This paper reports a death due to septic shock caused by Shewanella algae bloodstream infection and Epstein-Barr virus(EBV)co-infection in an elderly male patient who had no history of seawater exposure.She-wanella algae was identified in blood culture.Antimicrobial susceptibility testing showed that the strain was sus-ceptible to meropenem while resistance to ceftriaxone.EBV sequence was detected by metagenomic next-generation sequencing(mNGS)of blood specimen.Despite meropenem combined with antiviral and anti-shock treatment,the patient still rapidly progressed to multiple organ failure and died.This case suggests that Shewanella algae infec-tion relevant to freshwater environment exposure should be alerted,co-infection with EBV can exacerbate the severi-ty of sepsis,and potential risk of treatment failure should be paid attention in clinical practice despite carbapenems susceptibility confirmed by testing.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Objective:To investigate the mechanism of inhibition for Janus tyrosine kinase,signal transducer and activator of transcription(JAK/STAT)on ferroptosis,myocardial remodeling,and JAK/STAT melatonin receptor 1-nuclear factor E2-related factor 2-glutathione peroxidase 4(MT1-Nrf2-GPX4)signaling axis in rats with heart failure(HF)under echocardiography.Methods:Forty SD rats were selected,and they were randomly divided into blank control group,model group,interleukin-6(IL-6)group and tyrosine phosphorylation inhibitor(AG490)group according to random number table,with 10 rats in each group.HF rat models were established in three groups except the blank control group.The expression levels of JAK/STAT mRNA in myocardial tissue among 4 groups were compared and analyzed.The small animal ultrasound imaging system was used to measure a series of cardiac function indexes included interventricular septum(IVS)thickness,left ventricular posterior wall(LVPWs)thickness,left ventricular posterior wall(LVPWd)thickness,left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD)and ejection fraction(EF).The Fe2+concentration and lesions of myocardial tissue,as well as the expressions of MT1,Nrf2 and GPX4 proteins,in the four groups were compared and analyzed.Results:The increases of JAK1 and STAT3 mRNA levels,and Fe2+concentration in the model group,IL-6 group and AG490 group were higher than those in the blank control group,and the protein expression levels of MT1,Nrf2 and GPX4 in them were lower than those in the blank control group,and the differences of the above indicators between the model group and the blank control group were statistically significant(t=11.810,16.250,17.150,10.460,9.272,11.180,P＜0.05),and the differences of the above indicators between the IL-6 group and the blank control group were statistically significant(t=9.834,19.030,16.320,14.450,13.250,14.070,P＜0.05),and the differences of them between the AG490 group and the blank control group were statistically significant(t=8.025,11.050,17.590,4.173,4.179,4.183,P＜0.05),respectively.The levels of STAT3 mRNA level and Fe2+concentration in IL-6 group were higher than those in the model group,and the expression levels of MT1,Nrf2 and GPX4 proteins in that were lower than those in the model group,and the differences were statistically significant(t=2.224,2.582,3.550,3.078,2.624,P＜0.05),respectively.The levels of JAK1,STAT3 mRNA and Fe2+concentration in the AG490 group were lower than those in the model group,and the levels of MT1,Nrf2 and GPX4 in that were higher than those in the model group,and the differences were statistically significant(t=4.052,6.930,8.598,6.247,5.055,6.799,P＜0.05),respectively.The IVS,LVPWs,LVPWd and EF of the model group,IL-6 group and AG490 group were lower than those of the blank control group,and the LVEDD and LVESD of them were higher than those of the blank control group,and the differences of these indicators between the model group and the blank control group were statistically significant(t=13.740,11.100,5.654,7.049,13.440,14.260,P＜0.05),and the differences of them between the IL-6 group and the blank control group were statistically significant(t=16.090,13.140,8.103,9.174,15.940,17.010,P＜0.05),and the differences of them between the AG490 group and the blank control group were statistically significant(t=5.474,4.947,2.682,4.071,8.608,13.300,P＜0.05),respectively.The LVPWd and EF in the IL-6 group were lower than those in the model group,and the LVEDD and LVESD in the IL-6 group were higher than those in the model group,and the differences of them were statistically significant(t=2.417,2.327,2.236,2.818,P＜0.05),respectively.The IVS,LVPWs,LVPWd and EF in the AG490 group were higher than those in the model group,and the LVEDD and LVESD in that were lower than those in the model group,and the differences were statistically significant(t=8.598,7.147,3.514,3.361,4.914,2.970,P＜0.05),respectively.Conclusion:Inhibition of JAK/STAT expression can improve the cardiac structure of HF rats,and relieve ventricular remodeling,and inhibit ferroptosis of cardiomyocyte,and promote the expression of MT1,Nrf2 and GPX4 proteins.

This paper reports a death due to septic shock caused by Shewanella algae bloodstream infection and Epstein-Barr virus(EBV)co-infection in an elderly male patient who had no history of seawater exposure.She-wanella algae was identified in blood culture.Antimicrobial susceptibility testing showed that the strain was sus-ceptible to meropenem while resistance to ceftriaxone.EBV sequence was detected by metagenomic next-generation sequencing(mNGS)of blood specimen.Despite meropenem combined with antiviral and anti-shock treatment,the patient still rapidly progressed to multiple organ failure and died.This case suggests that Shewanella algae infec-tion relevant to freshwater environment exposure should be alerted,co-infection with EBV can exacerbate the severi-ty of sepsis,and potential risk of treatment failure should be paid attention in clinical practice despite carbapenems susceptibility confirmed by testing.

Objective:To investigate the mechanism of inhibition for Janus tyrosine kinase,signal transducer and activator of transcription(JAK/STAT)on ferroptosis,myocardial remodeling,and JAK/STAT melatonin receptor 1-nuclear factor E2-related factor 2-glutathione peroxidase 4(MT1-Nrf2-GPX4)signaling axis in rats with heart failure(HF)under echocardiography.Methods:Forty SD rats were selected,and they were randomly divided into blank control group,model group,interleukin-6(IL-6)group and tyrosine phosphorylation inhibitor(AG490)group according to random number table,with 10 rats in each group.HF rat models were established in three groups except the blank control group.The expression levels of JAK/STAT mRNA in myocardial tissue among 4 groups were compared and analyzed.The small animal ultrasound imaging system was used to measure a series of cardiac function indexes included interventricular septum(IVS)thickness,left ventricular posterior wall(LVPWs)thickness,left ventricular posterior wall(LVPWd)thickness,left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD)and ejection fraction(EF).The Fe2+concentration and lesions of myocardial tissue,as well as the expressions of MT1,Nrf2 and GPX4 proteins,in the four groups were compared and analyzed.Results:The increases of JAK1 and STAT3 mRNA levels,and Fe2+concentration in the model group,IL-6 group and AG490 group were higher than those in the blank control group,and the protein expression levels of MT1,Nrf2 and GPX4 in them were lower than those in the blank control group,and the differences of the above indicators between the model group and the blank control group were statistically significant(t=11.810,16.250,17.150,10.460,9.272,11.180,P＜0.05),and the differences of the above indicators between the IL-6 group and the blank control group were statistically significant(t=9.834,19.030,16.320,14.450,13.250,14.070,P＜0.05),and the differences of them between the AG490 group and the blank control group were statistically significant(t=8.025,11.050,17.590,4.173,4.179,4.183,P＜0.05),respectively.The levels of STAT3 mRNA level and Fe2+concentration in IL-6 group were higher than those in the model group,and the expression levels of MT1,Nrf2 and GPX4 proteins in that were lower than those in the model group,and the differences were statistically significant(t=2.224,2.582,3.550,3.078,2.624,P＜0.05),respectively.The levels of JAK1,STAT3 mRNA and Fe2+concentration in the AG490 group were lower than those in the model group,and the levels of MT1,Nrf2 and GPX4 in that were higher than those in the model group,and the differences were statistically significant(t=4.052,6.930,8.598,6.247,5.055,6.799,P＜0.05),respectively.The IVS,LVPWs,LVPWd and EF of the model group,IL-6 group and AG490 group were lower than those of the blank control group,and the LVEDD and LVESD of them were higher than those of the blank control group,and the differences of these indicators between the model group and the blank control group were statistically significant(t=13.740,11.100,5.654,7.049,13.440,14.260,P＜0.05),and the differences of them between the IL-6 group and the blank control group were statistically significant(t=16.090,13.140,8.103,9.174,15.940,17.010,P＜0.05),and the differences of them between the AG490 group and the blank control group were statistically significant(t=5.474,4.947,2.682,4.071,8.608,13.300,P＜0.05),respectively.The LVPWd and EF in the IL-6 group were lower than those in the model group,and the LVEDD and LVESD in the IL-6 group were higher than those in the model group,and the differences of them were statistically significant(t=2.417,2.327,2.236,2.818,P＜0.05),respectively.The IVS,LVPWs,LVPWd and EF in the AG490 group were higher than those in the model group,and the LVEDD and LVESD in that were lower than those in the model group,and the differences were statistically significant(t=8.598,7.147,3.514,3.361,4.914,2.970,P＜0.05),respectively.Conclusion:Inhibition of JAK/STAT expression can improve the cardiac structure of HF rats,and relieve ventricular remodeling,and inhibit ferroptosis of cardiomyocyte,and promote the expression of MT1,Nrf2 and GPX4 proteins.

Objective:To investigate the application of 3.0T multiparametric magnetic resonance imaging (Mp-MRI) prostate imaging-reporting and data system (PI-RADS) V2.1 score combined with prostate-specific antigen density (PSAD) in the diagnosis of prostate cancer (PCa).Methods:The clinical data of 82 patients with suspected PCa who were admitted to Nantong Second People's Hospital from May 2017 to Octorber 2021 were retrospectively analyzed. The 3.0T Mp-MRI PI-RADS V2.1 score, serum PSAD level and pathological diagnosis were obtained from all patients. The 3.0T Mp-MRI PI-RADS V2.1 score and its distribution as well as serum PSAD level between patients with pathologically diagnosed PCa and patients with prostatic hyperplasia (BPH) were compared. The diagnostic efficiency of 3.0T Mp-MRI PI-RADS V2.1 score and serum PSAD level alone and in combination for PCa was analyzed using receiver operating characteristic (ROC) curve, with pathological results as the gold standard.Results:Pathological diagnosis showed that there were 43 cases (52.44%) of PCa and 39 cases (47.56%) of BPH. There was a statistical difference in the distribution of 3.0T Mp-MRI PI-RADS V2.1 score between PCa and BPH patients ( Z = 32.25, P<0.001). The 3.0T Mp-MRI PI-RADS V2.1 score of PCa patients was higher than that of BPH patients [(4.29±0.25) points vs. (2.24±0.11) points, P < 0.001], the serum PSAD level was higher than that of BPH patients [(0.49±0.15) ng·ml -1·cm -3 vs. (0.27±0.08) ng·ml -1·cm -3, P < 0.001]. The ROC curve analysis showed that area under the curve of 3.0T Mp-MRI PI-RADS V2.1 score, serum PSAD level alone and both together for the diagnosis of PCa were 0.766 (95% CI 0.659-0.852, P < 0.001), 0.793 (95% CI 0.689- 0.874, P < 0.001) and 0.816 (95% CI 0.715-0.893, P < 0.001). Conclusions:3.0T Mp-MRI PI-RADS V2.1 score and serum PSAD level are both elevated in PCa patients. They have certain values in the diagnosis of PCa, and the combination of the two has higher diagnostic efficiency.

Objective:To explore the epidemiological characteristics and the antibiotic resistance of Streptococcus pneumoniae isolates, and to provide the evidence for the rational use of antimicrobial agents to treat Streptococcus pneumoniae infection. Methods:The positive microbiological laboratory identification and antimicrobial susceptibility testing of Streptococcus pneumoniae from sputum of children with respiratory infections during January 2010 to December 2017 in Children′s Hospital of Soochow University were retrospectively analyzed. The positive rates of Streptococcus pneumoniae of different genders, ages, years and seasons were compared. The annual detection rates and trends of drug resistance of Streptococcus pneumoniae to penicillin, amoxicillin and cefotaxime were analyzed by Mann-Kendall trend test. The seasonal decomposition of time series was conducted to assess the association between Streptococcus pneumoniae detection rate and season. Enumeration data was compared using χ2 test. Results:Of the 88 480 sputum specimens, the total positive rate of Streptococcus pneumoniae was 10.3%(9 081/88 480). The detection rates of Streptococcus pneumoniae in children aged 0 to <0.5 years old, 0.5 to <2 years old, 2 to <3 years old, 3 to <5 years old, and 5 to <15 years old were 4.2%(1 407/33 224), 13.1%(3 191/24 390), 14.9%(2 417/16 252), 17.9%(1 474/8 246) and 9.3%(592/6 368), respectively. The difference was statistically significant ( χ2=2 421.6, P<0.01). The detection rates were 8.1%(1 321/16 306) from January to March, 10.9%(2 194/20 207) from April to June, 8.5%(2 141/25 058) from July to September, and 12.7%(3 425/26 909) from October to December. The discrepancy of positive rates in different seasons showed statistical significance ( χ2=311.5, P<0.01). During 2010 to 2017, significant decreases in antibiotic resistant rates of Streptococcus pneumoniae to penicillin, amoxicillin and cefotaxime were detected (tau=-0.93, -0.93 and -0.71, respectively, all P<0.05). Conclusions:The detection rate of Streptococcus pneumoniae in sputum of children with respiratory infections may present seasonal pattern and vary between different ages of children. The resistance to β-lactam antibiotics has declined.

Objective:To explore the influence of bromodomain-containing protein 4 (BRD4) inhibitor on wild-type Kras differentiated thyroid carcinoma (DTC) and its mechanism.Methods:The DTC cell line Kras WT TPC-1 was selected and the mutant Kras G12D TPC-1 cells were constructed. CCK-8 assay was used to detect the effect of BRD4 inhibitor JQ-1 on the proliferation activity of Kras WT TPC-1 cells. Kras WT TPC-1 cells were treated with 0.2 μmol/L JQ-1 (JQ-1 group), and a negative control group (NC group) was set. Transwell invasion assay and flow cytometry were used to detect the effect of JQ-1 on the invasion and apoptosis of Kras WT TPC-1 cells. The effect of JQ-1 on the expressions of BRD4, miR-106b-5p and P21, and the effect of P21 inhibitor UC2288 on the expressions of P21 and BRD4 were detected. Kras WT TPC-1 cells were divided into JQ-1+ NC-OE group, JQ-1+ p21-OE group (overexpression of p21) and JQ-1+ p21-OE+ miR-106b-5p mimic group (overexpression of p21 and miR-106b-5 at the same time), and the proliferation, invasion and apoptosis of cells in each group were detected. TPC-1 cells were divided into Kras WT group, Kras WT+ JQ-1 group, Kras G12D group and Kras G12D+ JQ-1 group, and the cell proliferation, invasion and apoptosis of each group were detected. Results:JQ-1 inhibited the proliferation activity of Kras WT TPC-1 cells in a dose-dependent and time-dependent manner. In the NC group and JQ-1 group, the numbers of cell invasion were 124.67±9.61 and 82.67±8.02, and the apoptosis rates were (5.91±0.34)% and (10.33±1.10)%, respectively, with statistically significant differences ( t=5.812, P=0.004; t=6.653, P=0.003). JQ-1 significantly inhibited the expressions of BRD4 and miR-106b-5p, and promoted the expression of P21 in Kras WT TPC-1 cells. UC2288 significantly inhibited P21 expression, but had no significant effect on BRD4 expression. In the JQ-1+ NC-OE group, JQ-1+ p21-OE group and JQ-1+ p21-OE+ miR-106b-5p mimic group, the proliferation activities at 24 h of Kras WT TPC-1 cells was 0.46±0.03, 0.35±0.04 and 0.44±0.03 ( F=8.720, P=0.017), and the proliferation activity of JQ-1+ p21-OE group was significantly lower than that of the JQ-1+ NC-OE group ( P<0.05). The numbers of cell invasion in the three groups were 83.00±9.17, 56.67±6.03 and 79.67±10.07 ( F=8.347, P=0.018), and the number of cell invasion in the JQ-1+ p21-OE group was significantly lower than that in the JQ-1+ NC-OE group ( P=0.009). The apoptosis rates of the three groups were (10.00±0.49)%, (15.39±1.14)% and (10.32±0.80)% ( F=37.764, P<0.001), and the apoptosis rate of the JQ-1+ p21-OE group was significantly higher than that in the JQ-1+ NC-OE group ( P<0.001). There were no significant differences in cell proliferation activity, invasion number and apoptosis rate between JQ-1+ p21-OE+ miR-106b-5p mimic group and JQ-1+ NC-OE group (all P>0.05). In Kras WT group, Kras WT+ JQ-1 group, Kras G12D group and Kras G12D+ JQ-1 group, the cell proliferation activities at 24 h were 0.50±0.05, 0.39±0.04, 0.68±0.08 and 0.64±0.05 ( F=17.776, P<0.001). Compared with the Kras WT group, cell proliferation activity in the Kras WT+ JQ-1 group was significantly decreased, while that in the Kras G12D group was significantly increased (both P<0.05). The numbers of cell invasion in the four groups were 129.33±11.50, 86.00±9.54, 161.67±13.01 and 146.33±13.20 ( F=22.598, P<0.001). Compared with the Kras WT group, the number of cell invasion in the Kras WT+ JQ-1 group was significantly decreased ( P=0.002), and that in the Kras G12D group was significantly increased ( P=0.010). The apoptosis rates in the four groups were (6.17±0.50)%, (10.42±0.73)%, (3.43±0.47)% and (3.41±0.32)% ( F=119.170, P<0.001). Compared with the Kras WT group, the apoptosis rate in the Kras WT+ JQ-1 group was significantly increased ( P<0.001), and that in the Kras G12D group was significantly decreased ( P<0.001). There were no significant differences in cell proliferation activity, invasion number and apoptosis rate between Kras G12D+ JQ-1 group and Kras G12D group (all P>0.05). Conclusion:BRD4 inhibitor can specifically inhibit the development of wild-type Kras DTC via regulating the molecular axis of BRD4/miR-106b-5p/P21, but has no significant effect on the proliferation, invasion and apoptosis of mutant Kras DTC tumor cells.