ObjectiveTo explore the protective mechanism of paeoniflorin on mice with ulcerative colitis （UC） through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） autophagy pathway. MethodUC mouse model was established by allowing mice freely drink 4% DSS， and 56 BALB/c male mice were randomly divided into model group， AMPK inhibitor group （20 mg·kg^-1）， paeoniflorin （50 mg·kg^-1） + inhibitor （20 mg·kg^-1） group， and high dose （50 mg·kg^-1）， medium dose （25 mg·kg^-1）， and low dose （12.5 mg·kg^-1） paeoniflorin groups. After seven days of drug intervention， the protective effect of paeoniflorin on mice with UC was determined by comparing the body weight， disease activity index （DAI） changes， and Hematoxylin-eosin （HE） staining results. Enzyme linked immunosorbent assay （ELISA） was used to detect the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum of mice in each group， and immunofluorescence was utilized to detect microtubule-associated protein 1 light chain 3 （LC3） content in the colon， AMPK， mTOR proteins， and their phosphorylated proteins including p-AMPK and p-mTOR in the colon tissue were detected by Western blot， and the mRNA expression levels of AMPK， mTOR， Beclin1， LC3， and p62 were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the model group showed a decrease in body mass， an increase in DAI score， and severe pathological damage to the colon. The levels of inflammatory factors including TNF-α and IL-6 increased in serum （P<0.01）， while the protein levels of LC3 and p-AMPK/AMPK were down-regulated in colon tissue， and those of p-mTOR/mTOR were up-regulated （P<0.01）. The mRNA expression levels of AMPK and LC3 were down-regulated， while the mRNA expression levels of mTOR and p62 were up-regulated （P<0.01）. Compared with the model group and the paeoniflorin + inhibitor group， the mice treated with paeoniflorin showed an increase in body mass， a decrease in DAI score， a reduction in pathological damage to colon tissue， and a reduction in the levels of inflammatory factors of TNF-α and IL-6 in serum （P<0.05）. The protein levels of LC3 and p-AMPK/AMPK in colon tissue were up-regulated， while the protein levels of p-mTOR/mTOR were down-regulated （P<0.01）. The mRNA expression levels of AMPK， Beclin1， and LC3 were up-regulated， while the mRNA expression of mTOR and p62 were down-regulated （P<0.01）. The colon tissue of the inhibitor group was severely damaged， and the trend of various indicators was completely opposite to that of the high dose paeoniflorin group. ConclusionPaeoniflorin can enhance autophagy and reduce inflammatory damage in mice with UC by activating the AMPK/mTOR signaling pathway and thus play a protective role.

Objective For more focused prevention and management,this investigation examines the risk factors for multidrug resistant organisms(MDRO)infections in intensive care unit(ICU)patients.Methods Case-control studies and cohort studies of risk factors for MDRO infection in ICU patients were searched in the Embase,Website of Science,Cochrane Library,PubMed,CNKI,WanFang,and VIP databases from their start to October 26,2022.The Meta-analysis was carried out with RevMan 5.3.Results A total of 32 papers were included,with 10 985 cases studied,with the quality of the literature rated as moderate to high.The results of Meta-analysis of this study showed that gender[OR=1.21,95% CI=(1.08,1.36),P=0.002],ICU length of stay[WMD=5.36,95% CI=(3.99,6.73),P<0.000 01],total length of stay[WMD=8.96,95% CI=(6.51,11.41),P<0.000 01],hypertension[OR=1.33,95% CI=(1.10,1.60),P=0.003],abnormal renal function[OR=1.69,95% CI=(1.33,2.16),P<0.000 01],hypoproteinemia[OR=1.87,95% CI=(1.51,2.32),P<0.000 01],mechanical ventilation[OR=2.26,95% CI=(1.18,4.33),P=0.01],duration of mechanical ventilation[WMD=8.83,95% CI=(2.52,15.14),P=0.006],arteriovenous placement[OR=1.46,95% CI=(1.23,1.72),P<0.000 1],placement of urinary catheter[OR=1.71,95% CI=(1.25,2.36),P<0.000 01],gastrointestinal tube placement[OR=0.10,95% CI=(0.03,0.18),P=0.008],antimicrobial drug type≥3[OR=4.27,95% CI=(2.06,8.85),P<0.000 01],use of carbapenem antibiotics[OR=4.09,95% CI=(300,5.58),P<0.000 01],the use of the third-generation cephalosporin[OR=1.63,95% CI=(1.15,2.33),P=0.007],the use of quinolone antibacterials[OR=1.86,95% CI=(1.42,2.44),P<0.000 01],the use of aminoglycoside antibiotics[OR=1.99,95% CI=(1.49,2.67),P<0.000 01],use of piperacillin-tazobactam[OR=2.94,95% CI=(1.56,5.54),P=0.000 9],use of glycopeptide antibiotics[OR=3.78,95% CI=(2.48,5.78),P<0.000 01],use of sedatives[OR=3.25,95% CI=(2.06,5.14),P<0.000 01],and use of acid suppressants[OR=1.51,95% CI=(1.06,2.16),P=0.02]are risk factors for MDRO infection in ICU patients.Conclusion MDRO infections in ICU patients are associated with gender,duration of ICU stay,chronic lung disease,total length of stay,hypertension,abnormal renal function,hypoproteinemia,mechanical ventilation,duration of mechanical ventilation,arteriovenous placement,placement of urinary catheters,gastrointestinal placement,type of antimicrobial drugs≥3,use of carbapenem antibiotics,use of third-generation cephalosporin,use of quinolone antibacterials,use of aminoglycoside antibiotics,use of piperacillin-tazobactam,use of glycopeptide antibiotics,use of sedatives,use of acid suppressants,and other factors.Targeted controls of different factors such as underlying diseases,comorbidities,invasive procedures performed,and the use of antimicrobial medications and other therapeutic pharmaceuticals could limit the risk of infection in MDRO in ICU patients.

Objective:To discuss the protective effect of sodium butyrate(NaB)on acute liver injury in the mice induced by lipopolysaccharide(LPS)combined with D-galactosamine(D-Gal),and to clarify its mechanism.Methods:Thirty male Kunming mice were randomly divided into control group,model group,and NaB group,and there were 10 mice in each group.The mice in NaB group were given 200 mg·kg-1·d-1 NaB,while the mice in control group and model group were given an equal volume of sterile water.The mice in model group and NaB group were intraperitoneally injected with 20 μg·kg-1 LPS and 600 mg·kg-1 D-Gal to induce the acute liver injury models.The body weights and liver weights of the mice in various groups were detcted,and the liver index was calculated.HE staining was used to observe the pathomorphology of liver tissue of the mice in various groups;kits were used to detect the activities of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum,and the activities of total superoxide dismutase(T-SOD)and catalase(CAT),and the levels of malondialdehyde(MDA)in liver tissue of the mice in various groups;Western blotting method was used to detect the expression levels of nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins in liver tissue of the mice in various groups.Results:There were no significant differences in body weights of the mice among various groups(P>0.05).Compared with control group,the liver index of the mice in model group was significantly increased(P<0.01).Compared with model group,the liver index of the mice in NaB group was significantly decreased(P<0.01).The HE staining results showed that the liver tissue of the mice in control group exhibited normal structure,with clear boundaries of hepatocytes,consistent size,radially arranged around the central vein,and the nucleus located in the center of the cells;in model group,the arrangement of hepatocytes was disordered,the cells were swollen,there were multiple foci of hepatocellular necrosis,inflammatory cell infiltration,and hemorrhage;compared with model group,the cells in NaB group showed improved hepatocellular structure and reduced inflammatory infiltration.Compared with control group,the activities of ALT and AST in serum of the mice in model group were significantly increased(P<0.01);compared with model group,the activities of ALT and AST in serum of the mice in NaB group were significantly decreased(P<0.05 or P<0.01).Compared with control group,the activities of T-SOD and CAT in liver tissue of the mice in model group were significantly decreased(P<0.01),and the level of MDA was significantly increased(P<0.01);compared with model group,the activities of T-SOD and CAT in liver tissue of the mice in NaB group were significantly increased(P<0.05 or P<0.01),and the level of MDA was significantly decreased(P<0.01).The Western blotting results showed that compared with control group,the expression levels of Nrf2 and HO-1 proteins in liver tissue of the mice in model group were significantly decreased(P<0.05);compared with model group,the expression levels of Nrf2 and HO-1 proteins in liver tissue of the mice in NaB group were significantly increased(P<0.01).Conclusion:NaB has a protective effect on LPS/D-Gal induced acute liver injury in the mice,and its mechanism may be related to the upregulation of the expressions of Nrf2 and HO-1 proteins and the increas of the activity of oxidant enzyme in liver tissue by NaB,thereby reduces the liver oxidative stress level of liver.

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.

ObjectiveTo explore the predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating aplastic anemia （AA） in non-elderly adults， so as to provide a reference for predicting the prognosis of this therapy. MethodA retrospective study was conducted with the clinical data of non-elderly adult AA patients who visited 19 hospitals including Xiyuan Hospital of the China Academy of Chinese Medical Sciences from September 2018 to March 2021 and were treated with Yiqi Yangxue Prescription combined with western medicine. According to the efficacy evaluation results at the 6^th month of treatment， the patients were assigned into effective and ineffective groups. The two groups were compared in terms of the gender， age， disease classification ［non-severe aplastic anemia （NSAA）/severe aplastic anemia （SAA）］， course of disease， family history， complications， history of drug allergy， baseline blood routine examination ［hemoglobin （HGB）， white blood cell （WBC）， neutrophil （ANC）， platelet （PLT）， and reticulocyte （Ret）］， T lymphocyte subsets， degree of proliferation of nucleated cells in bone marrow， and expression of T-bet and GATA-3. ResultA total of 101 non-elderly adult AA patients were enrolled in this study， including 81 in the effective group and 20 in the ineffective group. The effective group had a higher proportion of the patients without a history of drug allergy than the ineffective group （P<0.05）. The body height， body weight， gender， age， disease classification， course of disease， family history， and complications showed no significant differences between two groups. The effective group had higher levels of ANC and PLT before treatment （P<0.05） and higher proportion of patients with ANC≥1.6×10⁹/L and PLT≥25×10⁹/L （P<0.05， P<0.01） than the ineffective group. The baseline levels of WBC， HGB， and Ret showed no significant statistical differences between two groups. The levels of CD3⁺HLA-DR⁺T cells in the effective group before treatment was higher than that in the ineffective group （P<0.05）. The levels of CD3⁺CD19^-T cells， CD4⁺T cells， CD8⁺T cells， Th1 cells， Th2 cells， and CD3⁺CD25⁺T cells showed no significant statistical differences between two groups before treatment. The proportion of patients with active bone marrow nucleated cells proliferation in the effective group before treatment were significantly higher than that in the ineffective group, while the proportion of patients with reduced or extremely reduced proliferation were significantly lower than that in the ineffective group （P<0.05）. The expression levels of T-bet and GATA-3 genes had no significant differences between two groups before treatment. The multivariate binary logistic regression analysis showed that the ANC level before treatment and history of drug allergy were independent influencing factors for efficacy （P<0.05， P<0.01）， while other indicators were not influencing factors for efficacy. The receiver operating characteristic （ROC） curve was applied to analyze the predictive value of the ANC level before treatment in the treatment of AA in non-elderly adults with Yiqi Yangxue prescription combined with western medicine. The area under the curve was 0.679 （P<0.05）， with the critical value of 1.595×10⁹/L， the sensitivity of 0.42， and the specificity of 0.95. ConclusionThe history of drug allergy， pre-treatment ANC， PLT， CD3⁺HLA-DR⁺ T cell levels， and proliferation of nucleated cells in bone marrow before treatment are predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating AA in non-elderly adults. This therapy tends to be more effective for the patients with no history of drug allergy， higher ANC and PLT levels before treatment， especially those with ANC≥1.6×10⁹/L， PLT≥25×10⁹/L， and higher CD3⁺ HLA-DR⁺T cell levels and the more active proliferation of nucleated cells in bone marrow before treatment.

Targeted temperature management (TTM) has been partially applied in patients with restoration of spontaneous circulation (ROSC) after cardiac arrest (CA). In the 2020 American Heart Association (AHA) cardiopulmonary resuscitation (CPR) guidelines, TTM is used as advanced life support after ROSC for the treatment of patients with CPR. TTM has a protective effect on cardiac function after CA, but the specific mechanism of its protective effect on cardiac function remains unclear. In this paper, the basic experimental progress, clinical trial progress and development prospect of TTM on the protective mechanism of cardiac function after CA are reviewed.
United States ; Humans ; Cardiopulmonary Resuscitation/methods* ; Temperature ; Heart Arrest/therapy* ; Hypothermia, Induced/methods* ; Body Temperature

OBJECTIVE: To observe the regulative effect of Tongdu Tiaoshen acupuncture on the depression-like behavior and cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/tyrosine protein kinase B (TrkB) signaling pathway of hippocampus in rats with post-stroke depression (PSD), and to explore its possible mechanism on improving PSD. METHODS: A total of 36 SPF SD rats were randomized into a sham operation group, a model group and a Tongdu Tiaoshen group, 12 rats in each group. The compound method of Zea Longa suture-occlusion and chronic unpredictable mild stress (CUMS) was used to establish the PSD model in rats of the model group and the Tongdu Tiaoshen group. On the 4th day after modeling, acupuncture was applied at "Dazhui" (GV 14), "Shuigou" (GV 26), "Baihui" (GV 20) and "Shenting" (GV 24) in the Tongdu Tiaoshen group, 40 min every time, once a day, 6 times a week for 4 weeks consecutively. On the 2nd day after PSD modeling and after 4-week intervention, Zea Longa neurobehavioral score was evaluated, sucrose water consumption test and open-field test were performed; biochemical method was used to detect the SOD, CAT activity and MDA level in hippocampal CA1 area; ELISA method was used to detect the serum level of BDNF; real-time PCR was used to detect the mRNA expression of BDNF, TrkB and CREB in hippocampal CA1 area; Western blot was used to detect the protein expression of BDNF, TrkB, CREB and p-CREB in hippocampal CA1 area. RESULTS: Compared with the sham operation group, Zea Longa neurobehavioral scores were increased (P<0.05), percentage of sucrose water consumption, horizontal motion and vertical motion scores of open-field test were decreased after modeling and intervention in the model group and after modeling in the Tongdu Tiaoshen group (P<0.05). Compared with the model group, Zea Longa neurobehavioral score was decreased (P<0.05), percentage of sucrose water consumption, horizontal motion and vertical motion scores of open-field test were increased after intervention in the Tongdu Tiaoshen group (P<0.05). Compared with the sham operation group, the SOD and CAT activity in hippocampal CA1 area and serum level of BDNF were decreased (P<0.05), MDA level in hippocampal CA1 area was increased in the model group (P<0.05); compared with the model group, the SOD and CAT activity in hippocampal CA1 area and serum level of BDNF were increased (P<0.05), MDA level was decreased in the Tongdu Tiaoshen group (P<0.05). Compared with the sham operation group, the mRNA expression of BDNF, TrkB and CREB as well as the protein expression of BDNF, TrkB, CREB and p-CREB were decreased in hippocampal CA1 area in the model group (P<0.05); compared with the model group, the mRNA expression of BDNF, TrkB and CREB, the protein expression of BDNF, TrkB and p-CREB as well as the ratio of p-CREB/CREB were increased in the Tongdu Tiaoshen group (P<0.05). CONCLUSION Tongdu Tiaoshen acupuncture can improve the depression-like behavior in PSD rats, the mechanism may be related to the inhibition of oxidative stress in hippocampal tissues and the enhanced activity of CREB/BDNF/TrkB signaling pathway.
Acupuncture Therapy ; Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Depression/therapy* ; Hippocampus/metabolism* ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Stroke/complications* ; Sucrose ; Superoxide Dismutase

[This corrects the article DOI: 10.1016/j.apsb.2021.04.022.].

ObjectiveTo investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells （T-bet） and GATA binding protein 3 （GATA3）. MethodA total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled. With the prospective， double-blind and randomized control methods， the patients were randomized into three groups： kidney deficiency group， Qi and blood deficiency group， and control group. The three groups were respectively treated with Bushen Shengxue prescription granule， Yiqi Yangxue prescription granule， and Placebo （half the dose of Bushen Shengxue formula granules）. In addition， all of them were given oral cyclosporin and androgen. The treatment lasted 6 months， with 3 months as a course. The blood routine indexes， T cell subsets， and fusion genes T-bet and GATA3 before and after treatment were analyzed， and the safety indexes were monitored. ResultDuring the observation， a total of 75 cases dropped out and 18 were rejected. Finally， 161 cases in the kidney deficiency group， 164 in the Qi and blood deficiency group， and 167 in the control group were included. After 6 months of treatment， the total effective rate was 98.8% （159/161） in the kidney deficiency group， which was higher than the 79.9% （131/164） in the Qi and blood deficiency group （χ²=30.135， P<0.01） and the 61.7% （103/167） in the control group （χ²=70.126， P<0.01）. The total effective rate was higher in the Qi and blood deficiency group than in the control group （χ²=13.232， P<0.01）. After treatment， the hemoglobin （HGB） content increased significantly in three groups （P<0.05） as compared with that before treatment， particularly the kidney deficiency group （P<0.01）. After treatment， the white blood cell （WBC） count and platelet （PLT） count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group （P<0.01）. There was no specific difference in neutrophils （ANC） after treatment among the three groups. At the same time point， the level of T helper type 1 （Th1） cells， Th1/Th2 ratio （P<0.05）， level of CD4⁺， and CD4⁺/CD8⁺ ratio （P<0.05） were significantly low in the kidney deficiency group among three groups. There was no significant difference in CD19^-， HLA/DR⁺， and CD25⁺ between the kidney deficiency group and the other two groups， but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group （P<0.05）. ConclusionBushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism， inhibiting the activity of immune system， modulating T cell subsets， suppressing Th1 and CD4⁺， and promoting bone marrow hematopoiesis. Moreover， it is safe with little side effects， which is worthy of further promotion.

Insurmountable blood‒brain barrier (BBB) and complex pathological features are the key factors affecting the treatment of Alzheimer's disease (AD). Poor accumulation of drugs in lesion sites and undesired effectiveness of simply reducing A