The interaction between immune response and metabolic regulation can be viewed as a central homeostatic mechanism,dysfunction of which will lead to many diseases.This nonlinear interaction,which has the characteristic of super-complexity,can’t be controlled unless it is studied as a holism and the change of condition is researched.To study this homeostasis,bottom-up method used in system biology is limited.Ying-wei theory of TCM uses another method to describe di erent states of metabolic and immune systems e ectively.The unique approaches and rich experiences applied in TCM are of great value.

There are three kinds of molecular targeted antitumor drugs: inhibitors of membrane?associated therapeutic targets, inhibitors of intracellular signaling pathways, and immunomodulators. Inhibitors of membrane?associated therapeutic targets include epidermal growth factor receptor inhibitors (EGFRIs), KIT and BCR?ABL inhibitors, antiangiogenic agents and multikinase inhibitors. Inhibitors of intracellular signals include inhibitors of the RAS?RAF?MEK?ERK pathway, PI3K?AKT?mTOR pathway and Hedgehog signaling pathway. Inhibitors of cytotoxic T lymphocyte associated?antigen(CTLA) and programmed death 1 (PD?1) belong to immunomodulatory agents. Cutaneous adverse effects of different molecular targeted antitumor drugs share some common features, but also differ from each other. Most of the side effects are dose?dependent and reversible. Management strategies should be adjusted according to the severity of skin eruptions. Dose tapering and even discontinuation of antitumor drugs are necessary for very severe cases, but for mild ones, symptomatic treatment might be enough. This article reviews cutaneous adverse reactions to molecular targeted therapy as well as their prevention and management.

Drugs, Chinese Herbal ; pharmacology ; Female ; Granulosa Cells ; drug effects ; secretion ; Humans

According to the onset age, a total of 5 674 outpatients with gout admitted in the affiliated hospital of Qingdao University from January 2011 to January 2016 were divided into youth group (≤44 years, n=3 058), middle age group (45~64 years, n=2 101), and elderly group (≥65 years, n=515).Their clinical and biochemical characteristics were analyzed.The results showed that the proportion of gout in the males in three groups was higher than that in the females.The proportions of gout in male youth, middle age, and elderly groups were 98.1%, 93.4%, and 83.1%, respectively.The proportion of gout in females increased with age.The proportion of gout family history in youth group was higher than that in middle age and elderly groups(P<0.05).The proportions of hypertension and impaired fasting glucose(IFG) in elderly group were higher than those in youth and middle age groups (P<0.05), with lower proportions of hypertriglyceride and obesity (P<0.05).The levels of systolic blood pressure, blood urea nitrogen, creatinine in elderly group were increased compared with youth and middle age groups (P<0.05) while the levels of uric acid and triglyceride were decreased (P<0.05), with higher ratio of renal dysfunction (P<0.05).There were no differences in tophus and kidney calculi among three groups (P>0.05).The distributions of the onset joint among three groups revealed statistical difference(P<0.05), but the first plantar toe joint was mostly involved in each group.These results suggest that the clinical characteristics of patients with gout at different onset ages are not identical, should be treated differently.

Background Stickler syndrome is a genetic connective tissue disorder that affects the ocular,skeletal,orofacial and auditory systems.To determine the gene mutation loci can offer a basis for genetic diagnosis and management of Stickler syndrome.Objective The aim of this study was to research the clinical characteristics of a pedigree with Stickler syndrome and identify the disease-causing gene mutation.Methods This study was approved by Ethic Committee of Peking Union Medical College Hospital.The clinical study and pedigree analysis were performed in one family with Stickler syndrome type Ⅰ (STL Ⅰ).Nine family members were examined with informed consent.The entire coding regions of COL2A1 gene with flanking intronic regions were amplified by PCR and directly sequenced.The detected sequence change was confirmed to be mutationloci by examining whether they existed in normal control individuals.Mutant proteins were predicted with online software.Results There were 4 generations and 11 members in this family,and 2 members died,including 1 patient.Three patients were found in 9living families.Inheritance of this family complicd with an autosomal dominant inheritance mode.All affected individuals showed the consistent phenotypes with STL Ⅰ,including high myopia,membranous vitreous anomaly and surface central flat,short nose,palatoschisis,etc.Mutation screening of COL2A1 gene revealed that the first base of intron 12 was deleted(IVS12+1G del).Nucleotide sequence analysis showed that this mutation led to the functional abnormal of this gene by forming termination cordon in advance.This mutation occurred in all affected individuals,however,no mutation was observed in any unaffected member or 100 normal unrelated individuals.Conclusions This study identifies a novel splice-site mutation(IVS12+ 1G del)in COL2A1 gene in a Chinese STL Ⅰ pedigree.This is the first report on a mutation in a Chinese STL Ⅰ family.

Aged ; Endoscopy ; Female ; Humans ; Male ; Middle Aged ; Mycoses ; pathology ; surgery ; Paranasal Sinuses ; microbiology ; pathology ; surgery ; Retrospective Studies

Objective To study the expression of skin aspartic protease (SASPase) in lesions of cutaneous lupus erythematosus (CLE) and its role in the pathogenesis of CLE.Methods Skin samples were resected from the lesions and normal skin of 9 patients with CLE,including 3 cases of subacute cutaneous lupus erythematosus (SCLE),4 cases of discoid lupus erythematosus (DLE) and 2 cases of acute cutaneous lupus erythematosus (ACLE).Keratinocytes were isolated from the tissue samples and cultured in serum-free medium.Total proteins were extracted from the keratinocytes and separated by two-dimensional gel electrophoresis.ImageMaster 2D analysis software was used to assess differentially expressed proteins in keratinocytes between the lesional and normal skin,which were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS).The expression levels of SASPase were further determined by Western blot.The data were analyzed statistically by Student's t test.Results Keratinocytes were isolated from the tissue samples and successfully cultured in vitro.Two-dimensional electrophoresis profiles of proteins from the keratinocytes were obtained with high resolution and reproducibility,and the average matching protein spots were about 1200 with the matching rate higher than 80％.As Western blot showed,the relative expression level of SASPase was 0.463 ± 0.018 in keratinocytes from the lesional skin,and 0.145 ± 0.011 in those from the normal skin (P ＜ 0.05).The Western blot results were consistent with those of two-dimensional electrophoresis.Conclusion The initiation and progression of CLE seem to be associated with the abnormal activation and overexpression of SASPase.

Objective To explore the effect of hepatitis B virus(HBV) on the expression of complement 3 (C3) and complement 4 (C4) and its regulatory mechanism.Methods Differentially expressed genes between HepG2 and HepG2.2.15 cells was screened by gene chip,serum complement component 3 (C3) and 4 (C4) levels in patients with HBV infection and in healthy individuals were measured by Immunoturbidimetry,HBV infectious clone pHBV1.3 was transfected into HepG2 cells,and expression of C3 and C4 was measured by RT-PCR and Western blot.Results Expression of C3 and C4 mRNA was lower in HepG2.2.15 cells than in HepG2 cells,serum C3 and C4 levels was much lower in patients with chronic hepatitis B and hepatic carcinoma as compared to healthy individuals (P＜0.05 ).HBV could downregulate the expression of C3 and C4 at mRNA and protein levels.Conclusion HBV may inhibit the expression both in vivo and in vitro.

Objectives To learn the effect of self-recognition-based healthy management on community diabetics. Methods A total of 40 community diabetics were evaluated and trained for 3 months.SPSS11.5 software was used for data analysis. Results At 3 months, some risk factors of diabetes,including body weight, body mass index (BMI), waist circumstance (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP) and 2 h postprandial blood sugar (PBS), were improved (P ＜0. 05). Male patients showed statistically significant reduction in body weight, BMI and WC ( P ＜ 0. 05 ).However, female subjects were found to have significant decline in body weight, BMI, WC, SBP and DBP (P＜0. 05). Those ＞60 year-old had significantly decreased body weight, BMI, WC, SBP, DBP and 2 h PBS ( P ＜ 0. 05). Lower levels of WC, SBP and triglyceride were seen in individuals ＜ 60 year-old ( P ＜0. 05 ). Conclusion Self-recognition-based healthy management could effectively reduce diabetic risk factors and prevent the development of diabetic complications.

Objective To evaluate the effect of Chinese gentian extracts on the proliferation of,apoptosis and phosphorylation of epidermal growth factor receptor (EGFR) in HaCaT cells induced by epidermal growth factor (EGF).Methods Methyl thiazolyl tetrazolium (MTT) assay was performed to evaluate the proliferation of HaCaT cells pretreated with EGF of 20 μg/L for 24 hours followed by 24 hours of treatment with various concentrations of Chinese gentian extracts.Flow cytometry was carried out to detect apoptosis in HaCaT cells pretreated with EGF of 20 μg/L for 24 hours followed by 4 hours of treatment with different concentrations of Chinese gentian extracts.Western blot was conducted to measure the level of phosphorylated EGFR in HaCaT cells treated with different concentrations of Chinese gentian extracts for 24 hours followed by treatment with EGF of 20 μg/L for 10 minutes.Results Chinese gentian extracts inhibited the proliferation (r =-0.991,P ＜ 0.01),but promoted the apoptosis (r =0.996,P ＜ 0.05) of HaCaT cells induced by EGF in a dose-dependent manner.At the same time,the extracts suppressed the phosphorylation of EGFR in HaCaT cells induced by EGF,and the suppressing effect increased with the rise in the concentration of the extracts.Conclusions Chinese gentian may inhibit the proliferation,but promote the apoptosis of keratinocytes by decreasing EGFR phosphorylation and blocking relevant intracellular signaling pathways.