Objective:To establish a predictive model for preoperative diagnosis of benign and malignant phyllodes tumor of the breast(PTB). Methods:The clinicopathological data of 69 patients with benign PTB and 41 patients with malignant PTB(24 borderline and 17 malignant)who underwent multiple(≥2)preoperative ultrasound follow-ups in the Cancer Hospital of Harbin Medical University from January 2011 to December 2018 were retrospectively analyzed.The preoperative prediction models of benign and malignant PTB were constructed by using the influencing factors determined by multivariate logistic regression analysis.The receiver operating characteristic(ROC)curve was used to evaluate the efficiency of the prediction model.In addition,the clinicopathological data of 22 patients of benign PTB and 19 patients of malignant PTB(12 borderline and 7 malignant)admitted to the hospital from January 2019 to April 2022 were selected for external verification. Results:Logistic regression analysis showed that growth rate of tumor>2 mm/month and ultrasound BI-RADS category≥4b were independent predictors for the diagnosis of malignant PTB(OR:4.476,95％CI:1.673～11.975;OR:9.448,95％CI:3.149～28.345;P<0.01).The logistic regression equation:Logit(P)=-1.868+1.499×growth rate of tumor+2.246×ultrasound BI-RADS category.The AUC for the training cohort was 0.795(95％CI:0.699～0.890),the best cut-off value was 0.421,the corresponding sensitivity was 0.732,the specificity was 0.826,and the Jorden index was 0.558,P<0.001.The AUC for the the validation cohort was 0.772(95％CI:0.624～0.919),with the sensitivity of 0.526 and the specificity of 0.773,positive predictive value was 0.667 and negative predictive value was 0.654,P = 0.003.The AUC of the training cohort and the validation cohort were both>0.75,indicating that the model has certain predictive ability. Conclusion:The predictive model constructed by clinicopathological parameters can be used for preoperative diagnosis of benign PTB and malignant PTB,and provide a certain reference value for clinicians to select the appropriate surgical resection scope.

Objective To evaluate the differences in efficacy,safety and economics of vancomycin hydrochloride for injection between two manufacturers based on real-world data.Methods A total of 6 757 cases of intravenous use of vancomycin hydrochloride for injection from different manufacturers between January 1,2013 and December 31,2019 in the Affiliated Drum Tower Hospital of Nanjing University Medical School were retrospectively analyzed,and 5308 cases were matched by 1∶1 propensity score method,including 2 654 cases in the group A(domestic drug group)and 2 654 cases in group B(the innovator drug group).The differences in efficacy and safety between the two groups were compared.Cost-effectiveness analysis was used to compare the drug economics of the two groups.Results There were no significant differences in clinical cure rate,bacterial clearance rate,and incidence of adverse events between the two groups(P>0.05).In terms of economics,the average cost of vancomycin per capita,average daily cost of vancomycin and average cost of antibiotics per capita were significantly different between the two groups(P<0.05),and the cost of group B was higher than that of group A.Conclusion The efficacy and safety of vancomycin hydrochloride for injection were consistent between the two manufacturers.

BACKGROUND: Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs). METHODS: A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure. RESULTS: In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36-6.32, P < 0.001). Also, tumor necrosis factor-α (TNF-α) inhibitors had a higher probability of developing tuberculosis than placebo (Peto OR: 3.98, 95% CI: 2.30-6.88, P < 0.001). However, network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA. Noticeably, tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib (Peto OR: 7.39, 95% CI: 2.00-27.31, P = 0.003). CONCLUSION This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-α inhibitors, and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.
Antirheumatic Agents/adverse effects* ; Arthritis, Rheumatoid/drug therapy* ; Humans ; Network Meta-Analysis ; Pharmaceutical Preparations ; Randomized Controlled Trials as Topic ; Tuberculosis/drug therapy*

Background::Concerns exist regarding the risk of infections in patients with spondyloarthritis (SpA) treated with biologics. We assessed the risk of infections of biological and targeted drugs in patients with SpA by performing a meta-analysis based on randomized controlled trials (RCTs).Methods::A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and China Biology Medicine Disc for RCTs evaluating the risk of infections of biological therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto odds ratio (OR) for infections in biologics-treated patients vs. placebo patients. The risk of bias on the included RCTs was assessed by using the Cochrane Risk of Bias Tool. Results::In total, 62 studies were included in this meta-analysis. Overall, the risk of infection (Peto OR: 1.16, 95% confidence interval [CI]: 1.07-1.26, P < 0.001), serious infection (Peto OR: 1.65, 95% CI: 1.26-2.17, P < 0.001), upper respiratory tract infection (URTI) (Peto OR: 1.17, 95% CI: 1.04-1.32, P = 0.008), nasopharyngitis (Peto OR: 1.25, 95% CI: 1.10-1.42, P < 0.001), and Candida infection (Peto OR: 2.64, 95% CI: 1.48-4.71, P = 0.001) were increased in SpA patients treated with biologics compared with placebo. Sensitivity analysis based on biologics classes was conducted, and results demonstrated that compared with placebo, there was a higher risk of infection for tumor necrosis factor (TNF)-α inhibitors (Peto OR: 1.38, 95% CI: 1.13-1.68, P = 0.001) and interleukin (IL)-17 inhibitors (Peto OR: 1.55, 95% CI: 1.08-2.22, P = 0.018) in axial SpA, and for Janus kinase inhibitors in peripheral SpA (Peto OR: 1.39, 95% CI: 1.14-1.69, P = 0.001); higher risk of serious infection for IL-17 inhibitors in peripheral SpA (Peto OR: 3.46, 95% CI: 1.26-9.55, P = 0.016) and axial SpA (Peto OR: 2.01, 95% CI: 1.38-2.91, P < 0.001); higher risk of URTI for TNF-α inhibitors in axial SpA (Peto OR: 1.37, 95% CI: 1.05-1.78, P= 0.019), and for apremilast in peripheral SpA (Peto OR: 1.60, 95% CI: 1.08-2.36, P = 0.018); higher risk of nasopharyngitis for TNF-α inhibitors in axial SpA (Peto OR: 1.41, 95% CI: 1.05-1.90, P = 0.022) and peripheral SpA (Peto OR: 1.49, 95% CI: 1.09-2.05, P = 0.013), and for IL-17 inhibitors in axial SpA (Peto OR: 1.35, 95% CI: 1.01-1.82, P = 0.044); higher risk of herpes zoster for Janus kinase inhibitors in peripheral SpA (Peto OR: 2.18, 95% CI: 1.03-4.62, P = 0.043); higher risk of Candida infection for IL-17 inhibitors in peripheral SpA (Peto OR: 2.52, 95% CI: 1.31-4.84, P= 0.006). Conclusions::This meta-analysis shows that biological therapy in patients with SpA may increase the risk of infections, including serious infections, URTI, nasopharyngitis, and Candida infection, which should be paid attention to in our clinical practice.

Objective:To analyze bone strength index, osteoporosis and fracture in ankylosing spondylitis (AS) patients with radiologic hip involvement and explore the characteristics of bone strength in these patients.Methods:According to bath ankylosing spondylitis radiology hip index (BASRI-hip) score, 339 AS patients were divided into two groups. The differences of bone strength in each group were analyzed by t-test, Mann-Whitney U test and χ2 test. Logistic regression was used to analyze the risk factors of bone strength index. The correlation between quantitative ultrasound and dualenergy X-ray absorptiometry (DXA) (total hip, g/cm 2) was analyzed. Pearson correlation analysis was used. Results:①Bone strength index of quantitative ultrasound was positively correlated with bone mineral density of DXA (total hip, g/cm 2), r=0.553, P<0.01. ② The age of 27(23, 37) years old in radiographic hip involvement was lower than 37(28, 48) years old in non-radiographic hip involvement, and the difference was statistically significant ( Z=-5.986, P<0.01). There were no differences in gender and course of disease between the two groups ( P>0.05).③ The radiographic hip involvement in AS patients whose ages were younger than 50, when compared with non-radiographic hip involvement patients, the bone strength index was lower (78±18 vs 84±16), while bone strength was lower than patients at the same age (41.0% vs 18.4%), however, the incidences of osteoporosis (42.7% vs 28.8%) and fragility fracture (3.7% vs 0%) were significantly higher ( t=3.028, P<0.01; χ2=16.758, P<0.01; χ2=5.886, P=0.019; χ2=4.67, P=0.038). For AS patients whose ages were ≥50, there were no significant differences between the two groups ( P>0.05). ④ Multivariate analysis showed that radiographic hip involvement [ OR (95% CI)=1.912(1.05, 3.48)], age [ OR (95% CI)=0.94(0.911, 0.97)] and body mass index (BMI) (kg/m 2) [ OR (95% CI) =0.875(0.807, 0.948)] were associated with lower bone strength. Conclusion:There is positive correlation between the bone strength index of quantitative ultrasound and bone mineral density of DXA. AS patients with radiographic hip involvement are characterized by decreased bone strength and are more likely to develop osteoporosis and fragile fractures. The risk factors of low bone strength are radiographic hip involvement, age and BMI.

Objective:To explore the value of pressure-strain loop (PSL) for non-invasive quantitative assessment of left ventricular myocardial work index (GWI), global work efficiency (GWE), global constructive work (GCW), global wasted work (GWW) in the evaluation of left ventricular myocardial work in patients with hypertrophic cardiomyopathy (HCM).Methods:Thirty-one HCM patients (HCM group) and 36 healthy volunteers (control group) from December 2018 to September 2019 in Henan Provincial People′s Hospital were selected. Relevant clinical data were collected, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), left ventricular end systolic diameter (LVEDs), left atrial diameter (LAD), the maximum wall thickness (MWT), left ventricular mass index (LVMI), the global longitudinal strain (GLS), the peak strain dispersion(PSD) and GWI, GWE, GCW and GWW between the two groups were compared.Results:Compared with the control group, MWT, LAD, E/e′, LVMI in HCM group were significantly increased (all P<0.05); left ventricular myocardial functional parameters of GLS, GWI, GWE, GCW were significantly decreased, and GWW and PSD were significantly increased (all P<0.05). Left ventricular GLS, PSD and GWI, GCW, GWW, GWE have better repeatability within the observer and between observers. ICC within the observer were 0.852, 0.707, 0.917, 0.955, 0.675, 0.618, respectively. And their ICC between observers were 0.837, 0.631, 0.927, 0.944, 0.555, 0.670, respectively. Correlation analysis showed that GLS was positively correlated with GWI, GWE, and GCW ( r=0.765, 0.737, 0.815; all P<0.001), and negatively correlated with GWW and PSD ( r=-0.517, -0.606; all P<0.001). Conclusions:The left ventricular GWI, GWE and GCW decreased in HCM patients, while the GWW increased. PSL can evaluate the damage of left ventricular myocardial work in HCM patients.

Objective:To explore the clinical characteristics of juvenile-onset ankylosing spondylitis.Methods:Clinical data of 350 cases of ankylosing spondylitis diagnosed in Beijing Jishuitan Hospital from January 2014 to December 2019 were collected. There were 75 cases with the symptom onset in age ≤16 years (juvenile-onset ankylosing spondylitis, JoAS), and 275 cases with the symptom onset in age>16 years (adult-onset ankylosing spondylitis, AoAS). The clinical characteristics of two groups were analyzed.Results:Compared with AoAS, JoAS had a higher proportion of males [98.7% (74/75) vs. 79.6% (219/275); χ 2=15.65, P<0.01] and longer course of disease [11(8,15) vs. 8(4,15) years; Z=-3.09, P<0.01]. Compared with AoAS, JoAS was more prone to have peripheral joint swelling and pain [45.3%(34/75) vs. 18.9%(52/275), χ 2=22.20, P<0.01], hip pain [26.7%(20/75) vs. 15.3%(42/275), χ 2=5.25, P=0.03] or heel pain [9.3%(7/75) vs. 2.9%(8/275), χ 2=5.93, P=0.02] as the first clinical manifestation. Compared with AoAS, JoAS had a higher incidence of radiological hip involvement [77.3%(58/75) vs. 43.3%(119/275), OR=4.71, Wald=25.60, P<0.01], lower bone mineral density than peers [34.7%(26/75) vs. 23.3%(64/275), OR=2.23, Wald=7.20, P<0.01], higher incidence of malnutrition [25.3%(19/75) vs. 13.8%(38/275), OR=2.16, Wald=5.84, P=0.02] and higher incidence of acute uveitis [17.3%(13/75) vs. 6.5%(18/275), OR=2.72, Wald=6.24, P=0.01] after adjusting the course of disease. Conclusion:Compared with adult-onset ankylosing spondylitis, juvenile-onset ankylosing spondylitis is more prone to have peripheral joint swelling or hip pain as the first clinical manifestation; the radiological hip involvement, lower bone mineral density than peers, malnutrition and uveitis are more likely to occur.

Objective:To compare the clinical efficacy of transjugular intrahepatic portosystemic shunt (TIPS) with expanded polytetrafluoroethylene (ePTFE)-covered stent and drug combined with gastroscopy as the secondary prevention of esophageal-gastric variceal bleeding in portal hypertension.Methods:Patients with esophageal-gastric variceal bleeding who received TIPS treatment (ePTFE covered stent) or gastroscopy for the first time as the secondary prevention for portal hypertension at Nanfang Hospital of Southern Medical University through March to July 2017 were selected. One year after the operation, liver function changes, ascites remission rates, incidence of hepatic encephalopathy, re-bleeding rate, average hospitalization frequency and expenses, survival time, as well as the TIPS patency conditions were analyzed in the two groups of patients. 2 test, Kaplan-Meier method and Mann-Whitney U test were used to analyze the data.Results:There were 74 and 66 cases in the TIPS and the drug combined gastroscopy group and the follow-up duration (14.57 ± 0.79) was 12-16 months. One year after surgery, the remission rate of ascites in the TIPS group was higher 57.1% (32/56) than that of the drug combined gastroscopy group (0), and the difference was statistically significant (χ 2 = 2 = 36.73, P < 0.01). The cumulative incidence of hepatic encephalopathy at 1, 3, 6, and 12 months after surgery in the TIPS group was 32.4% (24/74), 37.8% (28/74), 40.5% (30/74), and 40.5% (30/74), respectively. The cumulative incidence of hepatic encephalopathy in the drug combined gastroscopy group was 3.0% (2/66), 3.0% (2/66), 3.0% (2/66), and 6.1% (4/66), respectively. Kaplan-Meier analysis showed that the cumulative incidence of hepatic encephalopathy in the TIPS group was higher than that of the drug combined gastroscopy group (χ 2 = 11.29, P < 0.01). The incidence of severe hepatic encephalopathy ( grade III to IV) at 1, 3, 6, and 12 months after surgery in the TIPS group was 2.7% (2/74), 0, 0, and 0, respectively. The incidence of severe hepatic encephalopathy in drug combined gastroscopy group was 0, and there was no statistically significant difference in development of hepatic encephalopathy between the two groups ( P > 0.05). The re-bleeding rates of TIPS group and drug combined gastroscopy group were 0 and 27.3% (18/66), respectively, and the difference was statistically significant (χ 2 = 22.42, P < 0.01). There was no death reported during the follow-up period between both groups. The hospitalization frequency times (1.45 ± 0.80) in TIPS group was lower than that of the drug combined gastroscopy group times (3.24 ± 1.80), and the difference was statistically significant ( U = -4.52, P < 0.01). Conclusion:In the prevention of esophageal-gastric variceal bleeding, TIPS (ePTFE-covered stent) treatment has the advantages of reducing re-bleeding rate, high ascites remission rate and hospitalizations frequency. In addition, patients treated with TIPS have a higher incidence of hepatic encephalopathy than that of drugs combined with gastroscopy. However, TIPS did not exacerbate the incidence of hepatic encephalopathy, and there was no significant difference in the 1-year survival rate after TIPS and drugs combined with gastroscopy treatment.

Objective An optimal radiation dose was made research on tumor cells to develop effective tumor fusion vaccines. Methods We used the RS 2000 biological X-ray radiation instrument to produce different dose of X-rays.Mouse liver cancer cells line,BNL 1ME a.7R.1(MEAR),was used for experiment.The RS 2000 biological X-ray radiation was applied to create different tumor cell clones,which could help us to study the rela-tionship between irradiation dose and tumor cells′proliferation activity.Furthermore,the fusion cells′anti-tumor ef-fect was examined by flow cytometry. Results High-dose radiation would induce the lower proliferation of cancer cells than low-dose irradiation do.Conclusions During the preparation of fusion vaccines,irradiation dose should be considered as a factor that would influence the tumor cells′ proliferation activity. When the dose of irradiation was appropriate,we could make safe and efficient integration cell vaccines.

A method for measuring 13C isotopic abundance of intracellular metabolites of Saccharopolysporaerythraea by ultra-high performance liquid chromatography (UPLC)-triple quadrupole mass spectrometry was established.First, the chromatographic conditions of UPLC were optimized, and then the MS conditions such as unique tube lens voltage, collision energy, and ion pair were optimized.On the bases of length of the parent and daughter ions carbon chains and whether the daughter ions contain 13C atoms, the one-to-one method, one-to-many method and SIM method were established for measuring 13C isotopic abundance.Then these methods were used to measure naturally labeled intracellular metabolite standards and 13C labeled samples, and according to the gap between the experimental value and the theoretical value, the best method was established for each metabolite of different characteristics.The results showed that one-to-one method was most effective for measuring the metabolites of daughter ions not containing 13C atoms represented by sugar phosphates, one-to-many method was the best for measuring the metabolites of both parent and daughter ions containing 13C short carbon chains represented by carboxylic acids, SIM method could play a role in measuring the metabolites of both parent and daughter ions containing 13C long carbon chains represented by coenzyme A.This method had a good measurement precision and could be applied to the measurement of Saccharopolysporaerythraea intracellular metabolites, which contributed to the consequent study of metabolic mechanism and the efficient expression of erythromycin.