Objective : To investigate the mechanism of action of benvitimod (BVM) in the treatment of atopic der- matitis (AD) . Methods : HaCaT cells were stimulated by TNF-α and IFN-γ , and the cells were grouped into NC group , TNF-α/IFN-γ group , TNF-α/IFN-γ BVM group , and TNF-α/IFN-γ BVM ML385 group. The AD model of DNCB-induced Balb/c mice was divided into CON group , DNCB group , DNCB + BVM group , and DNCB + TAC group. The efficacy of BVM and its roles in antioxidant and pyroptosis regulation were evaluated. Results: Compared with the control group , BVM inhibited the inflammatory response of HaCaT cells stimulated by TNF-α and IFN-γ , and ameliorated the skin lesions and inflammation in the DNCB-induced AD mouse model ; at the same time , it significantly increased the expression of nuclearfactorerythroid-2-relatedfactor2 (NRF2)-related anti-oxida- tive stress proteins , and significantly reduced the expression of cellular reactive oxygen species (ROS) levels and pyroptosis proteins. At the same time , the levels of NRF2-related antioxidative stress proteins significantly in- creased , and the levels of ROS and pyroptosis proteins significantly decreased. Conclusion BVM activates the NRF2/ROS/NLRP3 pathway to inhibit pyroptosis , thereby reducing the inflammatory response in AD.

OBJECTIVE: To explore the genetic basis for a child with café-au-lait macules and juvenile xanthogranuloma. METHODS: Clinical data and peripheral blood samples of the patient and her family members were collected and subjected to targeted capture and high-throughput sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: A deletional variant in exon 23 of the NF1 gene was detected in the proband. Sanger sequencing has verified it as a de novo variant, which was highly correlated with the clinical manifestations of the patient and her mother. The diagnosis of neurofibromatosis 1 (NF1) was established. The variant was unreported previously. CONCLUSION Targeted capture and next-generation sequencing combined with Sanger sequencing can facilitate early diagnosis of NF1 and provide a basis for the clinical treatment, genetic counseling and prenatal diagnosis.
Child ; Female ; Humans ; Cafe-au-Lait Spots/genetics* ; Genes, Neurofibromatosis 1 ; Neurofibromatosis 1/genetics* ; Xanthogranuloma, Juvenile/genetics*

With the development of transcriptomic technologies such as gene chip technology and RNA sequencing technology, important related factors in the pathogenesis of atopic dermatitis (AD) have been gradually identified, such as different T helper (Th) cell subtypes and other immune-related cells (macrophages and Langerhans cells) ; abnormal changes in active substances such as interleukin-4, interleukin-13, fillagrin and loricrin released by immune-related cells such as Th2 cells and keratinocytes have been found to play major roles in pruritus and skin barrier damage in AD. In recent years, transcriptomic technologies have been applied to the analysis of changes in transcriptomic profiles of patients before and after treatment to evaluate patients′ condition and therapeutic effect. This review summarizes research progress in transcriptomics in AD in recent years.

Epidermal barrier defects and immune abnormalities are the main pathophysiological changes in the development of atopic dermatitis (AD) . Skin keratinocytes can release a variety of inflammatory factors and mediators under the treatment with various harmful factors. Three epithelium-derived cytokines interleukin (IL) -33, IL-25 and thymic stromal lymphopoietin are considered to be effective inducers of Th2 immune response in skin or mucosal barrier, which can activate immune cells, cause the secretion of Th2 cytokines, enhance the Th2 immune response, and participate in the occurrence and development of AD. This review focuses on the role of the above 3 epithelium-derived cytokines in the pathogenesis of AD.

Objective:To investigate the abnormal patterns of spontaneous neural activity of patients with type 2 diabetes comorbid depression (T2DD) by using resting-state functional magnetic resonance imaging (rs-fMRI) fractional amplitude of low-frequency (fALFF) analysis, and determine the neuroimaging features of brain damage in T2DD patients.Methods:A perspective study was performed. Fifty-nine type 2 diabetes mellitus (T2DM) patients and 52 T2DD patients, admitted to and accepted treatment in Department of Endocrinology of our hospital from November 2017 to November 2020, were chosen; another 57 healthy controls matched with gender, age and education level, admitted to our hospital at the same time period were enrolled. Their clinical data, neuropsychological test and rs-fMRI data were collected; whole brain fALFF values were calculated, and fALFF values of different brain regions were compared in subjects of the 3 groups. Pearson correlation analysis was used to verify the correlations of fALFF values with clinical variables and neuropsychological scale scores.Results:The fALFF values in bilateral precuneus showed significant difference among the three groups ( P<0.05). The fALFF values in bilateral precuneus of the T2DD and T2DM groups were significantly lower than those in heathy control group ( P<0.05), and those in the T2DD group were lower than those in the T2DM group without significant difference ( P>0.05). Pearson correlation analysis showed that there were no correlations of fALFF values with clinical data and psychometric scale scores in T2DD group and T2DM group ( P>0.05). Conclusion:The abnormal patterns of spontaneous brain activity in the bilateral precuneus may be the neuroimaging markers of brain damage in T2DD patients.

Dopamine is the precursor of a variety of natural antioxidant compounds. In the body, dopamine acts as a neurotransmitter that regulates a variety of physiological functions of the central nervous system. Thus, dopamine is used for the clinical treatment of various types of shock. Dopamine could be produced by engineered microbes, but with low efficiency. In this study, DOPA decarboxylase gene from Sus scrofa (Ssddc) was cloned into plasmids with different copy numbers, and transformed into a previously developed L-DOPA producing strain Escherichia coli T004. The resulted strain was capable of producing dopamine from glucose directly. To further improve the production of dopamine, a sequence-based homology alignment mining (SHAM) strategy was applied to screen more efficient DOPA decarboxylases, and five DOPA decarboxylase genes were selected from 100 candidates. In shake-flask fermentation, the DOPA decarboxylase gene from Homo sapiens (Hsddc) showed the highest dopamine production (3.33 g/L), while the DOPA decarboxylase gene from Drosophila Melanogaster (Dmddc) showed the least residual L-DOPA concentration (0.02 g/L). In 5 L fed-batch fermentations, production of dopamine by the two engineered strains reached 13.3 g/L and 16.2 g/L, respectively. The residual concentrations of L-DOPA were 0.45 g/L and 0.23 g/L, respectively. Finally, the Ssddc and Dmddc genes were integrated into the genome of E. coli T004 to obtain genetically stable dopamine-producing strains. In 5 L fed-batch fermentation, 17.7 g/L of dopamine was produced, which records the highest titer reported to date.
Animals ; Dopa Decarboxylase/genetics* ; Dopamine/biosynthesis* ; Drosophila melanogaster/genetics* ; Escherichia coli/metabolism* ; Humans ; Metabolic Engineering

Objective To explore the effect of proliferation and apoptosis,and research its mechanism associated with RAS/extracellular signal regulated kinase/mitogen-activated protein kinase (RAS/ ERK/MAPK) in Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation acute lymphocytic leukemia cell line MV4-11 cells treated by triptolide (TP).Methods MV4-11 cells were respectively treated by triptolide with diverse concentrations and different times.The proliferation inhibition rate was measured by methyl thiazolyl tetrazolium,the apoptosis rate was detected by flow cytometry,the mRNA expressions of FLT3,RAS,ERK,forkhead box protein M1 (FOXM1),and c-Myc were analyzed by realtime fluorescent quantitative polymerase chain reaction (PCR).Results The proliferation inhibition rate markedly increased in a dose-time dependent manner after MV4-11 cells were treated by TP.After cells were treated with 10,and 20 nmol/L TP,respectively,the apoptosis rates at 48 h were (17.30 ± 0.56) ％,(35.77 ±0.55)％,and those at 72 h were (49.83 ±0.45)％,(68.90 ±0.75)％ correspondingly.PCR data showed that the mRNA level of FLT3 mRNA decreased obviously,and that of RAS,ERK,FOXM1,and c-Myc also decreased.Conclusions Triptolide could significantly inhibit the MV4-11 cells proliferation and induce cell apoptosis,and its mechanism might be through inhibiting the expression of related genes on RAS/ERK/MAPK signaling pathway.

Objective To investigate the effect of continuous quality improvement on subjective well-being quality of life and satisfaction of esophageal cancer patients. Methods A total of 120 esophageal cancer patients in our hospital were randomly divided into two groups, 60 cases in the observation group treated with continuous quality improvement while the other 60 cases in the control group treated with routine care. The two groups were compared in terms of subjective well-being,quality of life and nursing satisfaction. Results Before the intervention, there were no significant differences between the two groups in view of the quality of life scale score and subjective well-being score (P>0.05). After the intervention, in view of symptoms, the scores on all the items in the boservation group were significantly lower than those in the control group (P<0.05), except constipation, economic difficulty and diarrhea and the function items were higher. The subjective satisfaction of the observation group was significantly better than that of the control group (P<0.05). Conclusion Continuous quality improvement care can promote the improvement of subjective well-being, improve the quality of life and satisfaction of patients with esophageal cancer.

When hepatitis B virus (HBV) invades the human body, innate immunity acts the earliest and plays an important role. When an adult is infected with HBV, HBV can often be eliminated spontaneously. However, if HBV infection occurs right after birth or when the patient is young, the disease tends to become chronic and affect the whole life. In the incipient stage of HBV infection, innate immune response plays an important role in inhibiting viral replication, and the prognosis of HBV infection depends on the combined effect of host and virus. This article briefly introduces the research advances in the cells, cytokines, and signaling pathways that play important roles in the host's innate immunity against HBV and their mechanisms of action, and points out their potential values in clinical treatment.

ObjectiveTo investigate the prevalence of preoperative malnutrition and nutrition support among gastrointestinal cancer patients.MethodsA retrospective study was conducted based on the nutritional status and nutrition support of 336 gastrointestinal cancer patients who received elective radical surgery in Peking Union Medical College Hospital from April to December 2009.ResultsMalnutrition was found in 34.6％ gastric cancer patients,23.8 ％ colorectal cancer patients,and 23 ％ esophageal and cardiac cancer patients.The patients with worse nutritional status were given longer duration of nutrition support and higher energy intake.Conclusion Malnutrition occurs in gastrointestinal cancer patients,yet sometimes treated with inappropriate nutrition support.