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 evaluate the short-term clinical efficacy of external fixation and internal fixation with steel plate in the treatment of unstable distal radius fractures (AO-23C type), based on the principles of Chinese osteosynthesis (CO). METHODS: Forty-eight patients with unstable distal radius fractures between January 2022 and February 2023 were retrospectively analyzed and divided into the CO external fixation group and internal fixation group. CO external fixation group consisted of 25 patients, including 7 males and 18 females, aged from 37 to 56 years old with an average of ( 52.6±11.3) years old. Among them, there were 7 patients of traffic accidents and 18 patients of falls, resulting in a total of 25 patients of closed fractures and no open fractures, the treatment was conducted using closed reduction and CO external fixation. The internal fixation group consisted of 23 patients, comprising 8 males and 15 females, age ranged from 41 to 59 years old, with an average age of(53.3±13.7) years old. Among them, 8 patients resulted from car accidents while the remaining 15 patients were caused by falls. All 23 patients were closed fractures without any open fractures observed. The technique of open reduction and internal fixation with steel plate was employed. The perioperative data, including injury-operation time, operation duration, blood loss, and length of hospital stay, were assessed in both groups. Additionally, the QuickDASH score and visual analogue scale (VAS) were evaluated. Range of motion and grip strength assessment, imaging findings such as palmar inclination angle, ulnar declination angle, radius length, articular surface step, intra-articular space measurements were also examined along with any complications. RESULTS: The follow-up duration ranged from 0 to 24 months, with an average duration of (16.0±3.8) months. The CO external fixation exhibited significantly shorter time from injury to operation (2.4±3.3) d vs (7.4±3.7) d, shorter operation duration (56.27±15.23) min vs (74.10±5.26) min, lower blood loss (14.52±6.54) ml vs (32.32±10.03) ml, and reduced hospitalization days (14.04±3.24 )d vs (16.45±3.05) d compared to the internal fixation group (P<0.05). The QuickDASH score at 12 months post-operation was (8.21±1.64) in the CO external fixation group, while no significant difference was observed in the internal fixation group (7.04±3.64), P>0.05. There were no statistically significant differences in VAS between two groups at 6 weeks, as well as 1 and 3 months post-surgery (P>0.05). Additionally, there were no significant disparities observed in terms of range of motion and grip strength between two groups at the 2-year follow-up after the operation (P>0.05). After 12 months of surgery, the CO external fixation group exhibited a significantly smaller palmar inclination angle (17.90±2.18) ° vs (19.87±3.21) °, reduced articular surface step (0.11±0.03) mm vs (0.17±0.02) mm, and shorter radius length (8.16±1.11) mm compared to the internal fixation group (9.59±1.02) mm, P<0.05. The ulnar deviation angle and intra-articular space did not show any significant difference between two groups (P>0.05). The reduced fell within the allowable range between the CO external fixation group (23 out of 25 cases) and the internal fixation group (21 out of 23 cases) was not statistically significant (P=0.29). There was no significant difference in complications between the two groups(P>0.05). CONCLUSION Both the CO external fixation and open reduction with plate internal fixation demonstrate clinical efficacy in managing unstable distal radius fractures. The CO external fixation offers advantages in shorter injury-to-operation times, reduced intraoperative blood loss, and decreased surgical durations, while radial shortening is more effectively controlled by internal fixation.
Humans ; Male ; Female ; Middle Aged ; Radius Fractures/physiopathology* ; Adult ; Bone Plates ; Fracture Fixation, Internal/methods* ; External Fixators ; Retrospective Studies ; Fracture Fixation/methods* ; Wrist Fractures

OBJECTIVE: To characterize the occurrence of SRSF2 mutations in chronic myelomonocytic leukemia(CMML) patients and their correlation with other gene mutations and some clinical characteristics. METHODS: The clinical data of 43 CMML patients diagnosed in Changzhou No.2 People's Hospital and Wuxi No.2 People's Hospital were retrospectively analyzed, and gene mutations detection was performed using next-generation sequencing (NGS). RESULTS: Among the 43 CMML patients the SRSF2 mutation detection rate was 39.5%(17/43). These mutations clustered collectively at the proline 95 residue in the splicing factor SRSF2. The other genes with mutation rate greater than 15% were ASXL1 (48.8%), TET2 (41.9%), NRAS (30.2%), RUNX1 (25.6%), and SETBP1 (16.3%). Among SRSF2- mutated patients, the most common co-mutation was ASXL1, followed by TET2. The median age of SRSF2 mutant patients was significantly higher than that of the wild type (68 vs 51.5, P < 0.001), but there was not statistically significant differences in gender, peripheral leukocytes, hemoglobin, platelets, karyotype, and blast cell compared to the wild-type (all P >0.05). Notably, 4 out of the 6 SRSF2 ^mutASXL1^mut CMML patients developed leukemia transformation, and 1 out of 10 SRSF2 ^wtASXL1^wt CMML patients developed leukemia transformation, with statistically significant difference in leukemia transformation rates (66.7% vs 10%, P =0.036). CONCLUSION SRSF2 mutations have a high incidence in CMML, occurring frequently in older patients, and often coexisting with ASXL1 and TET2 mutations. Patients with CMML carrying both SRSF2^mut ASXL1^mut double mutations have a higher risk of acute leukemia transformation.
Humans ; Serine-Arginine Splicing Factors/genetics* ; Mutation ; Leukemia, Myelomonocytic, Chronic/genetics* ; Retrospective Studies ; Male ; Female ; Repressor Proteins/genetics* ; DNA-Binding Proteins/genetics* ; Dioxygenases ; Middle Aged ; Aged ; Proto-Oncogene Proteins/genetics*

OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

Objective To evaluate the efficacy and safety of ozone injection therapy for lumbar disc hemiation(LDH).Methods A computerized retrieval of academic papers concerning the randomized controlled trial(RCT)on ozone injection therapy for LDH from the databases of Embase,PubMed,Cochrane library and Web of science was conducted.The retrieval time period was from the establishment of the database to February 2023.The literature retrieval,screening,and data extraction were independently performed by two researchers.Cochrane bias risk assessment tool was used to assess the quality of the included literature.Stata 17.0 software was used to make meta-analysis.Results A total of 9 RCTs including 702 patients were finally included in this study.The results of meta-analysis showed that compared with radiofrequency thermocoagulation,percutaneous rotation and other treatments for LDH,the combination use of ozone injection could signifiicantly improve the effective rate based on Macnab efficacy evaluation criteria(RR=1.097,95％CI:1.038～1.159,P=0.001)and the excellent rate(RR=1.185～95％CI:1.074～1.309,P=0.001),and decrease the visual analog scale(VAS)pain score(WMD=-0.810～95％CI:-1.205～-0.414,P=0.000),and the differences in the above indexes were statistically significant.Conclusion Compared with the simple use of radiofrequency thermocoagulation,percutaneous rotation,and other treatment for LDH,the combination use of ozone injection therapy can significantly improve the effective rate and excellent rate based on Macnab efficacy evaluation criteria,decrease VAS score,with a high clinical safety.Limited by the quantity and quality of the original studies included in this study,the above conclusions need to be further verified by multi-center,large-sample and high-quality studies.

A 68-year-old patient with non-small cell lung squamous carcinoma who received 6 cycles of sintilimab combination chemotherapy and sintilimab 200 mg,ivd,monotherapy developed severe diarrhea,abdominal pain,blood in the stool and other discomforts,and ultrasound and colonoscopy demonstrated extensive congestion and inflammation in the intestinal tract,and the pathologic biopsy was comprehensively considered to be an acute immune enteritis.Immunotherapy was suspended,adequate glucocorticoids and symptomatic treatment were given,and the patient's diarrhea and blood in stool improved after 2 days,and the symptoms were relieved and returned to normal after 6 days.The association between the patient's immune enteritis and sintilimab was assessed as probably relerant.This article reviews the literature on the case of immune-associated enteritis caused by sintilimab,describes how to use experimental methods and enteroscopy to detect the pathological changes in the clinic;and combines them with the clinical manifestations of diarrhea and blood in the stools to make the diagnosis and differentiation;and then refers to the guideline grading for timely management;and discusses the case to improve the clinicians'ability to recognize and deal with the relevant scenarios.

Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

Objective: To investigate the differences in enolase and laminin levels in vaginal epithelial tissues between mice successfully infected withGardnerellaand mice not infected with Gardnerella, providing information for further exploration of the correlation between enolase and laminin levels and the incidence of bacterial vaginosis. Methods: Gardnerella strains isolated, purified, and identified from vaginal secretions of patients with bacterial vaginosis were used to infect the vagina of mice and establish a mouse model of bacterial vaginosis. Successful and failed mice was defined as successful and failed groups, respectively. Differential expression of enolase and laminin in the vaginal epithelial tissue of two groups of mice was detected by Western blot. Modeling success rate was statistically analyzed, and the expression differences of enolase and laminin was compared between two groups. Results: One strain of Gardnerella vaginalis infected 10 SPF grade KM mice, 7 mice met the diagnostic criteria for bacterial vaginosis, and 3 mice failed to model, with a success rate of 70%. Western blot was used to detect protein expression levels, and the levels of laminin and enolase in the successfully modeled mouse vaginal epithelial tissue were significantly higher than those in the failed modeling group, with statistical differences between the two groups(P<0.05). Conclusion Enolase and laminin may be involved in the occurrence of bacterial vaginosis, however, further research is needed to determine the mechanisms through which they trigger the occurrence and development of the disease.

OBJECTIVE: This study investigates the sleep-modulating effects of ginsenoside Rg1 (Rg1, C₄₂H₇₂O₁₄), a key bioactive component of ginseng, and elucidates its underlying mechanisms. METHODS: C57BL/6J mice were intraperitoneally administered doses of Rg1 ranging from 12.5 to 100 mg/kg. Sleep parameters were assessed to determine the average duration of each sleep stage by monitoring the electrical activity of the brain and muscles. Further, orexin neurons in the lateral hypothalamus (LH) and corticotropin-releasing hormone (CRH) neurons in the paraventricular hypothalamic nucleus (PVH) were ablated using viral vector surgery and electrode embedding. The excitability of LH^orexin and PVH^CRH neurons was evaluated through the measurement of cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-Fos) expression. RESULTS: Rg1 (12.5-100 mg/kg) augmented the duration of non-rapid eye movement (NREM) sleep phases, while reducing the duration of wakefulness, in a dose dependent manner. The reduced latency from wakefulness to NREM sleep indicates an accelerated sleep initiation time. We found that these sleep-promoting effects were weakened in the LH^orexin and PVH^CRH neuron ablation groups, and disappeared in the orexin and CRH double-ablation group. Decreased c-Fos protein expression in the LH and PVH confirmed that Rg1 promoted NREM sleep by inhibiting orexin and CRH neurons. CONCLUSION Rg1 increases the duration of NREM sleep, underscoring the essential roles of LH^orexin and PVH^CRH neurons in facilitating the sleep-promoting effects of Rg1. Please cite this article as: Wang YY, Wu Y, Yu KW, Xie HY, Gui Y, Chen CR, Wang NH. Ginsenoside Rg1 promotes non-rapid eye movement sleep via inhibition of orexin neurons of the lateral hypothalamus and corticotropin-releasing hormone neurons of the paraventricular hypothalamic nucleus. J Integr Med. 2024; 22(6): 721-730.
Animals ; Ginsenosides/pharmacology* ; Orexins/metabolism* ; Mice, Inbred C57BL ; Neurons/metabolism* ; Paraventricular Hypothalamic Nucleus/metabolism* ; Male ; Hypothalamic Area, Lateral/metabolism* ; Corticotropin-Releasing Hormone/metabolism* ; Mice ; Sleep/drug effects*