ObjectiveTo investigate how vitamin B₁₂ eye drops regulate MMP-9 and TNF-α expression levels in the corneas of dry eye disease （DED） mouse model induced by a combination of an artificially simulated dry environment （air humidity 30%） and subcutaneous injection of hyoscine hydrobromide. MethodsFifty C57BL/6 female mice were used in the study. 10 mice formed A group （blank control）， while the remaining 40 mice were subjected to dry eye disease induction through subcutaneous injection of scopolamine hydrobromide in a controlled environment with 30% air humidity. All mice underwent schirmer I test （SIT）， tear break-up time （TBUT）， and corneal fluorescence staining score（CFS）evaluations. Mice meeting modeling criteria were randomly assigned to three groups： B group （model group）， C group （PBS control）， and D group （vitamin B₁₂ group）. 0， 7， 14， and 21 days after treatment， each group received TBUT， SIT， CFS， and corneal inflammation assessments. Macroscopic analysis evaluated the efficacy of vitamin B₁₂ eye drops in treating dry eye. After 21 days of treatment， all mice were euthanized via cervical dislocation and their corneas analyzed using HE staining to examine morphological changes. ELISA and immunohistochemical methods were employed to detect MMP-9 and TNF-α expression levels in corneal tissues across groups. ResultsIn dry environments （air humidity 30%）， subcutaneous injection of scopolamine hydrobromide induced changes in dry eye-related indicators in mice： SIT significantly decreased， TBUT significantly shortened， corneal fluorescein staining increased， and CFS all significantly elevated （P 0.05）， indicating successful establishment of the dry eye model. A total of 30 dry eye mice were enrolled. When the dry eye model was successfully established without drug intervention， no statistically significant differences were observed between B group， C group and D group in terms of TBUT， SIT， corneal fluorescein staining， or CFS. Compared with A group， B group， C group and D group showed statistically significant differences in reduced SIT， shortened TBUT， increased corneal fluorescein staining， and elevated CFS （P 0.05）. After drug intervention， D group （vitamin B₁₂ group） exhibited significantly increased SIT， prolonged TBUT， reduced corneal fluorescein staining， clearer corneas， decreased fluorescein staining， and lower CFS compared with B and C groups（P 0.05）. ELISA and immunohistochemical staining results showed that compared with A group， B and C groups exhibited significantly increased expression of MMP-9 and TNF-α in corneal tissues （P 0.05）. D group showed decreased expression of MMP-9 and TNF-α compared with B and C groups but remained higher than A group （P 0.05）. ConclusionThe expression of MMP-9 and TNF-α in the corneal tissues of mice with dry eye is elevated， suggesting that both inflammatory factors， MMP-9 and TNF-α， are involved in the development of dry eye. Vitamin B₁₂ eye drops may improve the symptoms of ocular surface discomfort by promoting the repair of the corneal epithelium. Vitamin B₁₂ eye drops may increase tear secretion， prolong tear film break up time， reduce corneal fluorescein staining， and alleviate the inflammatory reaction of the cornea by decreasing the expression of MMP-9 and TNF-α in the corneal tissues of the mice， thus playing a therapeutic role in the treatment of dry eye disease.

Objective:To analyze the interference of an exogenous glucose test on urinary creatinine-related renal injury biomarkers in patients with chronic kidney disease (CKD).Methods:This cross-sectional study enrolled CKD patients who visited Peking University First Hospital between October 2023 and March 2024. The patients (age: 50±18 years) included 90 males and 70 females. Fresh morning urine samples were collected, totaling 160 samples. Each urine sample was divided into 5 aliquots,each containing 225 μl. One aliquot received 75 μl of deionized water as the control. The other aliquots received 75 μl of glucose solutions at concentrations of 120, 480, 960, and 1200 mmol/L, resulting in final glucose concentrations of 30, 120, 240, and 300 mmol/L in the urine samples, respectively. Urinary creatinine in each sample was measured using both the enzymatic method and the picric acid (Jaffe) method. The following ratios were calculated: urinary albumin-to-creatinine ratio (uACR), urinary protein-to-creatinine ratio (uPCR), urinary transferrin-to-creatinine ratio (uTRF/uCr), urinary α1-microglobulin-to-creatinine ratio (uA1M/uCr), urinary immunoglobulin G-to-creatinine ratio (uIgG/uCr), and urinary N-acetyl-β-D-glucosaminidase-to-creatinine ratio (uNAG/uCr).Results:Under high glucose concentrations, significant differences ( P<0.05) were observed between the enzymatic method and the picric acid method in measuring urinary creatinine-related renal injury biomarkers. At glucose concentrations of 30, 120, 240, and 300 mmol/L, the mean percentage biases for creatinine measured by the enzymatic method were -0.19%, -0.27%, -0.20%, and -0.21%, respectively. The mean percentage biases for creatinine measured by the picric acid method were 0.78%, 1.26%, 1.35%, and 1.38%, respectively, showing an increasing deviation between the results before and after glucose addition as the glucose concentration rose. For uACR measurement, the mean absolute biases using the enzymatic method were -0.01, 1.27, 0.95, and 1.10 mg/g at the respective glucose concentrations. Using the picric acid method, the mean absolute biases for uACR were -11.69, -14.98, -16.91, and-18.51 mg/g. The biases of the picric acid method were significantly higher than the those of the enzymatic method, and the absolute value of the mean biases increased with rising glucose concentration. For uPCR, uTRF/uCr, uA1M/uCr, uNAG/uCr, and uIgG/uCr, the deviations measured by the enzymatic method were consistently smaller than those measured by the picric acid method. Conclusions:The measurement of creatinine and related renal injury biomarkers by the enzymatic method is less affected by glucose concentration. In contrast, the measurement results obtained using the picric acid method are significantly affected by glucose concentration.

Objective:To investigate the value of ultra micro angiography（UMA）imaging in evaluating the inflammation activity of pediatric Crohn's disease（CD）patients.Methods:In this prospective study，71 pediatric CD patients confirmed by clinical symptoms，laboratory and ileocolonoscopical results who planed to accept infliximab injection treatments in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from April to December 2024 were included. The CD patients were included and divided into 3 groups according to the pediatric Crohn's disease activity index（PCDAI）score：inactive CD group（ n=44），mild CD group（ n=17），and moderate-to-severe CD group（ n=10）. Before treatment，pediatric CD patients underwent B mode ultrasound（BMUS），the parameters such as bowel wall thickness（BWT），bowel wall stratification，mesenteric lymph nodes（MLNs），and existence of mesenteric fat hypertrophy（MFH）were recorded. Color Doppler flow imaging（CDFI）and UMA were used to evaluate the blood flow in the most thickened diseased bowel wall using Limberg scores. The diffierences of the above parameters among the 3 groups were compared. The diagnostic performance of UMA and CDFI in assessing the inflammatory activity of pediatric CD was evaluated. Results:There were statistically significant differences in BWT among the 3 groups（all P<0.05）. However，there were no statistically significant differences in MLNs among the 3 groups（all P>0.05）. Compared with the inactive CD，there were statistically significant differences in bowel wall stratification and MFH in both the mild and moderate-to-severe CD groups（all P<0.05）. When assessing bowel wall blood flow signals using CDFI，there was no statistically significant difference in blood flow signals in the bowel wall of the mild CD compared with the inactive CD（ P>0.05）. However，the blood flow signals in the bowel wall of the moderate-to-severe CD was significantly increased（ P<0.05）. There was also statistically significant difference in blood flow signals in the bowel wall between the mild and moderate-to-severe CD groups（ P<0.05）. When assessing bowel wall blood flow using UMA，there were statistically significant differences in blood flow signals in the bowel wall among all 3 groups（all P<0.05）. As the degree of inflammation increased，the blood flow signals in the bowel wall also increased significantly. ROC analysis revealed that diagnostic performance of the UMA-BMUS model was significantly better than that of the CDFI-BMUS model（AUC 0.945 vs. 0.873，sensitivity 88.9% vs. 74.1%，specificity 97.7% vs. 95.5%；all P<0.05）. Conclusions:By sensitively depicting the low-velocity and tiny blood flow signals of the inflamed bowel wall，UMA is an effective noninvasive imaging method to make semi-quantitative evaluation of the activity of pediatric Crohn's disease.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective:To evaluate the applicability of a new anti-G capability assessment trainer (AG-CAT) in high-performance (HP) anti-G maneuver training and positive pressure breathing for high-G (PHP) training for pilots.Methods:A total of 142 fighter pilots who were subjected to anti-G maneuver training at Dujiangyan Special Crew Sanatorium of PLA Air Force between January and November 2023 were enrolled. According to the Guidelines for Aviation Physiological Training, 123 pilots underwent both HP anti-G maneuver training and PHP positive pressure breathing training, 15 received only HP training, and 4 received only PHP training. Based on the training devices used, these pilots were divided into AG-CAT group and an anti-G and anti-hypoxia capability detection instrument (GHyCDI) group. The 2 groups were compared regarding the pedal force of lower limbs, blood pressure, and improvement of +G z tolerance during training. Results:Of the 138 pilots undergoing HP training, 88 used AG-CAT and 50 used GHyCDI. One hundred and twenty-seven pilots participated in PHP training, with 73 in the AG-CAT group and 54 in the GHyCDI group. During HP training, the pedal force of left lower limbs in the AG-CAT group was greater than that of the right limbs and of the GHyCDI group ( t=4.38, 2.64, P<0.001, =0.009). In PHP training, the AG-CAT group exhibited greater pedal force in left limbs than in right ones, while the GHyCDI group showed an opposite trend ( t=2.25, 3.37, P=0.029, 0.002). Systolic and diastolic blood pressures during HP training (with or without anti-G suits) were higher in the AG-CAT group than in the GHyCDI group ( t=3.50, 3.72, 2.55, 4.21, P=0.001,<0.001,=0.012,<0.001). Similarly, during PHP training, both systolic and diastolic pressures were higher in the AG-CAT group ( t=2.03, 3.81, P=0.045,<0.001). The AG-CAT group demonstrated superior improvements in +G z tolerance during HP training (without/with anti-G suits: Z=2.14, 3.21, P=0.049, 0.001) and PHP training ( Z=2.56, P=0.010) compared with the GHyCDI group. Conclusions:AG-CAT shows excellent applicability in aviation physiological training of pilots. Its ergonomic design, practical functionalities and enhanced compatibility with personnel protective equipment can better meet training requirements compared to conventional devices.

Objective To investigate the predictive performance of serum soluble CD40 ligand(sCD40L),interleukin-17(IL-17)and neutrophil extracellular traps(NETs)in combination for intracranial aneurysm rupture.Methods A total of 120 patients with intracranial aneurysms admitted from January 2022 to January 2025 were selected and divided into low-risk group and medium-high-risk group according to different rupture risks.After propensity score matching with 1:1 ratio and caliper matching(caliper=0.02),there were 60 patients in each group.The general data and serum levels of sCD40 L,IL-17 and NETs were compared between the two groups.Multivariate logistic regression analysis was used to analyze the risk factors of intracranial aneurysm rupture.The linear relationship between serum sCD40 L,IL-17,NETs and the risk of intracranial aneurysm rupture was analyzed by smoothing curve fitting.The receiver operating characteristic(ROC)curve,clinical impact curve(CIC)and clinical decision curve analysis(DCA)were used to evaluate the predictive performance of serum sCD40L,IL-17 and NETs for intracranial aneurysm rupture.Results The irregular shape of aneurysms,the proportion of the longest diameter of aneurysms≥7 mm and the levels of serum sCD40L,IL-17 and NETs in the low-risk group were lower than those in the medium-high-risk group(P<0.01).The shape of aneurysm,the longest diameter of aneurysm,sCD40L,IL-17 and NETs were the independent risk factors for intracranial aneurysm rupture(P<0.05).After adjusting for other covariates,serum sCD40L,IL-17 and NETs were positively correlated with the risk of intracranial aneurysm rupture(P<0.05).The ROC curve showed that the area under the curve of serum sCD40L,IL-17 and NETs in combination for predicting the risk of intracranial aneurysm rupture was the largest.The DCA and CIC showed that both the net benefit of the combined prediction model of serum sCD40L,IL-17 and NETs in predicting the risk of intracranial aneurysm rupture and the coincidence rate with the actual situation were relatively high.Conclusion The elevated levels of serum sCD40L,IL-17,and NETs in patients with intracranial aneurysms are associated with their rupture risk.The combination of the three indicators has a high predictive performance for the risk of intracranial aneurysm rupture.

Objective:To investigate the personnel, equipment, new technology of various radiotherapy units in Gansu Province, aiming to deeply understand the current status of radiotherapy in Gansu Province.Methods:From March 2023 to March 2024, the data of personnel, equipment and technology of different radiotherapy units in Gansu Province were investigated via online questionnaire survey and offline field visits by Gansu Provincial Quality Control Center for Radiation Oncology. The questionable data were reviewed, logical verification and outlier identification were conducted, and all information was entered according to the principle of double entry. Qualitative data were described by frequency (percentage).Results:As of March 2024, there are 26 radiotherapy units in Gansu Province, including 7 units in Lanzhou, capital city of Gansu Province and none in Linxia Hui Autonomous Prefecture and Gannan Tibetan Autonomous Prefecture. The ratio of radiotherapy physicians and physicists was 2.71 vs. 1, lower than the national level of 3.51 vs. 1. Radiotherapy physicians with intermediate and senior titles accounted for 66.2%, 54% for physicists with intermediate and senior titles and 34.0% for therapists with intermediate and senior titles, respectively. There were 1.70 accelerators per million population in Gansu Province. Among 42 accelerators in Gansu Province, 40 were linac and 2 heavy ion accelerators. In Lanzhou, 7 radiotherapy units had 17 linac, and the remaining 11 cities had 23 linac. All 40 linac could perform 3D conformal radiotherapy and intensity-modulated radiotherapy. The high-end equipment could apply advanced technologies such as volumetric modulated arc radiotherapy, stereotactic body radiotherapy, optical surface-guided radiation therapy and adaptive radiation therapy, etc. Relevant data in this survey were improved compared with those in the national surveys conducted in 2006, 2015 and 2019. Conclusions:The radiotherapy status has developed in Gansu Province, whereas uneven development still exists among regions. According to the actual demands of equipment, talents and technology in each region, the structural adjustment should be oriented to the underdeveloped cities and counties in the province to meet the local medical needs.

Objective To investigate the predictive performance of serum soluble CD40 ligand(sCD40L),interleukin-17(IL-17)and neutrophil extracellular traps(NETs)in combination for intracranial aneurysm rupture.Methods A total of 120 patients with intracranial aneurysms admitted from January 2022 to January 2025 were selected and divided into low-risk group and medium-high-risk group according to different rupture risks.After propensity score matching with 1:1 ratio and caliper matching(caliper=0.02),there were 60 patients in each group.The general data and serum levels of sCD40 L,IL-17 and NETs were compared between the two groups.Multivariate logistic regression analysis was used to analyze the risk factors of intracranial aneurysm rupture.The linear relationship between serum sCD40 L,IL-17,NETs and the risk of intracranial aneurysm rupture was analyzed by smoothing curve fitting.The receiver operating characteristic(ROC)curve,clinical impact curve(CIC)and clinical decision curve analysis(DCA)were used to evaluate the predictive performance of serum sCD40L,IL-17 and NETs for intracranial aneurysm rupture.Results The irregular shape of aneurysms,the proportion of the longest diameter of aneurysms≥7 mm and the levels of serum sCD40L,IL-17 and NETs in the low-risk group were lower than those in the medium-high-risk group(P<0.01).The shape of aneurysm,the longest diameter of aneurysm,sCD40L,IL-17 and NETs were the independent risk factors for intracranial aneurysm rupture(P<0.05).After adjusting for other covariates,serum sCD40L,IL-17 and NETs were positively correlated with the risk of intracranial aneurysm rupture(P<0.05).The ROC curve showed that the area under the curve of serum sCD40L,IL-17 and NETs in combination for predicting the risk of intracranial aneurysm rupture was the largest.The DCA and CIC showed that both the net benefit of the combined prediction model of serum sCD40L,IL-17 and NETs in predicting the risk of intracranial aneurysm rupture and the coincidence rate with the actual situation were relatively high.Conclusion The elevated levels of serum sCD40L,IL-17,and NETs in patients with intracranial aneurysms are associated with their rupture risk.The combination of the three indicators has a high predictive performance for the risk of intracranial aneurysm rupture.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective:To evaluate the applicability of a new anti-G capability assessment trainer (AG-CAT) in high-performance (HP) anti-G maneuver training and positive pressure breathing for high-G (PHP) training for pilots.Methods:A total of 142 fighter pilots who were subjected to anti-G maneuver training at Dujiangyan Special Crew Sanatorium of PLA Air Force between January and November 2023 were enrolled. According to the Guidelines for Aviation Physiological Training, 123 pilots underwent both HP anti-G maneuver training and PHP positive pressure breathing training, 15 received only HP training, and 4 received only PHP training. Based on the training devices used, these pilots were divided into AG-CAT group and an anti-G and anti-hypoxia capability detection instrument (GHyCDI) group. The 2 groups were compared regarding the pedal force of lower limbs, blood pressure, and improvement of +G z tolerance during training. Results:Of the 138 pilots undergoing HP training, 88 used AG-CAT and 50 used GHyCDI. One hundred and twenty-seven pilots participated in PHP training, with 73 in the AG-CAT group and 54 in the GHyCDI group. During HP training, the pedal force of left lower limbs in the AG-CAT group was greater than that of the right limbs and of the GHyCDI group ( t=4.38, 2.64, P<0.001, =0.009). In PHP training, the AG-CAT group exhibited greater pedal force in left limbs than in right ones, while the GHyCDI group showed an opposite trend ( t=2.25, 3.37, P=0.029, 0.002). Systolic and diastolic blood pressures during HP training (with or without anti-G suits) were higher in the AG-CAT group than in the GHyCDI group ( t=3.50, 3.72, 2.55, 4.21, P=0.001,<0.001,=0.012,<0.001). Similarly, during PHP training, both systolic and diastolic pressures were higher in the AG-CAT group ( t=2.03, 3.81, P=0.045,<0.001). The AG-CAT group demonstrated superior improvements in +G z tolerance during HP training (without/with anti-G suits: Z=2.14, 3.21, P=0.049, 0.001) and PHP training ( Z=2.56, P=0.010) compared with the GHyCDI group. Conclusions:AG-CAT shows excellent applicability in aviation physiological training of pilots. Its ergonomic design, practical functionalities and enhanced compatibility with personnel protective equipment can better meet training requirements compared to conventional devices.