ObjectiveTo systemically review the effects of timing of initiation of renal replacement therapy (RRT) on prognosis in septic patients with acute kidney injury (AKI).Methods A systematic search for randomized controlled trials (RCTs) and other clinical studies focused on comparing varied timing of initiation of RRT in septic AKI patients was performed in English or Chinese from PubMed, Web of Science, EMBASE, CNKI, Wanfang data, VIP from January 2000 to July 2014. Data screened were extracted with Cochrane systemically review method, and enrolled literature was collected for Meta analysis with RevMan 5.2 software. Total mortality, 28-day mortality, the total length of hospital stay and intensive care unit (ICU) stay in septic AKI patients with early or late initiation of RRT was analyzed. Funnel plots were drawn to detect publication bias.Results Five retrospective comparative studies with a total of 885 patients were enrolled. Random effect model in Meta analysis showed that there was no significant difference in total mortality between early RRT group and late RRT group [65.7% (226/344) vs. 68.7% (239/348), odds ratio (OR) = 0.71, 95% confidence interval (95%CI) = 0.38-1.31,P = 0.27]. The funnel plot demonstrated publication bias. Fixed effect model showed that there was significant difference in 28-day mortality between early RRT group and late RRT group [43.4% (66/152) vs. 55.3% (94/170),OR = 0.59, 95%CI = 0.36-0.94,P= 0.03]. The funnel plot demonstrated publication bias too. The data of total length of hospital stay and ICU stay could not be Meta-analyzed because of different data distribution, but no differences in total length of hospital stay and ICU stay between early and late RRT groups for septic AKI patients were found.ConclusionEarly RRT could reduce the 28-day mortality in patients with septic AKI compared with late RRT, but it did not lower the total mortality.

Objective To analyze the correlation between fluid equilibrium and oxygen index in patients at early stage (within 2 weeks) of severe acutepancreatitis (SAP),and to discuss the effects of fluid equilibrium after resuscitation on the prognosis.Methods A clinical study was conducted.Ninety-seven patients with SAP admitted into Shengjing Hospital of China Medical University directly or transferred into intensive care unit (ICU) in 24 hours after admission between March 201 1 to October 2013 were studied.Finally,65 patients were enrolled in statistical analysis,and those with termination of treatment prematurely were excluded.The patients received treatment protocol formulated by the same physician in ICU.Patients were divided into improved group and death group according to the outcome.The differences in fluid equilibrium on 1,2,3,7,14 days after admission of ICU between the two groups were compared.The correlation between fluid equilibrium and oxygen index was analyzed with curve fitting.Results Among 65 patients enrolled,53 of them were improved after intensive care and were transferred into ordinary wards.However,12 patients died in ICU.Patients in the improved group showed delayed positive fluid equilibrium,and some patients even showed negative fluid equilibrium.Patients in death group needed more fluid to achieve fluid equilibrium.There was a significant difference in the need of fluid to reach an equilibrium between improved group and death group [1 day:1 814.5 (905.2,2 152.8) vs.3 891.0 (2 524.2,5 714.5),Z=-3.303,P=0.001; 2 days:2 469.0 (1 456.0,3 696.0) vs.6 498.0(4 617.8,8 763.5),Z=-4.431,P＜0.001 ; 3 days:3 234.0 (1 098.0,4 295.5) vs.9 533.5 (6 748.8,10 689.0),Z=-4.684,P＜0.001 ; 7 days:3 234.0 (1 033.0,5 162.0) vs.13 986.5 (8 045.8,14 518.0),Z=-4.718,P＜0.001 ; 14 days:3 234.0 (978.5,4 924.0) vs.13 436.5 (8 045.8,14 518.0),Z=-4.769,P＜0.001].There was no correlation between fluid equilibrium and oxygen index in improved patients within 3 days of ICU admission (R 2=0.000,P=0.827),and it fit the logistic curve in a relatively low level after 3 days of ICU admission (R 2=0.036,P＜0.001).Conclusions Early fluid resuscitation could help maintain hemodynamics stability in SAP patients.Those SAP patients who showed a negative equilibrium in early stage showed a better prognosis,and the fluid equilibrium and oxygen index in improved patients fit the logistic curve after 3 days of ICU admission.

Objective To investigate the protective effect of autophagy inducer rapamycin on acute kidney injury (AKI) induced by sepsis. Methods Twenty-four Sprague-Dawley (SD) male rats were randomly divided into sham group, caecal ligation and puncture (CLP) model group, and rapamycin treatment group (Rap treatment group), with 8 rats in each group. The septic AKI model was reproduced by CLP in rats, and rats in sham group were given appendix isolation without ligation and puncture. The rats in Rap treatment group were given 1.6 mg rapamycin by intraperitoneal injection immediately after model reproduction, and the rats in CLP model group were injected with an equal amount of normal saline. The rats in all groups were sacrificed after collecting peripheral blood specimen at 24 hours after model reproduction, and the levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were determined. The pathomorphology change in renal tissue was observed under light microscope after periodic acid Schiff (PAS) staining. Real-time polymerase chain reaction (real-time PCR, RT-PCR) was used to determine the mRNA expressions of renal tubular autophagy related molecules Atg-5 and Beclin-1. Western Blot was used to detect the expressions of renal tubular autophagy associated protein microtubule labeled protein 1 light chain 3-Ⅱ (LC3-Ⅱ) and Beclin-1 as well as apoptosis protein cytochrome C (Cyt C), Bax and Bcl-2. TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to determine the renal tubular epithelial cell apoptosis. Results Rapamycin could alleviate pathomorphology changes in rats with septic AKI, and decrease the levels of BUN and SCr. Compared with sham group, the expressions of Atg-5, Beclin-1 and LC3-Ⅱ in CLP model group were significantly increased [Atg-5 mRNA (2-ΔΔCt): 2.34±0.04 vs. 1.00±0.03, Beclin-1 mRNA (2-ΔΔCt): 1.40±0.02 vs. 1.00±0.03, LC3-Ⅱ protein (gray value): 0.82±0.03 vs. 0.45±0.04, Beclin-1 protein (gray value): 0.59±0.06 vs. 0.29±0.03, all P < 0.01]. Rapamycin could further up-regulate the expressions of Atg-5, Beclin-1, and LC3 Ⅱ [Atg-5 mRNA (2-ΔΔCt): 3.28±0.19 vs. 2.34±0.04, Beclin-1 mRNA (2-ΔΔCt): 2.38±0.08 vs. 1.40±0.02, LC3-Ⅱ protein (gray value): 1.11±0.07 vs. 0.82±0.03, Beclin-1 protein (gray value): 0.85±0.05 vs. 0.59±0.06, all P < 0.01]. Compared with sham group, the apoptotic cells in CLP model group were increased significantly [(34.49±10.45)% vs. (2.78±1.40)%, P < 0.01], Cyt C and Bax protein expressions were significantly up-regulated (gray value: 0.87±0.02 vs. 0.46±0.03, 1.20±0.06 vs. 0.46±0.01, both P < 0.01), and Bcl-2 expression was significantly down-regulated (gray value: 0.64±0.02 vs. 1.33±0.09, P < 0.01). Rapamycin could effectively inhibit cell apoptosis [(15.44±5.50)% vs. (34.49±10.45)%, P < 0.01] and the protein expressions of Cyt C and Bax (gray value: 0.72±0.03 vs. 0.87±0.02, 0.84±0.03 vs. 1.20±0.06, both P < 0.01), and up-regulate the protein expression of Bcl-2 (gray value: 0.77±0.04 vs. 0.64±0.02, P < 0.01). Conclusion The protective effect of rapamycin on renal tissue of rat with AKI induced by sepsis was depended on cell apoptosis inhibition through inducing and promoting cell autophagy.

Objective:To explore the characteristics of functional connectivity (FC) and regional spontaneous brain activity in patients in a minimally-conscious state (MCS).Methods:Resting-state functional near-infrared spectroscopy (rs-fNIRS) was used. Ten minimally-conscious patients were studied along with 12 healthy counterparts as healthy controls (HC). Five minutes of rs-fNIRS data were recorded from each subject and FC and the fractional amplitude of low-frequency fluctuations (fALFFs) of 53 channels were computed using the NIRS-KIT toolbox. The results were compared between the two groups.Results:Compared with the HC group, a significant decrease was observed in the average FC strength of seventeen channel pairs after false discovery rate (FDR) correction. Most were in the right and left frontal pole, as well as the dorsolateral prefrontal lobe. Compared with the HC group, the average fALFF values of Broca′s area (channel 2), the premotor cortex and the supplementary motor cortex (channels 4, 10, and 40), the dorsolateral prefrontal lobe (channels 6, 11, 25, 39), the eye motor area of the frontal lobe (channel 12) and the frontal pole (channels 23, 27, 36) were significantly greater in the MCS group. The fluctuations of the frontal pole (channel 19) were significantly less (after FDR correction).Conclusion:In an MCS spontaneous neural activity is over-active in the prefrontal lobe and some speech- and motor-related brain regions, and coordination of the internal prefrontal functional network is disordered.

Objective:To investigate the role of Ribociclib in sepsis induced-acute kidney injury (AKI) and its possible mechanisms.Methods:① Twenty adult male C57BL/6 mice were divided into sham operation group (Sham group; only open the abdomen without ligating or perforating the cecum, administered with sodium lactate buffer 12 hours before the sham operation), Ribociclib control group (administered with 150 mg/kg Ribociclib), cecal ligation and puncture (CLP) group (sepsis model induced by CLP; lactate buffer was given by intragastric administration 12 hours before CLP), and Ribociclib pretreatment group (administered with 150 mg/kg Ribociclib 12 hours before CLP) according to random number table, with 5 mice in each group. Kidneys were harvested 12 hours after the operation. Pathological changes in kidney were observed by hematoxylin-eosin (HE) staining. Tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) levels in mice kidney homogenate were measured by enzyme linked immunosorbent assay (ELISA). Western Blot was used to detect the expression of cell cycle-related protein phosphorylate retinoblastoma protein (p-Rb), apoptosis-related protein Bcl-2 and Bax. ② Mouse renal tubular epithelial (TCMK-1) cell line was used for in vitro experiment. The cells were divided into control group, Ribociclib group (treated with 5 μmol/L Ribociclib for 24 hours), lipopolysaccharide (LPS) group (treated with 200 mg/L LPS for 6 hours), Ribociclib+LPS group (replaced with the medium containing 5 μmol/L Ribociclib and 200 mg/L LPS for 6 hours after exposing with 5 μmol/L Ribociclib for 18 hours). Inflammatory cytokines in cell culture medium were detected by ELISA. The expression of p-Rb, Bcl-2 and Bax, autophagy-related proteins microtubule associated protein 1 light chain LC3b (LC3bⅡ, LC3bⅠ) and p62, phosphate protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR) were measured by Western Blot. Results:① Animal experiments showed that, compared with the Sham group, the kidney tissue of mice were significantly damaged, the levels of TNF-α and IL-6 were increased, the expressions of p-Rb and Bcl-2/Bax ratio were decreased in kidney tissue in CLP group; but there was no significant difference in indexes between Ribociclib control group and Sham group. Compared with the CLP group, kidney injury in mice pretreated with Ribociclib was significantly ameliorated, the pathological score was significantly decreased (1.48±0.16 vs. 2.68±0.16, P < 0.01), the levels of TNF-α and IL-6 in kidney homogenate were significantly decreased [TNF-α(ng/g): 340.55±34.96 vs. 745.08±58.86, IL-6 (mg/g): 17.33±1.01 vs. 114.20±20.49, both P < 0.01], the expression of p-Rb was furtherly decreased (p-Rb/β-tubulin: 0.14±0.01 vs. 0.73±0.06, P < 0.01), Bcl-2/Bax ratio was increased (0.89±0.06 vs. 0.62±0.10, P < 0.01). ② In vitro experiments showed that, compared with the control group, the releases of TNF-α and IL-6 were increased, the expression of p-Rb was decreased, the ratios of Bcl-2/Bax and LC3bⅡ/Ⅰ were decreased, the expressions of p62, p-AKT and p-mTOR were increased in LPS group; the expression of p-Rb was decreased after Ribociclib treatment in TCMK-1 cells. Compared with the LPS group, TNF-α and IL-6 were decreased [TNF-α (ng/L): 2.73±0.23 vs. 4.96±0.10, IL-6 (ng/L): 36.05±5.83 vs. 53.78±24.08, both P < 0.01], the expression of p-Rb was furtherly decreased (p-Rb/β-tubulin: 0.25±0.05 vs. 0.65±0.05, P < 0.01), the ratios of Bcl-2/Bax and LC3bⅡ/Ⅰ were increased (Bcl-2/Bax: 1.01±0.07 vs. 0.73±0.05, LC3bⅡ/Ⅰ: 2.08±0.31 vs. 1.04±0.01, both P < 0.05), the expressions of p62, p-AKT and p-mTOR were decreased (p62/β-tubulin: 0.59±0.01 vs. 1.09±0.08, p-AKT/β-tubulin: 0.61±0.03 vs. 1.20±0.06, p-mTOR/β-tubulin: 0.50±0.05 vs. 1.15±0.08, all P < 0.01) in the Ribociclib+LPS group. Conclusion:Ribociclib pretreatment ameliorated sepsis-induced AKI and AKT/mTOR pathway may be involved in the protective role of Ribociclib on kidney.

Objective:To observe the clinical efficacy of micro-needle therapy combined with Biotrisse BTS Lumin OX and Biotrisse BTS Brightline in the treatment of melasma.Methods:From September 2019 to June 2021, 80 patients with facial chloasma, aged 28-48 (37.3±4.9) years, were selected from Nanjing Jiangning Guze Clinic. The micro-needle therapy was combined with lumin OX and brightline for 6 times, and the observation time was 120 days. The mMASI score and VISIA photos before and after treatment were used to improve the results.Results:Eighty patients with refractory melasma on the face were treated with micro-needle therapy for 7 times (1 time per week for the first 5 times, and twice a week for the 9th and 10th weeks). The photos before and after treatment were compared and the mMASI of the patients' facial chloasma was compared. The scores were analyzed statistically, and the melasma were improved to varying degrees. Before treatment, the mMASI score was 5.4±3.22; 90 days later, the mMASI was 3.22±2.16, and the score decreased significantly ( t=5.9, P<0.05); after 120 days, mMASI score was 1.6±0.68, and the score decreased significantly ( t=7.55, P<0.05). Pigmentation occurred in one patient after treatment, and hypopigmentation after repair treatment; none of the patients had adverse reactions such as hypopigmentation. All the 80 patients had different degrees of improvement in pores and skin texture. Conclusions:The combination of micro-needling with lumin OX and brightline in the treatment of chloasma has a definite effect without obvious side effects. It provides a new method for the treatment of chloasma.

OBJECTIVE: To compare the diagnostic efficacy among three RT-PCR test kits for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid detection. METHODS: The throat swab samples from 40 hospitalized patients clinically diagnosed as coronavirus disease 2019 (COVID-19) and 16 hospitalized non-COVID-19 patients were recruited. The SARS-CoV-2 nucleic acid was detected in throat swab samples with RT-PCR test kits from Sansure Biotech ("Sansure" for short), Jiangsu Bioperfectus Technologies ("Bioperfectus" for short) and BGI Genomics ("BGI" for short). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Kappa value were analyzed. The viral nucleic acid was extracted from the throat swab samples by one-step cleavage and magnetic bead methods, and the efficacy of two extraction methods was also compared. The results of magnetic bead method for nucleic acid extraction by two different extractors (Sansure Natch CS S12C Fully Automated Nucleic Acid Extraction System vs. Tianlong NP968-C Nucleic Acid Extractor) were also compared. RESULTS: The sensitivity, specificity, PPV, NPV and kappa value were 95.00%, 87.50%, 95.00%, 87.50%and 0.825 for Sansure kit; 90.00%, 87.50%, 94.74%, 77.78%and 0.747 for the Bioperfectus kit, and 82.50%, 81.25%, 91.67%, 65.00%and 0.593 for the BGI kit, respectively. The positive, negative and total coincident rates and kappa value of viral nucleic acid detection results using the samples extracted by one-step cleavage and magnetic bead methods were 95.24%, 100.00%, 96.43%and 0.909, respectively, but the one-step cleavage method took only 25 min, while the magnetic bead method required 180 min. The positive, negative and total coincident rates and kappa value of viral nucleic acid detection results using the samples extracted by the two different nucleic acid extractors were 85.00%, 100.00%, 89.29% and 0.764, respectively. CONCLUSIONS The detection efficacy for SARS-CoV-2 nucleic acid by the Sansure kit is relatively higher and the one-step cleavage method has advantages of convenient operation and less time consuming.
Betacoronavirus ; genetics ; isolation & purification ; Coronavirus Infections ; diagnosis ; virology ; Humans ; Pandemics ; Pneumonia, Viral ; diagnosis ; virology ; RNA, Viral ; genetics ; isolation & purification ; Reagent Kits, Diagnostic ; standards