Objective:To explore the clinical application effect of belimumab in the treatment of systemic lupus erythematosus(SLE)and its influence on cluster of differentiation(CD40)and cluster of differentiation 40 ligands(CD40L)expression in the peripheral blood,and to provide a theoretical basis for the effective treatment of SLE.Methods:A retrospective analysis was conducted on the clinical data of 150 patients with SLE admitted to our hospital,and they were divided into conventional treatment group(n=78,standard treatment plan)and belimumab group(n=72,standard treatment plan+belimumab)according to the treatment methods.The therapeutic effects and adverse reactions were compared.The clinical symptoms,organ involvement,disease activities,prednisone doses,the expression levels of CD40 and CD40L mRNA in peripheral blood mononuclear cells,and the levels of immunology-related indicators before and after treatment were analyzed.Results:Compared with conventional treatment group,the total effective rate,complement C3 and complement C4 levels in the belimumab group were significantly increased after treatment(P<0.01 or P<0.001),while the proportion of renal involvement,the SLE disease activity index-2K(SLEDAI-2K)score,the dosage of prednisone,immunoglobulin G(IgG)level and the expression levels of CD40 and CD40L mRNA in peripheral blood mononuclear cells were decreased(P<0.01 or P<0.001).There was no statistically significant difference in the total incidence of adverse reactions between two groups during treatment period(P>0.05).Conclusion:Belimumab can increase the effective rate of SLE treatment,reduce disease activity,decrease the involvement of the kidneys and the dose of hormones,and has good safety;its mechanism of action may be related to down-regulating the expression of CD40 and CD40L in peripheral blood and improving the immune function.

Objective To investigate the value of polar residual network(PResNet)model for assisting evaluation on rat myocardial infarction(MI)segment in myocardial contrast echocardiography(MCE).Methods Twenty-five male SD rats were randomly divided into MI group(n=15)and sham operation group(n=10).MI models were established in MI group through ligation of the left anterior descending coronary artery using atraumatic suture,while no intervention was given to those in sham operation group after thoracotomy.MCE images of both basal and papillary muscle levels on the short axis section of left ventricles were acquired after 1 week,which were assessed independently by 2 junior and 2 senior ultrasound physicians.The evaluating efficacy of MI segment,the mean interpretation time and the consistency were compared whether under the assistance of PResNet model or not.Results No significant difference of efficacy of evaluation on MI segment was found for senior physicians with or without assistance of PResNet model(both P＞0.05).Under the assistance of PResNet model,the efficacy of junior physicians for diagnosing MI segment was significantly improved compared with that without the assistance of PResNet model(both P＜0.01),and was comparable to that of senior physicians.Under the assistance of PResNet model,the mean interpretation time of each physician was significantly shorter than that without assistance(all P＜0.001),and the consistency between junior physicians and among junior and senior physicians were both moderate(Kappa=0.692,0.542),which became better under the assistance(Kappa=0.763,0.749).Conclusion PResNet could improve the efficacy of junior physicians for evaluation on rat MI segment in MCE images,shorten interpretation time with different aptitudes,also improve the consistency to some extent.

ObjectiveTo clarify the therapeutic effect of Huashi Baidu prescription on pneumonia in mice caused by influenza A （H1N1） virus and explore its mechanism based on the transcriptome. MethodA mouse influenza viral pneumonia model was built by intranasal infection with influenza A virus， and mice were continuously administered the drug for five days， so as to investigate the general condition， lung index， viral load， pathological morphology of lung tissue， survival time， and prolongation rate of survival time of mice and clarify the therapeutic effect of Huashi Baidu prescription on influenza viral pneumonia. Transcriptome technology was used to detect the differentially expressed genes in the lung tissue of mice in the model group and the normal group， as well as the Huashi Baidu prescription group and the model group， and the potential core target of the Huashi Baidu prescription for the treatment of influenza viral pneumonia was screened. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to verify the effect of Huashi Baidu prescription on the mRNA expression level of core target genes. ResultCompared with the normal group， the lung index and viral load in the lung tissue of the model group were significantly increased （P<0.05， P<0.01）. Compared with the model group， the high-dose group of Huashi Baidu prescription significantly prolonged the survival time of mice infected with influenza A virus （P<0.05） and significantly reduced the lung index value of mice （P<0.05） and the viral load of lung tissue. The high-dose， medium-dose， and low-dose groups of Huashi Baidu prescription could significantly reduce lung tissue inflammation， blood stasis， swelling， and other pathological changes in mice （P<0.05， P<0.01）. Transcriptome analysis of lung tissue showed that core genes were mainly enriched in the nuclear transcription factor-κB （NF-κB） signaling pathway， interleukin-17 （IL-17） signaling pathway， cytokine-cytokine receptor interaction， and other pathways after the intervention of Huashi Baidu prescription. TRAF6， NFKBIA， CCL2， CCL7， and CXCL2 were the top five node genes with combined score values. Real-time PCR validation showed that Huashi Baidu prescription significantly downregulated the mRNA expression of key genes TRAF6 and NFKBIA in the NF-κB signaling pathway， as well as chemokines CCL2， CCL7， and CXCL2 （P<0.05， P<0.01）. ConclusionHuashi Baidu prescription has a therapeutic effect on influenza viral pneumonia， possibly by inhibiting the expression of key nodes TRAF6 and NFKBIA in the NF-κB signaling pathway and that of chemokines CCL2， CCL7， and CXCL2， reducing the recruitment of inflammatory cells and viral load， and exerting anti-influenza viral pneumonia effects.

Objective: To investigate the effects of cathepsin S(Cat S) on proliferation, migration and invasion of osteosarcoma cells and its potential regulatory mechanism. Methods: Normal osteoblasts(hFOB) and osteosarcoma cells(SAOS2 and MG63) were selected as the subjects of this study.Cat S small interfering(si) RNA(si-Cat S) and negative control sequence(si-NC) were transfected into SAOS2 and MG63 cells to modulate the expression of Cat S in osteosarcoma cells.The experimental cells were randomly divided into four groups: hFOB group(hFOB cells),Control group(untransfected SAOS2 or MG63 cells),si-NC group(SAOS2 or MG63 cells transfected with si-NC) and si-Cat S group(SAOS2 or MG63 cells transfected with si-Cat S).The expression of Cat S in SAOS2 and MG63 cells was detected by RT-PCR and Western blot.Effect of Cat S knockdown on the proliferation of SAOS2 and MG63 cells was assessed by CCK-8 and clone formation assays.And effects of Cat S knockdown on the migration and invasion of SAOS2 and MG63 cells were determined by wound-healing and Transwell assays, respectively.Western blot assay was performed to measure the effects of SAOS2 knockdown on the expressions of apoptosis-related proteins(Bcl-2,Bax and Caspase-3) and Wnt/β-catenin pathway related proteins(LRP5,β-catenin, C-myc and Cyclin D1) in SAOS2 cells. Results: Compared with hFOB group, the expression of Cat S in SAOS2 group and MG63 group was upregulated(P<0.001).In addition, compared with si-NC group, the proliferation, migration and invasion of cells in si-Cat S group were reduced(P<0. 001). Results of Western blot showed that compared with si-NC group,the expression of Bcl-2 in si-Cat S group was downregulated,while the expression of Bax and Caspase-3 were upregulated(P<0. 001). Meanwhile,compared with si-NC group,the expression of LRP5,β-catenin,C-myc and Cyclin D1 in si-Cat S group was downregulated(P<0. 001). Conclusion Cat S siRNA knockdown can inhibit the proliferation,migration and invasion of osteosarcoma cells and induce apoptosis by regulating Wnt/β-catenin pathway,indicating that Cat S may be one of the potential targets for the treatment of osteosarcoma.

Objective:To evaluate the effect of anthracyclines on myocardial work in patients with breast cancer by left ventricular pressure strain loop (PSL).Methods:From April 2019 to June 2020, 30 breast cancer patients treated with AC-T regimen(Adriamycin/epirubicin+ cyclophosphamide+ docetaxel) in the Second Affiliated Hospital of Harbin Medical University were selected as case group, and 30 healthy volunteer were selected as control group. Transthoracic echocardiography was performed in the case group at 3 time points: before chemotherapy (T0 phase), after the third cycle of chemotherapy (T1 phase), and after the sixth cycle of chemotherapy (T2 phase) respectively. Conventional ultrasonic parameters were collected. Left ventricular PSL was used to evaluate the left ventricular myocardial work index, including global work index (GWI), global constructive work (GCW), global work waste (GWW) and global work efficiency (GWE). The same examination was performed in the control group, and the results between T0 phase and control group, among different phases were compared.Results:①There were no statistically significant differences of general information, conventional ultrasound parameters, left ventricular strain and myocardial work parameters between T0 phase and control group (all P>0.05). ②There were no statistically significant differences of LVEF, GLS, GWI, GCW, GWE and GWW between T1 phase and T0 phase (all P>0.05). ③There were no statistically significant differences in LVEF between T2 phase and T0 phase ( P>0.05). The absolute values of GLS, GWI, GCW and GWE decreased, but GWW increased, the difference was statistically significant (all P<0.05). ④There were no significant differences in LVEF between T2 phase and T1 phase ( P>0.05), but the absolute values of GLS, GWI, GCW and GWE decreased, while GWW increased (all P<0.05). Conclusions:Left ventricular PSL can effectively evaluate the myocardial work of anthracycline chemotherapy in breast cancer patients, which is superior to LVEF and provide a new evaluation method for asymptomatic patients.

Objective:To investigate the occurrence of human papillomavirus (HPV) single and multiple infections in different cervical lesions, and to analyze the distribution of HPV types in patients with single infection and the change of viral load before and after treatment.Methods:A total of 4 783 HPV-DNA-positive cases who were detected by cervical exfoliated cells HPV-DNA testing from May 2017 to March 2019 in Shanxi Provincial People's Hospital were retrospectively analyzed, of which 3 728 cases met the criteria and were included in this study. Fluorescence quantitative polymerase chain reaction (PCR) was used to determine HPV genotype and viral load, and liquid-based thin-layer cytology (TCT) test and colposcopic histopathological diagnosis were performed. According to the histopathological results, the patients were divided into chronic cervicitis+cervical intraepithelial neoplasia (CIN) Ⅰ group, CIN Ⅱ+CIN Ⅲ group and cervical cancer group.Results:A total of 3 364 cases had HPV single infection, of which chronic cervicitis+CIN Ⅰ accounted for 78.27% (2 633/3 364), CIN Ⅱ+CIN Ⅲ accounted for 18.73% (630/3 364), and cervical cancer accounted for 3.00% (101/3 364); 364 cases had HPV multiple infections, of which chronic cervicitis+CIN Ⅰ accounted for 51.65% (188/364), CIN Ⅱ+CIN Ⅲ accounted for 42.58% (155/364), and cervical cancer accounted for 5.77% (21/364). The difference in the proportion of cervical lesions with different pathological grades in HPV single infection and multiple infections was statistically significant ( χ2 = 127.21, P < 0.01). The top four HPV single infection genotypes in chronic cervicitis+CINⅠ group and CINⅡ+CINⅢ group were type 16, 52, 58 and 53, and their proportions were 17.05% (449/2 633), 12.91% (340/2 633), 9.08% (239/2 633) and 8.89% (234/2 633) in chronic cervicitis+CINⅠ group, and 32.22% (203/630), 10.32% (65/630), 8.41% (53/630) and 5.87% (37/630) in CINⅡ+CINⅢ group. In the cervical cancer group, the top two HPV single infection genotypes were type 16 and 18, and their proportions were 81.19% (82/101) and 6.93% (7/101). The viral load of 120 patients with HPV infection was 4.89±1.14 before treatment and 2.86±1.63 after treatment, and the difference was statistically significant ( t = 13.260, P < 0.01). Conclusions:HPV multiple infections are more likely to aggravate the degree of cervical lesions than single infection. Common HPV infection subtypes in different cervical lesions include type 16, 52, 58, 53 and 18.

Objective:To observe the change of the left ventricular(LV) wall shear stress (WSS) using vector flow mapping (VFM) in different segments at each phase of diastolic period among normal subjects.Methods:From August 2018 to March 2019, 200 healthy volunteers selected from the Physical Examination Center of the Second Affiliated Hospital of Harbin Medical University were recruited. The WSS values of LV segments at the same and at different phases[isovolumic relaxation period(D1), rapid filling period(D2), slow filling period(D3), atrial contraction period(D4)] in diastole were measured and analyzed.Results:①The relationships of the WSS of LV different segments at the same phase of diastolic period: The WSS values of anterior septum, posterior septum and posterior wall during D1, and the WSS values of posterior septum, posterior wall and inferior wall during D2 showed basal>middle>apical segments, the differences were statistically significant (all P<0.05). ②The changes of the WSS values of LV different segments during diastolic period: During D1-D2-D3-D4 period, the absolute values of WSS in anterior septum, posterior septum, anterior wall, lateral wall and inferior wall showed an increasing-decreasing-increasing trend. During D2-D3-D4 period, the absolute values of WSS in the posterior wall showed a decreasing-increasing trend. During D1-D2-D3-D4 period, the absolute values of WSS in the apical segment of anterior septum, basal and middle segments of posterior septum, basal, middle and apical segments of anterior wall, basal segment of lateral wall, the middle and apical segments of posterior wall, basal and middle segments of inferior wall all showed an increasing-decreasing-increasing trend, the difference was statistically significant (all P<0.05). Conclusions:The LV WSS in different segments at the same phase or in the same segment at the different phases in diastole exhibit a regular change and is consistent with the LV hemodynamic changes, which indicates that WSS can quantitatively reflect the hemodynamic changes of the LV in normal subjects.

Objective: This research studied the clinical manifestation, classification and countermeasure of nipple ischemia after the corrective surgery of congenitally inverted nipples using a tractor. Methods: From October 2014 to October 2016, the symptoms, treatments and outcomes of postsurgical nipple ischemia (n=81) of 43 patients were collected and analyzed to propose a clinical classification theory. Results: This theory divided nipple ischemia into 3 categories of incidence: Grade Ⅰ at 13.58% (11/81), Grade Ⅱ at 11.11% (9/81), and Grade Ⅲ at 2.47% (2/81). After changing dressing for 7-34 days (the average of 15 days), all GradeⅡand Ⅲ wounds healed eventually. Conclusions The clinical classification theory of nipple ischemia can provide significant guidance for clinical observations, treatments and prognosis.

Objective To discuss the clinical application value of serum procalcitonin(PCT) in patients with Candida bloodstream infection.Methods The data of 783 hospitalized patients of Tianjin Medical University General Hospital including blood culture and serum PCT test were retrospectively analyzed,and the medical records of patients with Candida or bacterial bloodstream infection were evaluated by univaxiate and multivariate logistic regression analysis.The comparison of PCT value were carried out among the different blood culture groups using the Mann-Whitney U test.A receiver operating characteristic(ROC) curve was used to determine the diagnostic performance of the PCT.Results The PCT was 0.21 (0.06,1.02) ng/mL in the 510 patients with negative blood culture,but in 121 patients with Candida infection and 152 patients with bacteria infections,the PCT levels were 1.15 (0.38,6.85) ng/ mL and 2.34 (0.77,15.12) ng/mL,respectively.There were statistically significant differences in PCT levels among three groups(P＜0.05).According to ROC,when the value of PCT was 0.355 ng/mL,the sensitivity was 76.9％,and the specificity was 60.8％ with 0.726 area under the curve (AUC) (P＜0.01) for the identification of Candida infection by blood cultures.Conclusions Serum PCT levels have a certain diagnostic value for Candida bloodstream infection.In critically ill patients with factors associated with candidemia,the combination of clinical symptoms with PCT as an adjuvant diagnostic marker and other laboratory findings can be used to make a prompt and effective initiation of antifungal therapy.

Objective: To explore the value of parameters obtained by dual-pulse wave Doppler to predict the recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation(RFCA) and the value of the technology to evaluate the left ventricular diastolic function of the AF. Methods: Sixty-seven AF patients who were subjected to ablation were selected as the case group, and 47 patients with sinus rhythm were matched as control group. The general clinical data of the case group and the control group was collected, routine ultrasound examination and dual-pulse wave Doppler examination were performed to all of them. A 24-hour Holter examination was performed at 3, 6 and 12 months after radiofrequency catheter ablation in the case group, the patients were divided into two groups with and without recurrence according to the results. Dual-pulse wave Doppler parameters included: ①the time interval between the onset of early transmitral flow velocity (E) and that of early diastolic mitral annular velocity (e′) (TE-e′); ②peak early diastolic transmitral flow velocity (E) and tissue Doppler septal (S) mitral annular early diastolic velocity (e′), peak early diastolic transmitral flow velocity (E) and tissue Doppler lateral (L) mitral annular early diastolic velocity (e′), E/e′(S) and E/e′(L). The differences between the case group and the control group, and between the recurrent and the non-recurrent group were compared. The factors influencing the recurrence of AF after RFCA were analyzed with univariate and multivariate Logistic regression. Results: ①The parameters E/e′(S), E/e′(L) and TE-e′ of case group were higher than those of control group (all P<0.05); ②During follow-up examinations after the ablation, 21 (31.34%) patients recurred. TE-e′ of the recurrence group was higher than that in the nonrecurrence group (P<0.001). The parameters E/e′(S) and E/e′(L) in the recurrence group had no difference compared with those in nonrecurrence group without recurrence(all P>0.05); ③Univariate and multivariate Logistic regression suggested that TE-e′ was an independent predictor for the recurrence of AF patients after the ablation(P=0.001). Conclusions Dual-pulse wave Doppler can evaluate left ventricular diastolic function of atrial fibrillation, TE-e′ is an independent predictor for the recurrence of AF patients after radiofrequency catheter ablation.