid for 24 hours was significantly increased(P＜0.05).Therefore,5,10,and 20 μg/mL vanillic acid was selected as the low,medium,and high dose groups for subsequent treatment of endplate chondrocytes.(3)Compared with the model group(complete medium containing 10 ng/mL interleukin-1β),the expression of NOD-like receptor thermal domain associated protein 3(NLRP3),matrix metalloproteinase 13,matrix metalloproteinase 3,and tumor necrosis factor alpha protein in the endplate chondrocytes of the low,medium,and high doses of vanillic acid groups were significantly reduced(P＜0.05).(4)Compared with the model group,the protein expression of aggrecan and collagen Ⅱ in the endplate chondrocytes of the low,medium,and high dose groups of vanillic acid significantly increased(P＜0.05).(5)Compared with the model group,the protein expression of phospho-nuclear factor κB and phospho-inhibitor of nuclear factor κB in the endplate chondrocytes of the low,medium,and high dose groups of vanillic acid was significantly reduced(P＜0.05).(6)The above results indicate that vanillic acid may alleviate the inflammatory response and extracellular matrix degradation induced by interleukin-1β in rat endplate chondrocytes by inhibiting the activation of the nuclear factor κB signaling pathway.

AIM:Study on the bioequivalence of rivaroxaban tablets from two different manufactur-ers in healthy subjects under fasting and postpran-dial conditions.METHODS:Adopting a single cen-ter,randomized,open,fasting and postprandial,four cycle,fully repeated crossover trial design.28 healthy male and female subjects were given oral administration of either the test or reference for-mulation(10 mg)on an empty stomach or in a post-prandial state,with a cleaning period of 7 days be-tween cycles.The concentration of rivaroxaban in the plasma(heparin sodium)of the subjects was measured using liquid chromatography tandem mass spectrometry(LC-MS/MS),and pharmacoki-netic(PK)parameters were calculated using Phoe-nix WinNonlin 7.0 software to evaluate the bio-equivalence of the test and reference formulations.RESULTS:Fasting group:After oral administration of the investigational drug,the Cmax of the test formula-tion and reference formulation were(200.96±68.99)ng/mL and(196.96±50.97)ng/mL,respec-tively,and the AUC0-t were(1 439.93±493.94)h·ng·mL-1 and(1 395.90±411.49)h·ng·mL-1,respectively,the AUC0-∞ were(1 506.56±511.47)h·ng·mL-1 and(1 451.94±417.89)h·ng·mL-1,respectively,the 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ were 91.87％-103.37％,95.00％-105.07％,95.33％-105.57％,respectively,the 90％CI of the intra-individual standard devia-tion ratio(SWT/SWR)for Cmax,AUC0-t,AUC0-∞were 0.88-1.73,0.74-1.45 and 0.72-1.41,respectively.Post-prandial group:After oral administration of the ex-perimental drug,the Cmax of the test and reference formulations were(241.23±54.44)ng/mL and(226.54±48.04)ng/mL,respectively,and the AUC0-t were(1 383.26±437.05)h·ng·mL-1 and(1 333.54±372.53)h·ng·mL-1,respectively,the AUC0-∞ were(1 404.01±439.89)h·ng·mL-1 and(1 352.31±374.45)h·ng·mL-1,respectively,the 90％confi-dence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ were 100.92％-110.50％,98.30％-108.31％,and 98.46％-108.39％,respective-ly,the 90％CI of the intra-individual standard devia-tion ratio(SWT/SWR)for Cmax,AUC0-t and AUC0-∞ were 0.63-1.29,0.78-1.61 and 0.79-1.61,respectively.CONCLUSION:Bioequivalence of the two prepara-tions in fasting and postprandial state in healthy subjects.

A scientific and efficient comprehensive operation system for the transformation of clinical research achievements is an important guarantee to fully release the capability of public hospitals of the achievement transformation. A public hospital, focusing on the bottleneck problems faced in the process of transforming scientific and technological achievements, began to explore the construction of a comprehensive operation system for the transformation of clinical research achievements and implemented it throughout the hospital from October 2023. By improving the organizational structure and setting up full-time management positions; formulating supporting policies and perfecting the incentive mechanism; drawing a systematic portrait and creating a standard pathway; expanding the transformation platform and promoting coordinated development; innovating management services and strengthening digital empowerment; and highlighting publicity and education to enhance the capability of transformation, the hospital has effectively promoted the transformation of clinical research achievements. This practice can provide a reference for other hospitals to improve the management of clinical research achievements transformation and promote high-quality hospital development.

AIM: To investigate the relationship between objective ocular torsion and near stereopsis in patients with primary superior oblique overaction(PSOOA).METHODS: Retrospective study. A total of 59 strabismus patients with PSOOA who underwent strabismus surgery at Renmin Hospital of Wuhan University between January 2019 and November 2023 were collected. Based on the collected fundus photographs and the position of the fovea relative to the horizontal line through the optic disc, the eyes were categorized as incyclotorsion, excyclotorsion, or no cyclotorsion. Additionally, the fovea-disc angle(FDA)and the relationship between objective ocular torsion status, FDA, and near stereopsis function in the patients were further measured and analyzed.RESULTS: Totally 59 patients(92 eyes)showed superior oblique overaction. There were no cases of excyclotorsion, 32 cases with no cyclotorsion, and 27 cases with incyclotorsion. The total binocular FDA was significantly smaller in the no-cyclotorsion group compared with the incyclotorsion group(2.83°±2.89° vs 16.12°±5.74°, P<0.001). The preservation rates of near stereopsis were 66% and 15% in the no-cyclotorsion and incyclotorsion groups, respectively, with a significant statistical difference(P<0.001), and the preservation rates of fine near stereopsis were 38% and 11% in the no-cyclotorsion and incyclotorsion groups, respectively, with a significant statistical difference(P=0.02). Among all patients, near stereopsis was correlated with total binocular FDA(r=-0.526, P<0.001), with the strongest correlation observed with the FDA of the incyclotorsion(r=-0.546, P<0.001). In the incyclotorsion group, there was no correlation between near stereopsis and total binocular FDA(r=-0.366, P=0.060), with a negative correlation between near stereopsis and the FDA of both the incyclotorsion and the overaction(r=-0.424, P=0.028; r=-0.485, P=0.010). In the no-cyclotorsion group, near stereopsis was not correlated with total binocular FDA, incyclotorsion FDA, or overaction FDA.CONCLUSION:PSOOA patients with incyclotorsion have a lower preservation rate of near stereopsis than those without cyclotorsion. Near stereopsis function of patients with PSOOA is negatively correlated with total binocular FDA, especially the greater the FDA of the incyclotorsion and overaction, the worse the near-stereoscopic function.

BACKGROUND:Total knee arthroplasty is an effective treatment for late-stage osteoarthritis,but postoperative pain and joint function recovery are the main challenges.Nerve block and mixed drug injection are two common pain relief methods,but the effect of their combined use is still unclear. OBJECTIVE:To investigate the effects of ultrasound-guided continuous adductor canal block+single sciatic nerve block+"cocktail"mixed drug analgesia on postoperative pain relief and joint function recovery in total knee arthroplasty. METHODS:120 patients with osteoarthritis admitted to Hebei Province Cangzhou Hospital of Integrated Traditional and Western Medicine from January to May 2022 were randomly divided into two groups(n=60).The observation group received ultrasound-guided continuous adductor canal block+single sciatic nerve block+"cocktail"mixed drug analgesia.The control group received ultrasound-guided continuous adductor canal block+single sciatic nerve block.The differences in visual analog scale score,hospital for special surgery score,pain mediators,expression levels of inflammatory factors,the occurrence of adverse reactions,and postoperative barehanded muscle strength test were compared between the two groups. RESULTS AND CONCLUSION:(1)The visual analog scale scores at rest and exercise were lower in the observation group than those in the control group at 6,8,12,24,48,and 72 hours postoperatively(P<0.05).(2)Hospital for special surgery scores at 1 and 3 months postoperatively were significantly higher in the observation group than those in the control group(P<0.05).(3)In terms of pain mediators and inflammatory factors,the expression levels were significantly lower in the observation group than those in the control group(P<0.05).(4)There was no statistically significant difference in terms of adverse effects and postoperative barehanded muscle strength examination between the two groups(P>0.05).(5)In total knee arthroplasty,ultrasound-guided continuous adductor canal block and single sciatic nerve block,together with a"cocktail"mixed drug analgesia injected into the joint cavity,can provide excellent analgesia,facilitate the recovery of joint function,and relieve postoperative pain and inflammation with a high degree of safety.

Objective:To explore the feasibility and effect of remote medical education model using online film reading training to improve the ability of ophthalmologists in the Xinjiang Uygur Autonomous Region (hereinafter referred to as "Xinjiang Region" ) in diagnosing fundus diseases.Methods:The three-level film reading training system of Xinjiang Production and Construction Corps system division hospital-Corps Hospital-Peking Union Medical College Hospital was established. From June 2022 to January 2023, 4 159 posterior color fundus images were continuously collected from Department of Ophthalmology of Xinjiang Corps Hospital and 4 divisional hospitals in the Corps medical system. Among them, hypertensive retinopathy, diabetic retinopathy, exudative age-related macular degeneration (AMD), atrophic AMD and retinal vein occlusion were 3 073, 651, 43, 186 and 206 cases, respectively. The images were divided into 3 rounds (first, second and last) according to the proportion of diseases. The doctors who participated in the training (hereinafter referred to as the "training") were 15 ophthalmologists from the Corps Hospital of Xinjiang Region and the division hospital of the Corps system. There were 7 male and 8 female. Age was (38.1±4.0) years. The titles of senior, deputy senior, intermediate and junior are 1, 6, 5 and 3 respectively; Bachelor's degree and master's degree are 13 and 2 respectively. The working time of fundus disease specialty was (9.6±3.3) years. The film reading system training was conducted before the first round of labeling, and after each round of film reading, the doctors of Peking Union Medical College Hospital gave feedback and explanation on the film reading results. The diagnostic consistency, sensitivity and specificity were compared by paired sample t test. Spearman or Pearson correlation analysis was conducted between the improvement of diagnostic level and professional title, education, age and working hours of ocular fundus disease. Results:All the participating doctors completed the first, second and last reading. After each round of film reading, the film reading summary was carried out for 2 hours. The average diagnostic agreement rates of participating physicians were 53.0%, 67.0% and 75.0%, respectively. The sensitivity and specificity were 0.38, 0.69, 054 and 0.66, 0.85, 0.96, respectively. There was significant difference between the first and last examination ( P<0.001). The sensitivity of the second reading was significantly higher than that of the first reading, and the sensitivity of the last reading was significantly lower than that of the second reading, with statistical significance ( P<0.05). The specificity of the second reading was significantly higher than that of the first reading, and the last reading was significantly higher than that of the second reading, with statistical significance ( P<0.05). There was no significant correlation ( P>0.05) between the improvement of diagnostic level of participating physicians and educational background ( Rho=0.07), professional title ( Rho=0.13), age ( r=0.20), and working time of ophthalmofundus disease specialty ( r=0.26). Conclusions:Relying on the three-level online telemedicine training, it can improve the ability of ophthalmologists in Xinjiang region to diagnose fundus diseases. The preliminary telemedicine education model has demonstrated potential for feasibility and effectiveness in remote areas with inadequate medical resources.