BACKGROUND:Osteoarthritis is a chronic degenerative disease of the joints that can lead to disability.Its main pathological features are persistent inflammation and cartilage destruction.Triptolide has been used to treat a variety of chronic joint diseases.However,the mechanism of triptolide in the treatment of osteoarthritis has not been clarifiedOBJECTIVE:To identify the effective targets of triptolide in the treatment of osteoarthritis by network pharmacology,and to investigate the therapeutic effect of triptolide on osteoarthritis in the osteoarthritis model.METHODS:Network pharmacology was used to anticipate the potential targets and signaling pathways of triptolide in the treatment of osteoarthritis,and molecular docking technology was used to validate the core targets.A rat osteoarthritis model was established by anterior cruciate ligament transection.Eight weeks after modeling,the rats were administered with triptolide and sodium hyaluronate by intra-articular injection for 6 weeks.After 6 weeks of intervention,the pathological changes in rat knee joints were observed by hematoxylin-eosin staining and safranin O-fast green staining.The levels of inflammatory factors in rat serum were detected by enzyme-linked immunosorbent assay.The expression of aggrecan,type Ⅰ platelet-responsive protein-containing desmoglein metalloproteinase 5,type Ⅱ collagen and matrix metalloproteinase 13 proteins in rat articular cartilage was tested by immunohistochemical staining.RESULTS AND CONCLUSION:(1)The results of network pharmacology indicated that the target of triptolide may be related to the inhibition of the release of factors such as interleukin 6,tumor necrosis factor a,interleukin 1β,matrix metalloproteinase 9,and the over-activation of the nuclear factor-κB/JAK2-STAT3 signaling pathway.(2)Triptplide could reduce the degree of joint swelling in osteoarthritic rats;pathologically improve the articular cartilage and maintain the cartilage structure;decrease the serum levels of interleukin 6,tumor necrosis factor a,interleukin 1β,matrix metalloproteinase 9,and matrix metalloproteinase 3 in osteoarthritic rats;reduce the protein expression of matrix metalloproteinase 13 and type Ⅰ platelet-responsive protein-containing desmoglein metalloproteinase 5 in the articular cartilage;and increase the expression of type Ⅱ collagen and aggrecan in the cartilage,thereby achieving cartilage protection.

BACKGROUND:Osteoarthritis is a chronic degenerative disease of the joints that can lead to disability.Its main pathological features are persistent inflammation and cartilage destruction.Triptolide has been used to treat a variety of chronic joint diseases.However,the mechanism of triptolide in the treatment of osteoarthritis has not been clarifiedOBJECTIVE:To identify the effective targets of triptolide in the treatment of osteoarthritis by network pharmacology,and to investigate the therapeutic effect of triptolide on osteoarthritis in the osteoarthritis model.METHODS:Network pharmacology was used to anticipate the potential targets and signaling pathways of triptolide in the treatment of osteoarthritis,and molecular docking technology was used to validate the core targets.A rat osteoarthritis model was established by anterior cruciate ligament transection.Eight weeks after modeling,the rats were administered with triptolide and sodium hyaluronate by intra-articular injection for 6 weeks.After 6 weeks of intervention,the pathological changes in rat knee joints were observed by hematoxylin-eosin staining and safranin O-fast green staining.The levels of inflammatory factors in rat serum were detected by enzyme-linked immunosorbent assay.The expression of aggrecan,type Ⅰ platelet-responsive protein-containing desmoglein metalloproteinase 5,type Ⅱ collagen and matrix metalloproteinase 13 proteins in rat articular cartilage was tested by immunohistochemical staining.RESULTS AND CONCLUSION:(1)The results of network pharmacology indicated that the target of triptolide may be related to the inhibition of the release of factors such as interleukin 6,tumor necrosis factor a,interleukin 1β,matrix metalloproteinase 9,and the over-activation of the nuclear factor-κB/JAK2-STAT3 signaling pathway.(2)Triptplide could reduce the degree of joint swelling in osteoarthritic rats;pathologically improve the articular cartilage and maintain the cartilage structure;decrease the serum levels of interleukin 6,tumor necrosis factor a,interleukin 1β,matrix metalloproteinase 9,and matrix metalloproteinase 3 in osteoarthritic rats;reduce the protein expression of matrix metalloproteinase 13 and type Ⅰ platelet-responsive protein-containing desmoglein metalloproteinase 5 in the articular cartilage;and increase the expression of type Ⅱ collagen and aggrecan in the cartilage,thereby achieving cartilage protection.

Objective:To investigate microstructural alterations in the optic chiasm and optic radiations of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) based on diffusion kurtosis imaging (DKI).Methods:This study was a cross-sectional study. Retrospective analyses were conducted on the clinical and imaging data of 63 patients with relapsing-remitting MS (RRMS) and 62 patients with NMOSD diagnosed at First Affiliated Hospital of Chongqing Medical University from January 2019 to December 2023. According to the occurrence of optic neuritis (ON), they were categorized into ON-positive MS (ON+MS) group (40 cases), ON-negative MS (ON-MS) group (23 cases), ON-positive NMOSD (ON+NMOSD) group (40 cases) and ON-negative NMOSD (ON-NMOSD) group (22 cases). In addition, 40 healthy controls were enrolled during the same period. DKI data of all subjects were collected, and DKI post-processing was performed to obtain fractional anisotropy (FA), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) values of the optic chiasm and bilateral optic radiations. The scores of the mini-mental state examination (MMSE), montreal cognitive assessment (MoCA), and expanded disability status scale (EDSS) were obtained. The Kruskal-Wallis test was used to analyze the differences in DKI parameters of the optic chiasm and bilateral optic radiation among the 5 groups, and the Holm-Bonferroni method was employed for multiple comparison correction in pairwise comparisons.Results:There were statistically significant overall differences in the DKI parameters of the optic chiasm and bilateral optic radiations among healthy control group, ON+MS group, ON-MS group, ON+NMOSD group, and ON-NMOSD group (all P0.05). The FA value of the optic chiasm in ON+NMOSD group was significantly lower than that of healthy control group and ON-MS group, as well as ON-NMOSD group ( P0.05). The FA value of the left optic radiation in ON+NMOSD group was lower than that in healthy control group and the ON-MS group. The RK value of the optic chiasm in ON+MS group was lower than that in the healthy control group and ON-NMOSD group ( P0.05). The MK and RK values of the left optic radiation in ON-MS group were significantly lower than those in the ON+NMOSD group and ON-NMOSD group ( P0.05). Conclusions:NMOSD and RRMS patients demonstrate varying degrees of microstructural damage in the optic chiasm and optic radiations. Differences of DKI parameters suggest different pathological mechanisms of visual pathway damage between NMOSD and MS, which may be helpful for early detection of occult visual pathway lesions.

Objective : To investigate the relationship between lower limb alignment and knee functional gait after total knee arthroplasty (TKA) for varus knee deformity. Methods: A total of 94 patients with knee osteoarthritis and varus deformity underwent mechanically aligned TKA. The knee society score ( KSS) , hip⁃knee⁃ankle angle (HKA) , medial proximal tibial angle ( mMPTA) , and gait parameters ( step length , gait speed , cadence , thigh jerk acceleration , and thigh swing work) were assessed preoperatively and one month postoperatively. The correlation between KSS scores and changes in lower limb alignment was also analyzed. Results: The KSS clinical score of the operated knee significantly improved from 39. 19 ± 9. 55 preoperatively to 73. 01 ± 6. 90 postoperatively (P <0. 001) . The KSS functional score increased from 41. 12 ± 10. 66 to 56. 33 ± 7. 41(P < 0. 001) . Postoperative gait analysis revealed significant improvements in step length , gait speed , cadence , and thigh swing work ( P <0. 001) , while thigh jerk acceleration showed no significant change (P = 0. 525) . The HKA angle of the affected limb increased from 170. 61 ± 4. 39 preoperatively to 177. 30 ± 3. 49 postoperatively ( P < 0. 001) . Similarly , the mMPTA angle increased from 83. 95 ± 3. 32 to 89. 15 ± 1. 94 (P < 0. 001) . Correlation analysis indicated that The KSS clinical score was positively correlated with HKA ( P < 0. 001) and mMPTA ( P < 0. 05 ) of the lower limb force line. The KSS functional score was positively correlated with HKA (P < 0. 05) but not with mMPTA (P > 0. 05) . Conclusion In patients with severe knee osteoarthritis due to varus deformity , TKA significantly alleviates pain and improves both clinical and functional KSS scores within one month postoperatively. Restoring lower limb mechanical alignment is positively associated with joint functional recovery and enhances gait performance.

Objective:To investigate microstructural alterations in the optic chiasm and optic radiations of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) based on diffusion kurtosis imaging (DKI).Methods:This study was a cross-sectional study. Retrospective analyses were conducted on the clinical and imaging data of 63 patients with relapsing-remitting MS (RRMS) and 62 patients with NMOSD diagnosed at First Affiliated Hospital of Chongqing Medical University from January 2019 to December 2023. According to the occurrence of optic neuritis (ON), they were categorized into ON-positive MS (ON+MS) group (40 cases), ON-negative MS (ON-MS) group (23 cases), ON-positive NMOSD (ON+NMOSD) group (40 cases) and ON-negative NMOSD (ON-NMOSD) group (22 cases). In addition, 40 healthy controls were enrolled during the same period. DKI data of all subjects were collected, and DKI post-processing was performed to obtain fractional anisotropy (FA), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) values of the optic chiasm and bilateral optic radiations. The scores of the mini-mental state examination (MMSE), montreal cognitive assessment (MoCA), and expanded disability status scale (EDSS) were obtained. The Kruskal-Wallis test was used to analyze the differences in DKI parameters of the optic chiasm and bilateral optic radiation among the 5 groups, and the Holm-Bonferroni method was employed for multiple comparison correction in pairwise comparisons.Results:There were statistically significant overall differences in the DKI parameters of the optic chiasm and bilateral optic radiations among healthy control group, ON+MS group, ON-MS group, ON+NMOSD group, and ON-NMOSD group (all P0.05). The FA value of the optic chiasm in ON+NMOSD group was significantly lower than that of healthy control group and ON-MS group, as well as ON-NMOSD group ( P0.05). The FA value of the left optic radiation in ON+NMOSD group was lower than that in healthy control group and the ON-MS group. The RK value of the optic chiasm in ON+MS group was lower than that in the healthy control group and ON-NMOSD group ( P0.05). The MK and RK values of the left optic radiation in ON-MS group were significantly lower than those in the ON+NMOSD group and ON-NMOSD group ( P0.05). Conclusions:NMOSD and RRMS patients demonstrate varying degrees of microstructural damage in the optic chiasm and optic radiations. Differences of DKI parameters suggest different pathological mechanisms of visual pathway damage between NMOSD and MS, which may be helpful for early detection of occult visual pathway lesions.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

ObjectiveTo explore the mental health status and its influencing factors among middle school students in Xide County， Liangshan Yi Autonomous Prefecture， and to provide references for mental health interventions for local middle school students. MethodsUsing a cross-sectional study design， one junior middle school and one senior middle school in Xide County， Liangshan Prefecture， Sichuan Province， were randomly selected on September 16， 2021， and two classes per grade in each school involving 288 students were recruited. Subjects were assessed using Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）， Generalized Anxiety Disorder Scale-7 item （GAD-7）， PTSD Checklist for DSM-5 （PCL-5）， Multidimensional Scale of Perceived Social Support （MSPSS） and UCLA Loneliness Scale （ULS-3）. Then the scores of above scales were compared among middle school students with different demographic characteristics， and binary Logistic regression analysis was conducted to screen the influencing factors of post-traumatic stress disorder (PTSD） symptoms. ResultsAmong the respondents， 17.71% （95% CI： 0.133~0.221）， 8.68% （95% CI： 0.054~0.120）， 2.78% （95% CI： 0.009~0.047） and 45.83% （95% CI： 0.400~0.516） were reported to have symptoms of depression， anxiety， PTSD and loneliness， respectively. Students in senior middle school scored lower on PCL-5 and ULS-3 than those in junior middle school ［（6.46±8.91） vs. （8.87±9.42）， t=2.202， P<0.05； （4.67±1.65） vs. （5.60±1.88）， t=4.431， P<0.01］. Regression analysis denoted that depressive symptoms （OR=7.630， P<0.05） and anxiety symptoms （OR=3.789， P<0.01） were risk factors for PTSD symptoms among middle school students. ConclusionThe middle school students in Xide County， Liangshan Yi Autonomous Prefecture suffer a high prevalence rate of depressive symptoms and loneliness， and those in junior middle school are more likely to feel a sense of strong loneliness， furthermore， depressive symptoms and anxiety symptoms are risk factors for PTSD symptoms.

Objective:To evaluate the clinical effect of high-intensity interval training and moderate continuous aerobic training on patients classified as low risk for exercise rehabilitation after a percutaneous coronary intervention (PCI).Methods:A total of 43 patients considered low-risk after a PCI were randomly divided into a high-intensity interval training group (HIIT group, 22 cases) and a moderate continuous aerobic training group (MCT group, 21 cases). The HIIT group received high-intensity, but aerobic interval training involving 8 rounds of 3 minutes of high-intensity exercise with 2-minute intervals at 80% of peak power over 40 minutes, 3 times a week. The MCT group trained continuously at 60% of peak power for the same duration. After 12 weeks both groups were given an ultrasound examination and a cardiopulmonary exercise test to assess their cardiac functioning and exercise endurance. The subjects′ life quality was evaluated and compared using some items from the SF-36 scale.Results:Before the training, no significant differences were observed in the average left ventricular ejection fraction, stroke volume, peak power, peak oxygen uptake, anaerobic threshold, physiological functioning, physical pain, general health or social functioning between the two groups. After the training significant improvement in all these indicators was observed in both groups, but compared with MCT group, the average left ventricular ejection fraction, stroke volume, peak power and peak oxygen uptake of the HIIT group were significantly better.Conclusions:High-intensity, aerobic interval training is superior to moderate but continuous aerobic training for improving the cardiac functioning and exercise endurance of patients suitable for exercise rehabilitation after a PCI. But there is no significant difference in their effect on the short-term quality of life.

Objective: To explore the curative effect and safety of botulintum toxin A (BTX-A) on depressive disorder in patients with Parkinson′s disease (PD). Methods: Forty-two cases of PD with depression prospectively recruited in the Second Hospital Affiliated to Soochow University from August 2016 to November 2018 were divided into two groups: 28 patients in BTX-A group (administered with 100 U BTX-A injection on patients′ eyebrow, forehead, bilateral lateral canthus and temporal region at 20 loci), 14 patients in sertraline (control) group (administered with 50-100 (55.36±14.47) mg/d sertraline). The scores of Hamilton Depression Rating Scale (HAMD), Self-rating Depression Scale (SDS), Hamilton Rating Scale for Anxiety (HAMA), Self-rating Anxiety Scale (SAS) after treatment for 2 weeks, 4 weeks, 8 weeks and 12 weeks were compared with the scores of each emotional rating scale for baseline respectively. Meanwhile, the differences in the scores of each emotional scale between the two treatment groups were compared. In addition, the remission rates of depression and anxiety (defined as HAMD, HAMA scores<7) at each follow-up time point between the two groups were compared to evaluate the efficacy and safety of BTX-A in the treatment of PD patients with depression. Results: The scores of HAMD, HAMA, SDS, SAS in the BTX-A group and the sertraline group reduced compared to baseline after treatment (at the 2nd, 4th, 8th, 12th weeks). The scores of HAMD and SDS in the BTX-A group (HAMD scores: F=12.930, P<0.01; SDS scores: F=5.022, P=0.001) and those in the sertraline group (HAMD scores: F=2.883, P=0.030; SDS scores: F=3.427, P=0.013) were significantly lower compared to baseline, but there was no statistically significant difference in the scores of HAMD and SDS between the two groups (P>0.05). HAMD score showed that the remission rate of depression in the BTX-A group (17.9% (5/28), 35.7% (10/28)) was higher than that of the sertraline group (2/14, 4/14) at the 2nd and 4th weeks. At the 8th and 12th weeks, the remission rate of depression in the sertraline group (7/14, 9/14) was higher than that of the BTX-A group (46.4% (13/28), 53.6% (15/28)). There was no statistically significant difference in remission rate of depression between the two groups at each follow-up time point (P>0.05). There was no statistically significant difference in HAMD scores between males and females in the BTX-A group (P>0.05). Two of the 28 patients in the BTX-A group had frown muscle stiffness, which lasted for two weeks and improved in one month. Two patients in the sertraline group had headache and dizziness, and two patients had dry mouth and nausea, which improved after two weeks. There was no statistically significant difference in the incidence of adverse reactions between the two groups (P=0.197). Conclusion BTX-A intraocular facial muscle injection can significantly improve the depressive symptoms of PD patients, and the effect lasts for a long time, with low incidence of side effects and high safety, which can be considered as a safe and effective new method for PD patients with depressive symptoms.

Objective To explore the curative effect and safety of botulintum toxin A (BTX?A) on depressive disorder in patients with Parkinson′s disease (PD). Methods Forty?two cases of PD with depression prospectively recruited in the Second Hospital Affiliated to Soochow University from August 2016 to November 2018 were divided into two groups: 28 patients in BTX?A group (administered with 100 U BTX?A injection on patients′eyebrow, forehead, bilateral lateral canthus and temporal region at 20 loci), 14 patients in sertraline (control) group (administered with 50-100 (55.36±14.47) mg/d sertraline). The scores of Hamilton Depression Rating Scale (HAMD), Self?rating Depression Scale (SDS), Hamilton Rating Scale for Anxiety (HAMA), Self?rating Anxiety Scale (SAS) after treatment for 2 weeks, 4 weeks, 8 weeks and 12 weeks were compared with the scores of each emotional rating scale for baseline respectively. Meanwhile, the differences in the scores of each emotional scale between the two treatment groups were compared. In addition, the remission rates of depression and anxiety (defined as HAMD, HAMA scores<7) at each follow?up time point between the two groups were compared to evaluate the efficacy and safety of BTX?A in the treatment of PD patients with depression. Results The scores of HAMD, HAMA, SDS, SAS in the BTX?A group and the sertraline group reduced compared to baseline after treatment (at the 2nd, 4th, 8th, 12th weeks). The scores of HAMD and SDS in the BTX?A group (HAMD scores: F=12.930, P<0.01; SDS scores: F=5.022, P=0.001) and those in the sertraline group (HAMD scores: F=2.883, P=0.030; SDS scores:F=3.427, P=0.013) were significantly lower compared to baseline, but there was no statistically significant difference in the scores of HAMD and SDS between the two groups (P>0.05). HAMD score showed that the remission rate of depression in the BTX?A group (17.9% (5/28), 35.7% (10/28)) was higher than that of the sertraline group (2/14, 4/14) at the 2nd and 4th weeks. At the 8th and 12th weeks, the remission rate of depression in the sertraline group (7/14, 9/14) was higher than that of the BTX?A group (46.4% (13/28), 53.6% (15/28)). There was no statistically significant difference in remission rate of depression between the two groups at each follow?up time point (P>0.05). There was no statistically significant difference in HAMD scores between males and females in the BTX?A group (P>0.05). Two of the 28 patients in the BTX?A group had frown muscle stiffness, which lasted for two weeks and improved in one month. Two patients in the sertraline group had headache and dizziness, and two patients had dry mouth and nausea, which improved after two weeks. There was no statistically significant difference in the incidence of adverse reactions between the two groups (P=0.197). Conclusion BTX?A intraocular facial muscle injection can significantly improve the depressive symptoms of PD patients, and the effect lasts for a long time, with low incidence of side effects and high safety, which can be considered as a safe and effective new method for PD patients with depressive symptoms.