Voriconazole is a broad spectrum triazole antifungal agent, widely used in the prevention and treatment of invasive fungal diseases.Long-term use of voriconazole can induce periostitis and cutaneous squamous cell carcinoma, accounting for serious adverse effects on patients, which has been reported in increasing clinical cases.This review is to characterize the epidemiological and clinical manifestations of periostitis and squamous cell carcinoma induced by voriconazole, and to analyze the mechanisms of triggering periostitis and squamous cell carcinoma, so as to promote the rational use of voriconazole in clinics.

Obstructive sleep apnea (OSA) is characterized by repeated intermittent hypoxia (IH), hypercapnia, sleep fragmentation and intrathoracic pressure change. IH is related to the clinical pathophysiological processes of hypertension, atherosclerosis, coronary heart disease, arrhythmia, stroke, heart failure and sudden death. IH from OSA can lead to metabol-ic dysregulation, endothelial dysfunction, systemic inflammation, oxidative stress and the change of nerve body fluids, which has been shown to increase the risk of cardiovascular diseases. This study mainly describes the pathogenesis of IH leading to the various cardiovascular diseases.

Objective To analyse the clinical manifestations of mycoplasma pneumoniae pneumonia(MPP) with 23SrRNA A2063G gene mutation,and improve the ability of diagnosis and treatment of patient infected with MPP.Methods MP-DNA was detected by fluorescent quantitative real-time PCR in sputum specimens from 36 children with MPP,then we detected the drug resistance gene mutation sites by nest-PCR and DNA sequencing,on this basis we classified into two groups of macrolide-resistant MP and macrolide-sensitive MP,and compared the clinical manifestations,laboratory findings,chest imagings and treatment between two groups.Results Of these 36 cases of MPP,24 cases had macrolide-resistant gene mutation with an A2063G transition in domain V of the 23SrRNA,12 cases had no macrolide-resistant gene mutation.Compared to macrolide-sensitive MP group,macrolide-resistant MP group had longer hospitalization duration,longer total cough period,longer total febrile period,longer fever duration after macrolide therapy,longer course of disease,and had higher white blood cells counts and CRP.In the macrolide-resistant MP group,the temperature subsided within 5 days after macrolide treatment alone of 12 cases,3 cases needed switch to fluoroquinolones therapy,10 cases combined with glucocorticoids and 6 cases combined with intravenous immunoglobulin,all 24 patients had good outcomes.While in macrolide-sensitive MP group,the temperature susided between 12 hours to 3 days after macrolide treatment of 8 cases.Conclusions Compared to patients infected by macrolide-sensitive MP,those mycoplasma pneumoniae pneumonia patients with 23SrRNA A2063G gene mutation have longer hospitalization duration,longer total cough period,longer total febrile period,longer fever duration after macrolide therapy,longer course of disease,and have higher white blood cells counts and CRP.Some macrolide-resistant MPP patients have good response to macrolide antibiotics treatment,while the severe cases need combined with glucocorticoids and immunoglobulin,or should change antibiotics.

Objective To investigate the cancer-related fatigues in oral cancer patients.Methods One hundred oral cancer patients were involved in the survey with self-designed general information questionnaire,revised Piper fatigue correction scale(RPFS).Results Seventy six cases(76.00%)had different degree of fatigue.The total score of RPFS was(5.51+1.23)points. In the descending order of scores,the dimensions were body fatigue,emotional fatigue,behavioral fatigue and cognitive fatigue. Conclusions Oral cancer patients have cancer-related fatigue commonly,with body fatigue the most intense and emotional fatigue at a higher level.Therefore,medical staff should ensure patients intake of enough nutrients in order to reduce the body fatigue and meanwhile should instruct patients to handle their bad moods correctly so as to relieve their metal fatigue.

Objective To study the clinical,pathological and genetic features of myofibrillar myopathy caused by BAG3 gene mutation.Methods The clinical features and pathological findings of a patient with myofibrillar myopathy were analyzed.Genomic DNA of the patient was extracted from peripheral blood and the next generation sequencing was performed to explore the mutation of genes about myopathies.Results The patient presented with nine-year-old onset myopathy characterized by progressive difficulty for squatting,rigid spine and muscle atrophy in the limbs symmetrically.Peripheral neurogenic damages were found on electromyography.On muscle biopsy,myogenic and neurogenic damages with rimmed vacuoles appeared,and the deposited materials were positive for sarcoglycan,dystrophin-R and dystrophin-C.There was a reported heterozygous mutation in the exons of the BAG3 gene (c.626C ＞ T).Conclusion There is no specificity of clinical manifestation in myofibrillar myopathy,and the diagnosis of this disease mainly depends on muscle biopsy and genetic screening.

Objective To investigate the effect of triptolide (TP) on the expression of hypoxia inducible factor 1 alpha (HIF1α) and vascular endothelial growth factor (VEGF) in the human umbilical vein endothelial cells (HUVECs) under hypoxia. Methods (1) HUVECs were treated with 0, 40, 80, 160 and 320 nmol/L TP (named with hypoxia group, TP40 group, TP80 group, TP160 group and TP320 group, respectively) under the hypoxic condition (37℃, 5%CO2, 1%O2, 94%N2) for culturing 12 hours. Meanwhile, cells cultured under normoxia condition (without TP added) were set as the normoxia group. Western blot assay was used to detect the expression of HIF1αin each group. (2) The cells were divided into normal control group, hypoxia group and TP80 group. The immunofluorescence method was performed to detect the localization of HIF1α in cells. (3) Expressions of VEGF were detected by Western blot assay in TP80 group and hypoxia group. (4) The cells were divided into hypoxia group, TP80 group, TP80+KF20 group (80 nmol/L TP and 20μmol/L KC7F2), and TP80+KF30 group (80 nmol/L TP and 30 μmol/L KC7F2). After 12-hour culturing, Western blot assay was used to detect the expressions of HIF1α and VEGF in each group. Results (1) Under the normoxia condition, no HIF1α was detected in HUVECs. The expression level of HIF1αwas significantly increased in TP80 group than that in hypoxia group (P<0.05), while there was no significant change in expression of hypoxia HIF1αin TP160 group and TP320 group compared with that of hypoxic group. (2) The immunofluorescence result showed that HIF1α was mainly expressed in the nucleus. (3) The expression of VEGF was significantly increased in TP80 group than that in hypoxia group (P < 0.05). (4) After the intervention of KC7F2, HIF1αand VEGF expression levels were significantly decreased in the TP80+KF20 group and the TP80+KF30 group than those in the TP80 group (P<0.05). Conclusion TP can improve the expression of HIF1αand VEGF to accelerate the proliferation of endothelial cells under hypoxia condition.

Objective To evaluate the effect of ropivacaine combined with low-dose naloxone or sufentanilropivacaine mixture on brachial plexus block carried under the guidance of ultrasound.Methods A total of 100 patients of our hospital undergoing upper limb surgery was randomly divided into four groups with 25 patients in each group.Four groups are patients receiving 20 mL of 0.375％ mesylate ropivacaine (Group D),20 mL of 0.375％ mesylate ropivacaine + 10 μg sufentanil (Group S),20 mL of 0.375％ mesylate ropivacaine + 100 ng naloxone (Group N) and 20 mL of 0.375％ mesylate ropivacaine + 10 μg sufentanil +100 ng naloxone (Group N+S).All patients underwent interscalene brachial plexus block under ultrasound guidance.The sensory block,motor block and other adverse reactions were observed and recorded at 5min,6,12,18,24 h.Results The sensory and motor block time of group D was (435.5 ± 77.9) min and (350.2 ± 69.8) min,group S (831.7 ± 52.0)min and (675.8 ± 48.1)min,group N (933.0 ± 117.1) min and (499.0 ± 40.5) min,group N+S (919.3 ± 59.0) min and (534.8 ± 56.6)min.The sensory block time of group N and group N + S were significantly longer than that of group D and S (P ＜0.05).The sensory and motor block time of group D were obviously shorter than that of other groups (P ＜ 0.05).There were no significant difference in the onset time of sensory and motor block in all groups.Conclusion Low dose of naloxone combined with ropivacaine or sufentanil-ropivacaine mixture can increase the duration of sensory block on brachial plexus.

Objective To investigate the expression of monocyte subsets and their chemokine,i.e.,monocyte chemoattractant protein (MCP-1) and fractalkine (FKN),in patients with acute coronary svndrome (ACS),and to analyze their correlation.Methods Patients with the syndrome of pectoralgia and to be inspected with coronary angiography (CAG) in our hospital from Sep.to Dec.,2016 were included.Patients' venous blood was collected on the operation day before operation,the level and proportion of monocyte (Mon) subsets,which was namely CD14 + CD16-Mon (Mon1),CD14+CD16 + Mon (Mon2) and CD14-CD16 + Mon (Mon3) according to the expression of cluster differentiation-14 (CD14) and CD16,were detected by flow cytometry (FCM).Patients' venous blood was collected on the operation day before operation and one day after operation,the concentrations of MCP-1 and FKN in plasma were measured by ELISA.We compared the expression levels of MCP-1-Mon1 and FKN-Mon3,and analyzed their relationship between each other respectively in different groups.Results Diagnosed according to the clinical symptoms,myocardial markers,electrocardiogram and CAG results,70 individuals were analyzed,including 30 patients with acute myocardial infarction (AMI group),25 patients with unstable angina pectoris (UAP group) and 15 patients with the chest pain symptoms and normal CAG results (control group).The percentage of Mon1 in the AMI group was higher than that in the other groups (P＜0.05);no difference was observed for Mon3 among the groups (P＞0.05).The Mon3/Mon1 ratio in the AMI group was lower than that in the control group (P＜0.05).Moreover,the levels of FKN and MCP-1 in the ACS group were greater than those in the control group.The level of red blood cell distribution width (RDW) was significantly increased in the AMI and UAP group than that in the control group (P＜0.05).There was a significant correlation between FKN and Mon3 (P＜0.05,R=0.650 2).Conclusions The monocyte subset of Mon1 and Mon3 increased in the early stage of ACS,with their chemokine (FKN and MCP-1) increasing at the same time.There is a significant correlation between FKN and Mon3,which indicates MCP-1-Mon1 and FKN-Mon3 may participate in the pathophysiological process of early ACS in patients.

Objective: To analyze the clinical data of a family with early-onset familial Alzheimer′s disease and to analyze the mutation of the pathogenic gene in the family. Methods: The clinical data of a proband who was clinically diagnosed as early-onset Alzheimer′s disease in the Department of Neurology, People′s Hospital of Zhengzhou University in October 2018 and her family members were collected. Moreover, whole exome sequencing was performed on blood sample from the proband, then its deleterious effects were assessed according to the Standards and guidelines for the interpretation of sequence variants, a joint consensus recommendation of the American College of Medical Genomics. Subsequently, the strong pathogenic mutation was validated by Sanger sequencing in the some members of the family and 50 sporadic Alzheimer′s disease and 50 normal individuals of the family. Apolipoprotein E (APOE) typing of 10 family members was all epsilon 3/epsilon 3. Results: The proband in this family showed decreased memory, visual space disorder, verbal repetition, personality change and abnormal mental behavior. The mutation at codon 717 of exon 17 of the proband amyloid precursor protein gene was detected by gene detection. The mutation at codon 717 of exon 17 of the proband beta-amyloid precursor protein gene was also found in the other five members of the family. The mutation was not found in 50 sporadic Alzheimer′s disease patients and 50 normal individuals outside the family. The proband′s head magnetic resonance imaging (MRI) showed bilateral hippocampal atrophy on plain scan, especially on the left side. No obvious abnormality was found in the head magnetic resonance angiography. The head MRI of the proband′s sister showed brain atrophy and bilateral hippocampal atrophy. Conclusions The study identified the pathogenic mutation of the beta-amyloid precursor protein gene p.V717I in six patients of a family with early-onset familial Alzheimer′s disease, and the mutation showed a phenomenon of family segregation. This finding is of great significance to the study of early-onset Alzheimer′s disease in Chinese population.

Objective:To evaluate the quality of a systematic review/Meta-analysis of auricular acupressure on pain, and provide decision making basis for Traditional Chinese Medicine (TCM) nursing.Methods:PubMed, Embase, Web of Science, Cochrane Library, CINAHL, CNKI, Wanfang Data, VIP, CBM databases were searched to collect systematic reviews or Meta-analysis on auricular acupressure intervention pain from inception to October, 2020. Two researchers independently screened literature, extracted the data, and used AMSTAR 2 and GRADE to evaluate methodological quality and evidence quality.Results:A total of 8 systematic reviews were included. The AMSTAT2 evaluation showed that all the studies were in low methodological quality; GRADE tool graded 26 outcome indicators, including 6 intermediate quality indicators, 16 low-level quality indicatorsand 4 extremely low-level quality indicators. The research results showed that auricular acupressure is safe and effective in chronic low back pain, primary dysmenorrhea and partial postoperative pain. Another study found that it has no significant effect, but it can reduce the rate of adverse reactions.Conclusions:These studies show that auricular acupressure is safe on pain and has certain advantages, but its methodological quality and evidence quality are not high, which requires further research to confirm.