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.

0.05), but significantly lower than 8.3% in Guangzhou area(P

Objective To investigate the roles of fiberoptic bronchoscopy in diagnosis and treatment for infants with refractory and persistent wheezing. Methods From Jun. 2012 to Dec. 2013, 52 hospitalized children with age between four 4 months and 1 year old were recruited for ifberoptic bronchoscopy, who had been wheezing for at least four weeks and treated ineffectively with conventional anti-inlfammatory agents:budesonide and compound ipratropium bromide solution. Then, the pathogenesis of refractory and persistent wheezing was summarized based on clinical features, detection of CT imaging of three-dimensional airway reconstruction and cardiac CT, results of bronchoscopy inspection, and bronchoalveolar lavage lfuid culture. Results Among the 52 cases, 40 were with ground glass-like changes (76.92%) in pulmonary spiral CT testing, 4 with mosaic perfusion syndrome (7.69%), 8 with segmental pulmonary consolidation (15.38%), 8 with obstructive pulmonary emphysema (15.38%), and 1 with left primary bronchial foreign body. In addition, through bronchofibroscopy, there were 52 cases with imlfammation (100%),3 with tracheal stenosis (5.77%), 3 with left and/or right main bronchus stenosis of the external pressure, 18 with bronchomalacia(34.62%), 2 cases with foreign body (3.84%), one in trachea (1.92%), the other in left main bronchus (1.92%), 10 with bronchial mucus plug (19.23%), and 8 (15.38%) with congenital airway malformations (including 3 at tracheal bronchus, 1 at left upper lobe bronchial stenosis and 1 at bronchial Bridge). The culture of bronchoalveolar lavage lfuid were conducted for all patients. The positive rate of bronchoalveolar lavage lfuid was 9.62%(5/52 cases), including 2 cases with tip Escherichia coli, 2 with Haemophilus inlfuenzae, and 1 with Acinetobacter baumannii. Conclusions First, infection is the primary cause of refractory and persistent wheezing, which is persistent in airway resulted from multi-drug resistant bacteriua. Second, refractory and persistent wheezing is often caused by multi-factors including infection, congenital airway malformations, the endogenous and exogenous foreign body, cardiovascular malformation, etc. These factors often lead to dififcult wheezing control. The last, the diagnosis rate of the refractory and persistent wheezing can be improved by combination of ifberoptic bronchoscopy and lung spiral CT.

Objective To explore the effect of L-dopa on plasma homocysteine and folic acid in patients with parkinsons' s disease(PD).Methods Twenty eight elderly PD patients and thirty normal subjects were enrolled in this group.The homocysteine,cobalamin and folate were examined in normal group and in PD group before treatment and after being treated with L-dopa for six moths respectively.Then the homocysteine,cobalamin and folate were compared between the two groups.Results The plasma homocysteine levels increased in PD patient group after being treated with L-dopa for six months(19.19? 8.01)?mol/L as compared with those of the PD group before treatment(12.50?3.78)?mol/L and those of control group(12.60?3.94)?mol/L(P

Small scale restricted online course (SPOCs)+flipped classroomteaching is expected to become an important complement to the traditional teaching of dermatology. In this teaching mode, first of all knowledge nodes are divided separately according to the syllabus and for each node, 7 to 10 minutes of micro video or micro-lecture is made, which enables students to make best use of fragmented time through the network to master relevant knowledge independently before the trainee. In the flipped classroom, based on the difficulties and misunderstandings of learning reflected from the network monitor data, teacher can make full use of time on demonstrating typical cases, organizing discussion, grouping students to take diag-nostic and therapeutic exercise, answering targeted questions, teaching clinical thinking, experience and doctor-patient communication skills. Through this teaching mode, the new teaching idea can be imple-mented that students are in dominant position while teachers are in leading position, which contributes to deepening the understanding , absorption and application of knowledge and improving students' ability of communication, cooperation, diagnosis and treatment.

Pyroptosis belongs to the programmed cell death of inflammatory cells, which is regulated by GSDMD (Caspase-1,-4,-5-11) and GSDME (Caspase-3, granzyme). Multiple regulatory pathways of pyroptosis are abnormally expressed in gastric cancer cells, indicating that pyroptosis is closely related to gastric cancer and has the potential to become a new target for gastric cancer treatment. Combined with current mainstream treatments such as chemotherapy and immunotherapy, it may improve clinical treatment effect of gastric cancer. This article reviews the molecular mechanism of pyroptosis, the related research on gastric cancer and pyroptosis, and the related research on pyroptosis and gastric cancer treatment to explore the possibility of pyroptosis as a new target for gastric cancer, and to provide new research ideas for gastric cancer treatment.

Objective To investigate procedure and therapeutic effect of resection and reconstruction for axis tumors through the sub mandible approach. Methods Between December 2004 to June 2010,17 patients with axis neoplasm underwent tumor resection and antero-posterior reconstruction through the combined the sub mandible-inner sternocleidomastoid muscle (SMIS) approach and posterior approach. Tumor lesions involved C2 in 11 cases, C2-3 in 4, C2-4 in 2. Eight cases involved vertebral body, and 9 involved both vertebral body and element. Fourteen primary lesions including 4 giant cell tumors, 4 plasmocytomas, 2 chordomas, 2 eosinophilic granulomas, 1 hemangiopericytomas and 1 lymphoma, and 3 metastatic lesions were involved in this study. Three types of reconstruction in upper cervical spine including titanium mesh plus vertically placed titanium plate, titanium mesh plus obliquely placed titanium plate and trimmed titanium mesh alone, were adopted after anterior tumor resection, and then posterior tumor resection and reconstruction were performed. Results All patients experienced pain relief and neurological improvement after surgery. Except for one incidence of screw pull-out which was corrected by a revision surgery, solid fusion was achieved in all patients. A follow-up period of 6 months to 6 years was available for this study. One patient died of cerebral infarction 9 months postoperative. Two patients with chordoma relapsed 13 months and18 months postoperative, respectively, of whom one died of high plegia and respiratory failure, and the other was alive with disease. Two patients with metastasis died of multiple remote metastases 12 months and 18 months postoperative, respectively. Conclusion Through the SMIS apporach, a satisfactory exposure can be obtained for axis tumor resection and reconstruction. Anterior reconstruction of upper cervical spine after tumor resection can be achieved with internal fixation system of cervical spine, which can improve intraopera-tive safety. The combined anterior reconstruction and posterior occipito-cervcial fixation can provide immediate stability, and benefit maintaining stability of upper cervical spine.

Objective To discuss the correlation between dynamic changes in pulmonary function and chronic cough in 5-to-14-year-old children with Mycoplasma pneumoniae pneumonia(MPP)after acute period(about 2 weeks after admission). Methods One hundred and fifty - six hospitalized children diagnosed with MPP from Lianyungang Maternal and Child Health Care Hospital Affiliated to Yangzhou University from February 2014 to May 2017 were selected. According to the results of routine ventilatory pulmonary function before discharge(10-14 days in hospital;acute phase group),there were 50 patients with normal pulmonary function and 106 patients with abnormal pulmonary function. All patients continued to take oral azithromycin for 2 to 3 courses after discharge,and the indexes of lung function were dynamically tracked in 1 month(1-month group)and 2 months(2-month group)in the group of abnormal lung function after leaving the hospital,and the incidences and causes of chronic cough were followed up. Results (1)There were 106 cases with abnormal pulmonary function in 156 cases with MPP in acute phase group,and the rate of incidence was 67. 95%. Twenty-seven(29. 35%)out of 97 children were still abnormal in pulmonary functional testing 1 month after leaving hospital( 1-month group). Among the 27 cases,about 18. 52%(5/27 cases) of them still did not return to normal 2 months after discharge( 2-month group ). There were significant differences in the occurrence of abnormal pulmonary function among 3 groups mentioned above(χ2 ＝162. 64,P<0. 001).(2)Ratios of measured values and predicted ones of forced vital capacity( FVC ),forced expiratory volume in one second (FEV1 ),peak expiratory flow(PEF)and maximum mid-expiratory flow(MMEF 25% -75%)in the lung function of 2-month group after the acute phase of MPP were significantly higher than those of 1-month group and acute phase group,and the values of 1 -month group were better than those in acute phase one,which were statistically different among 3 groups(P<0. 01).(3)The rate of occurrence of chronic cough in normal lung function group was about 18. 00%(9/50 cases),and in abnormal pulmonary function group,it was about 70. 75%(75/106 cases). There was a significant difference between them(χ2 ＝35. 96,P<0. 05). Abnormal pulmonary functions were the influencing factors of chronic cough(r＝0. 55,P<0. 01).(4)There were 5 cases with upper airway cough syndrome(UACS)and 4 cases with post-infection cough(PIC)found in the normal lung function group. By contrast,75 cases suffered from chronic cough in abnormal pulmonary functions group,of which 36 cases with cough variant asthma( CVA),24 cases with UACS,8 cases with comorbidity of CVA and UACS and 7 cases with PIC. Conclusions Abnormal lung function after acute period of MPP may last 4 to 8 weeks,or probably even longer. In normal lung function group,UACS is the most common cause,then followed by PIC. On the contrary,the main cause of chronic cough in abnormal pulmonary function group is CVA,followed by UACS. Chronic cough is related to abnormal lung function after acute phase of MPP.

Objective:To investigate effects of short-term cigarette smoke exposure combined with poly(I:C)stimulation on lung immune response and interferon expression in mice.Methods:BALB/c mice were randomly divided into 4 groups:control group,smoke group,poly(I:C)group and smoke combined poly(I:C)group.Total cell number and cell classification count of bronchoalveo-lar lavage fluid(BALF)were detected,and cell morphology was observed under ordinary light.Cytokines,chemokines,interferon and interferon stimulating genes expressions in lung tissues were detected by fluorescence quantitative PCR.Results:Compared with control group,total cell count,macrophage count and neutrophil count in smoke combined poly(I:C)group were significantly increased(P<0.05),and macrophage count was higher than that in poly(I:C)group.Macrophages of airway lavage fluid of mice in smoke combined with poly(I:C)group were larger in size,round or irregular in shape,and had more vacuoles in cytoplasm.Com-pared with control group,mRNA expressions of neutrophil chemokine CXCL1(P<0.05),CXCL2(P<0.01)and lymphocyte chemo-kine CCL2(P<0.01)in lung tissues of mice in smoke combined with poly(I:C)group were increased.IL-1β,IL-6,TNF-α mRNA expressions were significantly increased(P<0.01),IFN-β(P<0.01),IFN-γ(P<0.05),MX2(P<0.01)and IP-10(P<0.01)expre-ssions in lung tissues were significantly increased,and compared with poly(I:C)group,mRNA expressions of CXCL2(P<0.05),TNF-α(P<0.01)and IFN-β(P<0.05)in lung tissues of mice in smoke combined with poly(I:C)group were significantly increased.Conclusion:Cigarette smoke combined with poly(I:C)induces lung inflammation and expressions of interferon and interferon stimu-lating genes in mice.Cigarette exposure also increases poly(I:C)-induced acute lung inflammation and type Ⅰ interferon expression in mice.

Objective:To analyze clinical features and prognosis of Mycoplasma pneumoniae-induced rash and mucositis (MIRM) . Methods:Among patients who were diagnosed with erythema multiforme/severe erythema multiforme or Stevens-Johnson syndrome at discharge from the First Affiliated Hospital, Sun Yat-sen University from November 2004 to May 2021, patients with MIRM were screened out according to diagnostic criteria for MIRM and after exclusion of other causes, and their clinical manifestations, laboratory and auxiliary examinations, treatment and prognosis were analyzed.Results:Eight patients were found to meet the MIRM diagnostic criteria, including 4 males and 4 females, with the age at onset being 15.63 ± 9.16 years (range, 4 - 30 years) . All the 8 patients had fever, and 5 of them had upper respiratory symptoms such as cough and sore throat. Oral mucosal damage occurred in all the patients, 5 of whom presented with blood crusts on the lips; eye damage occurred in 7 patients, which manifested as conjunctiva hyperemia and increased secretions. All the patients presented with skin lesions, including 5 with targetoid lesions and 4 with blisters. All the patients were serologically positive for anti- Mycoplasma pneumoniae IgM. One patient experienced recurrent upper respiratory tract infections such as dry cough, each episode was closely related to Mycoplasma pneumoniae infection, and whole exome sequencing of the peripheral blood showed heterozygous mutations in the NLRC4 and IRGM genes. Histopathological examination of skin lesions was performed in 3 patients, and the results were consistent with the diagnosis of erythema multiforme. Seven patients were treated with systemic glucocorticoids, 6 with intravenous immunoglobulin, 5 with azithromycin, and 5 with acyclovir, valacyclovir or ribavirin. After an average 2.9-year follow-up, 3 patients were cured, 1 was blind, 1 experienced recurrent dry cough, oral ulcers and rashes on the limbs, and the remaining 3 developed eye damage such as meibomian gland dysfunction, punctal stenosis and corneal epithelial damage. Conclusions:MIRM mostly occurred in children and young adults, and was mainly accompanied by prodromal symptoms such as fever, sore throat and cough. MIRM mainly manifested as obvious mucosal damage and some targetoid lesions. Most patients could recover after a single attack, and recurrent episodes may be related to mutations in autoinflammation- and infection-related genes in some patients.