Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Objective:To investigate the application value of flexible traction suspension (FTS) strategy in pure single-incision laparoscopic distal gastrectomy (PSILDG).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 12 patients who underwent PSILDG in The Second Affiliated Hospital of Army Medical University from November 2021 to March 2024 were collected. There were 8 males and 4 females, aged (53±14)years. Observation indicators: (1) intraoperative conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absolute numbers. Results:(1) Intraoperative conditions. All 12 patients underwent PSILDG with FTS strategy successfully, with the operation time of (260±31) minutes, the volume of intraoperative blood loss of 103.3(37.5,150.0)mL, the length of surgical incision of (3.9±0.6)cm. There was no intra-operative special circumstance or complication. (2) Postoperative conditions. Results of histopatho-logical examination showed that among the 12 patients, there were 10 cases of adenocarcinoma, 1 case of signet ring cell carcinoma, and 1 case of high-grade intraepithelial neoplasia. The distance of the proximal tumor margin was 2.8(2.0,3.4)cm, the distance of distal margin was 5.9(5.0,7.5)cm, the tumor diameter was (2.3±1.0)cm, and the number of lymph node dissected was 34±10. On the post-operative first day, all 12 patients had a visual analog score of 1.0. The time to postoperative removal of gastric tube was 1.25(1.00,1.75)days, the time to postoperative first intake of liquid food was 2.00(1.00,2.00)days, the time to postoperative first out-of-bed activity was 1.67(1.00,2.00)days, the time to postoperative first flatus was 2.40(2.00,3.00)days, the time to postoperative first bowel movement was 3.50(2.00,5.00)days, the duration of postoperative hospital stay was (7.10±1.40) days, and the satisfaction score for the abdominal wall incision was 20.6±2.7. No patient experien-ced postopera-tive complications. (3) Follow-up. All 12 patients completed a 30-day follow-up after surgery, with no complication or need for secondary surgery.Conclusion:Application of FTS strategy in PSILDG is safe and feasible.

Objective:To investigate the application value of flexible traction suspension (FTS) strategy in pure single-incision laparoscopic distal gastrectomy (PSILDG).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 12 patients who underwent PSILDG in The Second Affiliated Hospital of Army Medical University from November 2021 to March 2024 were collected. There were 8 males and 4 females, aged (53±14)years. Observation indicators: (1) intraoperative conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absolute numbers. Results:(1) Intraoperative conditions. All 12 patients underwent PSILDG with FTS strategy successfully, with the operation time of (260±31) minutes, the volume of intraoperative blood loss of 103.3(37.5,150.0)mL, the length of surgical incision of (3.9±0.6)cm. There was no intra-operative special circumstance or complication. (2) Postoperative conditions. Results of histopatho-logical examination showed that among the 12 patients, there were 10 cases of adenocarcinoma, 1 case of signet ring cell carcinoma, and 1 case of high-grade intraepithelial neoplasia. The distance of the proximal tumor margin was 2.8(2.0,3.4)cm, the distance of distal margin was 5.9(5.0,7.5)cm, the tumor diameter was (2.3±1.0)cm, and the number of lymph node dissected was 34±10. On the post-operative first day, all 12 patients had a visual analog score of 1.0. The time to postoperative removal of gastric tube was 1.25(1.00,1.75)days, the time to postoperative first intake of liquid food was 2.00(1.00,2.00)days, the time to postoperative first out-of-bed activity was 1.67(1.00,2.00)days, the time to postoperative first flatus was 2.40(2.00,3.00)days, the time to postoperative first bowel movement was 3.50(2.00,5.00)days, the duration of postoperative hospital stay was (7.10±1.40) days, and the satisfaction score for the abdominal wall incision was 20.6±2.7. No patient experien-ced postopera-tive complications. (3) Follow-up. All 12 patients completed a 30-day follow-up after surgery, with no complication or need for secondary surgery.Conclusion:Application of FTS strategy in PSILDG is safe and feasible.

Macrophage-mediated inflammation plays a pivotal role in cardiovascular disease pathogenesis. However, current cell-based models lack a comprehensive understanding of crosstalk between macrophages and cardiomyocytes, hindering the discovery of effective therapeutic interventions. Here, a microfluidic model has been developed to facilitate the coculture of macrophages and cardiomyocytes, allowing for mapping key signaling pathways and screening potential therapeutic agents against inflammation-induced dynamic myocardial injury. Through metabolic profiling and bioinformatic enrichment analysis, the microchip model with dynamic cell-cell crosstalk reveals robust activation of inflammatory and oxidative stress-associated metabolic pathways, closely resembling metabolic profiles of myocardial infarction in both humans and rodents. Furthermore, an integrative screening strategy has been established to screen bioactive natural products precisely, identifying ginsenoside Rb₁ and protocatechualdehyde as promising cardioprotective candidates in vitro and in vivo. Taken together, the microfluidic coculture model advances mechanistic insight into macrophage-mediated cardio-immunology and may accelerate the discovery of therapeutics for myocardial injury.

Objective:To evaluate the role of succinate dehydrogenase (SDH) in hypoxic postconditioning (HPC)-induced reduction of hypoxia-reoxygenation (H/R) injury in myocardial cells of rats and the relationship with mitochondrial ATP-sensitive potassium channels (mito-K ATP). Methods:Myocardial cells isolated from adult male Sprague-Dawley rats were cultured for 48 h and then divided into 7 groups ( n=24 each) using a random number table method: blank control group (Nor group), H/R group, SDHA-siRNA adenovirus+ H/R group (siRNA+ H/R group), HPC group, SDHA-siRNA adenovirus+ HPC group (siRNA+ HPC group), 5-HD+ HPC group, and SDHA-siRNA adenovirus+ 5-HD+ HPC group (siRNA+ 5-HD+ HPC group). Nor group was continuously cultured for 195 min under normoxic conditions. The H/R injury model was prepared by exposing the cells to hypoxia for 45 min in 5% CO 2 + 1% O 2 + 94% N 2, followed by reoxygenation for 150 min. The HPC method involved three cycles of 5 min reoxygenation/5 min hypoxia at the end of 45 min ischemia before 120 min reoxygenation. The mito-K ATP blocker 5-HD administration method involved adding 5-HD at a final concentration of 100 μmol/L at 30 min of hypoxia. The myocardial cells in each siRNA group were successfully transfected with SDHA-siRNA adenovirus to silence SDHA expression. The cell viability, calcium ion level, SDH activity, ATP content, degree of mitochondrial permeability transition pore (mPTP) opening, and mitochondrial membrane potential (MMP) were measured at the end of reoxygenation. Results:Compared with Nor group, the cell viability, ATP content and MMP were significantly decreased, and the degree of mPTP opening, level of calcium ion and activity of SDH were increased in H/R group ( P<0.05). Compared with H/R group, the cell viability, ATP content and MMP were significantly increased, and the degree of mPTP opening, calcium ion level and SDH activity were decreased in siRNA+ H/R group and HPC group ( P<0.05). Compared with HPC group, the cell viability, ATP content and MMP were significantly decreased, and the degree of mPTP opening, calcium ion level and SDH activity were increased in 5-HD+ HPC group ( P<0.05), and the cell viability, ATP content and MMP were significantly increased, and the degree of mPTP opening, calcium ion level and SDH activity were decreased in siRNA+ HPC group ( P<0.05). Compared with siRNA+ HPC group, the cell viability, ATP content and MMP were significantly decreased, the opening degree of mPTP and calcium ion level were increased ( P<0.05), and no significant change was found in the SDH activity in siRNA+ 5-HD+ HPC group ( P>0.05). Compared with 5-HD+ HPC group, the SDH activity was significantly decreased, and no significant change was found in the other parameters in siRNA+ 5-HD+ HPC group ( P>0.05). Conclusions:HPC alleviates H/R injury probably by reducing SDH activity and opening mito-K ATP in myocardial cells of rats.

Dihydroflavonol 4-reductase (DFR) plays an essential role in the biosynthesis of anthocyanin and regulation of plant flower color. Based on the transcriptome data of Cistanche tubulosa (Schenk) Wight, a full-length cDNA sequence of CtDFR gene was cloned by reverse transcription-polymerase chain reaction (RT-PCR). CtDFR contains an open reading frame (ORF) of 1 263 bp which encodes 420 amino acids with a predicted molecular weight of 47.5 kDa. The sequence analysis showed that CtDFR contains a nicotinamide adenine dinucleotide phosphate (NADPH) binding domain and a specific substrate binding domain. The expression analysis indicated that CtDFR was highly expressed in red and purple flowers, and the relative expression levels were 4.04 and 19.37 times higher than those of white flowers, respectively. The recombinant CtDFR protein was expressed in E.coli BL21 (DE3) using vector pET-28a-CtDFR and was purified. In vitro enzyme activity analysis, CtDFR could reduce three types of dihydroflavonols including dihydrokaempferol, dihydroquercetin, and dihydromyricetin to leucopelargonidin, leucocyanidin and leucodelphinidin. Subcellular localization analysis showed that CtDFR was mainly localized in the cytoplasm. These results demonstrate that CtDFR plays an important role in regulation of flower color in C. tubulosa and make a valuable contribution for the further investigation on the regulation mechanism of C. tubulosa (Schenk) Wight flower color.

Qualitative and quantitative analysis of 2-(2-phenylethyl) chromones in sodium chloride(NaCl)-treated suspension cells of Aquilaria sinensis was conducted by UPLC-Q-Exactive-MS and UPLC-QQQ-MS/MS. Both analyses were performed on a Waters T3 column(2.1 mm×50 mm, 1.8 μm) with 0.1% formic acid aqueous solution(A)-acetonitrile(B) as mobile phases at gradient elution. MS data were collected by electrospray ionization in positive ion mode. Forty-seven phenylethylchromones was identified from NaCl-treated suspension cell samples of A. sinensis using UPLC-Q-Exactive-MS, including 22 flindersia-type 2-(2-phenylethyl) chromones and their glycosides, 10 5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones and 15 mono-epoxy or diepoxy-5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones. Additionally, 25 phenylethylchromones were quantitated by UPLC-QQQ-MS/MS. Overall, the rapid and efficient qualitative and quantitative analysis of phenylethylchromones in NaCl-treated suspension cells of A. sinensis by two LC-MS techniques, provides an important reference for the yield of phenylethylchromones in Aquilariae Lignum Resinatum using in vitro culture and other biotechnologies.
Chromones ; Sodium Chloride ; Chromatography, Liquid ; Flavonoids ; Tandem Mass Spectrometry ; Thymelaeaceae

Objective:To compare the clinical effects of acute shortening-lengthening technique with antibiotic calcium sulfate-loaded bone transport technique for the treatment of segmental tibial defects after trauma.Methods:The clinical data of 58 patients with large tibial defects treated by Ilizarov technique in Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University from May 2014 to December 2019 were retrospectively analyzed. Thirty patients were treated by acute shortening-lengthening (group A), and they were divided into those who were successful in one-time shortening during operation (group A1) and those who needed gradual shortening after operation (group A2) according to different shortening conditions. And 28 patients by antibiotic calcium sulfate-loaded bone transport (group B). The external fixation time (EFT) and external fixation index (EFI) of the two groups were compared. Bone defect healing and limb functions were evaluated according to the Association for the Study and Application of the Method of Ilizarov (ASAMI) criteria. Complications were compared by Paley classification. The measurement data of normal distribution were expressed as ± s, and t-test was used for comparison between groups; the count data were expressed as n(%), and the chi-square test, Fisher exact probability method or Mann-Whitney U test were used for comparison between groups. Results:Patients were followed for(27.5±5.1)months. There was no significant difference in EFT, EFI, bone defect healing and limb functions between the two groups( P>0.05). The incidence of Grade-Ⅱ[41.2% (7/17)], Grade-Ⅲ [47.1% (8/17)] pin-tract infection in group A1 and Grade-Ⅱ[46.2% (6/13)], Grade-Ⅲ pin-tract [53.8% (7/13)] in group A2 was significantly higher than those in group B[14.3% (4/28)], [17.9% (5/28)] ( P<0.05). The number of complications per capita in group A1 [(1.4±0.3) times/case] and in group A2 [(1.5±0.3) times/case]was significantly higher than that in group B [(1.1±0.5) times/case]. Conclusions:Patients can be cured successfully by both acute shortening-lengthening and bone transport techniques. Compared with acute shortening-lengthening group, the complication incidence in antibiotic calcium sulfate-loaded bone transport group was lower, especially, the infection-related complications. Therefore, antibiotic calcium sulfate-loaded bone transport technique has a greater application prospect in patients with large segmental bone defects caused by infection or osteomyelitis.

Objective:To analyze the therapeutic effect of sural neurocutaneous flap combined with antibiotic-impregnated calcium sulfate and autogenous iliac bone graft of chronic calcaneal osteomyelitis.Methods:A retrospective analysis was peformed in 29 patients with chronic calcaneal osteomyelitis treated with sural neurocutaneous flap combined with antibiotic-impregnated calcium sulfate and autogenous iliac bone graft in the Xi′an Honghui Hospital Affiliated to Xi′an Jiaotong University from April 2013 to January 2020. There were 19 males and 10 females, with the age of (45.38±12.85) years, ranged from 22 to 67 years. The course of disease was (16.00±6.96) months, ranged from 6 to 36 months. The skin defect area was (41.9±15.9) cm 2, ranged from 11.8 to 86.8 cm 2. The causes of injury: 18 cases of high fall, 6 cases of traffic accidents, 3 cases of heavy rolling, the remaining 2 cases were machine strangulation and sharp stab wounds. The inflammatory markers [white blood cell (WBC), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), C reactive protein (CRP)] and bone healing time were recorded before operation, 2, 4, 8 weeks and 6 months after operation. During the follow-up period, the flap texture, survival were observed, and the ankle-posterior foot function recovery was evaluated by the American Association of Foot and Ankle Surgery (AOFAS) score were observed before and after the operation, and the incidence of complications were recorded. The measurement data were expressed as mean±standard deviation ( ± s), and the t-test was used for inter-group comparison; the levels of WBC, ESR, PCT and CRP at different time points before and after operation were compared by repeated measurement ANOVA, and the LSD t-test was used for pairwise comparison. Results:All the 29 patients were followed up for (14.51±6.10) months, ranged from 6 to 30 months. All the flaps survived without abrasion, ulceration, or skin protrusion, and all patients could walk normally with shoes. There were 28 cases of stage I bone healing, with an average of (5.87±2.07) months, ranged from 3 to 12 months. The inflammatory indexes was significantly decreased at different time points after operation ( P<0.05). There was no significant difference between 6 months and 8 weeks after operation ( P>0.05), while there was significant difference at other time points ( P<0.05). The ankle-posterior foot score of AOFAS at 6 months after treatment was significantly higher than that before treatment (83.44±7.93 vs 55.37±8.07), the differences was statistically significant ( P<0.05). The clinical efficacy of foot function recovery was excellent in 12 cases, good in 15 cases and fair in 2 cases among 29 patients .The excellent and good rate was 93.1% (27/29). One patient recurred 1 month after operation and was re-implanted with antibiotic-loaded calcium sulfate mixed autogenous iliac bone after debridement, no recurrence was found. The total complication rate was 31.0%, but there was no significant impact on the patient's life in the later period. All patients returned to daily life and work. Conclusion:The treatment of chronic calcaneal osteomyelitis with sural neurocutaneous flap combined with antibiotic-impregnated calcium sulfate and autogenous iliac bone graft can effectively control infection, reconstruct calcaneal and soft tissue structure, promote functional recovery of affected limb, and ultimately improve the patient′s quality of life.

Objective: To investigate the clinicopathological features, treatment and prognosis of gastric intermediate-risk gastrointestinal stromal tumor (GIST), so as to provide a reference for clinical management and further research. Methods: A retrospective observational study of patients with gastric intermediate-risk GIST, who underwent surgical resection between January 1996 and December 2019 at Zhongshan Hospital of Fudan University, was carried out. Results: Totally, 360 patients with a median age of 59 years were included. There were 190 males and 170 females with median tumor diameter of 5.9 cm. Routine genetic testing was performed in 247 cases (68.6%, 247/360), and 198 cases (80.2%) showed KIT mutation, 26 cases (10.5%) showed PDGFRA mutation, and 23 cases were wild-type GIST. According to "Zhongshan Method"(including 12 parameters), there were 121 malignant and 239 non-malignant cases. Complete follow-up data were available in 241 patients; 55 patients (22.8%) received imatinib therapy, 10 patients (4.1%) experienced tumor progression, and one patient (PDGFRA mutation, 0.4%) died. Disease-free survival (DFS) and overall survival rate at 5 years was 96.0% and 99.6%, respectively. Among the intermediate-risk GIST, there was no difference in DFS between the overall population, KIT mutation, PDGFRA mutation, wild-type, non-malignant and malignant subgroups (all P>0.05). However, the non-malignancy/malignancy analysis showed that there were significant differences in DFS among the overall population (P<0.01), imatinib treatment group (P=0.044) and no imatinib treatment group (P<0.01). Adjuvant imatinib resulted in potential survival benefit for KIT mutated malignant and intermediate-risk GIST in DFS (P=0.241). Conclusions: Gastric intermediate-risk GIST shows a heterogeneous biologic behavior spectrum from benign to highly malignant. It can be further classified into benign and malignant, mainly nonmalignant and low-grade malignant. The overall disease progression rate after surgical resection is low, and real-world data show that there is no significant benefit from imatinib treatment after surgery. However, adjuvant imatinib potentially improves DFS of intermediate-risk patients with tumors harboring KIT mutation in the malignant group. Therefore, a comprehensive analysis of gene mutations in benign/malignant GIST will facilitate improvements in therapeutic decision-making.
Male ; Female ; Humans ; Middle Aged ; Gastrointestinal Stromal Tumors/surgery* ; Retrospective Studies ; Antineoplastic Agents/therapeutic use* ; Prognosis ; Imatinib Mesylate/therapeutic use* ; Mutation ; Proto-Oncogene Proteins c-kit/genetics*