Recently, plasma sterilization has attracted increasing attention in dental community for the atmospheric pressure non-equilibrium plasma jet (APNPs), which is driven by a kilohertz pulsed DC power, may be applied to the dental and oral diseases. However, it is still in doubt whether APNPs can effectively kill pathogenic bacteria in the oral cavity and produce no harmful effects on normal oral tissues, especially on normal mucosa. The aim of this study was to evaluate the bacterial-killing effect of APNPs in the biofilms containing a single breed of bacteria (Porphyromonas gingivalis, P.g.), and the pathological changes of the oral mucosa after treatment by APNPs. P.g. was incubated to form the biofilms in vitro, and the samples were divided into three groups randomly: group A (blank control); group B in which the biofilms were treated by APNPs (the setting of the equipment: 10 kHz, 1600 ns and 8 kV); group C in which the biofilms were exposed only to a gas jet without ignition of the plasma. Each group had three samples and each sample was processed for up to 5 min. The biofilms were then fluorescently stained, observed and photographed under a laser scanning confocal microscope. In the animal experiment, six male Japanese white rabbits were divided into two groups randomly (n=3 in each group) in terms of the different post-treatment time (1-day group and 5-day group). The buccal mucosa of the left side and the mucosa of the ventral surface of the tongue were treated by APNPs for 10 min in the same way as the bacterial biofilm experiment in each rabbit, and the corresponding mucosa of the other sides served as normal control. The clinical manifestations of the oral mucosa were observed and recorded every day. The rabbits were sacrificed one or five day(s) after APNPs treatment. The oral mucosa were harvested and prepared to haematoxylin and eosin-stained sections. Clinical observation and histopathological scores were used to assess mucosal changes. The results showed the obvious P.g. biofilms were formed at 10 days, and most of the bacteria in groups A and C were alive under a laser scanning confocal microscope, but the bacteria in the group B were almost all dead. In animal experiment, no ulcers, anabrosis and oral mucositis were found in both the 1-day and 5-day groups. The average mucous membrane irritation index was -0.83 and -0.67 in the 1-day and 5-day groups, respectively, suggesting that no intense mucosal membrane irritation responses occurred. It was concluded that APNPs could effectively kill P.g. in the biofilms and did not cause any pathological changes in the normal mucosa, suggesting that the plasma jet (APNPs) may be applied to oral diseases as a novel sterilization device in the future.

Objective:To investigate the associations between the hormone receptors,Ki67 expression and response to neoadjuvant anthracycline-based chemotherapy in breast cancer patients.Methods:One hundred sixty-eight primary breast cancer patients received anthracycline-based neoadjuvant chemotherapy.The expression of estrogen receptor(ER),progesterone receptor(PR),and Ki67 were determined by immunohistochemistry assay in core-needle biopsy specimens prior to the chemotherapy,and pathologic response was assessed by Miller & Payne grade(G1 to G5).Results:40%(67/168)of the patients had a good pathologic response,defined as complete pathologic response(pCR or G5)and minimal residual disease(G4).Among the patients,20%(33/168)had a complete pathologic response(G5).ER or PR status was significantly associated with pathological response.Patients with PR-negative tumors had a higher pathological response rate or pCR than those with PR-positive tumors(17/67 vs 45/90,P=0.002;6/67 vs 25/90,P=0.003,respectively),whereas patients with ER-negative tumors had a higher pathological response rate than those with ER-positive tumors.Moreover,Patients with both ER-and PR-negative tumors exhibited a remarkable pathological response as compared with those with any single factor(36/17 vs 26/86,P=0.009).No association between Ki67 expression and pathological was found in this cohort of patients.There was a linear correlation between the expression of Ki-67,ER or PR status and pathologic response.Conclusion:There is a significant association between the hormone receptors and pathological response to neoadjvant anthracycline-based chemotherapy in breast cancer patients,and patients with PR-negative tumors are more likely to respond to chemotherapy.

Recently,plasma sterilization has attracted increasing attention in dental community for the atmospheric pressure non-equilibrium plasma jet (APNPs),which is driven by a kilohertz pulsed DC power,may be applied to the dental and oral diseases.However,it is still in doubt whether APNPs can effectively kill pathogenic bacteria in the oral cavity and produce no harmful effects on normal oral tissues,especially on normal mucosa.The aim of this study was to evaluate the bacterial-killing effect of APNPs in the biofilms containing a single breed of bacteria (Porphyromonas gingivalis,Pg.),and the pathological changes of the oral mucosa after treatment by APNPs.Pg.was incubated to form the biofilms in vitro,and the samples were divided into three groups randomly:group A (blank control);group B in which the biofilms were treated by APNPs (the setting of the equipment:10 kHz,1600 ns and 8 kV); group C in which the biofilms were exposed only to a gas jet without ignition of the plasma.Each group had three samples and each sample was processed for up to 5 min.The biofilms were then fluorescently stained,observed and photographed under a laser scanning confocal microscope.In the animal experiment,six male Japanese white rabbits were divided into two groups randomly (n=3 in each group) in terms of the different post-treatment time (1-day group and 5-day group).The buccal mucosa of the left side and the mucosa of the ventral surface of the tongue were treated by APNPs for 10 min in the same way as the bacterial biofilm experiment in each rabbit,and the corresponding mucosa of the other sides served as normal control.The clinical manifestations of the oral mucosa were observed and recorded every day.The rabbits were sacrificed one or five day(s) after APNPs treatment.The oral mucosa were harvested and prepared to haematoxylin and eosin-stained sections.Clinical observation and histopathological scores were used to assess mucosal changes.The results showed the obvious P.g.biofilms were formed at 10 days,and most of the bacteria in groups A and C were alive under a laser scanning confocal microscope,but the bacteria in the group B were almost all dead.In animal experiment,no ulcers,anabrosis and oral mucositis were found in both the 1-day and 5-day groups.The average mucous membrane irritation index was -0.83 and -0.67 in the 1-day and 5-day groups,respectively,suggesting that no intense mucosal membrane irritation responses occurred.It was concluded that APNPs could effectively kill P.g.in the biofilms and did not cause any pathological changes in the normal mucosa,suggesting that the plasma jet (APNPs) may be applied to oral diseases as a novel sterilization device in the future.

Objective:To evaluate the relationship between silent information regulator 1 (SIRT1) and ferroptosis during curcumin-induced reduction of acute lung injury in a mouse model of sepsis.Methods:One hundred and fifty-two SPF-grade male C57BL/6J mice, aged 8 weeks, weighing 23-27 g, were divided into 4 groups ( n=38 each) using a random number table method: sham operation group (C group), sepsis group (S group), curcumin group (Cur group) and curcumin plus SIRT1 inhibitor EX527 group (CE group). Curcumin 200 mg/kg was administered by intragastric gavage every day in Cur group. Curcumin 200 mg/kg was administered by intragastric gavage every day and EX527 5 mg/kg was intraperitoneally injected in CE group. The equal volume of solvent dimethyl sulfoxide (DMSO) was given in C group and S group. Sepsis model was developed by cecal ligation and puncture (CLP) after 5 days of consecutive administration in anesthetized animals. Twenty mice in each group were randomly selected to observe the survival condition within 7 days after CLP. The bronchoalveolar lavage fluid (BALF) was collected at 24 h after developing the model to determine the concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), IL-6 and IL-18 (by enzyme-linked immunosorbent assay), and the lung tissues were obtained for microscopic examination of the pathological changes which were scored and for determination of wet-to-dry lung weight (W/D) ratio, contents of glutathione (GSH), malondialdehyde (MDA) and iron (by colorimetry), and expression of SIRT1, glutathione peroxidase 4 (GPX4) and Acyl-CoA synthetase long chain family member 4 (ACSL4) (by Western blot). Results:Compared with C group, the 7-day survival rate after CLP was significantly decreased, the concentrations of TNF-α, IL-1β, IL-6 and IL-18 in BALF, W/D ratio and lung injury score were increased, the content of GSH in lung tissues was decreased, the contents of MDA and iron were increased, the expression of SIRT1 and GPX4 was down-regulated, and the expression of ACSL4 was up-regulated in S group ( P<0.05). Compared with S group, the 7-day survival rate after CLP was significantly increased, the concentrations of TNF-α, IL-1β, IL-6 and IL-18 in BALF, W/D ratio and lung injury score were decreased, the content of GSH was increased, the contents of MDA and iron were decreased, the expression of SIRT1 and GPX4 was up-regulated, and the expression of ACSL4 was down-regulated in Cur group ( P<0.05). Compared with Cur group, the 7-day survival rate after CLP was significantly decreased, the concentrations of TNF-α, IL-1β, IL-6 and IL-18 in BALF, W/D ratio and lung injury score were increased, the content of GSH was decreased, the contents of MDA and iron were increased, the expression of SIRT1 and GPX4 was down-regulated, and the expression of ACSL4 was up-regulated in CE group ( P<0.05). Conclusions:The mechanism by which curcumin attenuates acute lung injury may be related to activation of SIRT1 and further inhibition of ferroptosis in mice.

Objective To evaluate the role of P2Y12 receptor in microglia in central post-stroke pain(CPSP)in mice and its mechanism.Methods Thirty-two specific pathogen-free(SPF)-grade male C57BL/6J mice were selected,aged 7 to 8 weeks,weighing 25 to 30 g,were divided into four groups using a random number table method:C group(sham operation group,n=8),CPSP group(n=8),CPSP-M group(CPSP plus P2Y12 receptor inhibitor MRS2395,n=8)and C-M group(sham operation plus P2 Y12 receptor inhibitor MRS2395,n=8).CPSP model was induced by injec-ting 10 nL type Ⅳ collagenase(0.001 U/nL)into the right ventral posterior medial nucleus andven-tral posterior lateral nucleus.MRS2395(1.5 mg/kg)was injected intraperitoneally at 30 min before model preparation in CPSP-M group and C-M group and then injected once a day for 5 consecutive days,mice in C group and CPSP group were given saline at the same volume.Before the modeling(T0)and 3,7 and 14 days(T1,T2,T3)after the establishment of the model,the thermal withdrawal latency(TWL),cold withdrawal latency(CWL)and paw withdrawal frequency(PWF)were measured.The mice were then sacrificed and the brain tissues were obtained for observing the location of P2Y12 receptor by double immunofluorescence staining and the pathological changes by HE staining,and for determination of the expression levels of P2Y12 receptor,toll-like receptor 4(TLR4),phospho-nuclear factor-κB p65(p-NF-KB p65)and NF-κB p65 by western blot.Results P2Y12 receptor was co-localized only with microglia,but not with neurons or astrocytes in brain tissue of CPSP group.Compared with C group,the TWL and CWL were significantly reduced and the PWF was sig-nificantly increased at T1 to T3,cerebral injury was aggravated significantly and the expressions of P2Y12 receptor,TLR4 and p-NF-κB p65 in brain tissue were up-regulated in CPSP group and CPSP-M group(P＜0.05).There was no statistically significant difference between C group and C-M group in the above indicators(P＞0.05).Compared with CPSP group,the TWL and CWL were significantly prolonged and the PWF was significantly reduced at T,to T3,cerebral injury was relieved significantly and the expressions of P2Y12 receptor,TLR4 and p-NF-κB p65 in brain tissue were down-regulated in CPSP group and CPSP-M group(P＜0.05).Conclusion P2Y12 receptors in microglia may be in-volved in the development of CPSP by activating TLR4/NF-κB signaling pathway in mice.

Objective To evaluate the role of P2Y12 receptor in microglia in central post-stroke pain(CPSP)in mice and its mechanism.Methods Thirty-two specific pathogen-free(SPF)-grade male C57BL/6J mice were selected,aged 7 to 8 weeks,weighing 25 to 30 g,were divided into four groups using a random number table method:C group(sham operation group,n=8),CPSP group(n=8),CPSP-M group(CPSP plus P2Y12 receptor inhibitor MRS2395,n=8)and C-M group(sham operation plus P2 Y12 receptor inhibitor MRS2395,n=8).CPSP model was induced by injec-ting 10 nL type Ⅳ collagenase(0.001 U/nL)into the right ventral posterior medial nucleus andven-tral posterior lateral nucleus.MRS2395(1.5 mg/kg)was injected intraperitoneally at 30 min before model preparation in CPSP-M group and C-M group and then injected once a day for 5 consecutive days,mice in C group and CPSP group were given saline at the same volume.Before the modeling(T0)and 3,7 and 14 days(T1,T2,T3)after the establishment of the model,the thermal withdrawal latency(TWL),cold withdrawal latency(CWL)and paw withdrawal frequency(PWF)were measured.The mice were then sacrificed and the brain tissues were obtained for observing the location of P2Y12 receptor by double immunofluorescence staining and the pathological changes by HE staining,and for determination of the expression levels of P2Y12 receptor,toll-like receptor 4(TLR4),phospho-nuclear factor-κB p65(p-NF-KB p65)and NF-κB p65 by western blot.Results P2Y12 receptor was co-localized only with microglia,but not with neurons or astrocytes in brain tissue of CPSP group.Compared with C group,the TWL and CWL were significantly reduced and the PWF was sig-nificantly increased at T1 to T3,cerebral injury was aggravated significantly and the expressions of P2Y12 receptor,TLR4 and p-NF-κB p65 in brain tissue were up-regulated in CPSP group and CPSP-M group(P＜0.05).There was no statistically significant difference between C group and C-M group in the above indicators(P＞0.05).Compared with CPSP group,the TWL and CWL were significantly prolonged and the PWF was significantly reduced at T,to T3,cerebral injury was relieved significantly and the expressions of P2Y12 receptor,TLR4 and p-NF-κB p65 in brain tissue were down-regulated in CPSP group and CPSP-M group(P＜0.05).Conclusion P2Y12 receptors in microglia may be in-volved in the development of CPSP by activating TLR4/NF-κB signaling pathway in mice.

Objective:To evaluate the role of silent information regulator 1 (SIRT1) in electroacupuncture (EA)-induced reduction of central post-stroke pain (CPSP) and the relationship with nod-like receptor pyrin domain containing 3 (NLRP3) in rats.Methods:Fifty SPF healthy male Sprague-Dawley rats, aged 6 weeks, weighing 180-220 g, were divided into 5 groups ( n=10 each) using a random number table method: sham operation group (group Sham), CPSP group, CPSP+ sham EA group (group SEA), CPSP+ EA group (group EA) and CPSP+ EA+ SIRT1 inhibitor EX527 group (group EX527). Type Ⅳ collagenase was injected into the right ventral posterolateral nucleus to establish the model of CPSP in CPSP, SEA, EA and EX527 groups.At 24 h after the model was established successfully, 30 min EA (frequency 2/15 Hz) stimulation of Neiguan, Renzhong and Sanyinjiao was performed once a day for 5 consecutive days in EA group.EA was performed at the points 5 mm lateral to the acupoints of Neiguan, Renzhong and Sanyinjiao in group SEA, and the other procedures were similar to those previously described in group EA.SIRT1 inhibitor EX527 5 mg/kg was injected intraperitoneally at 30 min before EA stimulation in group EX527, and the other procedures were similar to those previously described in group EA.At 1 day before the establishment of model (T 0) and at 1, 3 and 5 days after the establishment of model (T 1-3), the thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were measured.The animals were then sacrificed and brain tissues were taken for determination of the expression of SIRT1, NLRP3 and interleukin (IL)-18 and IL-1β. Results:Compared with Sham group, the TWL was significantly shortened and the MWT was decreased at T 1-3, the expression of SIRT1 was down-regulated, and the expression of NLRP3, IL-18 and IL-1β was up-regulated in CPSP, SEA, EA and EX527 groups ( P<0.05). Compared with CPSP group, the TWL was significantly prolonged and the MWT was increased at T 1-3, the expression of SIRT1 was up-regulated, and the expression of NLRP3, IL-18 and IL-1β was down-regulated in EA group ( P<0.05), and no significant change was found in the parameters mentioned above in group SEA ( P>0.05). Compared with EA group, the TWL was significantly shortened and the MWT was decreased at T 1-3, the expression of SIRT1 was down-regulated, and the expression of NLRP3, IL-18 and IL-1β was up-regulated in EX527 group ( P<0.05). Conclusion:SIRT1 is involved in the process of EA-induced reduction of CPSP, which is related to inhibiting NLRP3 expression in rats.

Objective:To explore the progress of microcirculation research in shock and sepsis from 2000 to 2019 based on knowledge visualization analysis.Methods:The literatures related to microcirculation of shock and sepsis published in Web of Science and Wanfang databases were collected from 2000 to 2019. Then, data collected was sorted out and used to make bar charts and curves reflecting the growth trend of the literatures using Excel software. The information about country, institution and author were extracted by CiteSpace 5.0 R1 for generating co-occurring network, to find the main research power and each cooperative relation. This software was also used to analyze the related-keywords and cited reference, so that the map of co-citation reference was drawn subsequently to explore the frontiers and hot spots in this field.Results:There were a total of 2 000 Chinese "papers" or "dissertations", 1 823 English "articles" or "reviews", collected preliminarily. The Chinese literatures were only statistically described for the amounts, institutions and authors, however, all retrieved English literatures were enrolled in the visualization analysis eventually. From 2009 to 2019, the number of English literatures rose steadily; however, the number of Chinese literatures had been sliding since 2011. On terms of quality, the impact factors of most literatures were under 6, lacking high quality ones, and the number remained stable every year. According to the analysis of English literatures, the top three countries that published related papers around the world were Germany ( n = 430), the United States ( n = 401) and Netherlands ( n = 223). In the aspect of research institutions, the University of Amsterdam (Netherlands) ranked first in the Web of Science ( n = 113), while the institution in China with the most publications was the Southern Medical University ( n = 71). According to the analysis of co-occurring author network, there were three major globe scientific groups in which Can Ince, Daniel De Backer and Jean-Louis Vincent contributed most to this research field. The top three authors who published most Chinese papers were Niu Chunyu ( n = 20), Zhao Zigang ( n = 18) and Duan Meili ( n = 13). By generating the co-occurring keyword mapping, the research hot spots mainly focused on "blood flow", "nitric oxide", "hemorrhagic shock" and "perfusion". However, these burst keywords, including "cardiogenic shock", "acute kidney injury", "fluid resuscitation", "sublingual microcirculation", "mortality", "oxidative stress", and "critically ill patient", represented the frontiers in microcirculation research of shock and sepsis field. Finally, the results of co-citation reference analysis showed that "sublingual microcirculation" and "mottling score" were most active, indicating that the research of microcirculation monitoring technology could be considered as a hot spot and also the frontier in this field, which was consistent with the results of co-occurring keywords network. Conclusions:Knowledge visualization analysis can visually exhibit the hot spot and trend of microcirculation research in shock and sepsis. The power was mainly focused on a few developed countries in Europe, and the trend was more inclined to the related microcirculation monitoring technology.

Out-of-hospital cardiac arrest (OHCA) is a global medical challenge. Early case recognition and initiating the chain of survival is associated with good prognosis of these patients. On the basis of former research, American Heart Association (AHA) published a policy statement related to telecommunicator cardiopulmonary resuscitation (T-CPR) in March 2020, and introduced its specific procedures, standards and precautions. To assist Chinese doctors in better understanding of the T-CPR, and give a reference for the emergency curing of OHCA, the guideline was translated and interpreted in this paper.

Objective:To explored the progress of intensive care unit (ICU) delirium between 2010 and 2020 based on knowledge visualization analysis.Methods:The literatures related to ICU delirium included in Web of Sciences (WOS) and China National Knowledge Infrastructure (CNKI) databases from 2010 to 2020 were collected. A bibliometric analysis was performed. The growth trend was showed by Excel 2019 software. The information about country, institution and author were extracted by VOSviewer 1.6.15 for generating cooperative network, to find the main research power and each cooperative relation. At the same time, Citespace 5.0.R1 was used to analyze those high frequency keywords and bursting keywords and build the map of co-citation reference, in order to explore the evolution of research in the field of ICU delirium and the hotspots about this field in recent 10 years.Results:A total of 1 102 Chinese journal articles and 2 422 English "Articles" or "Reviews" from 2010 to 2020 were collected preliminarily, and the number of published literatures increased steadily. In the respect of quality, the impact factors of most articles were concentrated between 2 and 3, and the literatures with impact factor over 5 accounted for 27.9% (337/1 209). According to the knowledge visualization analysis, the United States published most of the related articles (total 1 152) in this field, while the England and Canada ranked second and third respectively, totaling 220 and 204. In terms of the distribution of research institutions, the Vanderbilt University School of Medicine was not only far ahead in the number of publication ( n = 149), but more importantly, top three high-impact authors located in this institution. The amount of domestic publications was lower than developed countries, however, the burst index, which reflected the sudden increase, ranked first (7.09), suggesting that the interest and investment of Chinese researchers was increasing recently. The most productive institution in China was Capital Medical University School of Nursing with totaling 23 articles. Wu Ying, who published most Chinese papers ( n = 14), belongs to this institution. However, it was a pity that there was no large scientific community be constructed in China, and the cooperation between institutions was deficient. By generating the co-occuring keyword mapping, the research hotpots mainly focused on the prevention, treatment and prevention of delirium in mechanically ventilated patients, the effect of dexmedetomidine and exploring the risk factor of ICU delirium. Finally, the results of co-citation reference analysis showed that Cluster 4 (risk assessment) was still in the process of development, in hence it was the frontier in this domain. Conclusions:There was a big gap between China and leading countries in the field of ICU delirium research. The main research power was located in the United States, and the trending of future studies mainly focus on delirium-related risk assessment.