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 analyze the impact of artificial intelligence (AI) on colorectal adenoma detection rate (ADR) in fatigue state of endoscopists. Methods A total of 784 patients undergoing colonoscopy at the Endoscopy Center of Hengshui People's Hospital in Hebei Province were enrolled. Patients were divided into group A (n=405, time from 14: 00 to 15: 59) and group B (n=379, time from 16: 00 to 17: 30) based on the operation time. Patients in both groups who underwent AI-assisted examination were included in AI subgroup, while those without AI assistance were included in non-AI subgroup. Baseline data, including age, gender and bowel preparation quality [assessed by the Boston Bowel Preparation Scale (BBPS) score] were collected. The ADR and polyp detection rate (PDR) for colorectal lesions were calculated for both groups, and the ADR was compared between groups with and without AI assistance. Results The overall ADR was 32.10% in the group A, which was higher than 26.91% in the group B, but the difference was not statistically significant (P>0.05). Without AI assistance, the ADR in the group A was 25.85%, which was significantly higher than 17.30% in the group B (P < 0.05). In the group B with AI assistance, the ADR was significantly higher than that in the group A without AI assistance (P < 0.05). Without AI assistance, the PDR in the group A was 33.17%, which was significantly higher than 22.70% in the group B (P < 0.05). After using AI assistance, there was no significant difference in PDR between the two groups (P>0.05). In the group A, the ADR was 38.50% in the AI subgroup (n=200) and 25.80% in the non-AI subgroup (n=205), with a statistically significant difference (P=0.006). In the group B, the ADR was 36.08% in the AI subgroup (n=194) and 17.30% in the non-AI subgroup (n=185), with a statistically significant difference (P < 0.001). Conclusion AI-assisted colonoscopy can effectively improve the ADR of endoscopists under fatigue conditions.

Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by memory loss and cognitive dysfunction. The accumulation of misfolded protein aggregates including amyloid beta (Aβ) peptides and microtubule associated protein tau (MAPT/tau) in neuronal cells are hallmarks of AD. So far, the exact underlying mechanisms for the aetiologies of AD have not been fully understood and the effective treatment for AD is limited. Autophagy is an evolutionarily conserved cellular catabolic process by which damaged cellular organelles and protein aggregates are degraded via lysosomes. Recently, there is accumulating evidence linking the impairment of the autophagy-lysosomal pathway with AD pathogenesis. Interestingly, the enhancement of autophagy to remove protein aggregates has been proposed as a promising therapeutic strategy for AD. Here, we first summarize the recent genetic, pathological and experimental studies regarding the impairment of the autophagy-lysosomal pathway in AD. We then describe the interplay between the autophagy-lysosomal pathway and two pathological proteins, Aβ and MAPT/tau, in AD. Finally, we discuss potential therapeutic strategies and small molecules that target the autophagy-lysosomal pathway for AD treatment both in animal models and in clinical trials. Overall, this article highlights the pivotal functions of the autophagy-lysosomal pathway in AD pathogenesis and potential druggable targets in the autophagy-lysosomal pathway for AD treatment.

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

Objective:To evaluate the performance of Hybribio human papillomavirus (HPV) typing test kit for high risk HPV-DNA typing detection in screening of cervical precancer lesions.Methods:A total of 9 914 women were recruited in Henan, Shanxi, and Guangdong provinces from June to July 2017. All women underwent HPV DNA test. The women who diagnosed as HPV positive and cytological examination ≥ atypical squamous cells of undetermined significance (ASCUS) or HPV negative and cytological examination≥low-grade squamous intraepithelial lesions (LSIL) underwent colposcopy biopsy and pathological examination. Using the pathological diagnosis as the gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and 95% confidence interval ( CI) of high-risk HPV and HPV16/18 tests were calculated. Results:The mean age of 9 914 subjects was (45.0±9.3) years old. Among them, 1 302 subjects were detected as high risk HPV positive, including 211 of HPV16 positive and 64 of HPV18 positive. According to the pathological gold standard of cervical intraepithelial neoplasia grade 2 (CIN2) or worse, the sensitivity and specificity of high risk-HPV and HPV 16/18 for triaging ASCUS women were 90.6% (95% CI: 75.8%-96.8%) and 78.0% (95% CI: 74.5%-81.2%) as well as 56.3% (95% CI: 39.3%-71.8%) and 95.7% (95% CI: 93.8%-97.1%), respectively. The sensitivity and specificity of high risk-HPV and HPV 16/18 for cervical precancer lesions screening were 95.1% (95% CI: 88.1%-98.1%) and 87.6% (95% CI: 86.9%-88.2%) as well as 65.9% (95% CI: 55.1%-75.2%) and 97.8% (95% CI: 97.5%-98.1%), respectively. Conclusions:The Hybribio HPV test kit has a relative high sensitivity and specificity for cervical precancer lesions screening and ASCUS triaging. It is reliable for HPV DNA detection and cervical cancer screening.

Objective:To evaluate the performance of Hybribio human papillomavirus (HPV) typing test kit for high risk HPV-DNA typing detection in screening of cervical precancer lesions.Methods:A total of 9 914 women were recruited in Henan, Shanxi, and Guangdong provinces from June to July 2017. All women underwent HPV DNA test. The women who diagnosed as HPV positive and cytological examination ≥ atypical squamous cells of undetermined significance (ASCUS) or HPV negative and cytological examination≥low-grade squamous intraepithelial lesions (LSIL) underwent colposcopy biopsy and pathological examination. Using the pathological diagnosis as the gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and 95% confidence interval ( CI) of high-risk HPV and HPV16/18 tests were calculated. Results:The mean age of 9 914 subjects was (45.0±9.3) years old. Among them, 1 302 subjects were detected as high risk HPV positive, including 211 of HPV16 positive and 64 of HPV18 positive. According to the pathological gold standard of cervical intraepithelial neoplasia grade 2 (CIN2) or worse, the sensitivity and specificity of high risk-HPV and HPV 16/18 for triaging ASCUS women were 90.6% (95% CI: 75.8%-96.8%) and 78.0% (95% CI: 74.5%-81.2%) as well as 56.3% (95% CI: 39.3%-71.8%) and 95.7% (95% CI: 93.8%-97.1%), respectively. The sensitivity and specificity of high risk-HPV and HPV 16/18 for cervical precancer lesions screening were 95.1% (95% CI: 88.1%-98.1%) and 87.6% (95% CI: 86.9%-88.2%) as well as 65.9% (95% CI: 55.1%-75.2%) and 97.8% (95% CI: 97.5%-98.1%), respectively. Conclusions:The Hybribio HPV test kit has a relative high sensitivity and specificity for cervical precancer lesions screening and ASCUS triaging. It is reliable for HPV DNA detection and cervical cancer screening.

Objective To evaluate the safety of morphine hydrochloride injection. Methods Ear verin injection was used to evaluate the vascular irritation using the comparison of left side with right side in rabbits. Quadriceps femoris injection was used to evaluate the muscle irritation using the comparison of left side with right side in rabbits. Guinea pigs were intravenously injected with morphine hydrochloride injection at a dose of 2.8 mg·kg-1 once daily 3 times, stimulation was performed on 14 d after the last sensitization and the booster dose was 2 times the sensitization dose. The allergic reactions were observed. The different concentrations of morphine hydrochloride injection were placed in 2％ rabbit erythrocyte suspension, and then the hemolyzation and agglutination were observed. Results There were no significant vascular or muscular irritation and injury effects of morphine hydrochloride injection in rabbits. There were no evidenceof hemolyzation and agglutination in rabbit erythrocytes in vitro. No allergic reactions on guinea pigs in vivo were observed. Conclusion After treatment of morphine hydrochloride injection, neither obvious vascular /muscle stimulation or sensitization, nor hemolyzation or agglutination appeared in rabbits. The research results provide basic reference for the clinical rational and safe application of morphine hydrochloride injection.

Objective To analyze the differences in immune system between Npc1 gene mutant (Npc1-/ -) and wild-type (Npc1+/ +) mice for better understanding the pathogenesis of Niemann-Pick disease type C1 (NPC1) from an immunological perspective and providing reference for NPC1 treatment in clinic.Methods Body, thymus and spleen weight of Npc1-/ -and Npc1+/ + mice aged (14±2) days, (42±2) days and (63±2) days (Day14±2 , Day42±2 and Day63±2 ) were recorded and the associated organ index were calcu-lated. White blood cell count in peripheral blood of mice aged Day42±2 was examined by routine blood test. Expression of cytokines at mRNA level in mouse peripheral blood was detected by qPCR. Percentages of CD4+, CD8+ and CD19+ lymphocytes in peripheral blood and spleen of mice aged Day42±2 were measured by flow cytometry. Apoptosis and senescence of spleen in mice aged Day63±2 were examined by immunofluores-cence and β-galactosidase staining. Results Compared with Npc1+/ + mice, there was no significant differ-ence in the weight of spleen and thymus in Npc1-/ - mice aged Day14±2; the weight of spleen in Npc1-/ - mice aged Day42±2 significantly increased, but the weight of thymus showed a significant decrease; furthermore, both the weight of spleen and thymus in Npc1-/ - mice aged Day63±2 significantly decreased; and the body weight of Npc1-/ - mice of each age group significantly decreased. Moreover, compared with Npc1+/ + mice, the absolute number of lymphocytes in the peripheral blood of Npc1-/ - mice aged Day42±2 showed no signifi-cant difference, but the percentage in whole white blood cells significantly decreased due to the significantly increased neutrophils. Expression of cytokines ( IL-1, IL-2, IFN-γ, TNF-α, IL-4, granzyme A and granzyme B) at mRNA level in the peripheral blood leukocytes of Npc1-/ - mice aged Day42±2 was abnormal as compared with that in Npc1+/ + mice. The number of T (CD4+ and CD8+) lymphocytes in Npc1-/ - mice aged Day42±2 significantly decreased, while the number of B (CD19+) lymphocytes increased significantly as com-pared with those in the Npc1+/ + mice. Compared with Npc1+/ + mice, apoptosis and senescence of the spleen in Npc1-/ - mice aged Day63±2 aggravated significantly. Conclusion The abnormal lipid metabolism triggered by Npc1 gene mutation causes severe immune dysfunction in Npc1-/ - mice. Therefore, immune dysfunction should be taken into full consideration when treating patients with NPC1, which might help improve the life quality and prolong the survival time.

Complementary and alternative medicine (CAM) describes a broad category of practices and treatments for the prevention or treatment of disease outside the realm of conventional medicine. CAM is widely used in the treatment of allergic rhinitis, acute and chronic rhinosinusitis. This article summarizes a variety of CAM and the efficacy in the treatment of rhinitis and sinusitis, with the purpose of increasing people′s awareness of CAM and enriching the treatment of rhinitis and sinusitis, so that patients can benefit from it.

Objective To discuss the research status of TCM therapy for ADHD in China in recent ten years; To provide references for clinical workers. Methods Clinical research papers about TCM therapy for ADHD in CNKI, VIP, and CBM from 1st January 2005 to 1st April 2015 were retrieved. Metrology analysis was conducted from the aspects of publication time, diagnostic criteria, contrasted medicine, and types and features of TCM therapy. Results By eliminating duplication literature, 670 papers were screened out. After the screening of exclusion criteria, 148 papers were included. DSM-Ⅳ and CCMD-3 were the most commonly used diagnostic criteria in the 148 papers; internal therapy was the main therapy in TCM therapy; decoction was the main dosage form; liver-kidney yin deficiency syndrome and heart-liver fire syndrome were the main patterns of syndrome; Acori Tatarinowii Rhizoma, Rehmanniae Radix Praeparata and other 19 Chinese medicinal herbs were the main Chinese mateia medica; Xiaoer Zhili Syrup was the most commonly used Chinese patent medicine; acupuncture and moxibustion and auricular point therapy were the main external therapy, and external combined with internal therapy had the best efficacy. Conclusion TCM therapy for ADHD is with high effectiveness. External combined with internal therapy has the best efficacy.