Humans ; Arthroplasty, Replacement, Knee/adverse effects* ; Arthritis, Rheumatoid/surgery* ; Risk Factors ; Patients ; Arthroplasty, Replacement, Hip/adverse effects*

Objective:To evaluate right atrial (RA) volume and function in patients with hepatitis B cirrhosis by four-dimensional automatic quantitation analysis technique, and to explore its correlation with liver function grading.Methods:Ninety patients with hepatitis B cirrhosis who were clinically confirmed in Henan Provincial People′s Hospital from December 2020 to July 2021 were randomly enrolled as the research subjects. According to Child-Pugh liver function score criteria, the patients were divided into three groups: Child-Pugh A group ( n=31), Child-Pugh B group ( n=31), Child-Pugh C group ( n=28). Another 30 healthy volunteers with gender and age matched at the same period were selected as the control group. The RA maximum volume (RAVmax), RA minimum volume (RAVmin), RA presystolic volume (RAVpreA), RA maximum volume index (RAVImax), RA emptying volume (RAEV), RA ejection fraction (RAEF), RA reservoir longitudinal and circumferential strains (RASr, RASr-c), RA conduit longitudinal and circumferential strains (RAScd, RAScd-c), RA contraction longitudinal and circumferential strains (RASct, RASct-c) were obtained by four-dimensional automatic quantitation analysis technique. Spearman correlation analysis was used to explore the correlation between the volume and strain parameters of right atrium and liver function grading, and the independent correlation factors of RASr-c were analyzed by univariate and multivariate linear regression analyses. Results:Compared with the control group, Child-Pugh A and Child-Pugh B groups, RAVmax, RAVmin, RAVpreA, RAVImax, and RAEV were all increased in Child-Pugh C group (all P<0.05). Compared with control group, the absolute values of RASr, RASct, RASr-c and RASct-c were increased, and the absolute values of RAScd and RAScd-c were decreased in Child-Pugh A group (all P<0.05). Compared with control group, Child-Pugh A and Child-Pugh B groups, the absolute values of RASr, RAScd, RASct, RASr-c, RAScd-c and RASct-c were decreased in the Child-Pugh C group (all P<0.05). Correlation analysis showed that the volume and strain parameters of the right atrium were correlated with liver function grading. RASr-c was independently correlated with E/e, ALB and BNP(β=-0.543, 0.521, and -0.562 respectively, all P<0.05). Conclusions:During the compensatory stage in patients with hepatitis B cirrhosis, the RA functions of reservoir and contractile were increased, but the function of conduit was decreased. With the aggravation of liver cirrhosis, the RA functions of reservoir, conduit and contractile were all decreased. The four-dimensional volume and strain parameters of the right atrium were correlated with Child-Pugh liver function grading, and RASr-c was independently correlated with E/e, ALB and BNP.

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.

Currently, biomanufacturing technology and industry are receiving worldwide attention. However, there are still great challenges on bioprocess optimization and scale-up, including: lacing the process detection methods, which makes it difficult to meet the requirement of monitoring of key indicators and parameters; poor understanding of cell metabolism, which arouses problems to rationally achieve process optimization and regulation; the reactor environment is very different across the scales, resulting in low efficiency of stepwise scale-up. Considering the above key issues that need to be resolved, here we summarize the key technological innovations of the whole chain of fermentation process, i.e., real-time detection-dynamic regulation-rational scale-up, through case analysis. In the future, bioprocess design will be guided by a full lifecycle in-silico model integrating cellular physiology (spatiotemporal multiscale metabolic models) and fluid dynamics (CFD models). This will promote computer-aided design and development, accelerate the realization of large-scale intelligent production and serve to open a new era of green biomanufacturing.
Bioreactors ; Computer Simulation ; Fermentation ; Hydrodynamics

Objective:To investigate the value of early diastolic strain rate (e′SR) and peak value of early diastolic velocity (E) to e′SR (E/e′SR) in predicting the severity of coronary lesions in patients with coronary artery disease (CAD) without regional wall motion abnormalities (RWMA) and with preserved left ventricular ejection fraction (LVEF).Methods:A selection of 70 patients with CAD without RWMA and with preserved LVEF (>50%) admitted to Zhengzhou University People′s Hospital from October 2020 to March 2021 were collected and divided into two groups according to the Gensini score method: low group with a score<34 and high group with a score≥34. Another 30 healthy volunteers with matching gender and age at the same period were selected as the control group. Cardiac structural parameters left atrium diameter (LAD), left ventricular end diastolic diameter (LVEDd), left ventricular end systolic diameter (LVEDs), interventricular septum diastolic diameter (IVST), left atrial volume (LAV), E, peak value of late diastolic velocity (A) of mitral inflow, peak value of early diatolic tissue Doppler velocity of septal and lateral walls of mitral annulus and LVEF were routinely measured. Left atrial volume index (LAVI), mean of peak value of early diatolic tissue Doppler velocity of septal and lateral walls of mitral annulus (e′), E/e′were calculated. Speckle tracking imaging (STI) technique was used to collect systolic left ventricular global longitudinal strain (GLS) and e′SR, E/e′SR was calculated. The differences in each parameter among the three groups were compared. The ROC curve was used to obtain the best cut-off values of e′SR and E/e′SR for predicting the severity of coronary lesions in CAD patients, respectively, and the corresponding sensitivity and specificity were obtained, respectively.Results:Compared with the control group, LAV and LAVI were increased in the high group (all P<0.05). Compared with the control and the low group, e′ was decreased and E/e′ was increased in the high group (all P<0.05). Compared with the control group, e′SR and GLS were decreased and E/e′SR were increased in the high and low groups (all P<0.05). Compared with the low group, e′SR and GLS were decreased and E/e′SR was increased in the high group (all P<0.05). ROC curve analysis showed that the maximum area of E/e′SR under the curve was 0.717. When the Youden index was maximum, its best cut-off value was 0.75 m, and corresponding sensitivity and specificity were 60.0% and 85.7%, respectively. The maximum area under the e′SR curve was 0.785. When the Youden index was maximum, its best cut-off value was 1.12 s -1, and the corresponding sensitivity and specificity were 85.7% and 68.6%, respectively. Conclusions:For CAD patients without significant RWMA and with preserved LVEF, left ventricular diastolic and systolic function may be impaired to varying degrees, manifesting as decreased e′SR, increased E/e′SR, decreased GLS. The parameters of diastolic strain rate are a reliable basis for early detection of impaired diastolic function in CAD patients, and have certain clinical significance for predicting the severity of coronary lesions.

Epidemiological survey shows that the prevalence, incidence rate and symptoms of mental disorders are affected by sex. A large number of studies have shown that men and women respond differently to psychotropic drugs in clinical application. Moreover, some studies have shown that there are sex specific psychotropic drug use patterns in patients with depression. This paper summarizes the sex differences in pharmacokinetics of psychotropic drugs caused by physiological differences between men and women, and collates the current pharmacodynamic studies of mainstream clinical psychotropic drugs, with special attention to the effect of sex hormones on the therapeutic response of psychotropic drugs. This paper discusses the specific role and necessity of therapeutic drug monitoring in dealing with clinical sex differences in psychotropic drugs, hoping to provide reference for individual rational drug use.

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.