Objective To evaluate the effect of Kaixin San(KXS)combined with fluoxetine on hippocampal neural stem cells in mice with chronic stress stress and depression.Methods A mouse model of depression was constructed using the method of chronic unpredictable stress stress,and the highest dose of KXS water extract and fluoxetine for clinical application was given for 28 days,and behavioral tests were carried out.Nissl staining was used to detect the pathological status of hippocampal tissues in mice.The expression of TUNEL and Nestin in mouse hippocampus was determined by immunofluorescence.Western blotting was used to detect the expressions of apoptotic proteins cleaved caspase-3 and caspase-3,pyroptosis proteins GSDMD and cleaved caspase-1,as well as the expression of neural stem cell marker Nestin in the hippocampus,and the expression of Wnt/β-catenin signaling pathway-related proteins in the hippocampus.Results The combination of KXS extract and fluoxetine can significantly improve the depression-like behavior of model mice,and the effect is better than fluoxetine alone.The combination inhibited the activation of apoptosis and pyroptosis signaling pathways in the hippocampus when used alone with high-dose fluoxetine,significantly upregulated the expression of Nestin,and regulated the expression of Wnt/β-catenin signaling pathway protein.Conclusion The combination of KXS and high-dose fluoxetine can improve apoptosis and pyroptosis in the hippocampus of stress stress and depression model mice,and upregulate the expression of neural stem cell marker Nestin by regulating the Wnt/β-catenin signaling pathway,which may be a key link to improve the antidepressant effect of the combination drug.

OBJECTIVES: To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard. METHODS: Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard. RESULTS: Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively. CONCLUSIONS SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies ; Treatment Outcome ; Double-Balloon Enteroscopy/statistics & numerical data* ; Single-Balloon Enteroscopy/statistics & numerical data* ; Humans ; Male ; Female ; Child ; Operative Time ; Tomography, X-Ray Computed/statistics & numerical data* ; Sensitivity and Specificity ; Intestine, Small/surgery* ; Intestinal Diseases/surgery*

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

Objective To evaluate the effect of Kaixin San(KXS)combined with fluoxetine on hippocampal neural stem cells in mice with chronic stress stress and depression.Methods A mouse model of depression was constructed using the method of chronic unpredictable stress stress,and the highest dose of KXS water extract and fluoxetine for clinical application was given for 28 days,and behavioral tests were carried out.Nissl staining was used to detect the pathological status of hippocampal tissues in mice.The expression of TUNEL and Nestin in mouse hippocampus was determined by immunofluorescence.Western blotting was used to detect the expressions of apoptotic proteins cleaved caspase-3 and caspase-3,pyroptosis proteins GSDMD and cleaved caspase-1,as well as the expression of neural stem cell marker Nestin in the hippocampus,and the expression of Wnt/β-catenin signaling pathway-related proteins in the hippocampus.Results The combination of KXS extract and fluoxetine can significantly improve the depression-like behavior of model mice,and the effect is better than fluoxetine alone.The combination inhibited the activation of apoptosis and pyroptosis signaling pathways in the hippocampus when used alone with high-dose fluoxetine,significantly upregulated the expression of Nestin,and regulated the expression of Wnt/β-catenin signaling pathway protein.Conclusion The combination of KXS and high-dose fluoxetine can improve apoptosis and pyroptosis in the hippocampus of stress stress and depression model mice,and upregulate the expression of neural stem cell marker Nestin by regulating the Wnt/β-catenin signaling pathway,which may be a key link to improve the antidepressant effect of the combination drug.

Objective:To investigate the therapeutic outcomes of patients with horseshoe kidney and hydronephrosis under different surgical approaches and with or without isthmus division.Methods:This study is a retrospective case series research. A retrospective analysis was conducted on the clinical data of 23 patients with horseshoe kidney and hydronephrosis who underwent pyeloplasty at the Department of Urology, the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. Among them, there were 11 males and 12 females, with an age of (33±15) years (range:7 to 64 years). Patients underwent preoperative examinations, including ultrasonography of the urinary system, intravenous urography, CT urography, or magnetic resonance urography. Retrograde urography or antegrade ureteropyelography was performed when necessary to clarify the degree of hydronephrosis, the location and length of ureteral stricture. For patients with severe hydronephrosis, a ureteral stricture segment >2 cm, a thick renal isthmus in horseshoe kidney, and markedly variant vasculature, open surgery or robotic surgery is preferred. For those with mild to moderate hydronephrosis, a ureteral stricture segment <2 cm, a thin renal isthmus in horseshoe kidney, and no significant vascular variations, laparoscopic surgery is the first choice. The decision to perform isthmectomy should be made based on a comprehensive intraoperative assessment, including the vascular supply to the isthmus, the degree of surrounding adhesions, and the thickness of the isthmus. Perioperative parameters and complications were recorded and analyzed, and regular follow-up was conducted for all patients.Results:All surgeries were successfully completed. Surgical approaches included open surgery in 4 cases, laparoscopic surgery in 14 cases, and robot-assisted laparoscopic surgery in 5 cases. The operative time for open surgery, laparoscopic surgery and robot-assisted laparoscopic surgery was (125±12) minutes (range: 112 to 141 minutes), (122±50) minutes (range: 60 to 233 minutes), and (130±36) minutes (range: 76 to 174 minutes), respectively. The blood loss ( M(IQR)) was 100 (25) ml (range: 50 to 100 mL) for open surgery, 35 (30) ml (range: 10 to 100 mL) for laparoscopic surgery, and 20 (10) ml (range: 20 to 50 ml) for robot-assisted laparoscopic surgery. Among 15 patients who underwent isthmus division with pyeloplasty (division group), the operation time was (138±42) minutes (range: 73 to 233 minutes), with blood loss of 50 (80) ml (range: 20 to 100 ml). For 8 patients in the non-division group who only underwent pyeloureteroplasty, the operation time was (98±27) minutes (range: 60 to 135 minutes), with blood loss of 20 (50) ml (range: 10 to 100 ml). The follow-up time of patients after surgery was 16.0 (49.0) months (range: 1.7 to 84.2 months), with a surgical success rate of 100%. Among the 8 patients in the non-division group, all demonstrated significant improvement in hydronephrosis severity compared to preoperative conditions. Notably, 6 patients who previously experienced frequent lower back pain showed no recurrence of symptoms after ureteral stent removal. In the division group of 15 patients, both subjective symptoms and hydronephrosis severity were markedly reduced. Conclusion:For patients with horseshoe kidney and hydronephrosis, the choice of surgical approach and isthmus management strategy should be determined based on a comprehensive consideration of the etiology of hydronephrosis, the degree of ureteral stricture, anatomical abnormalities, and vascular variations.

Objective:To investigate the therapeutic outcomes of patients with horseshoe kidney and hydronephrosis under different surgical approaches and with or without isthmus division.Methods:This study is a retrospective case series research. A retrospective analysis was conducted on the clinical data of 23 patients with horseshoe kidney and hydronephrosis who underwent pyeloplasty at the Department of Urology, the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. Among them, there were 11 males and 12 females, with an age of (33±15) years (range:7 to 64 years). Patients underwent preoperative examinations, including ultrasonography of the urinary system, intravenous urography, CT urography, or magnetic resonance urography. Retrograde urography or antegrade ureteropyelography was performed when necessary to clarify the degree of hydronephrosis, the location and length of ureteral stricture. For patients with severe hydronephrosis, a ureteral stricture segment >2 cm, a thick renal isthmus in horseshoe kidney, and markedly variant vasculature, open surgery or robotic surgery is preferred. For those with mild to moderate hydronephrosis, a ureteral stricture segment <2 cm, a thin renal isthmus in horseshoe kidney, and no significant vascular variations, laparoscopic surgery is the first choice. The decision to perform isthmectomy should be made based on a comprehensive intraoperative assessment, including the vascular supply to the isthmus, the degree of surrounding adhesions, and the thickness of the isthmus. Perioperative parameters and complications were recorded and analyzed, and regular follow-up was conducted for all patients.Results:All surgeries were successfully completed. Surgical approaches included open surgery in 4 cases, laparoscopic surgery in 14 cases, and robot-assisted laparoscopic surgery in 5 cases. The operative time for open surgery, laparoscopic surgery and robot-assisted laparoscopic surgery was (125±12) minutes (range: 112 to 141 minutes), (122±50) minutes (range: 60 to 233 minutes), and (130±36) minutes (range: 76 to 174 minutes), respectively. The blood loss ( M(IQR)) was 100 (25) ml (range: 50 to 100 mL) for open surgery, 35 (30) ml (range: 10 to 100 mL) for laparoscopic surgery, and 20 (10) ml (range: 20 to 50 ml) for robot-assisted laparoscopic surgery. Among 15 patients who underwent isthmus division with pyeloplasty (division group), the operation time was (138±42) minutes (range: 73 to 233 minutes), with blood loss of 50 (80) ml (range: 20 to 100 ml). For 8 patients in the non-division group who only underwent pyeloureteroplasty, the operation time was (98±27) minutes (range: 60 to 135 minutes), with blood loss of 20 (50) ml (range: 10 to 100 ml). The follow-up time of patients after surgery was 16.0 (49.0) months (range: 1.7 to 84.2 months), with a surgical success rate of 100%. Among the 8 patients in the non-division group, all demonstrated significant improvement in hydronephrosis severity compared to preoperative conditions. Notably, 6 patients who previously experienced frequent lower back pain showed no recurrence of symptoms after ureteral stent removal. In the division group of 15 patients, both subjective symptoms and hydronephrosis severity were markedly reduced. Conclusion:For patients with horseshoe kidney and hydronephrosis, the choice of surgical approach and isthmus management strategy should be determined based on a comprehensive consideration of the etiology of hydronephrosis, the degree of ureteral stricture, anatomical abnormalities, and vascular variations.

Objective To investigate the beneficial effect of Kai-Xin-San combined with fluoxetine in improving depression-like behaviors on chronic unpredictable mild stress(CUMS)induced depression model mice.Methods The present study aimed to assess the potential of Kai-Xin-San in combination with fluoxetine to ameliorate depression-like behaviors in a CUMS induced mouse depression model.Behavioral tests,such as the sucrose preference test were employed to evaluate the efficacy of the treatment.Additionally,the levels of suppressed stress factors were measured using the ELISA method.The morphology of hippocampal tissue was evaluated using the HE staining method,Nissl Staining and TUNEL staining methods.Furthermore,western blotting analysis was utilized to determine the expression levels of proteins such as Caspase-3,and Caspase-9.Results The co-administration of Kai-Xin-San and fluoxetine resulted in a significant increase in sucrose preference rate in model mice.This effect was comparable to that of fluoxetine alone at the standard clinical dose.Furthermore,the combination treatment up-regulated the levels of suppressed stress factors,reduced the apoptosis of hippocampus induced by depression and regulated the apoptosis signaling pathway in hippocampus.Conclusion The combination of Kai-Xin-San and fluoxetine has been shown to be an effective treatment for depression-like behavior in animal models,resulting in a reduction in the required clinical dosage of fluoxetine.This effect may be attributed to the up-regulation of neurotransmitter expression,inhibition of stress axis activation,and central nervous inflammation.

Objective:To investigate the effects of intra-articular injection of exosomes derived from dental pulp stem cells from hu-man exfoliated deciduous teeth(SHED-EXO)on subchondral bone homeostasis in rat temporomandibular joint osteoarthritis(TMJ OA)process.Methods:36 male SD rats were randomly divided into 3 groups(n=12):control(CON),sodium iodoacetate(MIA)-induced TMJ OA(MIA),and SHED-EXO injection into TMJ OA(SHED-EXO)groups.At 2 and 6 weeks post-treatment,Micro-CT,Double labeling,TRAP staining,and immunohistochemical staining were employed to detect osteoclasts and osteoblasts in the subchondral bone.Additionally,the mRNA expression levels of ADAMTs5,IL-1β,OCN and OPG/RANKL were analyzed by qRT-PCR.Results:The MIA group exhibited significant bone loss and an enlarged bone marrow cavity.In comparison with the CON group,BV/TV and Tb.Th were lower(P＜0.001),while BS/BV,Tb.Sp,and Tb.N were higher(P＜0.01).Additionally,the bone formation rate within 5 days was low-er than that of the control group(P＜0.001).When compared to the MIA group,the SHED-EXO group showed a significant increase in bone morphology and bone mass.BV/TV and Tb.Th were increased(P＜0.01),while BS/BV,Tb.Sp and Tb.N were decreased(P＜0.05).The bone formation rate was higher(P＜0.01).Compared with both the control and treatment groups,the MIA group exhibited a significant increase in the number of osteoclasts in the subchondral bone(P＜0.01),along with a notable decrease in H-type blood vessels and OCN-positive areas(P＜0.01).Conclusion:Intra-articular injection of SHED-EXO can reg-ulate condylar subchondral bone homeostasis in TMJ OA of rats by promoting osteogenesis and inhibiting osteoclasts.

The aging disease associated with type 2 diabetes mellitus(T2DM)is a hot research topic in the field of diabetes at present.Sarcopenia has become the third major complication of T2DM after microvascular and macrovascular diseases,which could lead to the occurrence and development of various adverse events such as fracture,disability,and dysfunction.The spleen belongs to the earth,is in the middle jiao,governs transportation and transformation,and governs muscle.The functional activities of the spleen manifesting in normal transformation and transportation,the distribution of cereal essence,and the nourishment of muscles are necessary for normal physiological functions to be exerted.Recent studies have shown that skeletal muscle cell ferroptosis plays an important role in the pathogenesis of T2DM sarcopenia.Based on the theory of"spleen governing transportation and transportation and governing muscle",this study explores the pathogenesis of T2DM sarcopenia from the perspectives of the pathogenesis of"dysfunction of spleen in transportation,deficiency of cereal essence,obstruction of dampness and turbidity,and muscle dystrophy"in traditional Chinese medicine and the pathological mechanism of"skeletal muscle cell ferroptosis"in modern medicine.It summarizes the principles of traditional Chinese medicine prevention and treatment for T2DM sarcopenia based on the spleen,to provide theoretical support for enriching the theoretical connotation of spleen visceral state,as well as basic research and clinical trials on the prevention and treatment of T2DM sarcopenia with traditional Chinese medicine.

OBJECTIVES: To investigate the role of mitochondrial autophagy disorder caused by deletion of E3 ubiquitin ligase Parkin in neuroinflammation in a mouse model of MPTP-induced Parkinson's disease (PD). METHODS: Wild-type (WT) male C57BL/6 mice and Parkin^-/- mice were given intraperitoneal injections with MPTP or PBS for 5 consecutive days, and the changes in motor behaviors of the mice were observed using open field test. The effects of Parkin deletion on PD development and neuroinflammation were evaluated using immunofluorescence and Western blotting. The changes of the PINK 1/Parkin signaling pathway in the midbrain substantia nigra of the mice were examined to explore the molecular mechanism of Parkin-mediated regulation of mitochondrial autophagy and its effect on neuroinflammation in PD mice. RESULTS: Compared with their WT counterparts, the Parkin^-/- mice with MPTP injections exhibited significant impairment of motor function with decreased TH⁺ neurons, increased α-synuclein (α-syn) accumulation, and increased numbers of GFAP⁺ and I-ba1⁺ cells in the midbrain substantia nigra. Parkin deletion obviously affected PINK1/Parkin-mediated mitochondrial autophagy to result in significantly increased mtDNA and upregulated expressions of STING and NLRP3 inflammatosomes in the midbrain substantia nigra of MPTP-treated transgenic mice. CONCLUSIONS Parkin deletion causes mitochondrial autophagy disorder to accelerate PD progression and exacerbates neuroinflammation in mice by affecting the PINK1/Parkin signaling pathway, suggesting the important role of Parkin in early pathogenesis of PD.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Mice ; Mice, Inbred C57BL ; Male ; Parkinson Disease/genetics* ; Protein Kinases/genetics* ; Mitochondria/metabolism* ; Disease Models, Animal ; Autophagy ; Signal Transduction ; Neuroinflammatory Diseases/metabolism* ; Mice, Knockout ; alpha-Synuclein/metabolism* ; Substantia Nigra/metabolism* ; Mitophagy ; Disease Progression