The blood brain barrier (BBB) is a physical and metabolic barrier that maintains central nervous system homeostasis and protects brain tissues from potentially hazardous circulating substances. This article reviews the biological characteristics of caludin-5 during cerebral ischemia, its role in BBB integrity and permeability, as well as the research progress of related drug therapy based on calludin-5.

Objective:To explore the expression of indoleamine 2, 3-dioxygenase 1(IDO-1), lymphocyte-activation gene 3 (LAG-3) and T cell immunoglobulin domain and mucin domain-containing molecule 3 (TIM-3) in differentiated thyroid cancer (DTC), and the value of them on prognosis.Methods:From May 2014 to November 2015, 119 DTC patients (33 males, 86 females, media age: 42 years) who underwent surgical treatment in Shanghai Sixth People′s Hospital were retrospectively analyzed. The expressions of IDO-1, LAG-3 and TIM-3 in the specimens were analyzed by immunohistochemistry and the expression differences between cancer tissues and normal tissues were analyzed by χ2 test. The correlation of IDO-1, LAG-3 and TIM-3 with clinical characteristics were analyzed using logistic regression analysis. The patients were followed up for 5 years, and the relationships of the progression-free survival (PFS) rate with the expressions of the three immune checkpoints were analyzed by Kaplan-Meier method, log-rank test and Cox proportional hazard models. Results:The overall 5-year PFS rate for 119 DTC patients (median follow-up time: 55(2-66) months) was 76.47%(91/119). The positive expression rates of LAG-3 and TIM-3 in cancer tissues were 21.85%(26/119) and 78.15%(93/119) respectively, which were significantly higher than those in normal thyroid tissues (7.34%(8/109) and 62.39%(68/109); χ2 values: 9.43, 6.81, both P<0.05). While the positive expression rate of IDO-1 was 70.59%(84/119) in cancer tissues, which did not show a significant difference from that in normal thyroid tissues (64.22%(70/109); χ2=1.05, P>0.05). Factors associated with the positive expression of LAG-3 included tumors with a single lesion (odds ratio ( OR)=0.248, 95% CI: 0.086-0.716, P=0.010). Log-rank test ( χ2=4.96, P=0.026) and multivariate Cox regression analysis (hazard ratio ( HR)=2.239, 95% CI: 1.013-4.592, P=0.046) suggested that LAG-3 positive expression was an independent risk factor of PFS. The same analysis of TIM-3 found no clinicopathological factors related to TIM-3 positive expression ( OR: 0.309-3.084, all P>0.05) and no association between TIM-3 positive expression and PFS ( χ2=0.008, P=0.929). Conclusion:The expressions of LAG-3 and TIM-3 are significantly increased in DTC tissues, and the higher expression of LAG-3 is associated with the worse prognosis, suggesting that LAG-3 may be a potential target for immunotherapy in DTC patients.

Objective:To explore the efficacy of percutaneous osteoplasty (POP) combined with 131I therapy in patients with bone metastases from differentiated thyroid carcinoma (DTC) and assess the survival. Methods:From Januray 2008 to January 2020, 29 DTC patients with bone metastases (16 males, 13 females, age range: 24-64 years) who received POP combined with 131I therapy in Shanghai Sixth People′s Hospital were retrospectively analyzed. Clinical data and characteristics of patients were analyzed. The efficacy and prognosis were evaluated based on the changes of serum thyroglobulin (Tg) and relieving condition of bone pain after the combined treatment. χ2 test was used to determine the association between clinical characteristics and efficacy, and Kaplan-Meier analysis was used to estimate the overall survival (OS) rate. Results:The biochemical response rate of serum Tg was 68.97% (20/29) after the combined treatment. For the influence on changes of serum Tg, whether or not combined with non-osseous distant metastasis, and cumulative dose of 131I treatment(≥22.2 vs <22.2 GBq) were statistically significant ( χ2 values: 5.448 and 4.371, both P<0.05). The rate of bone pain relief was 65.52%(19/29). Age (≥55 vs <55 years) and the cumulative dose of 131I treatment had statistically influences on bone relief ( χ2 values: 7.486 and 5.154, both P<0.05). The 5-years OS rate of patients was 87.68%, while the 10-years OS rate was 65.76%. Conclusion:POP combined with 131I therapy is effective on relieving the pain, reducing the serum Tg to some extent, and improving the long-term survival of DTC patients with bone metastasis.

Objective To investigate germline mutation of breast cancer susceptibility genes BRCA1/2,TP53 and PTEN in Chinese breast cancer patients. Methods All of128 female breast cancer patients in Peking University People′s Hospital from January 2016 to August 2018 were selected as objects. Among them,44 cases were sporadic breast cancer and 84 werebreast cancer patients with genetic high risks. Germline mutations of BRCA1,BRCA2,TP53 and PTENwere detected by NGS.χ2 test was used to analyze the difference of pathogenic mutation rates between sporadic breast cancer group and breast cancer with high genetic risks.Groups were divided according to the clinical features of the patients(family history, triple-negative breast cancer,age and bilateral breast cancer).Among them,there were 42 cases with family history of breast cancer,34 cases of triple-negative breast cancer,33 cases of early-onset breast cancer and 7 cases of bilateral breast cancer. Fisher′s exact probability test compared the relationship between pathogenic mutations of BRCA1/2 gene and clinical characteristics of breast cancer patients with hereditary risk factors. Results In 128 cases of breast cancer,30 germline mutations of BRCA1/2 were detected, including 13 pathogenic mutations and 3 newly discovered mutations(BRCA1:c. 4760C>G,BRCA2:c. 44134414del and BRCA2:c. 64826485del). The new mutations may be unique mutations of Chinese population. There were 3 cases of TP53 mutations,including 1 pathogenic mutation. All of the 3 mutations were found in early-onset breast cancer. Germline mutation of T53 has important detection significance for early-onset hereditary breast cancer. There were 5 cases of PTEN mutations,including 3 pathogenic mutations. Among 84 breast cancer patients with genetic high risks,the carry mutation rate was 40.5％(34/84)and the pathogenic mutation rate was 15.4(13/84). Among 44 sporadic cases,the carry mutation rate was 9％(4/44). The pathogenic mutation rate was 6.8％(3/44). Breast cancer susceptibility genes were carried at a higher rate in breast cancer patients with genetic high risks(P<0.001). BRCA1/2 mutations did not show statistical differences among groups of breast cancer patients with hereditary high risk factors . Conclusion Germline mutation detection of breast cancer susceptibility genes by next-generation sequencing is of great significance in breast cancer risk prediction and prognosis evaluation.

OBJECTIVE:To provide reference for rational drug use and hospital infection control. METHODS:AmpC enzyme-producing Enterobacter cloacae were isolated from non-sputum specimen of a hospital during Jan. 2011-Oct. 2017. Drug sensitivity test was conducted by using MIC. The situation of AmpC enzyme production was confirmed by three dimensional test, and that of ESBLs-producing stain was detected with double-disk synergy test. RESULTS:There were 546 strains of AmpC enzyme-producing E. cloacae isolated from non-sputum specimen of the hospital,accounting for 4.80% of non-sputum specimen (546/11 375)and 38.97% of E. cloacae(546/1 401). Top 3 non-sputum samples in the list of detection rate were wound secretion (27.29%),midstream urine(25.82%)and blood(21.79%),and the departments with high detection rate were ICU(22.89%), neurosurgery department(18.68%)and general surgery department(16.67%). Resistance rate of AmpC enzyme-producing E. cloacae to most commonly used antibiotics was higher than 40%. There was statistical significance in resistant rate of the bacteria to ceftriaxone, cefotaxime, gentamicin, nitrofurantoin, levofloxacin, piperacillin/tazobactam, cefoperazone, ceftazidime,cefepime,tobramycin and minocycline among different years (P<0.05). The resistant rate to imipenem and meropenem was lower than 2%. Among 546 strains of AmpC enzyme-producing E. cloacae,68 strains of ESBLs were detected,and detection rates were 5.77%,6.06%,8.70%,10.26%,13.79%,17.35%,18.75% during 2011-2017. CONCLUSIONS:AmpC enzyme-producing E. cloacae are mainly isolated from samples as wound secretion and midstream urine,and mainly come from ICU and neurosurgery department. The drug resistance of the bacteria is severe,and drug resistance of the bacteria to antibiotics as β-lactams and quinolones is increased significantly. The detection rate of ESBLs-producing strain increases year by year. The bacteria are sensitive to carbapenems antibiotics,which can be regarded as first choice. It is necessary to strengthen drug resistance and enzyme production monitoring of AmpC enzyme-producing E. cloacae,select antibiotics combined with results of drug sensitivity test so as to prevent or delay the rapid increase of its resistance rate.

Objective To analyze the influencing factors for fungal infection in hospitalized patients with acquired immunodeficiency syndrome(AIDS),and provide basis for taking preventive and control measures.Methods Clini-cal data of 112 inpatients with AIDS in a tertiary first-class hospital from January 2010 to October 2015 were ana-lyzed retrospectively,related risk factors were analyzed in patients with fungal infection,univariate analysis was performed byχ2 or t test,and multivariate analysis was performed by logistic regression analysis.Results Among 112 AIDS inpatients,41 (36.61%)had fungal infection.Candida albicans was the main pathogen (n=52, 76.74%)and was mainly isolated from lower respiratory tract (n=29,42.65%).Univariate analysis showed that invasive procedures,duration of antimicrobial use,combined antimicrobial use,and decreased CD4+ T lymphocyte count in peripheral blood were risk factors for fungal infection in AIDS inpatients(all P<0.05),while oral cleaning care and systemic antiviral therapy were protective factors for fungal infection(all P<0.05);multivariate analysis showed that decreased CD4+ T lymphocyte count in peripheral blood(OR,1.017[95% CI,1.009-1.025])and combined antimicrobial use(OR,3.975[95%CI,1.093-14.448])were independent risk factors for fungal infection in AIDS inpatients,while systemic antiviral therapy was independent protective factor for fungal infection (OR, 0.288[95%CI,0.099-0.841]).Conclusion There are many factors influencing fungal infection in AIDS patients, rational use of antimicrobial agents,systemic antiviral therapy,and increasing serum albumin concentration are main methods to prevent fungal infection,avoid unnecessary invasive procedures and application of preventive antifungal therapy for high-risk patients are also effective to prevent fungal infection.

Objective To analyze the distribution and antimicrobial resistance of pathogenic strains in wound infec-tion,and provide scientific evidence for rational use of antimicrobial agents in treatment of wound infection as well as reducing the emergence of drug-resistant organisms.Methods Data about pathogenic strains isolated from wound specimens of patients with wound infection in a hospital between June 2011 and April 2014 were analyzed retrospectively.Results A total of 965 pathogenic strains were isolated from wound specimens,the main infection sites were limbs(50.47%);infected patients mainly distributed in department of orthopaedic surgery(44.97%);trauma and incisional wound infection were the major infection types(47.98%,36.48%,respectively).Among iso-lated pathogens,gram-positive bacteria,gram-negative bacteria,and fungi accounted for 37.20%,59.59%,and 3.21 % respectively.The main gram-positive bacteria were highly susceptible to vancomycin,teicoplanin,and linezolid,the main gram-negative bacteria were highly resistant to most commonly used antimicrobial agents except cefoperazone/sulbactam,piperacillin/ tazobactam,imipenem,and meropenem.Conclusion Patients with wound infection are mainly distributed in department of orthopedics,the main infection types are trauma and surgical site infection,antimicrobial resistant rates of the major gram-positive and gram-negative bacteria are both high.Sur-geons,especially orthopedics surgeons,should pay attention to the culture of pathogens and monitoring of antimi-crobial susceptibility,use antimicrobial agents rationally,and strengthen the prevention and control of surgical site infection,so as to reduce the infection incidence and occurrence of drug-resistant organisms.

Objective To compare the dosimetry and treatment efficiency between a multi-ple partial volumetric-modulated arcs therapy (MP-VMAT)and double-arc volumetric modulated arc therapy (DA-VMAT)for patients with breast cancer mastecomy.Methods 19 patients with breast cancer treated by mastecomy and requiring postoperative radiotherapy were collected.MP-VMAT and DA-VMAT plans were applied for each patient respectively.Dosimetry parameters for target volume and organ of risks (OARs)were compared.Machine unite and delivery times were compared.Results MP-VMAT plans had a more uniform target dose distribution with average Conformation Index (CI )andHomogeneity Index (HI )of0 .5 6 and 1 .0 6 compared to 1 .0 6 and 1.14 of the DA-VMAT plans(P <0.05).MP-VMAT plans predicted a reduction of 5.53% in V20 of contralateral lung,3.74 Gy in mean dose,6.27% in V5 and 5.53% in V20 of ispleratal lung respectively (P <0.05).MP-VMAT plans predicted a reduction of 10.33% and 7.82% in V5 and V10 of heartrespectively (P <0.05),MP-VMAT plans predicted a reduction of 9.14%, 2.72% and 0.06% inV5,V10 and V15 of contralateral breast respectively (P <0.05)plans. However,MP-VMAT plans improved monitor units 7 4 5 .9 MU and treatment time 3 0 4 .6 s compared with DA-VMAT 524.4 MU and 196.7 s (P <0.05).Conclusion MP-VMAT plans generate more uniformity in the target dose and decreased the dose of most of organs of risk com-pared to the DA-VMAT,But improved monitor units and treatment time.In clinical application, different techniqies are chosen based on the situation of every patient.

Objective To compare the dosimetry and treatment efficiency between a multi-ple partial volumetric-modulated arcs therapy (MP-VMAT)and double-arc volumetric modulated arc therapy (DA-VMAT)for patients with breast cancer mastecomy.Methods 19 patients with breast cancer treated by mastecomy and requiring postoperative radiotherapy were collected.MP-VMAT and DA-VMAT plans were applied for each patient respectively.Dosimetry parameters for target volume and organ of risks (OARs)were compared.Machine unite and delivery times were compared.Results MP-VMAT plans had a more uniform target dose distribution with average Conformation Index (CI )andHomogeneity Index (HI )of0 .5 6 and 1 .0 6 compared to 1 .0 6 and 1.14 of the DA-VMAT plans(P <0.05).MP-VMAT plans predicted a reduction of 5.53% in V20 of contralateral lung,3.74 Gy in mean dose,6.27% in V5 and 5.53% in V20 of ispleratal lung respectively (P <0.05).MP-VMAT plans predicted a reduction of 10.33% and 7.82% in V5 and V10 of heartrespectively (P <0.05),MP-VMAT plans predicted a reduction of 9.14%, 2.72% and 0.06% inV5,V10 and V15 of contralateral breast respectively (P <0.05)plans. However,MP-VMAT plans improved monitor units 7 4 5 .9 MU and treatment time 3 0 4 .6 s compared with DA-VMAT 524.4 MU and 196.7 s (P <0.05).Conclusion MP-VMAT plans generate more uniformity in the target dose and decreased the dose of most of organs of risk com-pared to the DA-VMAT,But improved monitor units and treatment time.In clinical application, different techniqies are chosen based on the situation of every patient.

Studies have shown that erythropoietin (EPO) may have neuroprotective effect on cerebral ischemia, and exogenous EPO may also exert neuroprotective effect on cerebral ischemic injury through blood-brain barrier. Its mechanisms may include the upregulation of the expressions of apoptosis inhibiting genes bcl-2 and bcl-xl, the expression of key proteases during the process of inhibiting apoptosis, inhibiting nitric oxide oversynthesis, protecting against glutamate-induced excitotoxicity, etc.