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.

Humans ; COVID-19 ; Consensus ; SARS-CoV-2 ; China

To construct cellular senescence model by stimulating primary hepatocytes with hydrogen peroxide (H 2O 2). Primary hepatocytes were transfected with p53 siRNA, progerin siRNA or IGF-1 adenovirus vector. The number of SA-β-Gal stained positive cells and the expression of p53 and progerin were detected. The results showed that p53 siRNA and progerin siRNA had knocked-down the expression of p53 and progerin, and had alleviated the hepatocyte senescence. Transfection of insulin-like growth factor (IGF)-1 adenovirus vector into primary hepatocytes had overexpressed IGF-1, and had alleviated the number of SA-β-Gal-positive cells. The expression of p53 and progerin was down-regulated in the nucleus, while the expression of p53 was up-regulated in the cytoplasm. The co-precipitation and co-localization of p53 and progerin was decreased in the nuclear region of hepatocytes. IGF-1 overexpression can inhibit intranuclear p53 translocation, alleviate the interaction between p53-progerin, and alleviate hepatocyte senescence.

Five patients with mediastinal bronchogenic cyst (MBC) were treated with endoscopic submucosal tunnel dissection (ESTD) between January 2018 and October 2019 at the Department of Gastroenterology in Henan Provincial People′s Hospital. Lesions were located in the middle or lower esophageal level, with diameters≤3.5 cm. The tunnel establishment time was 13-18 min, and the tumor stripping time was 30-51 min. The number of titanium clips used for tunnel closure was 5-8. The tumors were completely resected. No major bleeding or hypoxemia occurred during the operation and no serious adverse reactions occurred after the operation. Postoperative pain scores were all ≤3. The hospital stay was 4-7 days. There was no tumor residue and recurrence during 4-23 months of follow-up.It is suggested that ESTD for MBC which derived from post mediastinum and located at the lower or middle level esophagus is safe and effective.

Objective To investigate the relationship between prognostic nutritional index (PNI) and neutropenia after adjuvant chemotherapy in patients with colorectal cancer. Methods The clinical data of 44 patients with colorectal cancer performed adjuvant chemotherapy in Shunyi District Hospital from December 2014 to January 2018 were retrospectively analyzed, and the patients were divided into group A (grade 0-2 neutropenia) and group B (grade3-4 neutropenia) according to the degree of neutropenia. The serum albumin, peripheral lymphocyte counts, and neutrophil counts within 1 week before chemotherapy were collected, and the PNI was calculated. The chi-square test and rank sum test were used to compare the clinical data, body mass index (BMI), baseline neutrophil count, and PNI between the two groups. Logistic regression analysis was used to analyze the risk factors for neutropenia after chemotherapy. Results The baseline median neutrophil counts and median PNI in group A were 3.17×109/L [(1.38-7.79)×109/L] and 50.40 (37.40-57.05), and in group B were 2.54 ×109/L [(1.22-3.87) ×109/L] and 45.50 (37.95-50.95). The baseline neutrophil counts and PNI in group A were significantly higher than those in group B, the differences between the two groups were statistically significant (Z= -2.085, P= 0.037; Z= -2.615, P= 0.009). Logistic regression analysis showed that PNI was an independent risk factor for neutropenia after chemotherapy (HR=0.803, 95％CI 0.646-0.998, P= 0.048). Conclusion PNI has a certain role in predicting neutropenia after adjuvant chemotherapy in patients with colorectal cancer.

To establish the experts consensus on the management of delirium in critically ill patients.A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group.Each statement was assessed based on the GRADE (Grading of Recommendations Assessment,Development,and Evaluation) principle.Then the Delphi method was adopted by 36 experts to reassess all the statements.(1) Delirium is not only a mental change,but also a clinical syndrome with multiple pathophysiological changes.(2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function.(3) Pain is a common cause of delirium in critically ill patients.Analgesia can reduce the occurrence and development of delirium.(4) Anxiety or depression are important factors for delirium in critically ill patients.(5) The correlation between sedative and analgesic drugs and delirium is uncertain.(6) Pay attention to the relationship between delirium and withdrawal reactions.(7) Pay attention to the relationship between delirium and drug dependence/ withdrawal reactions.(8) Sleep disruption can induce delirium.(9) We should be vigilant against potential risk factors for persistent or recurrent delirium.(10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases,and can also be alleviated with the improvement of primary diseases.(11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis.(12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium,especially subclinical delirium.(13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium.(14) Daily assessment is helpful for early detection of delirium.(15) Hopoactive delirium and mixed delirium are common and should be emphasized.(16) Delirium may be accompanied by changes in electroencephalogram.Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant.(17) Pay attention to differential diagnosis of delirium and dementia/depression.(18) Pay attention to the role of rapid delirium screening method in delirium management.(19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium.(20) The key to the management of delirium is etiological treatment.(21) Improving environmental factors and making patient comfort can help reduce delirium.(22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium.(23) Communication with patients should be emphasized and strengthened.Family members participation can help reduce the incidence of delirium and promote the recovery of delirium.(24) Pay attention to the role of sleep management in the prevention and treatment of delirium.(25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium.(26) When using antipsychotics to treat delirium,we should be alert to its effect on the heart rhythm.(27) Delirium management should pay attention to brain functional exercise.(28) Compared with non-critically illness related delirium,the relief of critically illness related delirium will not accomplished at one stroke.(29) Multiple management strategies such as ABCDEF,eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients.(30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment.(31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management.Consensus can promote delirium management in critically ill patients,optimize analgesia and sedation therapy,and even affect prognosis.

Objective To explore the effects of psychological crisis intervention in amputation patients with limbs high-voltage burns. Methods A total of 68 amputation patients with limbs high-voltage burns who were treated in Harbin Fifth Hospital from January 2011 to December 2016 were selected in this study using purposive sampling. The participants were randomly divided into the observation group (n=34) and the control group (n=34). The control group received routine psychological nursing care while the observation group was given psychological crisis intervention. The Stress Reaction (SR), SAS, and SDS were used to evaluate the effects of the intervention. Results The observation group had significantly lower scores of SR, SAS, and SDS compared with the control group [(17.89±3.66) vs. (26.89±3.98) for SR; (42.31±8.48) vs. (50.32±10.25) for SAS; (45.32±8.96) vs. (52.77±11.18) for SDS; (t=17.328,4.512,3.581;P<0.05)]. Conclusions The psychological crisis intervention can effectively improve negative emotions such as anxiety and depression in amputation patients with limbs high-voltage burns. It helps patients to develop positive attitudes towards the reality of amputation.

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with cellular and molecular mechanisms yet to be fully described. Mutations in a number of genes including SOD1 and FUS are associated with familial ALS. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts of familial ALS patients bearing SOD1 and FUS mutations, respectively. We further generated gene corrected ALS iPSCs using CRISPR/Cas9 system. Genome-wide RNA sequencing (RNA-seq) analysis of motor neurons derived from SOD1 and corrected iPSCs revealed 899 aberrant transcripts. Our work may shed light on discovery of early biomarkers and pathways dysregulated in ALS, as well as provide a basis for novel therapeutic strategies to treat ALS.
Amyotrophic Lateral Sclerosis ; genetics ; metabolism ; therapy ; Cell Line ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genetic Therapy ; Genome-Wide Association Study ; Humans ; Induced Pluripotent Stem Cells ; metabolism ; Mutation, Missense ; RNA-Binding Protein FUS ; genetics ; metabolism ; Superoxide Dismutase-1 ; genetics ; metabolism

Objective To explore differences in phototest and photopatch test results, and in skin color?related parameters between healthy subjects and patients with chronic actinic dermatitis (CAD), and to examine their relationship with the melanocortin?1 receptor gene(MC1R)Arg163Gln variant. Methods Phototests were performed by using a sun simulator SUN1000, and skin color was analyzed by using Hexameter MX18 in 25 patients with CAD and 25 healthy subjects. The MC1R genotype at position?163 was determined by PCR. Photopatch tests were performed on 25 patients with CAD and 5 healthy subjects using a standard series of photoallergens(RuiMin)and an ultraviolet (UV)phototherapy equipment, SS?03A. Results Regarding phototest results, both UVA?minimal persistent pigment darkening dose(MPPD)and UVB?minimal erythema dose(MED)were significantly lower in CAD patients compared with healthy controls (both P < 0.05), with the reduction in UVB?MED being particularly notable. Sixteen patients (64%)in the CAD group had positive photopatch reactions, including 13(52%)cases of photoallergy. Skin color?related parameters were measured at four sites. Skin hemoglobin levels on the cheek, forehead, back of hands, inner upper arms were all significantly higher in CAD patients than in healthy controls(all P<0.05). However, skin melanin levels on the cheek, forehead and inner upper arms were similar between the two groups, and only those on the back of hands were significantly higher in CAD patients than in controls(P<0.01). Skin melanin and hemoglobin levels were significantly higher in exposed than in unexposed (inner upper arms) areas in CAD patients (all P < 0.05). The frequency of the CGA genotype at position?163 in the MC1R gene was similar between CAD patients and controls(P>0.05), but that of the CAA genotype differed significantly between the two groups(P<0.01). UVA?MPPD and UVB?MED were both significantly lower in CAD patients with the CAA genotype at position?163 in the MC1R gene than in those without the genotype(P=0.055, 0.325, respectively). Conclusions Skin photobiological testing plays a critical role in the diagnosis of CAD. Further studies are needed to clarify the role of the CAA genotype at position?163 in the MC1R gene in the diagnosis, prevention and treatment of CAD.

Xeroderma pigmentosum (XP) is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patient-specific induced pluripotent stem cells (iPSCs) harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells (NSCs) or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clarify the molecular mechanisms of neurological abnormalities in the XP patients.
DNA Damage ; DNA Repair ; DNA-Binding Proteins ; genetics ; metabolism ; Female ; Humans ; Induced Pluripotent Stem Cells ; metabolism ; pathology ; Male ; Models, Biological ; Mutation ; Neural Stem Cells ; metabolism ; pathology ; Xeroderma Pigmentosum ; genetics ; metabolism ; pathology