Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

Objective:To investigate the relationship between the level of prolyl 4-hydroxylase subunit alpha 2 (P4HA2) in peripheral blood and the adverse pregnancy outcome in patients with gestational diabetes mellitus (GDM).Methods:A retrospective collection of baseline data was conducted on 120 GDM patients who underwent regular prenatal check ups and deliveries in Wenzhou Central Hospital from March 2022 to March 2024, serving as the GDM group. Baseline data from 120 pregnant women with normal glucose tolerance (NGT) during the same period were collected as the NGT group. Baseline data of blood lipids, blood glucose, and peripheral blood P4HA2 between the two groups were compared, and Pearson correlation test was used to determine the correlation between P4HA2 and some clinical indicators. Statistical analysis was conducted on the pregnancy outcomes of GDM patients, divided into the adverse pregnancy group (32 cases) and the normal pregnancy group(88 cases). Baseline data on blood lipids, blood glucose, and peripheral blood P4HA2 were compared between the two groups. Univariate and multivariate Logistic regression analysis were used to screen for factors affecting adverse pregnancy outcomes in GDM patients. Receiver operating characteristic (ROC) curves were also plotted to analyze the predictive value of peripheral blood P4HA2 for adverse pregnancy outcomes in GDM patients.Results:Compared with the NGT group, the GDM group had higher levels of fasting glucose, 2-h glucose, 1-h glucose, glycosylated hemoglobin (HbA 1c), peripheral blood P4HA2, insulin resistance index, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC): (6.26 ± 0.24) mmol/L vs. (4.33 ± 0.15) mmol/L, (9.69 ± 0.18) mmol/L vs. (7.41 ± 0.19) mmol/L, (11.01 ± 0.29) mmol/L vs. (7.10 ± 0.27) mmol/L, (8.54 ± 0.43)% vs. (5.05 ± 0.61)%, (39.03 ± 3.33) μg/L vs. (35.55 ± 3.05) μg/L, 2.50 ± 0.34 vs. 1.95 ± 0.33, (2.56 ± 0.49) mmol/L vs. (2.08 ± 0.37) mmol/L, (3.85 ± 0.25) mmol/L vs. (3.26 ± 0.30) mmol/L, (6.92 ± 0.43) mmol/L vs. (6.25 ± 0.43) mmol/L, and significantly lower levels of high-density lipoprotein cholesterol (HDL)-C: (1.70 ± 0.11) mmol/L vs. (1.87 ± 0.22) mmol/L, there were statistical differences ( P<0.05). Pearson correlation analysis showed that peripheral blood P4HA2 was positively correlated with fasting blood glucose, 2-h blood glucose, 1-h blood glucose, HbA 1c, insulin resistance index, TG, LDL-C, and TC ( r>0, P<0.05); peripheral blood P4HA2 was negatively correlated with HDL-C ( r<0, P<0.05). The fasting blood glucose, 2-h blood glucose, 1-h blood glucose, insulin resistance index, peripheral blood P4HA2, and TC in the adverse pregnancy group were significantly higher than those in the normal pregnancy group:(6.35 ± 0.22) mmol/L vs. (6.23 ± 0.24) mmol/L, (9.78 ± 0.25) mmol/L vs. (9.66 ± 0.14) mmol/L, (11.12 ± 0.33) mmol/L vs. (10.97 ± 0.26) mmol/L, 2.61 ± 0.22 vs. 2.36 ± 0.37, (41.20 ± 3.62) μg/L vs. (38.24 ± 2.85) μg/L, (7.12 ± 0.55) mmol/L vs. (6.84 ± 0.35) mmol/L, there were statistical differences ( P<0.05). Logistic regression analysis showed that fasting blood glucose, 1-h blood glucose, 2-h blood glucose, TC, insulin resistance index, and peripheral blood P4HA2 were related factors affecting pregnancy outcomes in GDM patients ( P<0.05). The ROC curve showed that peripheral blood P4HA2 had good predictive value for adverse pregnancy outcomes in GDM patients, with an area under the curve of 0.729. Conclusions:The high expression of P4HA2 in peripheral blood of GDM patients is closely related to adverse pregnancy, which can provide some reference for clinical prediction of pregnancy outcomes in patients.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

AIM:To observe the defocus state and myopia control in myopic children wearing single-vision, defocus, and orthokeratology lenses using multispectral refraction topography(MRT).METHODS: A total of 279 myopic patients aged 8-14 years old, with a spherical equivalent(SE)from -7.00 to -0.50 D, treated at the Chengdu Aier Eye Hospital from June 2022 to December 2023. Patients who volunteered for the study were assigned to three groups. A total of 94 cases were provided with single-vision spectacle lenses(SVL group), 90 cases received individualized ocular refraction customization(IORC group), and 95 cases received orthokeratology lenses(OK group). Simultaneously, the three groups were further categorized into low(-3.00 to -0.50 D), moderate(-6.00 to -3.25 D), and high myopia(-7.00 to -6.25 D)groups according to different SE. MRT was used to measure and compare the defocus changes of the retina in supperior, inferior, nasal, and temporal quadrants(RDV-S, RDV-I, RDV-N, RDV-T), and three angles of field of view, including 0-15°, 15°-30°, and 30°-45°(RDV-15, RDV-30, RDV-45)in the three groups(the data divide for the connected regions is grouped to the latter group). A one-way analysis of variance was used for intergroup comparisons. Univariate and multivariate linear regression analyses were used to analyze the factors related to changes in the axial length(AL)at 1 a after intervention.RESULTS:There were significant differences in 1-year SE and AL growth among patients in the SVL, IORC, and OK groups before and after intervention(P<0.001). The 1-year SE and the difference of AL growth in patients with low myopia was significantly different among SVL, IORC, and OK groups(P<0.001); however, there was no significant difference between the IORC and OK groups(P>0.05); there were significant differences in the SE and AL growth changes between the OK group and the IORC and SVL groups in moderate myopia(P<0.001); and there were significant differences between the OK group and the IORC and SVL groups in SE and AL growth of high myopia group after wearing lenses for 1 a(P<0.001), while there were no significant differences between the IORC and SVL groups(P>0.05). In addition, there were significant differences in the relative peripheral refractive errors(RPRE)of 4 quadrants and 3 eccentric regions among the three groups of patients in different degrees of myopia groups(P<0.001). Pair-wise comparison of the growth difference of eccentric D-RDV-15 in low myopia group after wearing lenses for 1 a showed significant differences between the SVL, IORC, and OK groups(P<0.001), but no significant differences between the IORC and OK groups(P>0.05). The angle of field of view D-RDV-30 in moderate myopia subgroups was statistically different between the SVL group and the IORC and OK groups after wearing lenses for 1 a(P<0.001), while the IORC and OK groups showed no significant differences(P>0.05); the angle of field of view D-RDV-15 in high myopia subgroups was statistically different between the OK group and the IORC and SVL groups after wearing lenses for 1 a(P<0.001), but there was no significant difference between the IORC and SVL groups(P>0.05). Univariate and multivariate linear regression model analysis showed that the changes in D-TRVD, D-RDV-45, D-RDV-N, and D-RDV-I correlated with the increase in the difference in 1 a AL.CONCLUSION: MRT can be used to guide the clinical control of myopia. Myopia development is related to the peripheral retinal defocus state, and the difference of defocus quantity in the inferior nasal side at 30°-45° eccentricity may be a factor regulating the rapid progression of myopia.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Objective:To investigate the relationship between the level of prolyl 4-hydroxylase subunit alpha 2 (P4HA2) in peripheral blood and the adverse pregnancy outcome in patients with gestational diabetes mellitus (GDM).Methods:A retrospective collection of baseline data was conducted on 120 GDM patients who underwent regular prenatal check ups and deliveries in Wenzhou Central Hospital from March 2022 to March 2024, serving as the GDM group. Baseline data from 120 pregnant women with normal glucose tolerance (NGT) during the same period were collected as the NGT group. Baseline data of blood lipids, blood glucose, and peripheral blood P4HA2 between the two groups were compared, and Pearson correlation test was used to determine the correlation between P4HA2 and some clinical indicators. Statistical analysis was conducted on the pregnancy outcomes of GDM patients, divided into the adverse pregnancy group (32 cases) and the normal pregnancy group(88 cases). Baseline data on blood lipids, blood glucose, and peripheral blood P4HA2 were compared between the two groups. Univariate and multivariate Logistic regression analysis were used to screen for factors affecting adverse pregnancy outcomes in GDM patients. Receiver operating characteristic (ROC) curves were also plotted to analyze the predictive value of peripheral blood P4HA2 for adverse pregnancy outcomes in GDM patients.Results:Compared with the NGT group, the GDM group had higher levels of fasting glucose, 2-h glucose, 1-h glucose, glycosylated hemoglobin (HbA 1c), peripheral blood P4HA2, insulin resistance index, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC): (6.26 ± 0.24) mmol/L vs. (4.33 ± 0.15) mmol/L, (9.69 ± 0.18) mmol/L vs. (7.41 ± 0.19) mmol/L, (11.01 ± 0.29) mmol/L vs. (7.10 ± 0.27) mmol/L, (8.54 ± 0.43)% vs. (5.05 ± 0.61)%, (39.03 ± 3.33) μg/L vs. (35.55 ± 3.05) μg/L, 2.50 ± 0.34 vs. 1.95 ± 0.33, (2.56 ± 0.49) mmol/L vs. (2.08 ± 0.37) mmol/L, (3.85 ± 0.25) mmol/L vs. (3.26 ± 0.30) mmol/L, (6.92 ± 0.43) mmol/L vs. (6.25 ± 0.43) mmol/L, and significantly lower levels of high-density lipoprotein cholesterol (HDL)-C: (1.70 ± 0.11) mmol/L vs. (1.87 ± 0.22) mmol/L, there were statistical differences ( P<0.05). Pearson correlation analysis showed that peripheral blood P4HA2 was positively correlated with fasting blood glucose, 2-h blood glucose, 1-h blood glucose, HbA 1c, insulin resistance index, TG, LDL-C, and TC ( r>0, P<0.05); peripheral blood P4HA2 was negatively correlated with HDL-C ( r<0, P<0.05). The fasting blood glucose, 2-h blood glucose, 1-h blood glucose, insulin resistance index, peripheral blood P4HA2, and TC in the adverse pregnancy group were significantly higher than those in the normal pregnancy group:(6.35 ± 0.22) mmol/L vs. (6.23 ± 0.24) mmol/L, (9.78 ± 0.25) mmol/L vs. (9.66 ± 0.14) mmol/L, (11.12 ± 0.33) mmol/L vs. (10.97 ± 0.26) mmol/L, 2.61 ± 0.22 vs. 2.36 ± 0.37, (41.20 ± 3.62) μg/L vs. (38.24 ± 2.85) μg/L, (7.12 ± 0.55) mmol/L vs. (6.84 ± 0.35) mmol/L, there were statistical differences ( P<0.05). Logistic regression analysis showed that fasting blood glucose, 1-h blood glucose, 2-h blood glucose, TC, insulin resistance index, and peripheral blood P4HA2 were related factors affecting pregnancy outcomes in GDM patients ( P<0.05). The ROC curve showed that peripheral blood P4HA2 had good predictive value for adverse pregnancy outcomes in GDM patients, with an area under the curve of 0.729. Conclusions:The high expression of P4HA2 in peripheral blood of GDM patients is closely related to adverse pregnancy, which can provide some reference for clinical prediction of pregnancy outcomes in patients.

Objective To explore the changes of resting-state degree centrality(DC)in elderly patients with chronic insomnia disorder(CID).Methods Resting-state functional magnetic resonance imaging(rs-fMRI)data were collected from 26 untreated elderly patients with CID(CID group)and 45 healthy controls(HC)(HC group).Two-sample t-test was conducted to compare the intergroup differences in whole-brain DC values,and the correlation between DC values in different brain regions and clinical indicators were analyzed,and logistic regression analysis was performed to verify the diagnostic efficacy of changes in DC values for elderly CID.Results Compared with the HC group,the DC values of the right insula,left rolandic operculum,and opercular part of right inferior frontal gyrus in the elderly CID group decreased[P＜0.05,false discovery rate(FDR)corrected],while the DC values of the right middle frontal gyrus increased(P＜0.05,FDR corrected).And the DC values of the opercular part of right inferior frontal gyrus in the elderly CID group were positively correlated with sleep efficiency(r=0.504,P=0.009)and self-rating depression scale(SDS)(r=0.401,P=0.042),respectively.The sensitivity of DC value in the opercular part of right inferior frontal gyrus for diagnosing elderly CID was 0.822,the specificity was 0.615,and the accuracy was 0.701.Conclusion Elderly CID patients have abnormal DC values in the right insula,left rolandic operculum,opercular part of right inferior frontal gyrus and right middle frontal gyrus,which may provide imaging evidence for exploring the pathogenesis of CID and clinical diagnosis and treatment.

Objective:To explore the characteristics of gray matter volume (GMV) and structural covariant network (SCN) in patients with cerebral small vessel disease (CSVD) related cognitive impairment.Methods:This was a cross-sectional study. Ninety-eight patients with CSVD who attended Wuxi People′s Hospital of Nanjing Medical University between October 2021 and December 2022 were prospectively included. The patients were evaluated using the cognitive status assessment scale and were categorized into 57 cases in the CSVD with cognitive impairment group and 41 cases in the CSVD without cognitive impairment group according to the presence or absence of cognitive impairment. 3D-T 1WI structural image data were collected, and GMV differences between the two groups were compared by SPM 12 toolbox and CAT12 toolkit. At the same time, Pearson correlation analysis was also performed to analyze the GMV of differences between the 2 groups and cognitive status assessment scale scores. The BCT software package based on MATLAB platform was used to construct the GMV-related structural covariant network (SCN), and the graph theory method was utilized for SCN analysis to calculate the area under the curve (AUC) of the global and local parameters within the set sparsity range, and the permutation test was used to compare the differences in the AUC of the 2 groups. Results:In the CSVD with cognitive impairment group, GMV in bilateral hippocampus, parahippocampal gyrus, fusiform gyrus, and left amygdala was significantly lower than that in the CSVD without cognitive impairment group (family wise error corrected P<0.05), and the GMV in these regions had correlation with cognitive status assessment scale ( P<0.05). At the global network level of the SCN, the area under the curve (AUC) of the characteristic path length was significantly higher in the CSVD with cognitive impairment group than in the CSVD without cognitive impairment group ( P=0.023), while the AUC of global efficiency was significantly lower in CSVD with cognitive impairment group than in the CSVD without cognitive impairment group ( P=0.005). At the local level, the nodal degree and nodal efficiency of the left putamen were significantly decreased in the CSVD with cognitive impairment group compared to the CSVD without cognitive impairment group (false discovery rate corrected P<0.05). Conclusions:GMV reduce in patients of CSVD with cognitive impairment in the bilateral hippocampus, parahippocampal gyrus, fusiform gyrus, and left amygdala. In the structural covariance network, characteristic path length increase while global efficiency reduce, and node degree and nodal efficiency of the left putamen reduce.