Objective:To investigate whether the levels of 15 micronutrients could influence the risk of HER2-positive and negative breast cancer using Mendelian randomization (MR) .Methods:In this study, multivariate Mendelian randomization analysis was used to obtain the data of 15 micronutrients (copper, calcium, carotene, folate, iron, magnesium, potassium, selenium, zinc, vitamin A, vitamin B12, vitamin B6, vitamin C, vitamin D and vitamin E) and HER2 (+/-) breast cancer in the Genome-Wide Association Study (GWAS) database. Analyses were performed using R software and the TwoSampleMR package. This study used the inverse variance weighting (IVW) method as the main method to analyze the causal relationship between micronutrients and HER2 (+/-) breast cancer, combined with MR-Egger regression, weighted median (WM) , Simple mode, and Weighted mode as complementary methods. Heterogeneity and horizontal pleiotropy of our results were detected by the Cochran Q test, MR-Egger regression test, MR-PRESSO composite test, and MR Egger intercept to enhance the reliability and stability of the results. Reverse MR analysis was performed as HER2 (+/-) breast cancer exposure factors. The micronutrients screened by the MR above analysis were used as outcome variables for effect and sensitivity analyses. Multivariate Mendelian randomization analysis was performed on the relevant trace elements screened by MR to avoid interference between variables. The independent effects of trace elements were analyzed to improve the reliability of our results.Results:The results of MR analysis showed that micronutrient vitamin B6 was negatively associated with the risk of developing HER2-negative breast cancer (IVM: OR=0.69,95% CI:0.45-0.96, P=0.029) . The results of the Cochran Q test, MR-Egger regression test, MR-PRESSO composite test, and MR Egger intercept test showed that there was no heterogeneity and horizontal pleiotropy among the instrumental variables. At the same time, the analysis of leave-one-out test confirmed that a single SNP had no significant effect on the overall results, which further enhanced the reliability and stability of the results. Conclusions:Among the 15 micronutrients, our results suggested that vitamin B6 may be a protective factor for HER-negative breast cancer. Our study provided a reference for the pathogenesis of HER-negative breast cancer and its early prevention and treatment.

Objective:To investigate whether the levels of 15 micronutrients could influence the risk of HER2-positive and negative breast cancer using Mendelian randomization (MR) .Methods:In this study, multivariate Mendelian randomization analysis was used to obtain the data of 15 micronutrients (copper, calcium, carotene, folate, iron, magnesium, potassium, selenium, zinc, vitamin A, vitamin B12, vitamin B6, vitamin C, vitamin D and vitamin E) and HER2 (+/-) breast cancer in the Genome-Wide Association Study (GWAS) database. Analyses were performed using R software and the TwoSampleMR package. This study used the inverse variance weighting (IVW) method as the main method to analyze the causal relationship between micronutrients and HER2 (+/-) breast cancer, combined with MR-Egger regression, weighted median (WM) , Simple mode, and Weighted mode as complementary methods. Heterogeneity and horizontal pleiotropy of our results were detected by the Cochran Q test, MR-Egger regression test, MR-PRESSO composite test, and MR Egger intercept to enhance the reliability and stability of the results. Reverse MR analysis was performed as HER2 (+/-) breast cancer exposure factors. The micronutrients screened by the MR above analysis were used as outcome variables for effect and sensitivity analyses. Multivariate Mendelian randomization analysis was performed on the relevant trace elements screened by MR to avoid interference between variables. The independent effects of trace elements were analyzed to improve the reliability of our results.Results:The results of MR analysis showed that micronutrient vitamin B6 was negatively associated with the risk of developing HER2-negative breast cancer (IVM: OR=0.69,95% CI:0.45-0.96, P=0.029) . The results of the Cochran Q test, MR-Egger regression test, MR-PRESSO composite test, and MR Egger intercept test showed that there was no heterogeneity and horizontal pleiotropy among the instrumental variables. At the same time, the analysis of leave-one-out test confirmed that a single SNP had no significant effect on the overall results, which further enhanced the reliability and stability of the results. Conclusions:Among the 15 micronutrients, our results suggested that vitamin B6 may be a protective factor for HER-negative breast cancer. Our study provided a reference for the pathogenesis of HER-negative breast cancer and its early prevention and treatment.

Objectives:To examine the clinicopathological characteristics and the influencing factors of the residual tumor of patients with Breast Image Report and Data System (BI-RADS) grade 3 lesions diagnosed with malignancy after minimally invasive excision.Methods:In this retrospective case-control study, clinicopathological data of 69 cases, which had been evaluated as BI-RADS 3 lesions by ultrasound (4 151 cases) diagnosed with breast cancer by minimally invasive excision pathology, were analyzed between May 2012 and June 2016 at the Department of Breast Surgery of the Second Hospital of Shandong University and Linyi People′s Hospital. All patients were female, aged (43.4±8.2) years (range: 22 to 70 years). Based on residual tumor after minimally invasive excision, patients were classified into two subgroups: tumor residual group ( n=39) and non-tumor residual group ( n=30). The clinicopathological features between the two groups were compared. The differences in clinicopathological characteristics were compared in different groups using the χ 2 test and the t test. Potential variables identified in the univariate analysis and other relevant variables will be analyzed multivarially using Logistic regression models. The Kaplan-Meier method was applied for survival analysis and survival curves. Results:The breast cancer detection rate of ultrasound BI-RADS 3 lesions was 1.66% (69/4 151), and their maximum diameter of the masses was (1.27±0.45) cm (range: 0.5 to 2.3 cm). Among them, the maximum diameter were ≤1 cm in 28 cases and >1 cm in 41 cases. Histopathological results showed carcinoma in situ in 24 cases and invasive carcinoma in 41 cases, positive expression of the estrogen receptor in 47 cases, positive expression of the progesterone receptor in 43 cases, Ki-67 proliferation index elevated in 26 cases. Axillary metastasis positive rate was 10.1% (7/69). Residual tumor after minimally invasive surgery was found in 39 cases (56.5%). Univariate analysis showed that the tumour residual group showed a significantly increased rate of positive expression of the estrogen receptor (91.9%(34/37) vs. 61.9%(13/21), χ2=7.838, P=0.012). In multivariate analysis, the only variable found to significantly affect the residual tumor was the positive expression of the estrogen receptor ( OR=16.852, 95% CI: 1.819 to 156.130, P=0.013). The 5-year disease-free survival rate of breast cancer patients with breast ultrasound BI-RADS 3 lesions was 97.1% and the overall survival rate was 98.6%. Conclusions:BI-RADS 3 lesions diagnosed by ultrasound undergoing ultrasound-guided minimally invasive excision have a certain risk of detected malignancy, approximately 1.66%. Patients with positive expression of the estrogen receptor are more likely to develop residual tumor. A secondary operation should be considered to ensure that no tumor residues remain in the cavity.

Objectives:To examine the clinicopathological characteristics and the influencing factors of the residual tumor of patients with Breast Image Report and Data System (BI-RADS) grade 3 lesions diagnosed with malignancy after minimally invasive excision.Methods:In this retrospective case-control study, clinicopathological data of 69 cases, which had been evaluated as BI-RADS 3 lesions by ultrasound (4 151 cases) diagnosed with breast cancer by minimally invasive excision pathology, were analyzed between May 2012 and June 2016 at the Department of Breast Surgery of the Second Hospital of Shandong University and Linyi People′s Hospital. All patients were female, aged (43.4±8.2) years (range: 22 to 70 years). Based on residual tumor after minimally invasive excision, patients were classified into two subgroups: tumor residual group ( n=39) and non-tumor residual group ( n=30). The clinicopathological features between the two groups were compared. The differences in clinicopathological characteristics were compared in different groups using the χ 2 test and the t test. Potential variables identified in the univariate analysis and other relevant variables will be analyzed multivarially using Logistic regression models. The Kaplan-Meier method was applied for survival analysis and survival curves. Results:The breast cancer detection rate of ultrasound BI-RADS 3 lesions was 1.66% (69/4 151), and their maximum diameter of the masses was (1.27±0.45) cm (range: 0.5 to 2.3 cm). Among them, the maximum diameter were ≤1 cm in 28 cases and >1 cm in 41 cases. Histopathological results showed carcinoma in situ in 24 cases and invasive carcinoma in 41 cases, positive expression of the estrogen receptor in 47 cases, positive expression of the progesterone receptor in 43 cases, Ki-67 proliferation index elevated in 26 cases. Axillary metastasis positive rate was 10.1% (7/69). Residual tumor after minimally invasive surgery was found in 39 cases (56.5%). Univariate analysis showed that the tumour residual group showed a significantly increased rate of positive expression of the estrogen receptor (91.9%(34/37) vs. 61.9%(13/21), χ2=7.838, P=0.012). In multivariate analysis, the only variable found to significantly affect the residual tumor was the positive expression of the estrogen receptor ( OR=16.852, 95% CI: 1.819 to 156.130, P=0.013). The 5-year disease-free survival rate of breast cancer patients with breast ultrasound BI-RADS 3 lesions was 97.1% and the overall survival rate was 98.6%. Conclusions:BI-RADS 3 lesions diagnosed by ultrasound undergoing ultrasound-guided minimally invasive excision have a certain risk of detected malignancy, approximately 1.66%. Patients with positive expression of the estrogen receptor are more likely to develop residual tumor. A secondary operation should be considered to ensure that no tumor residues remain in the cavity.

Objective To provide reference for further perfection and revision of standards relevant to limb injury by comparing the evaluation results of different disability standards of long bone fracture. Methods Thirty cases were selected from the long bone fracture cases accepted by our institution in 2018. These cases include 5 cases of shoulder, elbow, wrist, hip, knee, ankle joints, respectively, to investigate the degree of loss of function of joints after long bone fracture. Disability evaluation was made according to Classification of the Impairment Related To Injury （hereinafter referred to as Classification）, Assessment for Body Impairment of the injured in road traffic accidents （now repealed, hereinafter referred to as original Road Standard） and Identifying Work Ability-Gradation of Disability Caused by Work-related Injuries and Occupational Diseases （hereinafter referred to as Work Standard）. The disability evaluation results of every domestic standard were compared with the joint damage rate of Guides to the Evaluation of Permanent Impairment （hereinafter referred to as GEPI）. Results The functional loss rate of joints （except ankle） was 26%-48%，and the ankle functional loss rate was 51%-64%. The mean value of GEPI joint impairment rate of the joints was 13%-22%, with the fluctuation range less than 10%. The rate of level 10 disability was 100% according to the Classification. The rate of level 10 disability was 27%, the rate of level 9 disability was 6% and 67% were not disabled according to the original Road Standard. The rate of level 10 disability was 10% according to the Work Standard and 90% had a disability above level 10 （47% were classified as level 7 disability）. Conclusion The people with limb joint dysfunction in this study had evaluation results with a smaller fluctuation range and better consistency according to the Classification and GEPI. The evaluation results according to the original Road Standard and the Work Standard has a less consistency. The Classification is more similar to GEPI and is more reasonable.
Disability Evaluation ; Disabled Persons ; Forensic Medicine/standards* ; Fractures, Bone ; Humans ; Knee Joint ; Wrist Joint

To investigate the anti-pyretic and anti-endotoxin effect of Chinese herb medicine Jinhuaqingre capsules.Thirty healthy male New Zealand rabbits with lipopolysaccharide-induced fever were divided into 5 groups (6 rabbits in each): animals in model group were given normal saline by gavage, animals in positive control group were given aspirin (0.2 g/kg), and animals in Jinhuaqingre groups were given Jinhuaqingre capsules 6.0, 3.0 or 1.5 g/kg, respectively. The changes in body temperature of rabbits were observed. Fifty healthy Kunming mice were divided into 5 groups (10 mice in each): mice in model group were given normal saline by gavage, mice in positive control group were given aspirin (0.2 g/kg), and those in Jinhuaqingre groups were given Jinhuaqingre capsules 6.0, 3.0, 1.5 g/kg, respectively. Matrix coloration method was used to detect the degradation rate of endotoxin in mice.The body temperature in rabbits of high and medium dose Jinhuaqingre capsule groups declined significantly 60 min after drug administration, and the temperature of high-dose group returned to the baseline after 300 min; while the body temperature of low-dose group started to decline at 180 min after drug administration. The endotoxin degradation rates in mice of high, medium and low dose groups was (56.73±3.12)%, (47.23±1.77)% and (21.08±2.30)% at 30 min after drug administration; those were (82.76±1.00)%, (64.75±1.77)% and (38.21±1.57)% at 60 min after drug administration, respectively.Chinese herb medicine Jinhuanigre capsules have anti-pyretic and anti-endotoxin effects, which may provide a new option for the treatment of heat-toxin syndrome.
Animals ; Antitoxins ; pharmacology ; Aspirin ; therapeutic use ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; Fever ; chemically induced ; drug therapy ; Lipopolysaccharides ; antagonists & inhibitors ; Male ; Medicine, Chinese Traditional ; Mice ; Rabbits ; Sodium Chloride ; therapeutic use

Objective To study the anti-inflammatory,antitussive,and analgesia effects of Jinhua qingre capsules.Methods The anti-inflammatory effect was assessed by the methods include xylene-induced mouse auricular swelling and histamine-induced pigment oozing from skin vessel in rats;The antitussive and analgesic effect were assessed by ammonia water induced cough model and acetic acid-induced twisting method.Results In anti-inflammation experiment,the high dose (12 g·kg-1) and moderate (6 g·kg-1) groups of Jinhua qingre capsules showed significant inhibitory effect on auricular swelling and significant difference compared with control group (P ＜ 0.01,P ＜ 0.05.);the high dose (10 g· kg-1) and moderate dose (5 g·kg-1) groups of Jinhua Qingre capsules play a marked inhibitory role in the increase in mouse peritoneal capillary permeability (P ＜ 0.01,P ＜ 0.05).In antitussive experiment,high dose (12 g· kg-1) and moderate dose (6 g· kg-1) groups had significant inhibitory effect on cough caused by ammonia water (P ＜ 0.01,P ＜ 0.05) compared with control group.In analgesic experiment,the high dose (12 g·kg-1),moderate dose (6 g·kg-1),and low dose (3 g·kg-1) groups effectively reduced the writhing frequency of mice (P ＜ 0.01,P ＜ 0.05).Conclusion Jinhua qingre capsules have potential effects on anti-inflammatory,antitussive,and analgesic.

Objective To investigate the relationship between plasma triglycerides ( TG ) , cholesterol (TC)levels and breast cancer.Methods 105 cases of breast cancer(age from 22 to 69 years)and 261 cases of healthy control(age from 16 to 52 years)admitted from May.2014 to Oct.2014 were studied.TG and TC were tested.Subgroup analysis was performed by age (<35, 35-45, ≥45 years) and BMI( <18.5, 18.5-24, ≥24).Results TG level in breast cancer group was significantly higher than that of the healthy control group (t=-3.97,P=0.00), and TC level was lower than that in the healthy control group (t=2.49, P=0.01).TG lev-el of breast cancer patients≥45 years old was higher than that in the healthy control group ( t=-4.31, P=0.00).TC level of breast cancer patients <35 years and from 35 to 45 years was lower than that of the healthy control group(t=3.12, P=0.00及t=2.41, P=0.02); TG levels in breast cancer group were significantly lower than those of the healthy control group for all BMI subgroup ( t=-3.67, P=0.01 for BMI<18.5; t=-3.87, P=0.00 for BMI from 18.5 to 24.0;t=-2.01, P=0.04 for BMI≥24).TC level of breast cancer patients was higher than that of the healthy control group for patients whose BMI <18.5(t=-3.41, P=0.01) and it was lower than that of the healthy control group for patients whose BMI≥24.Conclusions The relation-ship between TG , TC and breast cancer is associated with age .Compared with healthy group , breast cancer pa-tients≥45 years have a higher TG level and breast cancer patients <45 years have a lower TC level .

ObjectiveTo assess the cause of tadalafil failure and the feasibility of successfully rechallenging nonresponding patients.Methods A total of 80 consecutive erectile dysfunction ( ED ) patients who claimed poor response to tadalafil were enrolled into the study.A self-administered tadalafil-use questionnaire composed of eight questions was applied to assess how they had used tadalafil.Subjects were given thorough instruction based on individual answers and four doses of tadalafil 20mg.After a 2-week follow-up,end point efficacy of rechallenge was evaluated using the sexual encounter profile (SEP),which was recommended by international advisory panel in 2004.ResultsA total of 45 subjects had one or more areas of major suboptimal use of tadalafil:21.2％ did not know that sexual stimulation was necessary for tadalafil to work,87.5％ attempted to use tadalafil less than four times,57.5％ took a maximal dose less than 20 mg,and 84％ felt nervous or anxious.Of the 65 patients undergoing tadalafil rechallenge,30 patients answered “yes” to SEP2 and SEP3.The response rate to rechallenge was 46.2％ ( 30/65 ).ConclusionsInappropriate use of tadalafil was major cause of tadalafil non-pesponse.The efficacy of tadalafil could be improved to a better extent by education of patients.

Objective To assess the causes of sildenafil failure and the feasibility of successfully rechallenging non-responding patients. Methods A total of 126 consecutive erectile dysfunction (ED) patients from Jan 2009 to Dec 2009 who claimed poor response to sildenafil (sildenafil 100 mg on demand, at lease 4 epiodes) were enrolled into the study. All patients received sexual reeducation and were treated with sildenafil, taken on a daily dose of 50 mg for 4 weeks. The International Index of Erectile Function-5 (IIEF-5), Rigiscan, serum testosterone or penile Doppler were used to evaluate ED and the cause of on-demand sildenafil failure. End point efficacy of rechallenging was evaluated using the IIEF-5 and the sexual encounter profile (SEP) 'Were you able to insert your penis into your partner's vagina?' and 'Did your erection last long enough to achieve successful intercourse?'. Results The recruited patients comprised of 41 cases with psychological ED, 39 cases with hypogonadism ED, 28 cases with diabetes mellitus ED and 18 cases with vascular ED. Compared with pretreatment and on-demand sildenafil baseline, daily administration of sildenafil significantly enhanced all efficacy outcome variables. The IIEF-5 was significantly improved after daily sildenafil (12.3 ± 2.9 vs18. 8±4.4, P＜0.01), 78 patients responded to daily sildenafil. The overall salvage rate was 61.9%(78/126). Conclusions Sexual reeducation and daily administration of sildenafil may be able to salvage many patients with ED who were sildenafil non-responders.