ObjectiveThe nucleolar protein PES1 (Pescadillo homolog 1) plays critical roles in ribosome biogenesis and cell cycle regulation, yet its involvement in cellular senescence remains poorly understood. This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role. MethodsInitially, we assessed PES1 expression patterns in two distinct senescence models: replicative senescent mouse embryonic fibroblasts (MEFs) and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells. Subsequently, PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types. Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays, respectively. The expression of senescence-associated proteins (p53, p21, and Rb) and SASP factors (IL-6, IL-1β, and IL-8) were analyzed by Western blot or qPCR. Furthermore, Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology. ResultsPES1 expression was significantly downregulated in senescent MEFs and HepG2 cells. PES1 knockdown resulted in decreased EdU-positive cells and increased SA‑β‑gal-positive cells, indicating proliferation inhibition and senescence induction. Mechanistically, PES1 suppression activated the p53-p21 pathway without affecting Rb expression, while upregulating IL-6, IL-1β, and IL-8 production. Notably, PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress, as evidenced by aberrant nucleolar morphology. ConclusionOur findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent (but Rb-independent) cellular senescence, highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.

OBJECTIVE: To investigate the influencing factors of pathological positive surgical margins (PSM) after radical resection of prostate cancer. METHODS: The clinical data of 407 patients who underwent radical resection of prostate cancer in our hospital from 2011 to 2020 were retrospectively analyzed. And the patients were divided into two groups according to postoperative pathological results. Single factor analysis was used to evaluate the differences in postoperative Gleason score, preoperative total prostate-specific antigen (tPSA), preoperative serum free prostate-specific antigen to preoperative tPSA ratio (fPSA/ tPSA), clinical stage, postoperative pathological stage, operation method, age, body mass index (BMI), diameter and volume of prostate tumor. Multivariate logistic regression was used to determine the independent risk factor of PSM. RESULTS: Among 407 patients with prostate cancer, 179 cases (43.98%) were positive. Univariate analysis showed that there were significant differences in postoperative Gleason score, preoperative tPSA, clinical stage and postoperative pathological stage between the two groups (P<0.05). And Gleason score, preoperative tPSA and pathologic stage were independent risk factors for PSM. CONCLUSION There are relationships between PSM and postoperative Gleason score, tPSA, clinical T stage, postoperative pathologic pT stage. Among them, postoperative Gleason score (Gleason=7 points, Gleason≥8 points), preoperative total prostate-specific antigen (tPSA > 20 μg/L), and postoperative pathologic pT stage (pT3a, pT3b) were independent risk factors for positive pathological margins of prostate cancer.
Margins of Excision ; Prostatic Neoplasms/surgery* ; Prostatectomy/statistics & numerical data* ; Prostate/surgery* ; Retrospective Studies ; Neoplasm Grading/statistics & numerical data* ; Prostate-Specific Antigen/blood* ; Neoplasm Staging/statistics & numerical data* ; Postoperative Period ; Risk Factors ; Humans ; Male

OBJECTIVE: To elucidate the modulation mechanism of Suanzaoren Decoction (SZRD) on basolateral amygdala (BLA) neuronal activity to alleviate chronic restraint stress (CRS)-related behavioral deficits. METHODS: The male C57BL/6J mice were assigned to 4 groups using the complete randomization method, including control (CON, n=19), CRS (n=19), SZRD (n=21), and fluoxetine (Flu, n=22) groups. Mice were restrained for 6 h per day, over a 21-d period to establish CRS models. The CON group remained in their cages without food or water during the 6-h matching period. SZRD and Flu groups received intragastric administration of SZRD (4.68 g/kg) and Flu (20 mg/kg) daily, respectively, 30 min before restraint for 21 consecutive days. The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test, elevated plus maze test, and forced swimming test. The cellular Fletcher B. Judson murine osteosarcoma proto-oncogene (c-Fos) expression in the BLA was measured using immunofluorescence, while action potential (AP) firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings. RESULTS: SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time (P<0.05 or P<0.01). It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA (P<0.01). Additionally, SZRD selectively attenuated excitatory (P<0.01), but not inhibitory, synaptic transmission onto BLA pyramidal neurons. CONCLUSION SZRD alleviated CRS-induced anxiety- and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Depression/complications* ; Pyramidal Cells/pathology* ; Male ; Mice, Inbred C57BL ; Basolateral Nuclear Complex/pathology* ; Restraint, Physical ; Anxiety/complications* ; Behavior, Animal/drug effects* ; Stress, Psychological/physiopathology* ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Action Potentials/drug effects* ; Synaptic Transmission/drug effects*

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objectives: . A novel J-shaped anterolateral thigh (ALT) flap reconstruction technique was developed to simultaneously restore swallowing and speech functions in patients following total laryngopharyngectomy. This study aimed to assess the outcomes and surgical complications in patients who underwent J-flap reconstruction over time. Methods: . Patients who underwent J-shaped ALT flap phonatory tube reconstruction were enrolled. Surgical morbidities and outcomes were evaluated every 3 months post-surgery for a period of 12 months or until death. Results: . Of the 36 patients, 13 underwent circumferential pharyngeal wall resection (circumferential defect [CD] group), and 23 underwent partial resection (partial defect [PD] group). After 12 months, 97% of the patients were able to resume oral intake without the need for a nasogastric tube, and 50% achieved fluent speech using the reconstructed phonatory tube. The CD group experienced a higher rate of delayed healing than the PD group (30.8% vs. 0%, p=0.012). Additionally, the PD group showed significantly higher percentages of individuals consuming solid food at both the 3- and 12-month intervals than the CD group (81.0% vs. 23.1% and 78.9% vs. 40%, respectively). Conclusions . This study investigated the progression of speech and swallowing functions over time after reconstruction of the voice tube with a J-flap. Using a J-shaped ALT flap phonatory tube effectively restored both speech and swallowing functions, providing long-term benefits, regardless of whether the defect was circumferential or partial.

Objectives: . A novel J-shaped anterolateral thigh (ALT) flap reconstruction technique was developed to simultaneously restore swallowing and speech functions in patients following total laryngopharyngectomy. This study aimed to assess the outcomes and surgical complications in patients who underwent J-flap reconstruction over time. Methods: . Patients who underwent J-shaped ALT flap phonatory tube reconstruction were enrolled. Surgical morbidities and outcomes were evaluated every 3 months post-surgery for a period of 12 months or until death. Results: . Of the 36 patients, 13 underwent circumferential pharyngeal wall resection (circumferential defect [CD] group), and 23 underwent partial resection (partial defect [PD] group). After 12 months, 97% of the patients were able to resume oral intake without the need for a nasogastric tube, and 50% achieved fluent speech using the reconstructed phonatory tube. The CD group experienced a higher rate of delayed healing than the PD group (30.8% vs. 0%, p=0.012). Additionally, the PD group showed significantly higher percentages of individuals consuming solid food at both the 3- and 12-month intervals than the CD group (81.0% vs. 23.1% and 78.9% vs. 40%, respectively). Conclusions . This study investigated the progression of speech and swallowing functions over time after reconstruction of the voice tube with a J-flap. Using a J-shaped ALT flap phonatory tube effectively restored both speech and swallowing functions, providing long-term benefits, regardless of whether the defect was circumferential or partial.

Objectives: . A novel J-shaped anterolateral thigh (ALT) flap reconstruction technique was developed to simultaneously restore swallowing and speech functions in patients following total laryngopharyngectomy. This study aimed to assess the outcomes and surgical complications in patients who underwent J-flap reconstruction over time. Methods: . Patients who underwent J-shaped ALT flap phonatory tube reconstruction were enrolled. Surgical morbidities and outcomes were evaluated every 3 months post-surgery for a period of 12 months or until death. Results: . Of the 36 patients, 13 underwent circumferential pharyngeal wall resection (circumferential defect [CD] group), and 23 underwent partial resection (partial defect [PD] group). After 12 months, 97% of the patients were able to resume oral intake without the need for a nasogastric tube, and 50% achieved fluent speech using the reconstructed phonatory tube. The CD group experienced a higher rate of delayed healing than the PD group (30.8% vs. 0%, p=0.012). Additionally, the PD group showed significantly higher percentages of individuals consuming solid food at both the 3- and 12-month intervals than the CD group (81.0% vs. 23.1% and 78.9% vs. 40%, respectively). Conclusions . This study investigated the progression of speech and swallowing functions over time after reconstruction of the voice tube with a J-flap. Using a J-shaped ALT flap phonatory tube effectively restored both speech and swallowing functions, providing long-term benefits, regardless of whether the defect was circumferential or partial.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Obesity is a risk factor for various neurological diseases， and a comprehensive understanding of its harmful effects on the central nervous system is of great significance for the prevention and treatment of obesity-related neurological diseases. The blood-brain barrier （BBB） is a regulatory interface between blood and the brain tissue， which can prevent harmful substances from entering the brain while eliminating metabolic wastes from the brain tissue. It plays an important role in cerebral microenvironment homeostasis and physiological function. However， a large number of studies have shown that obesity can cause dysfunction of the BBB， directly or indirectly promoting the development and progression of various neurological diseases. This review systematically summarizes the latest research progress on the phenotypes and mechanisms of BBB dysfunction in obesity. From the aspects of altered BBB permeability， transport dysfunction， and neuroinflammation， we present the specific phenotypes of BBB dysfunction caused by obesity and regulatory mechanisms， and discuss the harmful effects of obesity on BBB function，aiming to provide theoretical guidance for relevant basic research and clinical practice.
Obesity