OBJECTIVE To investigate the protective effect proanthocyanidin B2(PC-B2) on oxidative damage and apoptosis of mouse astrocytes(AS) induced by hydrogen peroxide(H2O2) and its mechanism. METHODS AS were isolated and cultured from neonatal C57BL/6 mice(1−3 d). The optimal concentration of H2O2 and PC-B2 was divided into four groups: normal group, normal+PC-B2 group(100 μg·mL‒1 PC-B2 treated for 24 h), H2O2 model group(200 μmol·L‒1 H2O2 treated for 24 h), PC-B2 group(200 μmol·L‒1 H2O2 and 100 μg·mL‒1 PC-B2 treated for 24 h). The cell viability of each group was detected by CCK-8 method. Cytotoxicity was detected by LDH method. The antioxidant capacity was detected by ABTS and DPPH. The content of MDA and the activity of SOD, CAT and GSH-Px were detected by ELISA kit. Detection of apoptosis in each group was done by TUNEL staining. The mRNA and protein expression levels of Bax, Bcl-2, Caspase-3, Akt/Stat3, p-Akt, p-Stat3 and Nrf2/HO-1 in AS were detected by RT-PCR and Western blotting, respectively. RESULTS PC-B2 could significantly enhance cell viability and inhibit AS apoptosis. Compared with the H2O2 model group, PC-B2 intervention could significantly reduce the content of LDH and MDA in AS, and increase the activity of SOD, CAT and GSH-Px. PC-B2 intervention could inhibit the mRNA and protein expression of Bax and Caspase-3, and up-regulate the mRNA and protein expression of Akt/Stat3, Bcl-2, Nrf2/HO-1. CONCLUSION PC-B2 can enhance the antioxidant capacity of AS through Akt/Stat3 and Nrf2/HO-1 pathways, therefore reduce H2O2-induced AS oxidative damage and apoptosis.

Objective: To establish a non-derivatization-PriME-ultra-high performance liquid chromatography-tandem mass spectrometry method for simultaneou determination of 9 kinds of biogenic amines in yellow rice wine. Methods: Yellow rice wine samples were purified by PriME HLB solid phase extraction column purification, separated using Waters XSelect HSS T3 column (150 mm×2.1 mm, 3 μm), and qualified using multiple reaction monitoring mode, electrospray ion source positive ion and external standard method. Results: There was a good linear relationship for the 9 kinds of biogenic amines at 2.0 to 500.0 μg/L (r≥0.996). The limit of detection was 0.1 to 0.2 mg/L, and the limit of quantitation was 0.3 to 0.6 mg/L. The spike recovery rate of 9 kinds of biogenic amines ranged from 83.5% to 108.6% at 0.1 and 1.0 mg/L, with relative standard deviations of 2.8% to 8.7%. Conclusion Non-derivation-prime ultra-high performance liquid chromatography-tandem mass spectrometry can be used for the rapid quantitative detection of biogenic amines in yellow rice wine.

Objective:To investigate the value of soluble interleukin-6 (IL-6) receptor (sIL-6R) level in predicting ultrafiltration insufficiency in peritoneal dialysis (PD) patients.Methods:It was a prospective cohort study. The patients who received continuous ambulatory PD and regular follow-up between November 2016 and July 2018 in the PD Center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled. Enzyme-linked immunosorbent assay was used to determine dialysate sIL-6R and its appearance rate (AR) was calculated. Patients were divided into high sIL-6R AR group and low sIL-6R AR group according to median value of sIL-6R AR and prospectively followed up until death, PD cessation, or the end of the study (December 31, 2022). Multiple linear regression was used to analyze the related factors of sIL-6R AR. Kaplan-Meier method and log-rank test were used to compare the survival rate difference of ultrafiltration insufficiency between high sIL-6R AR group and low sIL-6R AR group. Multivariate Cox regression and multivariate competing risk models were used to assess the risk factors associated with occurrence of ultrafiltration insufficiency.Results:A total of 198 PD patients were enrolled, including 115 (58.1%) males, with age of (54.9±13.7) years old and PD duration of 22.5 (6.6, 65.0) months. The sIL-6R AR of the cohort was 2 094.7 (1 672.4, 2 920.9) pg/min. Compared with low sIL-6R AR（<2 094.7 pg/min）group, high sIL-6R AR（>2 094.7 pg/min）group had older age ( t=-3.269, P=0.001), higher body mass index ( t=-3.248, P=0.001), proportion of combined diabetes mellitus ( χ2=8.890, P=0.003), 24 h glucose exposure ( Z=-2.257, P=0.024), 24 h ultrafiltration capacity ( Z=-2.515, P=0.012), 4 h dialysate creatinine to serum creatinine ratio ( t=-2.609, P=0.010), mass transfer area coefficient of creatinine ( Z=-2.308, P=0.021), IL-6 AR ( Z=-3.533, P<0.001) and solute glycoprotein 130 AR ( Z=-8.670, P<0.001), and lower serum albumin ( t=2.595, P=0.010) and residual renal function ( t=2.133, P=0.033). Multiple linear regression analysis showed that body mass index ( β=0.194, P=0.005), serum albumin ( β=-0.215, P=0.002) and dialysate lg[IL-6 AR] ( β=0.197, P=0.011) were independently correlated with sIL-6R AR. By the end of the study, 57 (28.8%) patients developed ultrafiltration insufficiency. Kaplan-Meier analysis showed that high sIL-6R AR group had a significantly inferior ultrafiltration insufficiency-free survival rate than that in low sIL-6R AR group (log-rank χ 2=5.375, P=0.020). Multivariate Cox regression analysis and multivariate competing risk models showed that high dialysate sIL-6R AR (>2 094.7 pg/min) was an independent influencing factor of ultrafiltration insufficiency ( HR=2.286 , 95% CI 1.254-4.165 , P=0.007 ; SHR=2.074, 95% CI 1.124-3.828, P=0.020) in PD patients. Conclusions:Dialysate sIL-6R level was associated with body mass index, serum albumin and dialysate IL-6 level. Dialysate sIL-6R may be a predictive factor of ultrafiltration insufficiency in PD patients.

Evidence suggests that explicit reappraisal has limited regulatory effects on high-intensity emotions, mainly due to the depletion of cognitive resources occupied by the high-intensity emotional stimulus itself. The implicit form of reappraisal has proved to be resource-saving and therefore might be an ideal strategy to achieve the desired regulatory effect in high-intensity situations. In this study, we explored the regulatory effect of explicit and implicit reappraisal when participants encountered low- and high-intensity negative images. The subjective emotional rating indicated that both explicit and implicit reappraisal down-regulated negative experiences, irrespective of intensity. However, the amplitude of the parietal late positive potential (LPP; a neural index of experienced emotional intensity) showed that only implicit reappraisal had significant regulatory effects in the high-intensity context, though both explicit and implicit reappraisal successfully reduced the emotional neural responses elicited by low-intensity negative images. Meanwhile, implicit reappraisal led to a smaller frontal LPP amplitude (an index of cognitive cost) compared to explicit reappraisal, indicating that the implementation of implicit reappraisal consumes limited cognitive control resources. Furthermore, we found a prolonged effect of implicit emotion regulation introduced by training procedures. Taken together, these findings not only reveal that implicit reappraisal is suitable to relieve high-intensity negative experiences as well as neural responses, but also highlight the potential benefit of trained implicit regulation in clinical populations whose frontal control resources are limited.
Humans ; Emotional Regulation ; Electroencephalography ; Evoked Potentials/physiology* ; Cognition/physiology* ; Emotions/physiology*

Objective To investigate the combined effect of noise and hand-transmitted vibration on hearing loss in male noise-exposed workers. Methods A total of 952 male noise-exposed workers from an automobile manufacturing enterprise were selected as the research subjects using judgment sampling method. Occupational epidemiological surveys, assessments of occupational hazards in workplace, and pure-tone audiometry tests were conducted on the research subjects, and they were divided into low-level noise group, low-level combined group, high-level noise group, and high-level combined group according to whether the noise exposure level exceeded the national standard and whether they were jointly exposed to hand-transmitted vibration. The joint effects of noise and hand-transmitted vibration on hearing loss were analyzed. Results The detection rate of hearing loss in 952 noise-exposed workers was 21.7%. The detection rate of hearing loss of four groups, from high to low, was as follows： high-level combined group, high-level noise group, low-level combined group, and low-level noise group (44.9% vs 32.7% vs 12.9% vs 5.7%, P<0.01). The results of multivariate logistic regression analysis showed that the risk of hearing loss in the low-level noise group, the low-level combined group, the high-level noise group and the high-level combined group increased sequentially after adjusting for the confounding factors such as age, education level, smoking, drinking, listening to music with headphones, frequency of wearing noise-blocking earplugs and body mass index. The risk of hearing loss in the high-level noise group was 8.62 times more than that of the low-level noise group (P<0.01). The risk of hearing loss in the low-level noise combined group was 2.50 times more than that of the low-level noise group (P<0.01). The risks of hearing loss in the high-level combined group were 5.76 and 1.67 times more than that of the low-level combined group and the high-level noise group. Conclusion Combined exposure to noise and hand-transmitted vibration can increase the risk of hearing loss in male noise-exposed workers, and the higher the noise intensity, the greater the synergistic effect. Hand-transmitted vibration is a synergistic risk factor for occupational noise-induced hearing loss.

Objective:To study the distribution and antibiotics resistance of the main pathogens of neonatal purulent meningitis in different regions of China.Methods:A retrospective descriptive clinical epidemiological study was conducted in children with neonatal purulent meningitis which admitted to 18 tertiary hospitals in different regions of China between January 2015 to December 2019. The test results of blood and cerebrospinal fluid, and drug sensitivity test results of the main pathogens were collected. The distributions of pathogenic bacteria in children with neonatal purulent meningitis in preterm and term infants, early and late onset infants, in Zhejiang Province and other regions outside Zhejiang Province, and in Wenzhou region and other regions of Zhejiang Province were analyzed. The chi-square test was used for statistical analysis.Results:A total of 210 neonatal purulent meningitis cases were collected. The common pathogens were Escherichia coli ( E. coli)(41.4%(87/210)) and Streptococcus agalactiae ( S. agalactiae)(27.1%(57/210)). The proportion of Gram-negative bacteria in preterm infants (77.6%(45/58)) with neonatal purulent meningitis was higher than that in term infants (47.4%(72/152)), and the difference was statistically significant ( χ2=15.54, P=0.001). There were no significant differences in the constituent ratios of E. coli (36.5%(31/85) vs 44.8%(56/125)) and S. agalactiae (24.7%(21/85) vs 28.8%(36/125)) between early onset and late onset cases (both P>0.05). The most common pathogen was E. coli in different regions, with 46.7%(64/137) in Zhejiang Province and 31.5%(23/73) in other regions outside Zhejiang Province. In Zhejiang Province, S. agalactiae was detected in 49 out of 137 cases (35.8%), which was significantly higher than other regions outside Zhejiang Province (11.0%(8/73)). The proportions of Klebsiella pneumoniae, and coagulase-negative Staphylococcus in other regions outside Zhejiang Province (17.8%(13/73) and 16.4%(12/73)) were both higher than those in Zhejiang Province (2.9%(4/137) and 5.1%(7/137)). The differences were all statistically significant ( χ2=14.82, 12.26 and 7.43, respectively, all P<0.05). The proportion of Gram-positive bacteria in Wenzhou City (60.8%(31/51)) was higher than that in other regions in Zhejiang Province (38.4%(33/86)), and the difference was statistically significant ( χ2=6.46, P=0.011). E. coli was sensitive to meropenem (0/45), and 74.4%(32/43) of them were resistant to ampicillin. E. coli had different degrees of resistance to other common cephalosporins, among which, cefotaxime had the highest resistance rate of 41.8%(23/55), followed by ceftriaxone (32.4%(23/71)). S. agalactiae was sensitive to penicillin, vancomycin and linezolid. Conclusions:The composition ratios of pathogenic bacteria of neonatal purulent meningitis are different in different regions of China. The most common pathogen is E. coli, which is sensitive to meropenem, while it has different degrees of resistance to other common cephalosporins, especially to cefotaxime.

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

Objective:To systematically review the effect of preoperative pulmonary rehabilitation on postoperative pulmonary complications in patients with lung cancer.Methods:The randomized controlled trials of preoperative pulmonary rehabilitation for lung cancer published in the past 10 years were retrieved in China Biomedical Literature Database, China National Knowledge Infrastructure, VIP, WanFang Data, PubMed, Embase, Web of Science, Cochrane Library and Wiley Online Library. The search limit was from January 1, 2010 to January 1, 2021. The quality evaluation and data extraction of the included article were carried out, and the Meta-analysis of the outcome indicators of postoperative pulmonary complications was conducted.Results:A total of 12 articles were included. Meta-analysis showed that the incidence of postoperative pulmonary complications in the intervention group was lower than that in the control group, and the difference was statistically significant [ RR=0.42, 95% CI (0.32, 0.55) , P<0.01]. Subgroup analysis was performed according to the duration of intervention, and the results showed that when the intervention duration was one week, the difference between the intervention group and the control group was statistically significant [ RR=0.36, 95% CI (0.24, 0.55) , P<0.01], when the intervention duration was more than one week, the difference between the intervention group and the control group was statistically significant [ RR=0.48, 95% CI (0.33, 0.68) , P<0.01) ]. Subgroup analysis was conducted with different evaluation time after operation, and the results showed that when the evaluation time was one month, the difference between the intervention group and the control group was statistically significant [ RR=0.48, 95% CI (0.34, 0.68) , P<0.01], when the evaluation time was more than one month, there was no significant difference between the intervention group and the control group [ RR=0.39, 95% CI (0.08, 1.85) , P=0.24]. Except for pneumonia or pulmonary infection, atelectasis, and bronchopleural fistula, there was no significant difference in the incidence of postoperative pulmonary complications in patients with lung cancer ( P>0.05) . Conclusions:Exercise that includes breathing training for at least one week is a common intervention for preoperative pulmonary rehabilitation. Preoperative pulmonary rehabilitation is beneficial to reduce the overall and one month postoperative pulmonary complications after lung cancer surgery, but the impact on postoperative pulmonary complications evaluated for more than one month and specific complications requires further study.

Objective:To evaluate the influencing factors of carotid-femoral pulse wave velocity (CF-PWV) and its value to predict outcomes in peritoneal dialysis (PD) patients.Methods:Eligible patients undergoing PD in Renji Hospital of Shanghai Jiao Tong University between August 2016 and July 2018 were recruited and prospectively followed up until death, PD cessation, or to the end of the study. CF-PWV was measured by an arterial pulse wave velocity meter to assess arterial stiffness (July 31, 2020). Overhydration was measured by bioimpedance spectroscopy. The patients were divided into CF-PWV≤10 m/s group and CF-PWV>10 m/s group according to the measured value of CF-PWV. The influencing factors of elevated CF-PWV were analyzed by multivariate logistic regression. Survival curves were generated using the Kaplan-Meier method and multivariate Cox proportional hazards models were used to analyze the difference for all-cause mortality and cardiovascular disease (CVD) mortality between the two groups.Results:A total of 224 PD patients were enrolled, including 133 males (59.4%). The age was (55.2±13.4) years old, and median PD vintage was 22.3(6.5, 59.3) months. Among them, 47(21.0%) patients were comorbid with diabetes, and 37(16.5%) patients had CVD history. The median CF-PWV was 9.6(8.4, 11.4) m/s for the cohort, and 105(46.9%) participants had CF-PWV over 10 m/s. Compared with CF-PWV≤10 m/s group, CF-PWV>10 m/s group patients had older age, increased percentage of diabetes and CVD (all P<0.05). Multivariate logistic analysis showed that increased age ( OR=1.070, 95% CI 1.043-1.099, P<0.001), diabetes ( OR=3.693, 95% CI 1.646-8.287, P=0.002) and higher overhydration ( OR=1.238, 95% CI 1.034-1.483, P=0.020) were independent influencing factors for elevated CF-PWV in PD patients. After followed up for 37.4(25.6, 41.7) months, 24 patients died, including 19 cases of CVD-related deaths. Kaplan-Meier survival analysis showed that all-cause mortality and CVD mortality were significantly higher in the CF-PWV>10 m/s group than those in CF-PWV≤10 m/s group (Log-rank χ2=6.423, P=0.011; Log-rank χ2=6.243, P=0.012, respectively). Multivariate Cox proportional hazards models showed that increased age was an independent influencing factor for both all-cause mortality and CVD mortality ( HR=1.057, 95% CI 1.010-1.107, P=0.018; HR=1.062, 95% CI 1.009-1.118, P=0.022). Conclusions:Increased arterial stiffness is relatively common in PD patients. Higher CF-PWV in PD patients is associated with increased age, diabetes and higher overhydration, and it is probably a valuable predictor of outcome in PD patients.