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Cancer immunotherapy has become a promising strategy. However, the effectiveness of immunotherapy is restricted in "cold tumors" characterized with insufficient T cells intratumoral infiltration and failed T cells priming. Herein, an on-demand integrated nano-engager (JOT-Lip) was developed to convert cold tumors to hot via "increased DNA damage and dual immune checkpoint inhibition" strategy. JOT-Lip was engineered by co-loading oxaliplatin (Oxa) and JQ1 into liposomes with T-cell immunoglobulin mucin-3 antibodies (Tim-3 mAb) coupled on the liposomal surface by metalloproteinase-2 (MMP-2)-sensitive linker. JQ1 inhibited DNA repair to increase DNA damage and immunogenic cell death (ICD) of Oxa, thus promoting T cells intratumoral infiltration. In addition, JQ1 inhibited PD-1/PD-L1 pathway, achieving dual immune checkpoint inhibition combining with Tim-3 mAb, thus effectively promoting T cells priming. It is demonstrated that JOT-Lip not only increased DNA damage and promoted the release of damage-associated molecular patterns (DAMPs), but also enhanced T cells intratumoral infiltration and promoted T cell priming, which successfully converted cold tumors to hot and showed significant anti-tumor and anti-metastasis effects. Collectively, our study provides a rational design of an effective combination regimen and an ideal co-delivery system to convert cold tumors to hot, which holds great potential in clinical cancer chemoimmunotherapy.
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@#Au nanoplates (Au NPLs), a kind of novel two-dimensional metal materials with nanometer scale thickness, have attracted much attention due to their excellent properties; and have been widely used in the fields of tumor diagnosis and treatment in recent years.This article introduces the characteristics and preparation methods of Au nanoplates and summarizes their application in tumor diagnosis and treatment in recent years, in order to provide reference and ideas for the research and application of Au nanoplates in tumor.
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Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death. Although great progress has been made in chemotherapy, radiotherapy and targeted therapy, the emergence of acquired drug resistance hinders the efficacy of clinical treatment. Studies have shown that tumor is a class of diseases with damaged cell cycle regulation mechanism, in which checkpoint kinase (Chk) plays a core role, Chk1 and Chk2 are very important protein kinases in the checkpoint. In recent years, it has been found that the regulation of Chk1 and Chk2 plays an important role in the clinical treatment and drug resistance mechanism of lung cancer. This article reviews the mechanism of cell cycle checkpoint kinase and drug resistance of lung cancer, and expounds the effective therapeutic targets and methods of lung cancer. .
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Objective:To observe the effects of Etifoxine on proliferation and migration of RSC96 (Schwann cells of rat) and its potential molecular mechanisms.Methods:From March, 2020 to October, 2020, cultured RSC96 were treated with 20 μmol/L Etifoxine and saline respectively for 48 h. Cell proliferation was tested by EdU assay using Cell-Light EdU DNA Cell Proliferation Kit and the capability of migration was determined by wound healing assay and a transwell system. To investigate the effects of Etifoxine on CELSR2 protein expression, after treated with different concentrations of Etifoxine at 0-20 μmol/L for 48 hours, cells were subject to Western blot analysis to verify the expression of CELSR2 protein. To explore whether CELSR2 would be a potential target of Etifoxine, siRNA targeting CELSR2 and control siRNA groups were transfected into 20 μmol/L Etifoxine-treated RSC96 using Lipo3000. Again, the cell proliferation and migration of were investigated after 48 hours with the same procedures. The two-tailed Mann-Whitney U test was employed in statistical assessment.Results:EdU results showed a significant higher percentage of Edu-positive (proliferating) cells in the 20 μmol/L Etifoxine-treated group than the control group[(36.30±3.09)% vs (19.40±2.50)%, P<0.05]. Transwell migration assay demonstrated that the number of 20 μmol/L Etifoxine-treated RSC96 which migrated through the transwell membrane was higher than saline group, with significant statistical difference [(132.30±6.77) vs(65.33±7.37), P<0.05]. The percentage of reduction of wound area measured at 24 hours and 36 hours after the scratch also showed the similar results [(30.67±2.16)% vs (23.00±2.61)%; (86.00±2.19)% vs (49.67±2.81)%, respectively, P<0.05]. Besides, with increase of the concentration of etifoxine, the expression of CELSR2 showed an trend of increase in RSC96 ( P<0.05), but no significant statistical difference was found between 10 μmol/L and 20 μmol/L groups ( P>0.05). Interestingly, the rate of cell proliferation, the number of migrating cells and the percentage of wound area reduction of RSC96 in which were treated by Etifoxine and transfected with CELSR2 siRNA were significantly decreased compared with the control siRNA treatment ( P<0.05). Conclusion:Etifoxine could promote proliferation and migration of RSC96. Upregulation of CELSR2 protein expression in RSC96 is associated with the Etifoxine-induced enhancement of cell proliferation and migration.
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Clinicopathological data of 15 patients with pyloric early cancer and precancerous lesions, who received endoscopic submucosal dissection (ESD) in Zhejiang Cancer Hospital from March 2011 to January 2020 were retrospectively analyzed. Postoperative pathology showed 7 cases of low-grade intraepithelial neoplasia, 3 cases of high-grade intraepithelial neoplasia, and 5 cases of early gastric cancer. R0 complete resection was achieved in all patients. The mean operation time was 55.2 min (35-78 min). One patient had delayed postoperative bleeding, and no other complications such as bleeding, perforation or abdominal pain occurred in other 14 patients. No recurrence, metastasis or pyloric stenosis was found during the follow-up of 31.3 months (1-106 months). ESD is safe and effective for early cancer and precancerous lesions in the pylorus.
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Objective:To investigate the predictive value of myoglobin (Mb) for the prognosis of sepsis related chronic critical illness (CCI).Methods:Retrospective study was conducted on septic patients with the length of ICU stay equal or greater than 14 days, and sepsis-related organ failure assessment (SOFA) score equal or greater than 2 on the 14th day in ICU in the First Department of Critical Care Medicine at the First Affiliated Hospital of Sun Yat-sen University from January 2017 to March 2020. Patients′ clinical and laboratory data were collected on the 1st and 14th day in ICU. The survival on day 28 in ICU was recorded. According to the myoglobin levels on day 1 and day 14, all subjects were divided into myoglobin elevation group and decline group. Kaplan-Meier survival curve was used to compare the cumulative survival rate at day 28. Cox regression analysis was used to analyze the independent risk factors of mortality. Receiver operating characteristic (ROC) curve was used to analyze the prognostic value of myoglobin.Results:A total of 131 patients with sepsis related CCI were recruited, including 58 patients in the elevation group and 73 in the decline group. The Mb level in elevation group on day 1 was significantly lower than that in decline group [172.40(59.99, 430.53) μg/L vs. 413.60(184.40, 1 328.50) μg/L, Z=3.749, P=0.000], and the Mb level on day 14 was the opposite change in two groups [483.65(230.38, 1 471.75)μg/L in elevation group vs. 132.20(76.86, 274.35)μg/L in decline group, Z=5.595, P=0.000]. Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate of the elevation group was significantly lower than that of decline group (χ2=7.051, P=0.008). Cox ratio regression analysis suggested that elevated myoglobin was an independent risk factor for 28-day mortality in septic patients with CCI ( OR=2.534, 95% CI 1.212-5.295, P=0.013). ROC curve analysis suggested that the sensitivity of myoglobin elevation in predicting mortality related to CCI within 28 days was 64.5%, and the specificity was 32.0% with area under the curve(AUC) 0.661(95% CI 0.550-0.773, P=0.007) and Jorden Index was 0.325. Conclusion:Elevated myoglobin, an independent risk factor for mortality within 28 days in ICU, can predict the prognosis of sepsis related chronic critical illness.
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In all the carpal fractures, scaphoid fracture is the most common in clinic (from 60% to 70% in proportion) and likely leads to nonunion. If nonunion is not treated in time, it probably causes instability of the scaphoid lunate joint, further leading to scapholunate advanced collapse. Its comprehensive manifestations include degenerative arthropathy of radial styloid process, radial scaphoid joint, capitulolunate joint and even total wrist joint, eventually leading to wrist joint dysfunction. Therefore, more and more attention has been paid to treatments of scaphoid fracture nonunion. Bone grafting is the most common practical treatment, but new surgical procedures have emerged in recent years. This article thus reviews the research advances in bone grafting for scaphoid fracture nonunion, commenting on the advantages and disadvantages of various techniques.
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@#Bromodomain-containing protein 4 (BRD4), a new target for tumor therapy, is the most important member of the bromodomain and extra-terminal family. The overexpression of BRD4 is associated with genesis and development of various cancers.Used either alone or in combination with other treatments such as chemotherapy, photothermal therapy and immunotherapy, the BRD4 inhibitors or degraders exhibited excellent antitumor effects, providing a new direction in tumor treatment. In this review, the structure and function of BRD4, the inhibition strategies of BRD4, the application in tumor combination therapy and drug resistance are introduced, which provides reference for targeting BRD4 in tumor therapy.
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Informatization plays an important role in the management of clinical diagnosis and treatment. However, due to the specialty of the discipline, the informatization construction of critical care medicine(CCM)is faced with such problems as the inefficient application of data, the low compliance of diagnosis and treatment operation, and the lack of intelligent quality control tools. The authors discussed the new mode of CCM information management based on data driven. By upgrading clinical information system, establishing single disease control system, introducing comprehensive intelligent analysis platform and building open remote platform, the bottleneck of CCM informatization was broken. The information collection and interaction in ICU was realized, the automatic monitoring and early warning of diagnosis and treatment process was realized, the operation of medical staff according to the guidelines was effectively improved, and the ability of diagnosis and treatment and management efficiency was improved.Furthermore, the homogenization of regional critical medical information could be promoted.
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Lung cancer is the most common malignant tumor in the world with the highest incidence of deaths. In recent years, the treatment of lung cancer has made a significant breakthrough. However, as the tumor progresses, lung cancer cells inevitably acquire resistance and the efficacy of the treatment are greatly reduced. P21 protein plays a dual role in tumors, which not only regulates the cell cycle, induces apoptosis, inhibits cell proliferation, but also protects cells against apoptosis and promotes tumor cell resistance. This article reviews the research on P21 and lung cancer resistance, to provide new ideas for individualized treatment of lung cancer and overcoming lung cancer resistance.
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@#As a new member of two-dimensional materials, black phosphorus has shown good application prospects in the fields of photoacoustic imaging, photothermal photodynamic therapy, and drug loading due to its excellent characteristics such as good biodegradability, biocompatibility, thickness-dependent tunable direct band-gap, and high surface-to-mass ratio. Because black phosphorus has the characteristics of easy oxidation and degradation, it is coated with relatively stable liposomes or polymeric materials to construct a black phosphorus-based drug delivery system, which shows great potential in tumor treatment and diagnosis and has become a new focus in drug delivery research. In this paper, we introduce the role of black phosphorus in tumor diagnosis and treatment in detail, and summarize the design of black phosphorus-based drug delivery system in recent years as well as its research progress in tumor diagnosis and treatment, in order to provide reference for the research and application of black phosphorus.
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Objective To examine the effects of ethyl pyruvate (EP) on mitochondrial dynamics and cell apoptosis in lipopolysaccharide (LPS)-induced human kidney-2 (HK-2) cells. Methods HK-2 cells were divided into three groups: HK-2 cells were challenged with LPS (800 μg/L) for 24 hours as LPS group, or LPS mixed with EP (0.25 mmol/L) for 24 hours as EP group. Cells were incubated with normal saline for 24 hours as control group. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and intracellular adenosine triphosphate (ATP) were detected by enzyme linked immunosorbent assay (ELISA). JC-1 staining and Annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) assays were used to evaluate mitochondrial membrane potential and cell apoptosis, respectively. Western Blot was used to evaluate the protein expressions of mitochondrial dynamics, including death-associated protein kinase 2 (DAPK-2), mitofusin (Mfn-1 and Mfn-2), and apoptotic associated biomarkers, including caspase-3, caspase-9, Bcl-2, Bcl-xL, cytochrome C (Cyt C), and DNA repair enzyme poly ADP-ribose polymerase (PARP). Results Compared with the NC group, MDA, IL-6, TNF-α of LPS group were significantly increased, the expression of SOD, mitochondrial membrane potential and ATP level were significantly decreased, the expression of mitochondrial fission protein DAPK-2 was significantly increased, and mitochondrial fusion proteins Mfn-1 and Mfn-2 were significantly decreased, cell apoptosis and apoptotic protein caspase-3, caspase-9 and Cyt C were increased, and anti-apoptotic protein Bcl-2, Bcl-xL, PARP were significantly decreased. Compared with the LPS group, the oxidative activities and inflammatory factors above were inhibited in EP group [MDA (μmol/L):12.35±2.21 vs. 45.95±1.76, SOD (kU/L): 54.68±1.42 vs. 40.73±1.60, IL-6 (ng/L): 67.87±2.61 vs. 338.92±20.91, TNF-α (ng/L): 19.23±1.80 vs. 180.69±6.51], mitochondrial membrane potential and ATP level were significantly increased [mitochondrial membrane potential: (99.43±0.25)％ vs. (69.40±0.75)％, ATP (×106 RLU): 0.19±0.01 vs. 0.12±0.05], the expression of mitochondrial fission protein was significantly decreased (DAPK-2/β-actin:0.03±0.01 vs. 0.61±0.02), mitochondrial fusion proteins were significantly increased (Mfn-1/β-actin: 0.43±0.04 vs. 0.17±0.01, Mfn-2/β-actin: 0.201±0.004 vs. 0.001±0.001), percentage of cell apoptosis was significantly decreased [(5.25±0.17)％ vs. (34.42±0.64)％], the expressions of apoptotic proteins were significantly decreased (caspase-3/β-actin: 0.25±0.15 vs. 1.76±0.01, caspase-9/β-actin: 0.09±0.02 vs. 1.52±0.12, Cyt C/β-actin: 0.001± 0.001 vs. 0.350±0.030), and the expressions of anti-apoptotic proteins and PARP were significantly increased (Bcl-2/β-actin: 0.500±0.010 vs. 0.009±0.004, Bcl-xL/β-actin: 0.550±0.010 vs. 0.009±0.001, PARP/β-actin:0.94±0.01 vs. 0.16±0.13), with statistically significant differences (all P < 0.05). Conclusions There are enhanced mitochondrial fission and diminished mitochondrial fusion in LPS-induced HK-2 cells. EP can protect mitochondria functions by regulate mitochondrial dynamics, and reducethe apoptosis of LPS-induced HK-2 cells.
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Objective@#To examine the effects of ethyl pyruvate (EP) on mitochondrial dynamics and cell apoptosis in lipopolysaccharide (LPS)-induced human kidney-2 (HK-2) cells.@*Methods@#HK-2 cells were divided into three groups: HK-2 cells were challenged with LPS (800 μg/L) for 24 hours as LPS group, or LPS mixed with EP (0.25 mmol/L) for 24 hours as EP group. Cells were incubated with normal saline for 24 hours as control group. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and intracellular adenosine triphosphate (ATP) were detected by enzyme linked immunosorbent assay (ELISA). JC-1 staining and Annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) assays were used to evaluate mitochondrial membrane potential and cell apoptosis, respectively. Western Blot was used to evaluate the protein expressions of mitochondrial dynamics, including death-associated protein kinase 2 (DAPK-2), mitofusin (Mfn-1 and Mfn-2), and apoptotic associated biomarkers, including caspase-3, caspase-9, Bcl-2, Bcl-xL, cytochrome C (Cyt C), and DNA repair enzyme poly ADP-ribose polymerase (PARP).@*Results@#Compared with the NC group, MDA, IL-6, TNF-α of LPS group were significantly increased, the expression of SOD, mitochondrial membrane potential and ATP level were significantly decreased, the expression of mitochondrial fission protein DAPK-2 was significantly increased, and mitochondrial fusion proteins Mfn-1 and Mfn-2 were significantly decreased, cell apoptosis and apoptotic protein caspase-3, caspase-9 and Cyt C were increased, and anti-apoptotic protein Bcl-2, Bcl-xL, PARP were significantly decreased. Compared with the LPS group, the oxidative activities and inflammatory factors above were inhibited in EP group [MDA (μmol/L): 12.35±2.21 vs. 45.95±1.76, SOD (kU/L): 54.68±1.42 vs. 40.73±1.60, IL-6 (ng/L): 67.87±2.61 vs. 338.92±20.91, TNF-α (ng/L): 19.23±1.80 vs. 180.69±6.51], mitochondrial membrane potential and ATP level were significantly increased [mitochondrial membrane potential: (99.43±0.25)% vs. (69.40±0.75)%, ATP (×106 RLU): 0.19±0.01 vs. 0.12±0.05], the expression of mitochondrial fission protein was significantly decreased (DAPK-2/β-actin: 0.03±0.01 vs. 0.61±0.02), mitochondrial fusion proteins were significantly increased (Mfn-1/β-actin: 0.43±0.04 vs. 0.17±0.01, Mfn-2/β-actin: 0.201±0.004 vs. 0.001±0.001), percentage of cell apoptosis was significantly decreased [(5.25±0.17)% vs. (34.42±0.64)%], the expressions of apoptotic proteins were significantly decreased (caspase-3/β-actin: 0.25±0.15 vs. 1.76±0.01, caspase-9/β-actin: 0.09±0.02 vs. 1.52±0.12, Cyt C/β-actin: 0.001±0.001 vs. 0.350±0.030), and the expressions of anti-apoptotic proteins and PARP were significantly increased (Bcl-2/β-actin: 0.500±0.010 vs. 0.009±0.004, Bcl-xL/β-actin: 0.550±0.010 vs. 0.009±0.001, PARP/β-actin: 0.94±0.01 vs. 0.16±0.13), with statistically significant differences (all P < 0.05).@*Conclusions@#There are enhanced mitochondrial fission and diminished mitochondrial fusion in LPS-induced HK-2 cells. EP can protect mitochondria functions by regulate mitochondrial dynamics, and reducethe apoptosis of LPS-induced HK-2 cells.
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Objective To investigate the efficacy of dopamine producing cells (DPCs) derived from human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in treatment in model rats with Parkinson’s disease (PD). Methods The cultured hUC-MSCs were induced into DPCs in vitro. The dopamine (DA) and glial cell line-derived neurotrophic factor (GDNF) expression levels were detected by ELISA to identify the DPCs. The PD rat model was established by injecting 6-OHDA into the right substantia nigra (SN). A total of 60 successfulled PD model rats were randomized into hUC-MSCs-DPCs group (5 × 105 hUC-MSCs-DPCs were transplanted into right striatum, n=20), hUC-MSCs group (5 × 105 hUC-MSCs were transplanted, n=20) and control group (same volume PBS, n=20). All the transplanted cells were labeled with CM-Dil. The apomorphine induced rotation behavior was assessed at 4, 8 and 12 weeks after cell transplantation. The rats were executed after 12 weeks. The immunofluorescence staining was used to detect the tyrosine hydroxylase (TH) expression level, and FLUORO-JADE? C staining was used to test the apoptotic neurons in brain of rats. Results The hUC-MSCs-DPCs were induced successfully in vitro, which showed a high expression level of DA and GDNF. Furthermore, at 4, 8 and 12 weeks after cell transplantation, the rotation behavior was improved, and expression levels of GDNF were significantly higher in hUC-MSCs-DPCs group than those of hUC-MSCs group and control group (P<0.05). In addition, we found that most of the transplanted TH+hUC-MSCs-DPCs at the right striatum and a few cells around both the left and the right substantia nigra at 12 weeks after transplantation. The apoptotic neurons were decreased after cell transplantation in hUC-MSCs-DPCs group than that of control group (P<0.05). Conclusion The hUC-MSCs-DPCs can improve the rotational behavior induced by apomorphine in PD model rats, which may be involved in improving levels of DA and GDNF in damaged striatum and protecting neurons.
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OBJECTIVE:To observe the efficacy and safety of tripterygium glycosides combined with mizolastine in the treatment of dermatitis and eczema. METHODS:138 patients with dermatitis and eczema were randomly divided into control group (69 cases) and observation group (69 cases). Control group received Mizolastine sustained release tablet 10 mg,orally,once a day. Observation group additionally received Tripterygium glycosides tablet 20-30 mg,orally taking after a meal,3 times a day. All patients treated for 3 weeks,patients’life way remained unchanged during treatment. Clinical efficacy,total score of symptoms, IL-2,IL-6,CRP levels and the incidence of adverse reactions in 2 groups were observed. RESULTS:The total effective rate in observation group was significantly higher than control group,with significant difference (P<0.01). After treatment,the total score of symptoms,IL-2,IL-6,CRP levels in 2 groups were significantly lower than before,and observation group was lower than control group,with significant differences(P<0.05 or P<0.01). The incidence of adverse reactions in observation group was significantly lower than control group,with significant difference (P<0.05). CONCLUSIONS:Tripterygium glycosides combined with mizolastine shows better efficacy than mizolastine alone in the treatment of dermatitis and eczema,with better safety.
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Objective To explore the effect of microRNA‐21(miR‐21) on the migration and invasion ability in human laryn‐geal squamous carcinoma cell Hep2 .Methods The MTT method was used to detect the viability of Hep2 cells at 48 h after miR‐21 inhibitor and miR‐21 NC transferring into Hep2 cells by LipofectamineTM 2000 .The cell migration ability was detected by using the scratch test .The cell invasion ability was detected by using the Transwell method .The activation of phosphatase and tensin homo‐logue deleted on chromosome 10 (PTEN)/phosphatidylinositol 3 kinase (PI3K) /protein kinase B(Akt) signal pathway and the expression of matrix metalloproteinase 2 (MMP2) ,MMP9 ,reversion inducing cysteine rich protein with kazal motif (RECK) was detected by using the Western blotting .Results Compared with miR‐21 NC ,miR‐21 inhibitor could significantly reduce the Hep2 cellviability[(0.688±0.043)vs.(0.375±0.012)],inhibitedthemigrationability[(6.57±0.02)μm vs.(20.49±2.18)μm]and invasion ability[(100 .7 ± 10 .2) vs .(46 .8 ± 4 .3)] ,and the differences were statistically significant (P<0 .01) ,meanwhile miR‐21 inhibitor could down‐regulate the expression of PI3K ,MMP2 and MMP9(P<0 .01) ,and reduced the phosphorylation level of Akt (P<0 .01) ,up‐regulated the expression of PTEN and RECK (P<0 .01) .Conclusion miR‐21 inhibitor can significantly suppress the migration and invasion ability of Hep2 ,which may be related with the PTEN/PI3K/Akt signal pathway .
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OBJECTIVE:To systematically review the efficacy of isotretinoin in the treatment of acne vulgaris,and to provide evidence-based reference for clinical treatment. METHODS:Retrieved from PubMed, Cochrane Library, Wanfang, VIP and CJFD,randomized controlled trials (RCT) about isotretinoin (test group) versus viaminati,macrolides,tetracyclines antibiotics and other drugs (control group) in the treatment of acne vulgaris were collected. Meta-analysis was performed by using Rev Man 5.2 software after data extract and quality evaluation by Cochrane 5.1.0. RESULTS:Totally 28 RCTs were enrolled,involving 3 534 patients. Results of Meta-analysis showed,the total effective rate of isotretinoin was significantly higher than viaminati [RR=1.56, 95%CI(1.27,1.91),P<0.001],macrolides[RR=1.44,95%CI(1.31,1.58),P<0.001] and tetracyclines antibiotics [RR=3.05,95%CI(2.29,4.07),P<0.001];improvement of skin lesions scores was significantly better than control group [MD=0.33,95%CI(0.04, 0.62),P<0.05],the differences were statistically significant. Dry lips,cheilitis,dry skin and nasal mucosa and pruritus were the main adverse reactions,and no serious adverse reactions were showed. CONCLUSIONS:Isotretinoin has better efficacy and safety than viaminati,macrolides and tetracyclines antibiotics.
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ObjectiveTo assess the value of passive leg raising (PLR) test in predicting fluid responsiveness in patients with sepsis-induced cardiac dysfunction.Methods A prospective observational cohort study was conducted. Thirty-eight patients under mechanical ventilation suffering from sepsis-induced cardiac dysfunction admitted to Department of Surgical Intensive Care Unit of First Affiliated Hospital of Sun Yat-Sen University from September 2013 to July 2014 were enrolled. The patients were studied in four phases: before PLR (semi-recumbent position with the trunk in 45°), PLR (the lower limbs were raised to a 45° angle while the trunk was in a supine position), before volume expansion (VE, return to the semi-recumbent position), and VE with infusing of 250 mL 5% albumin within 30 minutes. Hemodynamic parameters were recorded in every phase. The patients were classified into two groups according to their response to VE: responders (at least a 15% increase in stroke volume,ΔSVVE≥15%), and non-responders. The correlations among all changes in hemodynamic parameters were analyzed by linear correlation analysis, and the receiver operating characteristic curve (ROC) was plotted to assess the value of hemodynamic parameters before and after PLR in predicting fluid responsiveness.Results Of 38 patients, 25 patients were responders, and 13 non-responders. There was no significant difference in the baseline and hemodynamic parameters at semi-recumbent position between the two groups. The changes in SV and cardiac output (CO) after PLR (ΔSVPLR andΔCOPLR) were significantly higher in responders than those of non-responders [ΔSVPLR: (14.7±5.7)%vs. (6.4±5.3)%,t = 4.304,P = 0.000;ΔCOPLR: (11.2±7.5)% vs. (3.4±2.3)%,t = 3.454,P = 0.001], but there was no significant difference in the changes in systolic blood pressure, mean arterial pressure, pulse pressure, and heart rate after PLR (ΔSBPPLR,ΔMAPPLR,ΔPPPLR andΔHRPLR) between two groups.ΔSVVE in responders was significantly higher than that of the non-responders [(20.8±5.5) % vs. (5.0±3.7) %,t = 8.347,P = 0.000]. It was shown by correlation analysis thatΔSVPLR was positively correlated withΔSVVE (r = 0.593,P = 0.000),ΔCOPLR was positively correlated withΔSVVE (r = 0.494,P = 0.002). The area under ROC curve (AUC) ofΔSVPLR≥8.1% for predicting fluid responsiveness was 0.860±0.062 (P = 0.000), with sensitivity of 92.0% and specificity of 70.0%; the AUC ofΔCOPLR≥5.6% for predicting fluid responsiveness was 0.840±0.070 (P = 0.000), with sensitivity of 84.0%and specificity of 76.9%; the AUC ofΔMAPPLR≥6.9% for predicting fluid responsiveness was 0.662±0.089, with sensitivity of 68.0% and specificity of 76.9%; the AUC ofΔSBPPLR≥6.4% for predicting fluid responsiveness was 0.628±0.098, with sensitivity of 76.0% and specificity of 61.5%; the AUC ofΔPPPLR≥6.2% for predicting fluid responsiveness was 0.502±0.094, with sensitivity of 56.0% and specificity of 53.8%; the AUC ofΔHRPLR≥-1.7%for predicting fluid responsiveness was 0.457±0.100, with sensitivity of 56.0% and specificity of 46.2%.Conclusion In patients with sepsis-induced cardiac dysfunction, changes in SV and CO induced by PLR are accurate indices for predicting fluid responsiveness, but the changes in HR, MAP, SBP and PP cannot predict the fluid responsiveness.
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<p><b>BACKGROUND</b>Many studies have shown that continuous renal replacement therapy (CRRT) could clean lactate and treat the hyper-lactatemia. On the contrary, some other studies found that filter lactate clearance only accounted for a very small part of total lactate clearance and the hemofilter's contribution to the overall lactate clearance was negligible. The objective of this study was to evaluate the effects of various doses of continuous veno-venous hemofiltration (CVVH) on plasma lactate elimination in critically ill patients.</p><p><b>METHODS</b>Patients were divided into three groups according to their incipient plasma lactate concentration. Group A: lactate ≤ 2 mmol/L, group B: lactate 2-5 mmol/L, group C: lactate ≥ 5 mmol/L. Three different doses (20 ml × kg(-1)× h(-1), 35 ml × kg(-1)× h(-1) and 45 ml × kg(-1)× h(-1)) of CVVH were applied to critically ill patients who experiencing CVVH. The concentrations of plasma lactate in pre-(A), post-dialyzer (V) sites and ultrafiltrate were measured after each dosage of CVVH was carried out for 30 minutes. Rate of lactate clearance by the filter (RLC) and filter lactate clearance (FLC) and Lactate-Sieving Coefficient (LSC) were calculated under different circumstances, including different doses of CVVH and different incipient lactate levels.</p><p><b>RESULTS</b>Fifteen patients were enrolled and 104 blood samples were drawn and lactate concentrations were measured in this study. RLC was found increased ((9.36 ± 9.73) mmol/h, (13.92 ± 12.56) mmol/h and (16.52 ± 12.71) mmol/h, P < 0.05 respectively) with the dose of CVVH increased. RLC was also increased ((3.46 ± 1.46), (10.38 ± 5.50) and (24.53 ± 14.69) mmol/h, P < 0.05 respectively) with the incipient lactate increased. FLC was increased ((1.95 ± 0.63), (2.95 ± 0.74) and (3.45 ± 0.54) L/h, P < 0.05 respectively) with the dose of CVVH increased. There was no significant difference of LSC in different doses of CVVH and different incipient lactate levels.</p><p><b>CONCLUSIONS</b>Plasma lactate can be eliminated by CVVH and different doses of CVVH affect the rate of lactate clearance in critically ill patients.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Critical Illness , Hemofiltration , Lactic Acid , BloodABSTRACT
BACKGROUND:Rheumatoid arthritis is an autoimmune disease, and traditional treatment methods are difficult to effectively solve the patient's lack of immune tolerance mechanisms. With the development of stem cel s in regenerative medicine, stem cel therapy has become a hot spot in the treatment of autoimmune diseases. Currently, studies on cel transplantation for the treatment of rheumatoid arthritis are rarely reported. OBJECTIVE:To study the influence of umbilical cord mesenchymal stem cel therapy on the changes of Th1/Th2 and Treg in rheumatoid arthritis patients, thereby seeking new therapies for rheumatoid arthritis. METHODS:We selected 180 cases of rheumatoid arthritis, including 27 patients as control group undergoing non-steroidal anti-inflammatory drugs and anti-rheumatic drugs and 153 patients as cel treatment group undergoing intravenous infusion of 40 mL umbilical cord mesenchymal stem cel s at a density of 4×107. Dosing regimen was same in the two groups. The 76 of 153 patients accepted second cel therapy at 3-4 months after the first cel therapy. After fol ow-up of 3 and 6 months, clinical effectiveness evaluation (DAS28, HAQ, ACR20), rheumatoid factor, anti-CCP antibodies, T cel subsets, Th cytokine were detected;for patients with second cel therapy, T cel subsets and Treg were detected at 8 months after treatment. RESULTS AND CONCLUSION:(1) At 3 months after treatment, the DAS28, HAQ and ACR20 scores were significantly lower in the cel treatment group than the control group (P0.05). (5) B cel levels were significantly decreased at 6 months after treatment (P>0.05);the rheumatoid factor value was significantly decreased at 3-6 months after treatment (P<0.05). (6) There was no change in anti-CCP antibody and interleukin-17 levels at 3-6 months after treatment. These findings indicate that after treatment with umbilical cord mesenchymal stem cel s, the Th1/Th2 tends to balance and Treg level is elevated in rheumatoid arthritis patients, which are directly related to clinical trials and symptomatic relief. Therefore, standard rheumatism medication combined with umbilical cord mesenchymal stem cel transplantation can improve immune network effects, adjust the immune tolerance and prevent il ness progress in rheumatoid arthritis patients.