Dysregulation of p53 and phosphoinositide (PIPn) signaling are both key drivers of oncogenesis and metastasis. Our recent findings reveal a previously unrecognized interaction between these pathways, converging in the nucleus to form a PIPn-p53 signalosome that modulates nuclear AKT activation and downstream signaling, thereby influencing cancer cell survival and motility. This review examines recent insights into nuclear PIPn signaling in the context of established roles for p53 in cell dynamics and migration while also deliberating current research on how nuclear PIPns interact with p53 to form signalosomes that affect cell motility. We emphasize the critical role of PIPns in stabilizing p53 and activating de novo nuclear AKT signaling, which subsequently modulates key motility-related pathways. Understanding the unique operation and function of the PIPn-p53 signalosome in nuclear phosphatidylinositol 3-kinase (PI3K)-AKT activation offers novel therapeutic strategies for controlling cancer metastasis by targeting pertinent interactions and events.
Humans ; Tumor Suppressor Protein p53/metabolism* ; Signal Transduction ; Cell Movement ; Cell Nucleus/metabolism* ; Phosphatidylinositols/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Animals ; Neoplasms/pathology* ; Phosphatidylinositol 3-Kinases/metabolism*

Objective:To investigate the clinical efficacy of early versus delayed open reduction and internal fixation in the treatment of tibial pilon fracture. Methods:Sixty patients with tibial pilon fractures admitted to Zhejiang Veteran Hospital from May 2018 to May 2021 were included in this study. They were randomly divided into a control group and a study group ( n = 30/group) using the coin-tossing method. Patients in the control group underwent early reduction and internal fixation within 3 days after injury. Patients in the study group underwent delayed reduction and internal fixation during 7-14 days after injury. The time to bone fracture healing and the time to independent weight-bearing walking were recorded. At 3 and 6 months after surgery, the American Orthopedic Foot and Ankle Society score, Visual Analogue Scale score, clinical efficacy, and incidence of complications were compared between the two groups. Results:The time to bone fracture healing and the time to independent weight-bearing walking in the study group were (8.23 ± 0.63) weeks and (11.77 ± 0.82) weeks, respectively, which were significantly shorter than (9.57 ± 0.86) weeks and (13.40 ± 0.93) weeks in the control group ( t = 6.87, 7.21, both P < 0.001). At 3 months after surgery, American Orthopedic Foot and Ankle Society score in the study group was significantly higher than that in the control group, and the Visual Analogue Scale score in the study group was significantly lower than that in the control group ( t = 6.69, 5.16, both P < 0.001). Overall excellent and good rate of clinical efficacy in the study group was significantly higher than that in the control group (86.6% vs. 63.3%, χ2 = 4.35, P = 0.037). At 6 months after surgery, there were no significant differences in American Orthopedic Foot and Ankle Society score and Visual Analogue Scale score between the two groups ( t = 0.96, 1.12, P = 0.339, 0.267). At 6 months after surgery, there was no significant difference in the overall excellent and good rate of clinical efficacy between the study and control groups (96.6% vs. 90.0%, χ2 = 0.26, P = 0.605). The incidence of complications in the study group was significantly lower than that in the control group (3.3% vs. 26.6%, χ2 = 4.70, P = 0.030). Conclusion:Delayed open reduction and internal fixation after reducing injury to the soft tissue of the affected limbs can effectively shorten the rehabilitation cycle of tibial pilon fracture, increase short-term efficacy, and decrease the risk of postoperative complications.

Objective To investigate the relationship between occupational noise exposure and glycated hemoglobin (HbA1c) levels, as well as prediabetes diagnosed by HbA1c. Methods A total of 1 181 workers from a cigarette factory were selected as the research subjects using a judgment sampling method. Workers were divided into control, low-level noise exposure and high-level noise exposure groups, consisting of 236, 359, and 586 individuals, respectively. The blood sample was collected for HbA1c test and occupation noise exposure intensity in workplace was detected by an area-sampling method. Results There were no statistical significant differences in HbA1c levels and prediabetes prevalence among the three groups of workers (all P>0.05). After adjusting for potential confounding factors such as years of service, gender, smoking, pack-years of smoking, alcohol consumption, and body mass index, multiple linear regression analysis showed that the high-level noise exposure group had higher HbA1c level than the control group (P<0.05). Multivariable logistic regression analysis results showed that the high-level noise exposure group had higher risk of prediabetes compared with the control group (P<0.05). Conclusion Occupational noise exposure could be a risk factor for the increased HbA1c levels and prediabetes incidence among the occupational population. More attention should be paid to the effects of occupational noise exposure on the HbA1c level in occupational health surveillance.

Objective:To evaluate the early efficacy and safety of transnasal endoscopic decompression in the annulus of zinn (AZ) region for refractory dysthyroid optic neuropathy (DON) and to preliminarily analyze the correlated factors of postoperative visual function outcome.Methods:From July 2021 to January 2023, 35 patients (56 eyes) with DON who received AZ area decompression in Peking University Third Hospital were included retrospectively, including 9 males (13 eyes) and 26 females (43 eyes), aging (52.2±12.0) years. Among them, 35 eyes underwent two-wall (medial and inferior) orbital decompression using an endonasal endoscopic approach, while 21 eyes received three-wall (medial, lateral, and inferior) orbital decompression through a combined approach. Key parameters such as best corrected visual acuity (BCVA), visual field (MD value), eyeball prominence, intraocular pressure, and complications were recorded. Postoperative data were collected one month after surgery. The statistical analysis was performed using paired t-test and Spearman correlation analysis. Results:Significant outcomes were observed post surgery in BCVA, visual field, intraocular pressure and proptosis ( t value was 8.37, 6.17, 4.50, and 9.20, respectively, all P<0.001). The reduction in proptosis was statistically significant between the 2-wall and 3-wall orbital decompression groups ( t=-2.82, P=0.007). Changes in BCVA, visual field, and intraocular pressure before and after surgery was greater in the 3-wall orbital decompression group compared to 2-wall orbital decompression group, although the difference was not statistically significant (all P>0.05). Change in postoperative visual acuity and visual field was significantly positively correlated with preoperative visual acuity and preoperative visual field (all P<0.001). Similarly, change in intraocular pressure and proptosis was positively correlated with preoperative intraocular pressure and preoperative protrusion (all P<0.001). Preoperative diplopia was reported in seven patients (20.0%), and two new cases (5.7%) were noted post-operation, which resolved within 3 months after surgery. Conclusions:Endoscopic endonasal decompression of the AZ area is a safe and effective surgical treatment for DON, with notable improvements in BCVA. Furthermore, three-orbital wall decompression seems to yield better outcomes in terms of eye retraction.

Non-coding RNAs (ncRNAs), which are thought to regulate articular cartilage through endochondral osteogenesis, consist of mRNA-interfering complementary RNA (miRNA) and long non-coding RNAs (lncRNA). More and more experimental evidence reveals the role of ncRNAs in chondrocyte differentiation and the pathogenesis of several skeletal diseases, including osteoarthritis. In the past few years, increasingly sophisticated DNA sequencing methods and a large number of sepigenetic modifications have greatly contributed to our understanding of the pathophysiological mechanisms of osteoarthritis. Recent studies have revealed that RNA interacts with RNA-binding proteins, regulates gene transcription and protein translation, and is involved in various pathological processes in OA, promising to be a therapeutic target for osteoarthritis.

Objective:To investigate the application effects of flipped classroom combined with mini-clinical evaluation exercise (Mini-CEX) evaluation on the cultivation of clinical ability of professional postgraduates majoring in clinical medicine.Methods:A total of 32 trainees, the professional postgraduates majoring in clinical medicine integrated with standardized residency training who rotated in the Department of Neurology, The Southwest Hospital of Army Medical University from January 2019 to January 2020 were selected and divided into control group and the experimental group, with 16 ones in each group. The control group were taught with the traditional standardized residency training program, while the experimental group were assessed by Mini-CEX evaluation once every two weeks combined with flipped classroom in stages on the basis of the control group. At the end of the training, the application effects of these two teaching methods were evaluated by theoretical knowledge and clinical comprehensive ability (including 7 aspects of medical history collection, physical examination, clinical diagnosis, treatment plan, medical ethics, doctor-patient communication and overall evaluation). SPSS 22.0 was used for t test. Results:At the end of the training, the scores of theoretical knowledge in the experimental group were higher than those in the control group [(89.83±3.93) points vs. (85.75±5.34) points], with statistical differences ( P<0.05). For the clinical comprehensive ability, the scores of history collection, physical examination, clinical diagnosis, treatment plan, doctor-patient communication and overall evaluation were higher in the experimental group than in the control group ( P<0.05), except for the medical ethics. Conclusion:The application of flipped classroom combined with Mini-CEX evaluation improves the teaching quality and strengthens the clinical comprehensive ability of students, which is worth promoting in clinical practice.

Objective:To document the clinical efficacy of supplementing intra-articular injection of sodium hyaluronate with Baduanjin exercise in the treatment of knee osteoarthritis (KOA).Methods:Forty patients with KOA were randomly divided into an observation group and a control group, each of 20. Both groups received health education and intra-articular injection of sodium hyaluronate once a week for 5 consecutive weeks. The observation group additionally underwent Baduanjin exercise 3 times a week for the 5 weeks. Before and after the treatment, knee joint function, pain and surface integrated electromyography (iEMG) values of the affected quadriceps were assessed using the Western Ontario and McMaster University (WOMAC) Osteoarthritis Index Scale, and a visual analogue scale (VAS).Results:After the treatment the average VAS and WOMAC scores of both groups had decreased significantly, while the average iEMG value of the quadriceps on the affected side had increased significantly. The average VAS and WOMAC scores of the observation group were significantly lower than the control group′s averages after the treatment, while the average iEMG value of the quadriceps on the affected side was significantly higher.Conclusion:Combining Baduanjin exercise with sodium hyaluronate joint injection in the treatment of KOA has a synergistic effect which can better relieve knee pain, improve knee functioning, and delay the progression of KOA. The combined treatment is worthy of clinical promotion and application.

Objective:To investigate the protective effect and mechanism of Acronychia pedunculata water extracts on UV-induced light damage of human keratinocytes.Methods:The experiment was conducted from December 2018 to April 2020 in the Guangxi Medical University Laboratory of Genetics. The photoaged keratinocyte model was used, the cells were co-cultured with different concentrations of Acronychia pedunculata water extracts. The cell proliferation rate was detected by CCK-8 method. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and total antioxidant capacity (T-AOC) of cells were detected by a test kit. The levels of IL-1β, IL-6 and tumor necrosis factor-alpha (TNF-α) were determined by ELISA.Results:The proliferation of HaCaT cells was promoted by 0.5 mg/L-2.0 mg/L of the extracts. Compared with control group, the proliferation rate of HaCaT cells in the experimental group was significantly increased ( P<0.05). Compared with control group, the contents of ROS was decreased ( F=214.67, P<0.05), MDA was decreased ( F=811.88, P<0.05), SOD was increased ( F=28.95, P<0.05), CAT was increased ( F=213.31, P<0.05), GPX was increased ( F=65.10, P<0.05), T-AOC was increased ( F=305.58, P<0.05), IL-1β was decreased ( F=15.46, P<0.05), IL-6 was decreased ( F=59.2, P<0.05), and TNF-α was decreased ( F=33.13, P<0.05). Conclusions:The extracts of 0.5-2.0 mg/L of Acronychia pedunculata have protective effects on the photoaging cell model, which may be related to the increase of SOD, CAT, GPX and other antioxidant enzymes and the level of T-AOC in photoaging HaCaT cells, and the decrease of ROS, MDA content and the expression of inflammatory cytokines.

Objective:To access the feasibility and efficacy of percutaneous endoscopic debridement (PED) combined with percutaneous pedicle screw fixation (PPSF) in the treatment of lumbar pyogenic spondylodiscitis.Methods:49 patients (male 29, female 20), aged 51.2±13.9 years (range 19-81 years), who were diagnosed with lumbar pyogenic spondylodiscitis and received PED with PPSF in Orthopedic Department, Sun Yat-Sen Memorial Hospital and Zhuhai People's Hospital from January 2014 to March 2017, were retrospectively reviewed. The patients were operated in the prone position with the infected locus thoroughly debrided, vertebrae fixed and clinical outcomes were assessed by observing the changes of complaining symptoms, laboratory parameters, clinical functional scores (American Spinal Injury Association impairment scale, AIS; visual analog scale, VAS; Oswestry disability index, ODI) and imaging studies during perioperative and follow-up stages.Results:The mean operative time was 110.1±19.8 min (80-165 min), with intra-operative blood loss 47.8±20.6 ml (range 20-120 ml). All patients reported relief of back pain. Causative pathogens were identified in 36 of 49 biopsy specimens, with staphylococcal bacteria being the most prevalent strain (accounting for 50.0%). During 3-12 months' follow-up, 95.9% (47/49) patients' infection was well-controlled. At 3 month post-operative, C-reactive protein declined from 62.1±37.2 mg/L to 7.5±5.8 mg/L, white blood cell declined from (14.2±3.9)×10 9/L to (6.2±1.1)×10 9/L, ESR declined from 90.3±37.4 mm/1 h to 16.9±7.2 mm/1 h, and the values at 3 months post-operative had significant difference compared with values at pre-operative ( t=10.15, P<0.001; t=13.49, P<0.001; t=13.82, P<0.001). Spontaneous fusion was observed among 56.8% (21/37) of the patients during long-term radiological follow-ups (more than 1.5 years). At the last follow-up, the VAS declined from 7.4±0.6 points pre-operative to 0.5±0.3 post-operative, ODI declined from 78.2%±9.1% pre-operative to 14.0%±8.6% post-operative, and the values at the last follow-up had significant difference compared with values at pre-operative ( t=72.00, P<0.001; t=35.89, P<0.001). There were 38 cases of AIS E, and 11 cases of AIS D at pre-operative, while 43 cases of AIS E and 6 cases of AIS D. However, there were 11 patients developed post-operative complications, among whom 2 with recurrent infection, 2 with secondary neurological impairment. Conclusion:PED combined with PPSF effectively eliminated infected locus, stabilized the affected vertebrae, improved patients' clinical outcomes with small trauma, thereby offering an alternative for the treatment of lumbar pyogenic spondylodiscitis.

The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines—with a focus on China—will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.
Adult ; Asian Continental Ancestry Group ; Biomarkers ; China ; Consensus ; Diagnosis ; Diagnosis, Differential ; Drug Therapy ; Eosinophils ; Epidemiology ; Epigenomics ; Genetics ; Humans ; Hypersensitivity ; Inflammation ; International Agencies ; Medical Staff ; Neck ; Phenotype ; Precision Medicine