Acute kidney injury (AKI) is a common clinical syndrome of critical illness in the world, with high incidence in critically ill patients and having strong association with short-term and long-term poor prognosis in patients. It carries an increased risk of mortality, chronic kidney disease (CKD), end stage renal disease (ESRD) and cardiovascular adverse events, causing a huge burden of disease around the world. Yet AKI can be preventable and treatable. With the continuous exploration into the clinical research of AKI, renal recovery becomes a new target for AKI prevention and treatment. Here, we focused on influence factors of kidney recovery after AKI, integrating the new advances in AKI early risk prediction, early identification of AKI based on biomarkers, AKI electronic alert system, AKI care Bundle and standardized acute renal replacement therapy, to clarify how to prevent and treat AKI to accelerate renal recovery.

Objective　Trihostatin A (TSA) is a histone deacetylase inhibitor of oxime salts, which has certain anti-tumor activity. This article mainly investigates the molecular mechanism of TSA inhibiting cell proliferation through p-AKT/p-mTOR pathway in gastric cancer cells.　Methods　Gastric cancer cell line-SGC-7901 were treated with TSA of different concentrations, and the inhibition rate of TSA on the cells was detected by MTT assay. The cells were divided into control group (without any treatment), TSA-treated group (200ng/ml TSA), p-AKT covering group (200 ng/mL TSA+8 μg/mL SC79) and autophagy inhibition group (5 mmol/mL 3-methyladenine+200 ng/mL TSA). The protein expression distribution of Lc3 in control and TSA group were detected by cell immunofluorescence staining. The relative expression levels of p-AKT, p-mTOR and autophagy related proteins Lc3 and P62 in control group, TSA group and p-AKT covering group were detected by Western blot. The proliferation of cells in control group, TSA group, p-AKT covering group and autophagy inhibition group were measured by EdU and cell count assay.　Results　After 24h of treatment, Lc3 in TSA group formed a large number of granular aggregates in the cytoplasm, and the fluorescence distribution changed from the initial diffuse to dense. The TSA group showed a significant reduction in green fluorescence compared with the control group in the EdU experiment. The expression levels of p-AKT in the control group, TSA group and the autophagy inhibition group were 1.78±0.19, 0.92±0.03 and 1.71±0.19, respectively, and Lc3 were 0.21±0.01, 0.79±0.06 and 0.55±0.10, respectively. Compared with the control group, the relative expression level of p-AKT in the TSA group all decreased, while the expression level of Lc3 increased (P <0.05). p-mTOR in the three groups was 0.80±0.16, 0.45±0.04 and 0.98±0.16, respectively. Compared with the control group, the relative expression level of p-mTOR in the TSA group all decreased (P <0.05). P62 in the three groups was 1.17±0.15, 0.48±0.08 and 0.77±0.10, respectively. Compared with the control group, the relative expression level of P62 in the TSA group all decreased (P<0.05). Compared with the TSA group, p-AKT, p-mTOR and P62 expression in the p-AKT covering group increased (P<0.05), while Lc3 expression decreased (P<0.05). Compared with the control group, the inhibition effect of cell growth curve was the most obvious in the TSA group, while the cell growth curve of p-AKT covering group and autophagy inhibition group showed a partial recovery compared with the TSA group.　Conclusion　TSA can promote autophagy by inhibiting p-AKt/p-mTOR pathway, thus inhibiting the proliferation of gastric cancer cells.

Objective　The activation of P2X7 receptor in ventrolateral periaqueductal gray (vlPAG) is involved in the formation and maintenance of bone cancer pain (BCP). This study will establish a rat model of BCP and observe the effect of the activation of P2X7 receptor in vlPAG on D-serine level through brain microdialysis combined with ELISA.　Methods　Forty-two female SD rats were divided into four groups by random number table: normal control group (n=12), sham group (n=12), BCP group (n=12) and P2X7 receptor antagonist group (n= 6). The model of metastatic BCP in the tibias of the rats was established in the BCP group, and 20μL of RPMI-1640 medium cell suspension containing SHZ-88 breast cancer cells was injected (1×107 cancer cells/0.5 mL). The sham group was injected with treated cancer cells of the same volume (SHZ-88 breast cancer cells were kept in boiling water at 90 ℃ for 20 min), and the rest of the operation was the same as the BCP group. The normal control group received no treatment. The P2X7 receptor antagonist group was treated the same as the BCP group, except that the P2X7 receptor-specific antagonist A-438079 was added to the perfusion solution. The thermal pain threshold and mechanical pain threshold were detected at the same time in the normal control group, the sham group and the BCP group. The positive expression of P2X7 receptor in vlPAG of rats was detected by immunohistochemistry in each group in 21 days. The changes of D-serine in vlPAG dialysate were detected by ELISA in each group.　Results　The mechanical pain threshold and thermal pain threshold of the rats in BCP group on Day 5, 7, 10, 14, 18 and 21 were lower than those of the normal control group and sham group (P<0.01). The positive expression of P2X7 was scattered in vlPAG in normal control group and sham group. The number of P2X7 receptor positive cells in the BCP group was significantly higher than that in the control group and sham group (P<0.01). The content of D-serine in vlPAG of the rats in BCP group [(220.28±63.38)ng/mL] was significantly higher than that in the control group [(148.09±46.89)ng/mL] and the sham group [(147.32±51.44)ng/mL] (P<0.05). The content of D-serine in vlPAG [(134.20±41.77)ng/mL] in P2X7 receptor antagonist group was significantly lower than that in BCP group (P<0.05).　Conclusion　The activation of the P2X7 receptor in ventrolateral periaqueductal gray promotes D-serine release and participates in the mechanisms of BCP in rats .

Objective　Acinetobacter baumannii (A. baumannii) is a commonly infective bacterium in the hospital. This study aims to analyze its molecular epidemiological characteristics, detect the carrying rate of efflux pump and regulatory protein genes, and investigate the effects of tigecycline on the efflux pump and expression of regulatory protein genes.　Methods　A total of 183 A. baumannii strains were collected from inpatients of the affiliated hospital of Jiangsu University from May 2017 to March 2019. They were divided into an antimicrobial-resistant group (one or more antimicrobial-resistant strains, 139 strains) and a sensitive group (the drugs in the drug sensitivity test were all non-resistant strains, 44 strains). Repeated sequence PCR was used for homology analysis of the strains, and pulse-field gel electrophoresis (PFGE) was used as the gold standard for homology analysis to verify and compare some strains. PCR was used to detect the occurrence of drug resistance-related genes. Based on homology analysis, efflux pump carrying rate detection and antibiotics sensitivity test results, 6 clinical strains carrying all efflux pump genes but different resistance phenotypes were selected as experimental strains, including sensitive strains (SAB), the multidrug resistance strain (MDRAB) and the extensively drug-resistant strain (XDRAB). All strains were induced in vitro with the minimum inhibitory concentration (MIC) of tigecycline. The induced strains were categorized as induction group, and the same strains cultured in LB agar without tigecycline was used as a control group. MIC was used to analyze the tigecycline susceptibility, and RT-qPCR was used to detect the gene expression of efflux pumps, such as TetB, AbaQ and regulatory proteins (AdeS and BaeS), in drug-resistant strains.　Results　Homology analysis showed that there were 45 clonal groups in the detected clinical isolates, with no obvious outbreak of epidemic clonal groups. Efflux pumps and regulatory proteins were widely distributed in the clinical isolates, and the expression of AdeB, TetB, AbeS, AdeS in MDRAB and XDRAB is significantly higher than that insensitive group SAB. Continuous in vitro induction with tigecycline could increase the antimicrobial resistance of some clinical strains and even significantly increase the expression levels of efflux pumps and regulatory proteins.　Conclusion　A. baumannii is widely distributed in the clinic, and efflux pumps and regulatory proteins might play an important role in drug resistance process. The unreasonable use of tigecycline could enhance the tolerance of A. baumannii by up-regulating the expression of some bacterial efflux pumps.

Objective　To investigate the role of fatty acid binding protein 4 (FABP4) in the apoptosis of mouse podocytes induced by hyperhomocysteinemia (HHcy).　Methods　Nine wild male C57BL/6J mice (Cbs+/+) and nine C57BL/6J male mice with cystathionine beta synthase gene knockout heterozygote (Cbs+/-) were used as the control group and HHcy model group, respectively. All mice were fed with 2% high methionine diet for 8 weeks to replicate the HHcy model. The ultrastructure of glomerular podocytes was observed by transmission electron microscopy. Glomerular podocytes were cultured in vitro and divided into blank control group (Control group) podocytes treated with Hcy concentration of 0 μmol•L-1 for 48 hours. The podocytes of homocysteine group (Hcy group) were treated with Hcy concentration of 80 μmol•L-1 for 48 hours. Podocytes were infected with GFP-labeled adenovirus (Ad-GFP group) and FABP4 overexpression adenovirus (Ad-FABP4 group), respectively. Podocytes were treated with Hcy and FABP4 adenovirus, named as Hcy+Ad-FABP4 group. The expression of FABP4 was detected by qRT-PCR and Western blot. The changes of apoptosis-related proteins Bax, Bcl-2 and Caspase-12 were analyzed by Western blot. The apoptosis rate of cells was measured by flow cytometry.　Results　Compared with the control group, the podocyte injury was aggravated and accompanied by the increasing number of apoptotic cells in the kidney tissues of model group mice. At the same time, the expression of FABP4 mRNA (3.20±0.42) and protein (4.98±1.12) in model group were higher than those in control group (2.09±0.13, 3.04±0.11)(P<0.05). The expression of FABP4 mRNA (5.34±0.28) and the expression of FABP4 protein (11.94±0.22) in Hcy group were higher than those in control group (4.00±0.17, 5.10±0.20)(P<0.05). After infection with FABP4 adenovirus, the mRNA expression levels (3.05±0.22) and protein expression (4.07±0.20) of FABP4 in Ad-GFP group were not significantly different from those in control group (3.07±0.15, 3.93±0.15) (P>0.05); the mRNA expression levels (4.59±0.28) and protein expression (10.07±0.82) of FABP4 in Ad-FABP4 group were higher than those in Ad-GFP group (P<0.05). Bax/Bcl-2 value (3.15±0.65) and Caspase-12 protein expression (4.30±0.89) in Hcy group were higher than those in control group (2.19±0.10, 3.19±0.47) (P<0.05). The Bax/Bcl-2 values (5.42±0.55) and Caspase-12 protein expression (7.87±1.27) in the Hcy+Ad-FABP4 group were significantly higher than those in the Hcy+Ad-GFP group (3.19±0.47, 4.34±0.64) (P<0.05).　FABP4 plays an important role in the apoptosis of mouse podocytes induced by HHcy. Flow cytometry analysis showed that the total apoptotic rate of Hcy group was (10.85±1.25) higher than that of control group (3.77±0.12) (P<0.05). Hcy + Ad-FABP4 group (15.72±1.60) was higher than that of Hcy+Ad-GFP group (11.22±0.43) (P< 0.05).　Conclusion　FABP4 promotes the apoptosis of podocytes in mice treated with HHcy.

Objective　At present, the main studies of ginsenoside Rg1 are almost on the field of solid tumors and acute leukemias, and few on chronic leukemias. We aims to figure out the role of ATR-Chk1 pathway on cell aging in ginsenoside Rg1-treated leukemia K562 cells.　Methods　K562 cells were treated with ginsenoside Rg1 at different concentrations and divided into a control group (with 50 μL PBS culture solution) and 5 μmol/L ginsenoside group, 10 μmol/L ginsenoside group, 20 μmol/L ginsenoside group, 40 μmol/L ginsenoside group, 80 μmol/L ginsenoside group. CCK-8 assay，colony formation assay and flow cytometry for cell cycle detection were used to determine the effect of ginsenoside Rg1 on the aging of K562 cells. SA-β-Gal staining and Wright’s staining were used to observe the morphological changes of K562 cells’ aging. Real-time quantitative PCR and Western blot were used to detect the changes of ATR and Chk1 expression.　Results　The colony formation rate of K562 cells in the 20 μmol/L ginsenoside group was significantly lower than that in the other groups (P<0.05). CCK-8 test results showed that K562 cell proliferation of ginsenoside Rg1 induced groups was higher than that of the control group at 24, 48, and 72 hours (P<0.05). K562 cell proliferation inhibition rate was the highest in 20 μmol/L ginsenoside group for 48 hours treatment (P<0.05). The rate of SA-β-Gal positive cells [(95.833 ± 1.528) %] in 20 μmol/L ginsenoside-treated K562 cells for 48 h was significantly higher than that of the control group [(3.083 ± 0.764) %]. Cells blocked in G0/G1 phase and entered S and G2/M phases were significantly higher and lower than those in the control group, respectively (P<0.05).The ATR and Chk1 mRNA expression levels [(0.0117 ± 0.0038) %, (0.0120 ± 0.0021) %] were significantly higher than that of the control group ([0.0027 ± 0.0006) %, (0.0058 ± 0.0019) %) (P<0.05). ATR and Chk1 relative protein expression levels [(19.370 ± 0.994) %, (43.520 ± 1.236) %] were significantly increased compared with that of the control group [(17.080 ± 1.274) %, (39.100 ± 0.969) %) (P<0.05).　Conclusion　Ginsenoside Rg1 can induce the aging of K562 cells by regulating the ATR-Chk1 pathway, providing a new target for clinical leukemia treatment.

Objective　To observe the protective effect of bisoprolol against hypoxia/reoxygenation injury of cardiac microvascular endothelial cells and explore the mechanism.　Methods　Left ventricular of cardiac microvascular endothelial cells (CMECs) were isolated from 8-week-old male C57BL/6N mice. CMECs were randomized into four groups: control group, vehicle group, hypoxia/reoxygenation group (H/R group), hypoxia/reoxygenation + bisoprolol group. The level of cell proliferation, apoptosis, superoxide anion, Cleaved caspase-3 and Nox2 expression were measured in each group.　Results　Compared with control group, H/R group had lower cell proliferation, higher apoptotic level, more superoxide anion level and the expression of Cleaved caspase-3 and Nox2 (P < 0.05). Furthermore, bisoprolol reversed hypoxia/reoxygenation-induced the decreased cell proliferation, the increased apoptosis, superoxide anion level, Cleaved caspase-3 and Nox2 expression (P < 0.05).　Conclusion　Bisoprolol can protect CMECs against hypoxia/reoxygenation injury by reducing the expression of Nox 2 that decreases oxidative stress.

Objective　The relationship between calcified nanoparticles (CNPs) and the formation of urinary stones is drawing increasing attention and the specific mechanisms involved. This study aims to investigate the mechanisms of the formation of kidney stone caused by CNPs.　Methods　A total of 48 rats were randomly and equally divided into a CNPs group (each rat was injected with 2 mL CNPs through the tail vein to establish a rat kidney stone model of CNPs), and a control group (injected the same amount of sterile isotonic saline instead of CNPs). We compared the expression levels of autophagy-related proteins, such as Beclin-1 and LC-3, the formation of autophagosomes and calcium salt crystals in renal tissues at time points of 3h, 6h, 12h, 24h, 1w, 2w, 4w and 8w in two groups.　Results　The relative expression levels and positive cells of Beclin-1 and LC-3 in CNPs group at 3h,6h,12h,24h, 1w, 2w, 4w, 8w were significantly higher than those in the control group (P< 0.05), and reached the highest value at 24 (P< 0.05). The number of autophagosomes at 24h, 1w, 2w, 4w, and 8w in the CNPs group ((2.83±0.32), (3.00±0.26), (3.70±0.44), (3.90±0.98), (4.70±0.51)/HP, respectively) were significantly higher than those in the control group (0.73±0.15)/HP (P <0.05). The scores of calcium salt crystals in the CNPs group at 2w, 4w, and 8w significantly increased compared to the control group (P <0.05). The calcium salt crystal formation score ((0.92 ± 0.98) points) was positively correlated with the expression intensities of Beclin-1 and LC-3 ((6.78 ± 4.25), (2.61 ± 2.57), respectively) (r = 0.843, 0.628, P <0.05), which was positively correlated with the number of autophagosomes (2.53 ± 1.41) (r = 0.923, P <0.001).　Conclusion　CNPs may damage renal tubular epithelial cells, and induce immediate autophagic activity, also increase expression of autophagy-related proteins and autophagosome formation, which will promote the formation and aggregation of calcium salt crystals in renal tubules to some extent.

Objective　The active protein of traditional Chinese medicine has anti-tumor effect, and salvia miltiorrhiza is an important anti-tumor traditional Chinese medicine. Here, the effect of Salvia miltiorrhiza lectin protein (SMLP) on the apoptosis of gastric cancer cells was studied.　Methods　SMLP expressed and purified from prokaryotic cells was used to treat the gastric cancer cells SGC-7901. The experiment was divided into the control group (untreated) and the SMLP treatment group (final concentration of 10 μmol / L of SMLP was treated for 24 h). Real-time RT-PCR and Western blot were used to detect the changes of apoptosis gene expression. Flow cytometry and Hoechst staining were applied to detect the apoptotic status. Caspase-3 and Caspase-9 activity assay kits were used to detect the apoptotic level.　Results　The result of RT-PCR showed that the mRNA level of Bax in the SMLP treatment group was significantly higher than in the control group (1.00±0.12 vs 0.67±0.10）(P<0.05). After treatment with SMLP to gastric cancer cells, the activity and expression level of cleaved Caspase-3 and Caspase-9 were increased significantly compared with the control group (P<0.05). The cell nucleus in the control group was bigger and rounder, with smooth surface and uniform staining, whilst in the SMLP-treated group, the cell nucleus became deeper with pyknosis, representing typical morphological characteristics of apoptosis. The early apoptosis level in the control group was 6.55%, and the SMLP treatment group reached 10.18%, showing an increase in the level of apoptosis.　Conclusion　SMLP expressed and purified in vitro can promote the apoptosis of gastric cancer cells, which is of great significance for further revealing the function of plant lectin and investigating the anti-tumor effect on the protein of traditional Chinese medicine.

Objective　By now, there is no unified definition of aspiration pneumonia. However, patients with community-acquired pneumonia (CAP) often have aspiration risk factors. The aims of our study is to explore the clinical characteristics and outcomes of CAP patients with aspiration risk factors.　Methods　Cases data of all patients hospitalized with CAP in 5 teaching hospitals in Beijing, Shandong Province and Yunnan Province from January 1, 2013 to December 31, 2015 were collected. Data from patients with (AR-CAP) and without (non AR-CAP) aspiration risk factors were compared, including demographic features, clinical and radiologic findings and outcomes. A Cox proportional hazard model was used to determine the impact of aspiration risk factors on the 30-day mortality in CAP patients. Receiver operating characteristic curves (ROCs) was performed to verify the accuracy of CURB-65 score and PSI risk classification as 30-day mortality predictors in AR-CAP patients.　Results　Totally, 3561 CAP cases were entered into the final analysis. AR-CAP cases accounted for 5.1% (180/3561), who showed older age [78.0 yrs (M1,M3: 70.0 yrs, 85.0 yrs) vs 63.0 yrs (M1,M3: 52.0 yrs, 77.0 yrs), P < 0.001), more underlying diseases (91.1% vs 71.3%, P < 0.001), more frequently classified as CURB-65 score ≥ 3 (13.3% vs 1.5%, P < 0.001) and PSI risk classification ≥ Ⅳ (53.7% vs 17.0%，P< 0.001), and higher 30-day mortality (10.0% vs 1.8%, P < 0.001). Adjusted for age, sex, comorbidities and CURB-65/PSI score, aspiration risk factors were associated with increased 30-day mortality of CAP patients (HR 2.844, 95% CI 1.331~6.078, P = 0.007). The area under the ROC curve for predicting 30-day mortality in AR-CAP patients by PSI risk class was 0.716, which was higher than CURB-65 score (AUC=0.518, P = 0.019). The difference was statistically significant.　Conclusion　AR-CAP is a distinctive pneumonia phenotype with unique clinical characteristics, which shows more illness severity and worsen outcomes.