ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.

Objective To investigate the predictive value of endotracheal tube cuff pressure change(△Pcuff)on extubation outcome in mechanically ventilated patients with acute exacerbation of chronic obstructive pulmonary diseas(AECOPD).Methods A total of 93 AECOPD patients who underwent mechanical ventilation for at least 48 hours and required extubation through spontaneous breathing trial(SBT)from March 2023 to August 2024 in the Department of Critical Care Medicine of Deyang People's Hospital were selected as study subjects.According to the outcome of extubation,they were divided into successful extubation group and failed extubation group.General clinical data,laboratory results,△Pcuff at the start and at 30min of SBT were compared between two groups.Binary Logistic regression was used to analyze the risk factors affecting the outcome of extubation in AECOPD patients.The predictive value of △Pcuff for extubation outcome was evaluated by receiver operating characteristic(ROC)curve.Results Of the 93 patients,81 were successfully extubed and 12 were failed.Univariate analysis showed that △Pcuff(at the beginning of SBT),△Pcuff(SBT 30min),systolic blood pressure,pH,arterial partial pressure of oxygen,arterial partial pressure of carbon dioxide,and oxygenation index were all factors influencing the outcome of extubation(P＜0.05).Binary Logistic regression analysis showed that △Pcuff(at the beginning of SBT)was an independent risk factor for extubation outcome(P＜0.05).The ROC curve showed that △Pcuff(at the beginning of SBT)predicted extubation outcome with an area under the curve of 0.913,sensitivity of 84.0％,specificity of 83.3％,and Yoden index of 0.673,with an optimal cutoff of 34.5cmH2O(1cmH2O=0.098kPa).Conclusion The △Pcuff(at the beginning of SBT)has a good predictive value for the extubation outcome of mechanically ventilated patients with AECOPD,and the probability of successful extubation of a patient is higher when the △Pcuff is ≥34.5 cmH2O.

Objective To investigate the predictive value of endotracheal tube cuff pressure change(△Pcuff)on extubation outcome in mechanically ventilated patients with acute exacerbation of chronic obstructive pulmonary diseas(AECOPD).Methods A total of 93 AECOPD patients who underwent mechanical ventilation for at least 48 hours and required extubation through spontaneous breathing trial(SBT)from March 2023 to August 2024 in the Department of Critical Care Medicine of Deyang People's Hospital were selected as study subjects.According to the outcome of extubation,they were divided into successful extubation group and failed extubation group.General clinical data,laboratory results,△Pcuff at the start and at 30min of SBT were compared between two groups.Binary Logistic regression was used to analyze the risk factors affecting the outcome of extubation in AECOPD patients.The predictive value of △Pcuff for extubation outcome was evaluated by receiver operating characteristic(ROC)curve.Results Of the 93 patients,81 were successfully extubed and 12 were failed.Univariate analysis showed that △Pcuff(at the beginning of SBT),△Pcuff(SBT 30min),systolic blood pressure,pH,arterial partial pressure of oxygen,arterial partial pressure of carbon dioxide,and oxygenation index were all factors influencing the outcome of extubation(P＜0.05).Binary Logistic regression analysis showed that △Pcuff(at the beginning of SBT)was an independent risk factor for extubation outcome(P＜0.05).The ROC curve showed that △Pcuff(at the beginning of SBT)predicted extubation outcome with an area under the curve of 0.913,sensitivity of 84.0％,specificity of 83.3％,and Yoden index of 0.673,with an optimal cutoff of 34.5cmH2O(1cmH2O=0.098kPa).Conclusion The △Pcuff(at the beginning of SBT)has a good predictive value for the extubation outcome of mechanically ventilated patients with AECOPD,and the probability of successful extubation of a patient is higher when the △Pcuff is ≥34.5 cmH2O.

Panax species are mostly valuable medicinal plants. While some species' seeds are sensitive to dehydration, the dehydration tolerance of seeds from other Panax species remains unclear. The phospholipase D(PLD) gene plays an important role in plant responses to dehydration stress. However, the characteristics of the PLD gene family and their mechanisms of response to dehydration stress in seeds of Panax species with different dehydration tolerances are not well understood. This study used seeds from eight Panax species to measure the germination rates and PLD activity after dehydration and to analyze the correlation between dehydration tolerance and seed traits. Bioinformatics analysis was also conducted to characterize the PnPLD and PvPLD gene families and to evaluate their expression patterns under dehydration stress. The dehydration tolerance of Panax seeds was ranked from high to low as follows: P. ginseng, P. zingiberensis, P. quinquefolius, P. vietnamensis var. fuscidiscus, P. japonicus var. angustifolius, P. japonicus, P. notoginseng, and P. stipuleanatus. A significant negative correlation was found between dehydration tolerance and seed shape(three-dimensional variance), with flatter seeds exhibiting stronger dehydration tolerance(r=-0.792). Eighteen and nineteen PLD members were identified in P. notoginseng and P. vietnamensis var. fuscidiscus, respectively. These members were classified into five isoforms: α, β, γ, δ, and ζ. The gene structures, subcellular localization, physicochemical properties, and other characteristics of PnPLD and PvPLD were similar. Both promoters contained regulatory elements associated with plant growth and development, hormone responses, and both abiotic and biotic stress. During dehydration, the PLD enzyme activity in P. notoginseng seeds gradually increased as the water content decreased, whereas in P. vietnamensis var. fuscidiscus, PLD activity first decreased and then increased. The expression of PLDα and PLDδ in P. notoginseng seeds initially increased and then decreased, whereas in P. vietnamensis var. fuscidiscus, the expression of PLDα and PLDδ consistently decreased. In conclusion, the dehydration tolerance of Panax seeds showed a significant negative correlation with seed shape. The dehydration tolerance in P. vietnamensis var. fuscidiscus and dehydration sensitivity of P. notoginseng seeds may be related to differences in PLD enzyme activity and the expression of PLDα and PLDδ genes. This study provided the first systematic comparison of dehydration tolerance in Panax seeds and analyzed the causes of tolerance differences and the optimal water content for long-term storage at ultra-low temperatures, thus providing a theoretical basis for the short-term and ultra-low temperature long-term storage of medicinal plant seeds with varying dehydration tolerances.
Seeds/metabolism* ; Panax/physiology* ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant ; Phospholipase D/metabolism* ; Plants, Medicinal/enzymology* ; Germination ; Multigene Family ; Water/metabolism* ; Dehydration ; Phylogeny

The study aimed to investigate the effect of the CD200R1 gene deletion on microglia activation and nigrostriatal dopamine neuron loss in the Parkinson's disease (PD) process. The CRISPR-Cas9 technology was applied to construct the CD200R1^-/- mice. The primary microglia cells of wild-type and CD200R1^-/- mice were cultured and treated with bacterial lipopolysaccharide (LPS). Microglia phagocytosis level was assessed by a fluorescent microsphere phagocytosis assay. PD mouse model was prepared by nigral stereotaxic injection of recombinant adeno-associated virus vector carrying human α-synuclein (α-syn). The changes in the motor behavior of the mice with both genotypes were evaluated by cylinder test, open field test, and rotarod test. Immunohistochemical staining was used to assess the loss of dopamine neurons in substantia nigra. Immunofluorescence staining was used to detect the expression level of CD68 (a key molecule involved in phagocytosis) in microglia. The results showed that CD200R1 deletion markedly enhanced LPS-induced phagocytosis in vitro by the microglial cells. In the mouse model of PD, CD200R1 deletion exacerbated motor behavior impairment and dopamine neuron loss in substantia nigra. Fluorescence intensity analysis results revealed a significant increase in CD68 expression in microglia located in the substantia nigra of CD200R1^-/- mice. The above results suggest that CD200R1 deletion may further activates microglia by promoting microglial phagocytosis, leading to increased loss of the nigrostriatal dopamine neurons in the PD model mice. Therefore, targeting CD200R1 could potentially serve as a novel therapeutic target for the treatment of early-stage PD.
Animals ; Microglia/physiology* ; Mice ; Phagocytosis ; Parkinson Disease/genetics* ; Disease Models, Animal ; Receptors, Cell Surface/physiology* ; Dopaminergic Neurons/pathology* ; Antigens, CD/metabolism* ; Gene Deletion ; Substantia Nigra ; Mice, Inbred C57BL ; Mice, Knockout ; Cells, Cultured ; Male ; alpha-Synuclein ; CD68 Molecule ; Orexin Receptors

OBJECTIVE: To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) against cholestatic liver fibrosis in mice. METHODS: BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells (HSCs). HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation (BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues. RESULTS: BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore, BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell (HSC) activation and collagen fiber formation. CONCLUSION The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.
Animals ; Mice ; Mesenchymal Stem Cell Transplantation ; Liver Cirrhosis/etiology* ; Male ; Cholestasis/therapy* ; Mice, Inbred C57BL ; Hepatic Stellate Cells ; Mesenchymal Stem Cells

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*

Objective:To evaluate the efficacy of different surgical approaches in treating various types of small-volume benign prostatic hyperplasia (BPH).Methods:The data of 62 patients with small-volume BPH (≤30 ml) who were treated at Affiliated Jinhua Hospital, Zhejiang University School of Medicine from March 2018 to March 2023 were retrospective analyzed.The average age of the patients was (63.21 ± 5.38) years old.Among them, 9 patients had bladder calculi and 12 presented with urinary retention. Patients were stratified into two groups based on preoperative cystoscopy findings: 38 patients with hyperplasia of the middle or bilateral lobes underwent anterior lobe-sparing holmium laser enucleation of the prostate (HoLEP)(group A); 24 patients with bladder neck elevation and no significant hyperplasia received transurethral holmium laser incision of the prostate (group B). Preoperative baseline characteristics: international prostate symptom score(IPSS) were (23.68±4.89) and (22.59±3.62) respectively, quality of life (QOL) were (4.82±0.43) and (4.59±0.31) respectively, maximum flow rate (Q max)(7.89±1.83) ml/s and (7.26±1.72)ml/s respectively. The operative parameters (including procedure duration and catheterization time), postoperative complications (infection, urinary incontinence, and bladder neck contracture) were evaluated. Results:All 62 procedures were successfully completed. The mean operative time of group A was (32.36±6.17) minutes, postoperative catheterization duration was 1-3 days, and no cases of urinary incontinence or infection at 1-month follow-up. During the 12-month follow-up period, no cases of bladder neck contracture were observed in group A. The mean operative time of group B was (19.58 ± 3.87) minutes, and postoperative catheterization duration was 5-7 days. One case of fever with epididymitis was observed after operation, and there was no urinary incontinence at 1-month follow-up. During the 12-month follow-up period, no case of bladder neck contracture was observed in group B. Postoperative outcomes of group A and B at 1 month were as follows: IPSS (7.20±1.72) and (7.80±1.52) respectively, QOL (2.12±0.33) and (2.36±0.25) respectively, Q max(19.32±3.55)ml/s and (18.29±2.83)ml/s respectively.All postoperative parameters showed significant improvement compared with preoperative values ( P<0.05). Conclusions:For small-volume BPH, patients with middle or bilateral lobe hyperplasia can benefit from anterior lobe-sparing HoLEP, patients with bladder neck elevation and minimal hyperplasia can achieve optimal outcomes with transurethral holmium laser incision. Both approaches demonstrate significant symptom improvement with low rates of postoperative urinary incontinence and bladder neck contracture.

Objective:To evaluate the efficacy of different surgical approaches in treating various types of small-volume benign prostatic hyperplasia (BPH).Methods:The data of 62 patients with small-volume BPH (≤30 ml) who were treated at Affiliated Jinhua Hospital, Zhejiang University School of Medicine from March 2018 to March 2023 were retrospective analyzed.The average age of the patients was (63.21 ± 5.38) years old.Among them, 9 patients had bladder calculi and 12 presented with urinary retention. Patients were stratified into two groups based on preoperative cystoscopy findings: 38 patients with hyperplasia of the middle or bilateral lobes underwent anterior lobe-sparing holmium laser enucleation of the prostate (HoLEP)(group A); 24 patients with bladder neck elevation and no significant hyperplasia received transurethral holmium laser incision of the prostate (group B). Preoperative baseline characteristics: international prostate symptom score(IPSS) were (23.68±4.89) and (22.59±3.62) respectively, quality of life (QOL) were (4.82±0.43) and (4.59±0.31) respectively, maximum flow rate (Q max)(7.89±1.83) ml/s and (7.26±1.72)ml/s respectively. The operative parameters (including procedure duration and catheterization time), postoperative complications (infection, urinary incontinence, and bladder neck contracture) were evaluated. Results:All 62 procedures were successfully completed. The mean operative time of group A was (32.36±6.17) minutes, postoperative catheterization duration was 1-3 days, and no cases of urinary incontinence or infection at 1-month follow-up. During the 12-month follow-up period, no cases of bladder neck contracture were observed in group A. The mean operative time of group B was (19.58 ± 3.87) minutes, and postoperative catheterization duration was 5-7 days. One case of fever with epididymitis was observed after operation, and there was no urinary incontinence at 1-month follow-up. During the 12-month follow-up period, no case of bladder neck contracture was observed in group B. Postoperative outcomes of group A and B at 1 month were as follows: IPSS (7.20±1.72) and (7.80±1.52) respectively, QOL (2.12±0.33) and (2.36±0.25) respectively, Q max(19.32±3.55)ml/s and (18.29±2.83)ml/s respectively.All postoperative parameters showed significant improvement compared with preoperative values ( P<0.05). Conclusions:For small-volume BPH, patients with middle or bilateral lobe hyperplasia can benefit from anterior lobe-sparing HoLEP, patients with bladder neck elevation and minimal hyperplasia can achieve optimal outcomes with transurethral holmium laser incision. Both approaches demonstrate significant symptom improvement with low rates of postoperative urinary incontinence and bladder neck contracture.

Acute kidney disease (AKD) is a critical transitional period between acute kidney injury and chronic kidney disease. The incidence of AKD following acute kidney injury is approximately 33.6%, and it can occur without identifiable preceding acute kidney injury. The development of AKD is associated with increased risks of chronic kidney disease, dialysis, and mortality. Biomarkers and subphenotypes are promising tools to predict prognosis in AKD. The complex clinical situations in patients with AKD necessitate a comprehensive and structured approach, termed “KAMPS” (kidney function check, advocacy, medications, pressure, sick day protocols). We introduce “MAND-MASS,” an acronym devised to summarize the reconciliation of medications during episodes of acute illness, as a critical component of the sick day protocols at AKD. A multidisciplinary team care, consisting of nephrologists, pharmacists, dietitians, health educators, and nurses, is an optimal model to achieve the care bundle in KAMPS. Although the evidence for patients with AKD is still lacking, several potential pharmacological agents may improve outcomes, including but not limited to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide 1 receptor agonists. In conclusion, accurate prognosis prediction and effective treatment for AKD are critical yet unmet clinical needs. Future studies are urgently needed to improve patient care in this complex and rapidly evolving field.