OBJECTIVE To provide a reference for accurately identifying and treating adverse reactions of osteonecrosis induced by bevacizumab. METHODS Clinical pharmacists participated in the treatment process of an adult patient with glioma who developed femoral head necrosis after the use of bevacizumab. By searching the FDA Adverse Event Reporting System （FAERS） and consulting relevant literature and drug instructions， the association between femoral head necrosis and bevacizumab was assessed. Medication recommendations were provided to the physician， and medication educations were provided to the patient. RESULTS The association between the patient’s femoral head necrosis and bevacizumab was assessed as “possibly related”. The physicians accepted the clinical pharmacists’ advice to discontinue bevacizumab and switched to anlotinib to continue antitumor treatment. The patient also followed the clinical pharmacists’ advice to avoid prolonged standing. Upon re-examination， the patient’s pain symptoms were under control， and the femoral head necrosis had not progressed. CONCLUSIONS Patients who receive long-term bevacizumab should attach great importance to bone pain and osteonecrosis， undergo regular imaging examinations， and detect and treat symptoms early to prevent the occurrence of severe osteonecrosis.

Objective To summarize clinicopathologic features of papillary thyroid carcinoma (PTC) coexistent with chronic lymphocytic thyroiditis (CLT) and investigate risk factors for lymph node metastasis.Methods The medical records of 4 264 consecutive papillary thyroid carcinoma patients who received surgical treatment from Oct 2013 to Oct 2015 in Peking Union Medical College Hospital were reviewed.The diagnoses was confirmed by histopathological tests.Univariate analysis was performed to identify specific clinicopathologic features of PTC with CLT.Univariate and multivariate analysis were performed to determine whether each clinicopathologic feature was an independent risk factor for lymph node metastasis.Results In all 4 265 cases,there were 3 059 papillary thyroid microcarcinoma (PTMC) (71.7％),1 010 PTC patients (23.7％) with CLT.909 female patients (90％),624 cases with multifocal lesions (61.8％),422 cases with extra-thyroid extension (41.8％),429 cases with lymph node metastasis (42.5％),and 133 cases with metastatic lymph nodes(LNs) ≥6 (13.2％).The median age was 43 years old and median tumor size was 0.8 cm.Patients with CLT were more females (90.0％ vs.70.2％;P ＜ 0.001),younger median age (43 vs.44 years;P =0.001),and lower incidence of lymph node metastasis (42.5％ vs.50.9％;P ＜0.001).CLT was not associated with tumor size,multifocal lesions,extra-thyroid extension and metastatic LNs≥6 (0.8 cm vs.0.7 cm,61.8％ vs.62.9％,41.8％ vs.42.1％ and 13.2％ vs.14.8％,respectively,all P ＞ 0.05).In multivariate analysis,CLT was an independent protective factor for lymph node metastasis (OR =0.713,95％ CI 0.609-0.835,P ＜0.001).In PTC patients with lymph node metastasis,CLT was not associated with lymph node metastasis number (3 vs.3,P =0.300).Conclusions Chronic lymphocytic thyroiditis was an independent protective factor for papillary thyroid carcinoma patients with lymph node metastasis.But in patients with lymph node metastasis,the metastatic number didn't decrease.

Objectives To evaluate the relationship between body mass index (BMI) and the incidence risk of papillary thyroid microcarcinoma (PTMC).Methods This retrospective study included 1210 PTMC patients who underwent surgery between November 2013 and October 2014 in Peking Union Medical College Hospital,China Academy of Medical Science.A population-based 1∶1 matched case-control study was conducted,and each PTMC patients was matched with one who received thyroid function and ultrasonic to confirm that there was no disease in the thyroid.The clinical profiles of these patients were collected.According to Guidelines for Prevention and Control of Overweight and Obesity in Chinese Adults,all subjects were divided into three groups:underweight (BMI ≤ 18.5 kg/m2),normal(18.5 kg/m2 ＜ BMI ≤ 23.9 kg/m2),overweight (24.0 kg/m2 ＜ BMI ＜ 27.9 kg/m2) and obese group(BMI≥28.0 kg/m2).The relationship between BMI and PTMC incidence risk was analyzed by casecontrol study.Univariate and multivariate logistic regression analysis was applied to analyze the relationship between BMI and PTMC severity.Results The BMI of PTMC patients was significant higher than in normal control [(24.30 ±3.33) kg/m2 vs (23.31 ± 3.50) kg/m2,P ＜ 0.0001].Compared with BMI normal group,the incidence risk of PTMC in underweight group was significantly lower (OR =0.449,95 ％ CI:0.270-0.747),which is higher in overweight and obese group (OR =1.559,95％ CI:1.261-1.928;OR =2.059,95％ CI:1.501-2.823).Histopathological review of 1210 PTMC patients with surgical resection revealed.The proportions of underweight,normal,overweight and obese group of the patients with extrathyroid extension (3.1％,48.0％,36.7％,12.2％) have significant differences with those in the patients whose tumor are limited to the thyroid (0.7％,45.2％,36.0％,18.1％) (P =0.0090).The proportions of 4 group of the patients with multiple lesions (3.2％,49.0％,35.6％,12.2％) were significantly differences to those in the patients with single lesion (0.8％,43.3％,38.7％,17.2％) (P =0.0050).Multivariate analysis showed that underweight is a protective factor of extrathyroidal extension (OR =0.219,95 ％ CI:0.051-0.932;OR =0.279,95 ％ CI:0.085-0.935) and mulifocality,and obese is an independent risk factors(OR =1.556,95％CI:1.047-2.312;OR =1.764,95％CI:1.204-2.584).Conclusions This study identified that the incidence risk of PTMC is positive related with BMI.In PTMC patients,obesity increases the risk of mulifocality and extrathyroidal extension.Attention should be paid to the effect of obesity on the incidence risk of PTMC and the diagnosis and treatment in clinical practice.

Objective: To investigate the distribution patterns of arboviruses in Yunnan province near the China-Laos-Myanmar border, China, and to provide evidence for prevention and control of arboviruses diseases. Methods: Mosquito samples were collected in Daluo county of Xishuangbanna Dai Autonomous Prefecture and Zhengdong county of Pu’er city in Yunnan province, 2012. Viruses were isolated from the samples by tissue culture, positive isolates were identified by RT-PCR with arbovirus species-specific primers, for further sequencing and phylogenetic analysis. Results: A total of 17 species of mosquitoes from 6 genera were collected. A total of 24 strains of viruses were isolated from the mosquito pools and identified as Tembusu virus (TMUV) (2 strains), Japanese encephalitis virus (JEV) (3 strains), Getah virus (GETV) (2 strains), Banna virus (BAV) (4 strains), Densovirus (DNV) (9 strains) and Nam Dinh virus (NDiV) (3 strains). Conclusions The China-Laos-Myanmar border of Yunnan province is rich in species of mosquitoes and arboviruses.

Objective To compare the accuracy of ultrasound,pulse indicator continuous cardiac output monitoring (PiCCO) and traditional methods in predicting fluid responsiveness in septic patients.Methods Forty-six septic patients of both sexes,aged 18-72 yr,requiring mechanical ventilation treatment in the intensive care unit,were enrolled in the study.Venous blood samples were collected for determination of plasma B-type natriuretic peptide (BNP) concentrations by chemiluminescence assay,and central venous pressure (CVP) was recorded.Stroke volume variation (SVVTTE),distensibility index of inferior vena cava (dIVC) and velocity time integral changes of aortic blood flow (△VTI) were measured by ultrasound method.SVVPiCCO and global end-diastolic volume index (GEDVI) were measured by PiCCO method.The patients were divided into negative fluid responsiveness group and positive fluid responsiveness group according to the fluid responsiveness after volume expansion.The receiver operating characteristic curves of the parameters mentioned above in predicting fluid responsiveness were drawn.A consistency check for dIVC,△VTI and SVVPiCCO thresholds was conducted by using Kappa statistics.The agreement between SVVTTEand SVVPiCCO was analyzed by the Bland-Altman analysis.Results There were 24 patients in positive fluid responsiveness group and 22 patients in negative fluid responsiveness group.Compared with negative fluid responsiveness group,the plasma BNP concentration,CVP and GEDVI were significantly decreased,and SVVPiCCO,SVVTTE,dIVC and △VTI were increased before volume expansion in positive fluid responsiveness group (P＜0.05).The area under the curve (95％ confidence interval),sensitivity and specificity of the plasma BNP concentration were 0.894 (0.807-0.981),81.8％ and 79.2％,respectively,of CVP 0.859 (0.752-0.965),81.8％ and 79.2％,respectively,of GEDVI 0.772 (0.628-0.915),72.7％ and 75.0％,respectively,of SVVPiCCO 0.965 (0.922-1.008),95.8％ and 81.8％,respectively,of SVVTTE 0.940 (0.874--1.006),91.7％ and 86.4％,respectively,of dIVC 0.964 (0.920-1.008),83.3％ and 95.5％,respectively,and of △VTI 0.958 (0.909-1.008),87.5％ and 90.9％,respectively.The Kappa value for dIVC threshold and SVVPiCCO threshold was 0.826,and for △VTI threshold and SVVPiCCO threshold was 0.743 (P＜0.01).The mean deviation of SVVTTE and SVVPiCCO was 0.209,95％ confidence interval (-2.967-3.385)％,and the limit of agreement (-2.46-2.62)％ (P＜ 0.05).Conclusion Ultrasound and PiCCO methods can accurately predict fluid responsiveness,have a good agreement and are superior to the traditional method in septic patients.

Objective To explore the value of predicting fluid responsiveness using velocity time index variation (△VTI) and stroke volume variation (△SV) before and after passive leg raising (PLR)monitored by bedside temporary test equipment (TTE).Methods A cohort of 42 patients supported with mechanical ventilation in our hospital admitted from October 2014 to October 2015 were prospectively selected.The hemodynamic variables including heart rate (HR),mean arterial pressure (MAP),central venous pressure (CVP),VTI,SV and other parameters were monitored before and after after undergoing PLR.Fluid resuscitation volume expansion test was carried out after stroke volume index (SVI) monitored by pulse indicator continuous cardiac output monitoring (PICCO).Patients were divided into fluid responsiveness positive group and fluid responsiveness negative group according to presence or absence of SVI ≥ 15％ after fluid resuscitation volume expansion.Results Of 42 patients,22 belonged to fluid responsiveness positive group,20 got into fluid responsiveness negative group.There were no significant differences in basic clinical data between two groups.Before and after PLR,there were no distinct changes in HR and CVP (P ＞ 0.05),while MAP,VTI and SV increased significantly (P ＜ 0.05) after PLR in fluid responsiveness positive group.Contrarily,there were no noticeable changes in MAP and SV after PLR (P ＞ 0.05),but HR,CVP and VTI increased significantly (P ＜ 0.05) in fluid responsiveness negative group.The degrees of △VTI and △SV in fluid responsiveness positive group were much higher than those in fluid responsiveness negative group (P ＜0.05).According to SVI ≥ 15％ monitored by PICCO after fluid resuscitation volume expansion test as a standard,the area under the ROC (AUC) of △VTI between prePLR and post-PLR was 0.75 (95％ CI:O.593-0.907,P ＜ 0.01),the sensitivity and specificity were 63.6％ and 95％ respectively using △VTI 15.6％ as threshold value.The AUC of △SV was 0.844 (95％CI:O.716-0.972,P ＜0.01),the sensitivity and specificity were 81.8％ and 85.0％ respectively using △SV 10.5％ as threshold value.Conclusion △VTI and △SV monitored by TTE before and after PLR could be employed for predicting fluid responsiveness of critical patients under the status of spontaneous respiration.Their value for prediction of critical patients could be further improved by combined employment of these two indexes of variation.

Objective To investigate the effect of endovascular treatment in iliac femoral artery occlusive disease of TransAtlantic Inter-Society Consensus (TASC) C,D lesions in elderly patients.Methods Totally 104 elderly TASC C,D patients with iliac femoral artery occlusion were treated,including TASC C (n =73),TASC D (n =31).Occlusive length range were 4.25-17.61 cm,with an average of (13.46±1.24)cm.The curative effect,complications and following up after surgery were analyzed.Results Ninty-four patients were treated successfully,and the technical success rate was 90.38％ (94/104);12 patients underwent balloon dilation,92 patients underwent balloon dilation combined stent.There were 8 cases (8/104,7.69 ％) with periprocedural complications,included arterial thrombosis (n =2),pseudoaneurysm (n=1),heart failure (n=4),and radiographic contrast nephropathy (n=1).Doppler ankle-brachial index increased from 0.32±0.12 to 0.81±0.11 (P＜0.01) at 1 week after treatment.The patency rates were 88.46 ％ (69/78) and 81.13％ (43/53) at 6 and 12 months followed-up respectively.Conclusion Minimally invasive endovascular treatment has high technical success rate,low complication rate,and satisfactory clinical curative effect for iliac femoral artery occlusive disease of TASC C,D lesions in elderly patients.

Objective To evaluate the clinical and pathological feature,as well as risk factors of lymph node metastasis (LNM) and high-volume LNM (hvLNM) in papillary thyroid microcarcinoma (PTMC) with di ameter ≤0.5 cm.Methods PTMC patients who received surgical treatments in Peking Union Medical College Hospital from Nov.2013 to Nov.2014 were reviewed.Patients were allocated into the ≤0.5 cm group and (0.5-1)cm group according to tumor diameter.Clinical and pathological features were assessed and compared.Risk factors of LNM and hvLNM were also assessed through univariate and multivariate analysis.Results 1414 patients were enrolled,of which 315 patients (22.3％) were in the ≤0.5 cm group.76 LNM (24.1％) and 9 hvLNM (2.9％) were detected in the ≤0.5 cm group.There was significantly less capsule invasion (14.3％ vs 25.0％,P＜0.05),LNM (24.1％ vs 39.8％,P＜0.05) and hvLNM (2.9％ vs 7.9％,P＜0.05) in ≤0.5 cm group than in (0.5-1)cm group.In univariate analysis,patients aging ＜40 years old were more likely to have LNM than those older than 40(38.0％ vs 20.1％,P＜0.05),while male patients tended to have more LNM than female (32.4％ vs 21.9％,P=0.073).No risk factors were identified for hvLNM.In multivariate analysis,multifocality and younger than 40 years old were the independent risk factors of LNM (OR=2.082 and 2.899,P＜0.05),while male tended to be the independent risk factors of LNM (OR=l.807,P=0.058).No independent risk factors was identified for hvLNM.Conclusions A certain proportion of PTMC patients are with tumor diameter ≤0.5 cm,who have lower risk of LNM and hvLNM.Dynamic observation may be an option,especially in older ≥40 years old),unifocal and female patients.

Recent studies find that the expression of hepatoma-derived growth factor (HDGF) is closely correlated with the tumorigenesis,progression,metastasis,therapy and prognosis of various malignancies.Though the mechanism of the interaction of HDGF and tumors is still unclear,the research of HDGF serving as a tumor marker in malignancies and a new target for tumor treatment has become a hotspot in the research of tumor.

Objective To prepare the rat model of type 2 diabetes mellitus (T2DM), and to ob-serve the characteristics of peripheral neuropathy. Methods High fat and high sugar diets were fed for 8 weeks to induce insulin resistance and then low dose streptozotocin ( STZ) was injected intraperitoneally to induce type 2 diabetes mellitus models in Sprague Dawley rats. Blood glucose and serum insulin levels con-tinuous were monitored. Tactile allodynia in response to von Frey ( VF) filament stimulation of the plantar hind paws and paw withdrawal thermal latency ( PWTL) to plantar test were used as the criterion for diabetic neuropathy. Instruments AD was used to detect nerve conduction velocity ( NCV) of sciatic nerve in rat and the morphological and pathological changes of sciatic nerve were detected by electron microscope. Results The characteristics of T2DM rats by peripheral neuropathy in this method were that 50％ force withdrawal threshold and PWTL were measured. Both values of diabetic rats were decreased from the day of STZ injec-tion until 4 weeks after STZ injection, and then increased 8 weeks after STZ injection (50％ force withdraw-al threshold values, (11.8 ±0.8)g, (8.4 ±0.7)g and (16.2 ±1.4)g; PWTL (10.2 ±0.9)s, (8.3 ± 1. 2)s and (13. 2 ± 1. 0)s. These results indicated that tactile sensation changed from hypersensitive to hy-posensitive. Compared to the NC group, the sciatic nerve motor and sensory conduction velocity were signifi-cantly decreased at 4 and 8 weeks in DM group, respectively. Compared to DM group at 4 weeks, the sciat-ic nerve motor and sensory conduction velocities were further decreased in the DM group at 8 weeks. Con-clusively, sciatic nerve showed obvious demyelination and axonal collapse. Conclusions T2DM rat model was successfully induced by high fat and sugar diet combined with small dose of STZ injection. The rat mod-el has typical pathological change of peripheral nerve. It might provide a particularly advantageous tool for investigations of diabetes and its chronic complications.