BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P＜0.05),and the separation of trabeculae increased(P＜0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P＜0.05),and the separation of trabeculae decreased(P＜0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P＜0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P＜0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.

BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P＜0.05),and the separation of trabeculae increased(P＜0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P＜0.05),and the separation of trabeculae decreased(P＜0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P＜0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P＜0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.

Lower urinary tract dysfunction (LUTD) is common in children, but treatment is difficult in some cases, and it might causes upper urinary tract damage in the late stage. Recently, botulinum toxin A(BTX-A) has been recommended as an effective procedure for refractory LUTD, which has significantly improved symptoms and reduced the occurrence of upper urinary tract damage in children with LUTD. At present, there is a lack of international consensus on the application indication and dose selection of BTX-A in LUTD children, and the safety and long-term efficacy of repeated BTX-A injection are also clinical concerns. This article reviews the current application perspectives and progress of BTX-A in the treatment of children with LUTD, especially the clinical application indications and methods.BTX-A provides a minimally invasive, safe and effective treatment option for children with LUTD, which can significantly improve clinical symptoms and urodynamic parameters. With the further clarification of indications and the improvement of administration methods, BTX-A will be able to assist more children with LUTD in enhancing their quality of life and lessening their physical and mental burden.

"When warm evil is received,it first attacks the lungs and then spread to the pericardium reversely"is the general rule of warm diseases.Doctors of different dynasties have different views on the phrase"reverse spread to the pericardium",especially the word"reverse".Professor Tong Xiaolin proposed that the heart governs the mind,the pericardium and the heart are connected in qi,and when the heart is affected by evil,the pericardium instead suffers from the evil.The"reverse spread to the pericardium"proposed by Ye Tianshi is actually the spread of warm evil to the brain.Taking meningococcal meningitis as the basic disease,it can be matched one by one with the typical stages of the transmission of Wei-Qi-Ying-Xue.Combined with the theory of Dingjiao,it is believed that the function of"the heart governing the mind"focuses more on the brain in the modern anatomical sense.Combining traditional Chinese medicine's ideas on diagnosis and treatment of warm diseases with modern medicine,revealing the essence of the disease,grasping the core of the pathogenesis,analyzing the word"reverse"from a new perspective,and exploring its true meaning,is of great significance for clarifying its connotation,exploring the development laws of warm diseases,and guiding the diagnosis and treatment of warm disea-ses.

Mental disorders frequently co-occur with other physical illnesses,becoming one of the leading causes of disability worldwide.Early diagnosis and intervention are crucial for the effective management of these disorders.Currently,biomarker studies on mental disorders predominantly concentrate on genes,blood indicators,and imaging features of the brain.There is a growing interest in objective phenotypic markers as a research focus.It is established that the retina is part of the central nervous system(CNS),which extends from the mesencephalon and develops concurrently with the brain during the embryonic period.Given the overlapping pathophysiological mechanisms between neurodegenerative diseases and mental disorders,studying the structural and functional changes in the inner layers of the retina has emerged as a new direction in mental health research.The advent of optical coherence tomography(OCT)has enabled microscopic imaging of retinal structures.OCT is capable of objectively quantifying the retinal sub-layers and offers the advantages of being non-invasive,non-contact,and high-resolution.The use of OCT to explore structural changes in the retina among individuals with schizophrenia,bipolar disorder,major depression and other psychiatric disorders has been well documented;however,there is a paucity of reviews on this topic.This review summarizes current research on retinal structural alterations in patients with mental disorders,and the results demonstrate reduced thickness in certain sub-layers of the retina structure in patients with several mental disorders,which supports that the retina structure has the potential to be a biomarker for mental disorders and offers a novel avenue for research in the diagnosis and treatment.

Background and Aims:Abdominal aortic aneurysm(AAA)is a common arterial dilation disease in vascular surgery,with aneurysm rupture being its most serious complication,often leading to fatal hemorrhage and posing a severe threat to patients'lives.Endovascular aneurysm repair(EVAR),due to its minimally invasive nature,safety,and rapid recovery,has become the preferred treatment for AAA.However,endoleak,a complication unique to EVAR,remains a major clinical challenge.Persistent endoleak can lead to sustained high pressure within the aneurysm sac,increasing the risk of continued expansion and rupture.It is one of the main causes of the high reintervention rate following EVAR.In particular,the treatment strategy for type Ⅱ endoleaks remains controversial.This study was conducted to evaluate the clinical value of selective sac embolization via the iliac approach combined with standard EVAR in managing intraoperative immediate endoleaks.Methods:The clinical data of AAA patients with a risk of endoleak who underwent standard EVAR at the First Hospital of China Medical University between March 2023 and September 2024 were retrospectively collected.Patients were divided into an intervention group(n=42)and a non-intervention group(n=32)based on whether selective sac embolization via the iliac approach was performed during operation.General clinical data,preoperative anatomical characteristics of the AAA,surgical details,and postoperative follow-up results were compared between the two groups.Results:There were no statistically significant differences between the two groups in terms of age,sex,anatomical features,rupture rate,or off-label use(all P>0.05).The technical success rate during surgery was 100%in both groups.One patient in the intervention group experienced transient sigmoid colon ischemia after operation,which resolved with conservative treatment.The mean follow-up period was(6.49±4.68)months.The proportions of aneurysm sac shrinkage,stability,and enlargement in the intervention group were 40.5%,57.1%,and 2.4%,respectively,compared to 59.4%,40.6%,and 0.0%in the non-intervention group,with no statistically significant differences(all P>0.05).The incidence of endoleak during follow-up was also comparable between the two groups(P>0.05).Conclusion:For intraoperative endoleaks during standard EVAR,selective sac embolization via the iliac approach is a technically simple and safe method that provides short-term outcomes comparable to those in patients without intraoperative endoleaks.Its long-term efficacy warrants further investigation through extended follow-up.

Mental disorders frequently co-occur with other physical illnesses,becoming one of the leading causes of disability worldwide.Early diagnosis and intervention are crucial for the effective management of these disorders.Currently,biomarker studies on mental disorders predominantly concentrate on genes,blood indicators,and imaging features of the brain.There is a growing interest in objective phenotypic markers as a research focus.It is established that the retina is part of the central nervous system(CNS),which extends from the mesencephalon and develops concurrently with the brain during the embryonic period.Given the overlapping pathophysiological mechanisms between neurodegenerative diseases and mental disorders,studying the structural and functional changes in the inner layers of the retina has emerged as a new direction in mental health research.The advent of optical coherence tomography(OCT)has enabled microscopic imaging of retinal structures.OCT is capable of objectively quantifying the retinal sub-layers and offers the advantages of being non-invasive,non-contact,and high-resolution.The use of OCT to explore structural changes in the retina among individuals with schizophrenia,bipolar disorder,major depression and other psychiatric disorders has been well documented;however,there is a paucity of reviews on this topic.This review summarizes current research on retinal structural alterations in patients with mental disorders,and the results demonstrate reduced thickness in certain sub-layers of the retina structure in patients with several mental disorders,which supports that the retina structure has the potential to be a biomarker for mental disorders and offers a novel avenue for research in the diagnosis and treatment.

Objective:To investigate the efficacy and safety of intravesical injections of botulinum toxin A (BTX-A) for the treatment of pediatric refractory urinary frequency and incontinence (UFI), and to analyze the factors predicting the therapeutic effect of BTX-A injections.Methods:A retrospective case series study was made on 35 children with UFI [(12.3±4.2) years old], including 13 males (37.1%) and 22 females (62.9%), treated in the First Affiliated Hospital of Zhengzhou University from January 2021 to March 2024.Urotherapy and drug treatments were ineffective in all children, who then received intravesical injections of BTX-A.The urodynamic study (UDS) was performed 1 week before treatment and 3 months after treatment, and the Overactive Bladder Symptom Score (OABSS) and Incontinence Quality of Life (I-QOL) were collected.Perioperative and postoperative adverse events were also recorded.A global response assessment (GRA) score of ≥2 at 3 months postoperatively was defined as effective treatment.According to the postoperative GRA score, the patients were divided into effective and ineffective groups to explore the predictive factors affecting the outcome of BTX-A treatment, such as age, gender, preoperative urodynamic parameters, and the types of urinary incontinence. t-test was used to compare quantitative data such as age, UDS parameters, OABSS, and I-QOL scores.The comparison of count data such as gender and urinary incontinence types was conducted using Fisher′s exact test. Results:The bladder compliance, bladder capacity ratio, OABSS and I-QOL scores of patients significantly improved after BTX-A injection (all P<0.05).The 77.1% (27/35) of the patients were satisfied with BTX-A treatment effects.The main adverse event during the follow-up was a temporary increase in postvoid residual urine after injecting BTX-A (7 cases), which was alleviated by the Creade action or clean intermittent catheterization.There was significant difference in age [(13.00±4.32) years vs.(10.00±2.67) years] and preoperative bladder compliance [(11.21±5.74) mL/cmH 2O vs.(5.13±2.42) mL/cmH 2O] between effective (27 cases) and ineffective groups (8 cases) ( t=2.383, 2.899, all P<0.05).The differences in preoperative bladder capacity ratio, maximum filling detrusor pressure, postvoid residual urine, voiding efficiency, gender, and the types of urinary incontinence were not statistically significant between the two groups (all P>0.05). Conclusions:Intravesical injection of BTX-A is a safe and effective treatment for children with refractory UFI.A young age and poor bladder compliance at treatment are associated with poor prognosis of BTX-A treatment.

Objective:To elucidate the molecular mechanisms through which high-dose dexamethasone exerts long-term effects on bone marrow mesenchymal stem cells (BMSCs), specifically its role in suppressing osteogenic differentiation, accelerating cellular senescence, triggering the senescence-associated secretory phenotype (SASP), and inducing apoptosis.Methods:Primary rat BMSCs were isolated and treated with high-dose dexamethasone (1×10 -4 mol/L) to establish the experimental group, while untreated cells served as the control. The gene and protein expression levels of osteogenic markers, bone alkaline phosphatase (bALP) and Runt-related transcription factor 2 (Runx2), were analyzed in both groups. Cellular senescence was evaluated using senescence-associated β-galactosidase (SA-β-gal) staining. The expression of senescence-related markers (P16 and P21), components of the senescence-associated secretory phenotype (SASP), including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and interferon (IFN)-γ, as well as apoptosis-related proteins (Bcl-2, Bax, and Cleaved-Caspase-3), and key factors of the Nrf2/HO-1 signaling pathway were assessed at both transcriptional and protein levels using qRT-PCR, immunofluorescence, and Western-blot analyses. These comprehensive evaluations aimed to determine the senescent state, apoptotic features, and alterations in osteogenic differentiation of BMSCs. Results:Following treatment with dexamethasone and subsequent withdrawal, both qRT-PCR and Western blot analyses indicated a significant reduction in the expression of the osteogenic markers bALP and Runx2 at both mRNA and protein levels. The proportion of SA-β-gal positive cells was markedly higher in the dexamethasone group (74.33%±6.89%) than in the control group (20.30%±1.57%, t=17.300, P<0.001). qRT-PCR analysis revealed upregulated mRNA expression of the senescence-related genes P16 and P21 after dexamethasone treatment, which was further supported at the protein level by immunofluorescence showing increased P21 expression. Western-blot results confirmed that protein expression levels of P16 and P21 were significantly elevated in the dexamethasone group (7.025±0.255 and 6.362±0.456, respectively) compared with the control group (1.016±0.115 and 0.816±0.172; both P<0.05). Furthermore, gene expression levels of the senescence-associated secretory phenotype (SASP) factors TNF-α and IL-1β were significantly increased (TNF-α: 3.539±0.599 vs. 0.742±0.095; IL-1β: 4.469±0.331 vs. 0.799±0.175; both P<0.05), and their protein expression was consistently upregulated as validated by Western-blot. Additionally, protein expression levels of TNF-α, IL-1β, and IFN-γ were significantly higher in the dexamethasone-treated group (3.476±0.932 vs. 0.945±0.095; 4.111±0.220 vs. 0.762±0.105; 2.155±0.240 vs. 0.656±0.104; all P<0.05).Western-blot analysis also demonstrated that protein expression of Nrf2 and HO-1 was significantly suppressed in the dexamethasone group (0.21±0.07 and 0.19±0.06, respectively) compared with the control group (1.13±0.15 and 0.92±0.21; P<0.05). Moreover, Western-blot analysis revealed that the expression levels of the pro-apoptotic proteins Bax and Cleaved-Caspase-3 were significantly up, regulated in the dexamethasone, treated BMSCs (Bax: 3.673±0.397 vs. 0.453±0.111; Cleaved-Caspase-3: 3.863±0.399 vs. 0.465±0.057), while the expression of the anti-apoptotic protein Bcl-2 was markedly down, regulated (0.959±0.073 vs. 2.126±0.195), with all differences being statistically significant ( P<0.05). Conclusions:High-dose dexamethasone treatment of BMSCs, followed by withdrawal of dexamethasone, induces cellular senescence and enhances the expression of the senescence-associated secretory phenotype (SASP) through suppression of the Nrf2/HO-1 signaling pathway. Concurrently, it promotes apoptosis by activating the mitochondrial apoptotic pathway, collectively leading to impaired osteogenic differentiation of BMSCs.

Objective:To investigate the efficacy and safety of intravesical injections of botulinum toxin A (BTX-A) for the treatment of pediatric refractory urinary frequency and incontinence (UFI), and to analyze the factors predicting the therapeutic effect of BTX-A injections.Methods:A retrospective case series study was made on 35 children with UFI [(12.3±4.2) years old], including 13 males (37.1%) and 22 females (62.9%), treated in the First Affiliated Hospital of Zhengzhou University from January 2021 to March 2024.Urotherapy and drug treatments were ineffective in all children, who then received intravesical injections of BTX-A.The urodynamic study (UDS) was performed 1 week before treatment and 3 months after treatment, and the Overactive Bladder Symptom Score (OABSS) and Incontinence Quality of Life (I-QOL) were collected.Perioperative and postoperative adverse events were also recorded.A global response assessment (GRA) score of ≥2 at 3 months postoperatively was defined as effective treatment.According to the postoperative GRA score, the patients were divided into effective and ineffective groups to explore the predictive factors affecting the outcome of BTX-A treatment, such as age, gender, preoperative urodynamic parameters, and the types of urinary incontinence. t-test was used to compare quantitative data such as age, UDS parameters, OABSS, and I-QOL scores.The comparison of count data such as gender and urinary incontinence types was conducted using Fisher′s exact test. Results:The bladder compliance, bladder capacity ratio, OABSS and I-QOL scores of patients significantly improved after BTX-A injection (all P<0.05).The 77.1% (27/35) of the patients were satisfied with BTX-A treatment effects.The main adverse event during the follow-up was a temporary increase in postvoid residual urine after injecting BTX-A (7 cases), which was alleviated by the Creade action or clean intermittent catheterization.There was significant difference in age [(13.00±4.32) years vs.(10.00±2.67) years] and preoperative bladder compliance [(11.21±5.74) mL/cmH 2O vs.(5.13±2.42) mL/cmH 2O] between effective (27 cases) and ineffective groups (8 cases) ( t=2.383, 2.899, all P<0.05).The differences in preoperative bladder capacity ratio, maximum filling detrusor pressure, postvoid residual urine, voiding efficiency, gender, and the types of urinary incontinence were not statistically significant between the two groups (all P>0.05). Conclusions:Intravesical injection of BTX-A is a safe and effective treatment for children with refractory UFI.A young age and poor bladder compliance at treatment are associated with poor prognosis of BTX-A treatment.