p53 is one of the most crucial tumor suppressor genes in mammalian cells.Over 50％of hu-man tumors exhibit p53 mutations,predominantly consisting of the missense mutations,leading to the generation and accumulation of mutant p53 protein in tumor cells.Apart from losing its normal biological functions and inhibiting the transactivity and tumor suppressive action of wildtype p53 through dominant negative effect,accumulating evidences indicate that the"gain-of-function"of mutant p53 plays critical roles in promoting tumor progression and metastasis.The posttranslational modifications(PTMs)repre-sent a key mechanism by which the molecular functions of both the wildtype p53 and a spectrum of vari-ous mutant p53 can be regulated through universal or mutant p53-specific ways.Thus,the PTMs may re-present an emerging potential target for reversing mutant p53-driven tumors.Here by focusing on the PT-Ms of mutant p53,the review provides an overview of how mutant p53 participates in the process of tumor initiation and progression through"gain-of-function",the regulatory mechanisms of PTMs on mutant p53,and the applications of targeting mutant p53 and its PTMs in cancer treatment.Additionally,we discuss unresolved issues regarding the roles of mutant p53 in cancer biology and provide insights into fu-ture research direction.This review comprehensively summarizes the regulatory networks of mutant p53"gain-of-function"by PTMs in tumor development,serving as a basis for developing intervention strate-gies by targeting the PTMs of mutant p53 in cancer.

Objective: To investigate the misdiagnosis of area postrema syndrome (APS) manifesting as intractable nausea, vomiting and hiccups in neuromyelitis optic spectrum disease (NMOSD) and reduce the risk of misdiagnosis. Methods: We retrospectively analyzed data from NMOSD patients attending the Department of Neurology at the First Medical Center of PLA General Hospital between January 2019 and July 2021. SPSS25.0 was then used to analyze the manifestations, misdiagnosis, and mistreatment of APS. Results: A total of 207 patients with NMOSD were included, including 21 males and 186 females. The mean age of onset was 39±15 years (range: 5-72 years). The proportion of patients who were positive for serum aquaporin 4 antibody was 82.6% (171/207). In total, 35.7% (74/207) of the NMOSD patients experienced APS during the disease course; of these patients, 70.3% (52/74) had APS as the first symptom and 29.7% (22/74) had APS as a secondary symptom. The misdiagnosis rates for these conditions were 90.4% (47/52) and 50.0% (11/22), respectively. As the first symptom, 19.2% (10/52) of patients during APS presented only with intractable nausea, vomiting and hiccups; 80.8% (42/52) of patients experienced other neurological symptoms. The Departments of Gastroenterology and General Medicine were the departments that most frequently made the first diagnosis of APS, accounting for 54.1% and 17.6% of patients, respectively. The most common misdiagnoses related to diseases of the digestive system and the median duration of misdiagnosis was 37 days. Conclusions: APS is a common symptom of NMOSD and is associated with a high rate of misdiagnosis. Other concomitant symptoms often occur with APS. Gaining an increased awareness of this disease/syndrome, obtaining a detailed patient history, and performing physical examinations are essential if we are to reduce and avoid misdiagnosis.
Male ; Female ; Humans ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Neuromyelitis Optica/diagnosis* ; Area Postrema ; Retrospective Studies ; Hiccup/complications* ; Vomiting/etiology* ; Nausea/etiology* ; Inflammation ; Syndrome ; Autoantibodies ; Diagnostic Errors ; Aquaporin 4

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Objective: The neuropeptide oxytocin has been found to improve human social cognition and promote prosocial behavior. However, itis still unclear about the mechanisms underlying these effects of oxytocin on neural processes, such as visual perception and awareness.Especially, it is still unclear whether oxytocin influences perceptual salience of social stimuli in the absence of awareness. Methods: In a randomized double-blind, placebo-controlled trial we applied an interocular suppression paradigm and eye tracking methods: to investigate the influence of intranasally administered oxytocin on perceptual salience of social stimuli. Suppression times andpupillometric data were measured during subjects being presented with gradually introduced pictures of social stimuli (neutral expressionfaces) or nonsocial stimuli (grayscale watch pictures) that were suppressed and invisible in 10 men who were administered 24 IU oxytocinand 10 men who were administered a placebo. Results: The results demonstrated that the oxytocin group perceived social stimuli more quickly accompanied by subsequent larger increasingpupil diameter than nonsocial stimuli, indicating an increased unconscious salience of social stimuli. Conclusion These findings provided new insights into oxytocin’s modulatory role to social information processing, suggesting that oxytocinmight enhance attentional bias to social stimuli even after removal of awareness. Psychiatry Investig 2020;17(4):292-298

Humans ; Mutation ; Myelodysplastic Syndromes/genetics* ; Prognosis ; Splicing Factor U2AF/genetics*

OBJECTIVE: To explore the protective mechanism of electroacupuncture preconditioning on myocardial ischemia-reperfusion injury in rats. METHODS: A total of 88 SPF-grade Wistar male rats were randomized into a normal group, a sham-operation group, a model group and an electroacupuncture (EA) group, 22 rats in each one. The rats in the normal group received normal diet and no intervention was given for 7 d. The rats in the sham-operation and the model group were bound for 20 min, once a day for 7 d. In the EA group, EA, continuous wave, 2 Hz and 1 mA, was applied at "Neiguan" (PC 6), "Zusanli" (ST 36) and "Guanyuan" (CV 4) for 20 min, once a day for 7 d. In the 8th day, the blood was collected by abdominal aortic method 60 min after intraperitoneal injection of 10% urethane anesthesia by 10 mL/kg in the normal group, and then the tissue of heart was collected. In the model group and the EA group, ligating the left anterior descending coronary artery (LAD) was adopted for 20 min and reperfusion was applied for 40 min, then the samples were collected. The rats in the sham-operation group recevied open-chest operation and no other intervention, the samples were collected in 60 min. Nitro Blue Tetrazolium Chloride monohydrate (NBT) stain was used to detected myocardial infarct size and weight, ELISA was used to measured myocardial injury markers and inflammatory factors (LDH、CK、cTnI), and the fluorescent quantitative PCR method was used to determine the expressions of FXR and SHP gene. RESULTS: ①There was no significant difference between the normal group and the sham-operation group in myocardial infarct size and weight (>0.05) .Compared with the normal group, myocardial infarct size and weight were higher in the model group (<0.01). Compared with the model group, myocardial infarct size and weight were lower in the EA group (<0.01). ②There was no significant difference between the normal group and the sham-operation group in serum contents of LDH、CK、cTnI (>0.05). Compared with the normal group, the serum contents of LDH、CK、cTnI were higher in the model group (<0.05). Compared with the model group, the serum contents of LDH、CK、cTnI were lower in the EA group (<0.05). ③The expressions of FXR and SHP gene in the model group were higher than those in the normal group (<0.05). The expressions of FXR and SHP gene in the EA group were lower than those in the model group (<0.05). CONCLUSION Electroacupuncture preconditioning could significantly improve cardiac function of rats with myocardial ischemia-reperfusion, reduce infarct size and inflammatory factors, and down-regulate the expressions of FXR and SHP gene. The protective effect may generate based on regulation of FXR/SHP apoptosis signal pathway.
Animals ; Electroacupuncture ; Humans ; Male ; Myocardial Ischemia ; Myocardial Reperfusion Injury ; therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar

Kawasaki disease shock syndrome (KDSS) is a serious manifestation of Kawasaki disease. It is a clinical symptom of hypoperfusion, which occurs hemodynamic instability on the basis of the diagnosis of Kawasaki disease. KDSS can occur in the early stage of Kawasaki disease, and can be easily missed and misdiagnosed. Now, the clinical features, pathogenesis and treatment of KDSS are reviewed, in order to improve the ability of clinical pediatricians to identify the disease early and reduce the occurrence of life-threatening complications.

Disorders of Excessive Somnolence ; Humans ; Parkinson Disease ; complications ; REM Sleep Behavior Disorder ; therapy ; Restless Legs Syndrome ; therapy ; Sleep Apnea, Obstructive ; therapy ; Sleep Wake Disorders ; therapy