High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

[Effects of Earthworm, Straw, and Citric Acid on the Remediation of Zn, Pb, and Cd Contaminated Soil by Solanum photeinocarpum and Pterocypsela indica].

Regulation of exogenous substances and intercropping are effective methods to improve the efficiency of phytoremediation of heavy metal contaminated soil. A pot experiment was used to study the effects of earthworms, straw, and citric acid on the remediation of Zn, Pb, and Cd contaminated soil by monocropping and intercropping of Solanum photeinocarpum and Pterocypsela indica. The results showed that the bioaccumulation factors (BCF) of earthworms for Zn, Pb, and Cd were 0.07-0.13, 0.10-0.26, and 5.64-15.52, respectively. The addition of straw in the soil increased the biomass of earthworms by 22.29%-223.87% but reduced the heavy metal concentrations by 8.15%-62.58%. Straw and citric acid showed passivation and activation effects, respectively, but earthworms had no significant effect on the available concentrations of heavy metals in the soil. Earthworms had no significant effect on the heavy metal concentrations of P. indica but reduced the heavy metal concentrations of S. photeinocarpum. Straw showed an inhibitory effect on the concentrations of heavy metals in P. indica but promoted the concentrations of Cd in S. photeinocarpum. Citric acid had no significant effect on the heavy metal concentrations in S. photeinocarpum but significantly increased the Pb concentrations in P. indica. Intercropping significantly reduced the soil available heavy metal concentrations and increased the heavy metal concentrations in plant roots; however, it had no significant effect on heavy metal concentrations in plant shoots. The total extraction amounts of Zn, Pb, and Cd by plants were mainly manifested as P. indica>intercropping>S. photeinocarpum. The addition of earthworms increased the total extraction amounts of Zn, Pb, and Cd by 12.49%, 35.89%, and 29.01%, respectively, and the addition of straw+earthworms increased the total extraction amounts of Pb by 87.21%. The results indicated that straw significantly promoted the growth of earthworms and reduced their accumulation of heavy metals, and the addition of earthworms alone or in combination with straw can effectively improve the remediation potential of P. indica of Zn, Pb, and Cd contaminated soil.

Vincosamide Has a Function for Inhibiting Malignant Behaviors of Hepatocellular Carcinoma Cells.

Background: Vincosamide (Vinco) was first identified in the methanolic extract of the leaves of Psychotria leiocarpa, and Vinco has important anti-inflammatory effects and activity against cholinesterase, Vinco also has a trait to anti-tumor. However, whether Vinco can inhibit the malignant behaviors of hepatocellular carcinoma (HCC) cells is still unclear. In the present study, we explored the role of Vinco in suppressing the malignant behaviors of HCC cells. Methods: MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide), trypan blue exclusion assay, the Cell Counting Kit (CCK)-8 and flow cytometric analysis were applied to detect the proliferation and apoptosis of HCC cells; electron microscopy was performed to observe the change of cellular mitochondrial morphology; scratch repair and Transwell assays were used to analyze the migration and invasion of HCC cells; expression and localization of proteins were detected by laser confocal microscopy and Western blotting; the growth of the cancer cells in vivo was assessed in a mouse tumorous model. Results: At a dose of 10 - 80 µg/mL, Vinco inhibited the proliferation, migration, invasion and promoted apoptosis of HCC cells in a dose-dependent manner but had low cytotoxicity effect on normal liver cells. Additionally, 80 µg/mL of Vinco could significantly disrupt the morphology of mitochondria, suppress the migration and invasion of HCC cells. The growth of HCC cells in the animal tumorous model was significantly inhibited after treatment with Vinco (10 mg/kg/day) for 3 days. The results of the present study indicated that Vinco (10 - 80 µg/mL) played a role in activating caspase-3, promoting the expression of phosphate and tension homology deleted on chromosome 10 (PTEN), and inhibiting the phosphorylation of AKT (Ser473) and mTOR (Thr2448); Vinco also has a trait for suppressing the expression of CXCR4, Src, MMP9, EpCAM, Ras, Oct4 and cancer stem cell "stemness markers" CD133 and CD44 in HCC cells. Conclusions: Vinco has a role in inhibiting the malignant behaviors of HCC cells; the role molecular mechanism of Vinco may be involved in restraining expression of the growth-, metastasis-related factors, such as Src, Ras, MMP9, EpCAM, CXCR4; activating the activity of caspase-3 and blocking PI3K/AKT signaling pathway. Thus, Vinco should be considered as a new chemotherapy agent for HCC patients.

Changes of NOD-like receptor family pyrin domain-containing protein 3 inflammasomes in peripheral blood of patients with diabetic nephropathy and its clinical significance / 中华内分泌外科杂志

Objective:To analyze the changes of NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasomes in peripheral blood of patients with diabetic nephropathy (DN) and its clinical significance.Methods:208 patients with type 2 diabetes (T2DM) admitted to our hospital from Feb. 2018 to Dec. 2020 were selected and were divided them into 3 groups according to the urine albumin (UA) /urinary creatinine (UC) ratio (UACR) : simple T2DM group (UACR<30 mg/g) 83 cases, microalbuminuria group (UACR 30-300 mg/g) 70 cases, and massive proteinuria group (UACR>300 mg/g) 55 cases; Fifty healthy volunteers were selected as the control group. General data of each group were collected. Western blot was used to detect the level of NLRP3 in peripheral blood, and enzyme-linked immunosorbent assay (ELISA) kit was used to detect the level of serum interleukin (IL) -1β and IL-18. Logistic regression was employed to analyze the occurrence of DN in T2DM patients. Receiver operating characteristic curve (ROC) curve was used to analyze the value of NLRP3, IL-1β, IL-18 in the diagnosis of DN in peripheral blood.Results:Compared with the control group, the course of disease, FBG, LDL-C, TG, TC, SCr, BUN, HbA1c, NLRP3 protein, IL-1β and IL-18 significant increased in the other 3 groups, and HDL-C, ALB, and eGFR were significant decreased, and the difference was statistically significant ( P<0.05) . The order of their level changes was: massive proteinuria group>microalbuminuria group>pure T2DM group; Pearson test found that peripheral blood NLRP3, IL-1β, IL-18 levels were significantly positively correlated with UACR, LDL-C, TG, and TC ( P<0.001) , while they were significantly negatively correlated with HDL-C ( P<0.001) .The results of unconditional Logistic regression analysis showed that the course of disease, FBG, HDL-C, LDL-C, TG, TC, SCr, BUN, ALB, HbA1c, eGFR, NLRP3 protein, IL-1β and IL-18 may all be related to DN-related in patients with T2DM ( P<0.05) . Multivariate analysis found that high levels of BUN, ALB, HbA1c, EGFR, NLRP3 protein and IL-1 were found β and IL-18 are high risk factors for DN in patients with T2DM ( P<0.05) . The ROC curve showed that the combination of peripheral blood NLRP3, IL-1β, and IL-18 predicted the highest AUC, sensitivity, and specificity of DN in patients with T2DM as 0.918, 93.40%, and 90.13%, respectively. Conclusions:Different stages of DN are often accompanied by increased levels of NLRP3, IL-1β, and IL-18 in peripheral blood. Strengthening the monitoring of NLRP3 inflammasome levels can help assess the renal function of patients and provides a theoretical basis for early diagnosis of DN.

Effects of Cognitive Behavioral Therapy for Depression and Anxiety, Response Rates and Adverse Events in Patients with Locoregional Advanced Nasopharyngeal Carcinoma.

PURPOSE: This retrospective study investigated the effects of cognitive behavioral therapy (CBT) on depression, anxiety, response rates, and adverse events in patients with locoregional advanced nasopharyngeal carcinoma (NPC). METHODS: A total of 269 patients with diagnosis of stage III-IVA NPC received either CBT plus chemoradiotherapy (CBT group, n = 136) or treatment as usual (TAU) plus chemoradiotherapy (TAU group, n = 133). Patients in the CBT group received a series of 6 CBT sessions for 6 weeks during concurrent chemoradiotherapy. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale (HADS) score at baseline, the completion of radiotherapy, and 6, 12, and 24 months after radiotherapy. Response rates and adverse events were also evaluated. RESULTS: Patients in the CBT group showed significantly less depression and anxiety than patients in the TAU group after the completion of radiotherapy (P < .05). Complete response rates were 99.3% (135/136) and 92.5% (123/133) in the CBT group and TAU group with a small effect size (Phi coefficient = .171), respectively (P = .005). Compared with the TAU group, the CBT group showed a significantly lower incidence of acute adverse events and late toxic effects. CONCLUSIONS: The addition of CBT to chemoradiotherapy significantly reduced depressive and anxiety symptoms. CBT combined with chemoradiotherapy is associated with improved response rates, with reduced incidence of toxic effects in patients with locoregional advanced NPC. Based on this study, we registered a randomized controlled clinical trials to better define the role of CBT in patients with locoregional advanced NPC (Registration number: ChiCTR2000034701).

In vitro and in vivo preclinical studies predict REGEN-COV protection against emergence of viral escape in humans

Monoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option against COVID-19. As rapidly emerging virus mutants are becoming the next major concern in the fight against the global pandemic, it is imperative that these therapeutic treatments provide coverage against circulating variants and do not contribute to development of treatment emergent resistance. To this end, we investigated the sequence diversity of the spike protein and monitored emergence of minor virus variants in SARS-COV-2 isolates found in COVID-19 patients or identified from preclinical in vitro and in vivo studies. This study demonstrates that a combination of non-competing antibodies, REGEN-COV, not only provides full coverage against current variants of concern/interest but also protects against emergence of new such variants and their potential seeding into the population in a clinical setting.

Dual roles of p62/SQSTM1 in the injury and recovery phases of acetaminophen-induced liver injury in mice

Acetaminophen (APAP) overdose can induce liver injury and is the most frequent cause of acute liver failure in the United States. We investigated the role of p62/SQSTM1 (referred to as p62) in APAP-induced liver injury (AILI) in mice. We found that the hepatic protein levels of p62 dramatically increased at 24 h after APAP treatment, which was inversely correlated with the hepatic levels of APAP-adducts. APAP also activated mTOR at 24 h, which is associated with increased cell proliferation. In contrast, p62 knockout (KO) mice showed increased hepatic levels of APAP-adducts detected by a specific antibody using Western blot analysis but decreased mTOR activation and cell proliferation with aggravated liver injury at 24 h after APAP treatment. Surprisingly, p62 KO mice recovered from AILI whereas the wild-type mice still sustained liver injury at 48 h. We found increased number of infiltrated macrophages in p62 KO mice that were accompanied with decreased hepatic von Willebrand factor (VWF) and platelet aggregation, which are associated with increased cell proliferation and improved liver injury at 48 h after APAP treatment. Our data indicate that p62 inhibits the late injury phase of AILI by increasing autophagic selective removal of APAP-adducts and mitochondria but impairs the recovery phase of AILI likely by enhancing hepatic blood coagulation.

Newborn screening, gene variation analysis and follow-up study of very long chain acyl CoA dehydrogenase deficiency / 中华实用儿科临床杂志

Objective:To investigate the prevalence, gene variation and prognosis of very long chain acyl CoA dehydrogenase deficiency (VLCADD) in newborns in Henan Province.Methods:From January 2013 to December 2019, 867 103 newborns were investigated for VLCADD by tandem mass spectrometry.Children who diagnosed as VLCADD and their families were subjected to next-generation sequencing and Sanger sequencing.Clinical data, biochemical changes and gene variation characteristics of the confirmed cases of VLCADD were analyzed.Dietary guidance was given, and their growth and development were followed up.Results:Six neonates were diagnosed as VLCADD, and the prevalence of VLCADD in the Henan Province was 1/144 517.A total of 11 mutations in the ACADVL gene were found, including 5 new variants c. 692-2_692-1delAG, c.753-23_753-22del, c.960delG, c.1361A>G, and c. 1955C>T.The newborns were given a high-carbohydrate, low-fat diet, and followed up for 8-56 months.Except for two deaths, all patients had a good outcome. Conclusions:The prevalence of neonatal VLCADD in Henan Province is 1/144 517.This results has enriched the ACADVL gene mutation spectrum and provided an important basis for the screening and diagnosis of VLCADD.

The antichlamydial activity of 1, 2-disubstituted pyrrole derivatives in vitro / 中国药理学通报

Aim To evaluate the antichlamydial activity of our previously synthesized sixteen 1, 2-disubstituted pyrroles in vitro, providing candidate for the development of novel agents against Chlamydia. Methods Firstly, the inhibitory effect of compounds on the generation of infectious progeny EBs at different concentrations was analyzed for Chlamydia trachomatis L2 (Ct L2), C. muridarum (Nigg II strain, known as MoPn) and C. pneumonia (Cpn AR39). The IC

REGN-COV2 antibody cocktail prevents and treats SARS-CoV-2 infection in rhesus macaques and hamsters

An urgent global quest for effective therapies to prevent and treat COVID-19 disease is ongoing. We previously described REGN-COV2, a cocktail of two potent neutralizing antibodies (REGN10987+REGN10933) targeting non-overlapping epitopes on the SARS-CoV-2 spike protein. In this report, we evaluate the in vivo efficacy of this antibody cocktail in both rhesus macaques and golden hamsters and demonstrate that REGN-COV-2 can greatly reduce virus load in lower and upper airway and decrease virus induced pathological sequalae when administered prophylactically or therapeutically. Our results provide evidence of the therapeutic potential of this antibody cocktail.

Inorganic Arsenic Exposure Decreases Muscle Mass and Enhances Denervation-Induced Muscle Atrophy in Mice.

Arsenic is a toxic metalloid. Infants with a low birth-weight have been observed in areas with high-level arsenic in drinking water ranging from 463 to 1025 µg/L. A distal muscular atrophy side effect has been observed in acute promyelocytic leukemia patients treated with arsenic trioxide (As2O3) for therapy. The potential of As2O3 on muscle atrophy remains to be clarified. In this study, the myoatrophic effect of arsenic was evaluated in normal mice and sciatic nerve denervated mice exposed with or without As2O3 (0.05 and 0.5 ppm) in drinking water for 4 weeks. We found that both 0.05 and 0.5 ppm As2O3 increased the fasting plasma glucose level; but only 0.5 ppm arsenic exposure significantly decreased muscle mass, muscle endurance, and cross-sectional area of muscle fibers, and increased muscle Atrogin-1 protein expression in the normal mice. Both 0.05 and 0.5 ppm As2O3 also significantly enhanced the inhibitory effects on muscle endurance, muscle mass, and cross-sectional area of muscle fibers, and increased the effect on muscle Atrogin-1 protein expression in the denervated mice. These in vivo results suggest that inorganic arsenic at doses relevant to humans may possess myoatrophic potential.

Cyclosporin A suppresses Porphyromonas gingivalis lipopolysaccharide induced matrix metalloproteinases activities in the co-culture of human gingival fibroblasts and monocyte cell line THP-1.

Cyclosporine-A (CsA) is a widely used immunosuppressant. In this study, we explore the pathway through which CsA suppressed the Porphyromonas gingivalis lipopolysaccharide (P.g-LPS)-induced increase in matrix metalloproteinase (MMP) activities in co-cultured human gingival fibroblasts (HGFs) and THP-1 monocytes. In the co-culture, we found that CsA inhibited the expression of cyclophilin A (CyPA), CD147 and the activities of MMPs, which were all induced by P.g-LPS. We also found that P.g-LPS and recombinant human CyPA increased activation of ERK1/2 and IκB (an NF-κB inhibitory protein), but CsA and the anti-CD147 antibody significantly inhibited these effects. Taken together, CsA in the presence of P.g-LPS might suppress MMP activities by blocking the CyPA/CD147 interaction that results in the inhibition of ERK1/2 and NF-κB signaling by interfering with the phosphorylation of ERK1/2 and IκB.

Exposure of low-concentration arsenic induces myotube atrophy by inhibiting an Akt signaling pathway.

Arsenic, a widely distributed toxic metalloid, has been found to be associated with the low-birth-weight infants and the impairment of muscle regenerative capacity in areas with high levels of arsenic in drinking water. The distal muscular atrophy is one of side effects of arsenic trioxide (As2O3) for acute promyelocytic leukemia therapy. We hypothesized that arsenic may be a potential risk factor for skeletal muscle atrophy. Here, we investigated the action and molecular mechanism of low-dose arsenic on the induction of skeletal muscle atrophy in a skeletal muscle cell model. The differentiated C2C12 myotubes were treated with As2O3 (0.25-1 µM) for 48 h without apparent effects on cell viability. The signaling molecules for myotube atrophy were assessed. Submicromolar-concentration As2O3 dose-dependently triggered C2C12 myotube atrophy and increased the protein expressions of atrogenes Atrogin1 and MuRF1 and inhibited the upstream phosphorylated proteins Akt and FoxO1, while As2O3 dose-dependently increased AMPK phosphorylation in myotubes. Akt activator SC79 could significantly reverse the As2O3-induced myotube atrophy. These results suggest that arsenic is capable of inducing myotube atrophy by inhibiting an Akt signaling pathway.

Evaluation of multidisciplinary collaborative nursing model for people with critical conditions during physical examination / 中华健康管理学杂志

Objective This study explored the effect of the multidisciplinary-team collaborative nursing model in physical examinations of people with critical conditions (based on test results).Methods We selected 962 patients with critical conditions based on test-result values found from February to April 2018 as the general process group treated through the routine nursing model,and we also selected 1009 patients with critical conditions based on test-result values found from May to July 2018 as the multidisciplinary collaborating group using a team nursing model.The multidisciplinary collaborative nursing team members included health management center nurses,outpatient nurses,resident nurses,and ward nurses.We compared visiting rates,hospitalization rates,average visiting times,and overall satisfaction after the patients received notification of their abnormal results.There were 488 male patients (50.7％) and 474 female patients (49.3％) in the general process group,with an average age of 51.9 ± 14.9 years;there were 537 male patients (53.2％) and 472 female patients (46.8％) in the multidisciplinary collaboration group,with an average age of 51.0 ± 13.0.Results For the multidisciplinary collaboration group and the general process group,respectively,the visiting rate was 53.0％ and 44.7％ (x2=13.65);the hospitalization rate was 26.7％ and 20.9％ (x2=4.38);overall satisfaction was 97.9％ and 95.9％ (x2=6.49);and the average visiting time was 4 days and 6 days (Z=5.04).The differences were statistically significant (P＜0.05).By category,the visiting rate for radiology and ultrasound patients among the multidisciplinary collaboration group was significantly higher than in the general process group (64.4％ vs.50.8％ for radiology,45.9％ vs.37.3％ for ultrasound,x2=7.65,7.11,P＜0.05).The hospitalization rate for ultrasound patients in the multidisciplinary collaboration group was significantly higher than in the general process group (12.5％ vs.6.4％,x2=10.17,P＜0.05).The average visiting time of ultrasound,abnormal blood pressure,and laboratory testing patients was significantly lower in the general process group (4 days vs.6 days,4 d vs.7 days,4 days vs.5 days,Z=3.37,1.97,2.62,P＜0.05).The overall satisfaction of radiology patients was significantly higher than in the general process group (98.6％ vs.94.3％,x2=5.39,P＜0.05).Conclusion The multidisciplinary team collaborative nursing model improves the rate of visiting and hospitalization of patients with critical conditions after physical examination,shortening their stays,helping patients get timely diagnoses and treatment,and improving patient satisfaction,making the model worth popularizing and applying more broadly.

Clinical and genetic characteristics of primary carnitine deficiency identified by neonatal screening / 中华医学遗传学杂志

Objective@#To study the prevalence, clinical and genetic characteristics of primary carnitine deficiency (PCD).@*Methods@#From January 2013 to December 2017, 720 667 newborns and their mothers were tested for PCD by tandem mass spectrometry. Potential mutations of carnitine transporter gene SLC22A5 among suspected PCD patients were analyzed. Dietary guidance and L-carnitine supplementation were provided to the parents. Growth and intelligence development were surveyed during follow-up.@*Results@#In total 21 neonates and 6 mothers were diagnosed with PCD, which yielded an incidence of 1 in 34 317. Eighteen SLC22A5 mutations were detected, which included 4 novel mutations, namely c. 1484T>C, c. 394-1G>T, c. 431T>C and c. 265-266insGGCTCGCCACC. Eighteen patients were found to carry compound heterozygous mutations and 3 have carried homozygous SLC22A5 mutations. Three mothers carried compound heterozygous mutations and 2 carried homozygous mutations. Common mutations included c. 1400C>G (42.3%), c. 760C>T (11.5%) and c. 51C>G (7.7%). During the 8 ~ 42 month follow-up, neonates with PCD showed no clinical symptoms but normal growth. Blood level of free carnitine was raised in all mothers after the treatment.@*Conclusion@#The incidence of neonatal PCD in Henan is 1 in 34 317, with the most common mutation being c. 1400C>G. Above finding has enriched the spectrum of SLC22A5 gene mutations.

Effects of early mobilization combined with occupational therapy on delirium of mechanical ventilated patients / 中国实用护理杂志

Objective To evaluate the effects of early mobilization combined with occupational therapy on delirium of mechanical ventilated patients. Methods Sixty- eight patients who were undergoing mechanical ventilation and met the inclusion as well as exclusion criteria were randomized into an intervention group (35 patients) and a control group (33 patients). Patients in both group were provided with ICU routine care to prevent delirium, while early mobilization combined with occupational therapy was given in intervention group. Incidence rate of delirium, length of delirium, dosage of sedation, length of mechanical ventilation, length of ICU stay and physical restraint rate were compared. Occurrence of adverse events during intervention was also observed. Results In intervention group ,the incidence rate of delirium was 25.71% (9/35), length of delirium was (1.69 ± 2.98)days, dosage of propofol was(2 189.71±1 222.23)mg, length of ventilation was (4.86±1.31)days, and physical restraint rate was 43.64% (146/275), all of which were significantly better than those in control group, which were 53.28%(17/33), (2 736.36±1 298.99) mg, (5.88±1.52)days, 53.28%(160/254) (χ2=4.788, 7.251, t=3.910, 2.980, P＜0.05 or 0.01). There was no unpredicted issue occurred during intervention. Conclusions Early mobilization combined with occupational therapy is feasible which could alleviate ICU delirium, reduce the dosage of sedation, the length of mechanical ventilation, and the physical restraint rate.

Effects of early mobilization combined with occupational therapy on delirium of mechanical ventilated patients / 中国实用护理杂志

Objective@#To evaluate the effects of early mobilization combined with occupational therapy on delirium of mechanical ventilated patients.@*Methods@#Sixty-eight patients who were undergoing mechanical ventilation and met the inclusion as well as exclusion criteria were randomized into an intervention group (35 patients) and a control group (33 patients). Patients in both group were provided with ICU routine care to prevent delirium, while early mobilization combined with occupational therapy was given in intervention group. Incidence rate of delirium, length of delirium, dosage of sedation, length of mechanical ventilation, length of ICU stay and physical restraint rate were compared. Occurrence of adverse events during intervention was also observed.@*Results@#In intervention group,the incidence rate of delirium was 25.71%(9/35), length of delirium was (1.69±2.98) days, dosage of propofol was (2 189.71±1 222.23) mg, length of ventilation was (4.86±1.31)days, and physical restraint rate was 43.64%(146/275), all of which were significantly better than those in control group, which were 53.28%(17/33), (2 736.36±1 298.99) mg, (5.88±1.52)days, 53.28%(160/254) (χ2=4.788, 7.251, t=3.910, 2.980, P<0.05 or 0.01). There was no unpredicted issue occurred during intervention.@*Conclusions@#Early mobilization combined with occupational therapy is feasible which could alleviate ICU delirium, reduce the dosage of sedation, the length of mechanical ventilation, and the physical restraint rate.

Correlation between preoperative controlling nutritional status (CONUT) score and adjuvant chemotherapy in stage Ⅱ-Ⅲ gastric cancer after curative resection / 中华普通外科杂志

Objectives@#To elucidate the prognostic impact of preoperative control of nutritional status (CONUT) scores on gastric cancer patients undergoing adjuvant chemotherapy after radical gastrectomy.@*Methods@#A retrospective analysis of 536 stage Ⅱ-Ⅲ gastric cancer patients undergoing adjuvant chemotherapy after radical resection from Jul 1998 to Dec 2014 was performed. Patients were divided into high (≥3) and low (≤2) CONUT groups with a CONUT score of 3 divided into critical values.@*Results@#The 5-year survival rate of the high CONUT group was significantly lower than that of the low CONUT group (37.3 % vs. 55.7%, P<0.001). Univariate analysis showed that the high CONUT group was associated with larger tumors, more lymph node metastasis, lower body mass index, higher prognostic nutritional index, and preoperative anemia (all P<0.05). Multivariate analysis showed that the CONUT score was an independent prognostic factor for patients with gastric cancer (HR: 1.564, 95% CI: 1.090-2.321, P=0.016). The 5-year survival rate of the high CONUT group was significantly lower than that of the low CONUT group (P<0.05).@*Conclusion@#The CONUT score is an indicator for predicting the prognosis of patients with stage Ⅱ-Ⅲ gastric cancer after adjuvant chemotherapy. The nutritional evaluation is helpful to develop a plan for preoperative nutritional intervention.

Correlation between preoperative controlling nutritional status (CONUT) score and adjuvant chemotherapy in stage Ⅱ-Ⅲ gastric cancer after curative resection / 中华普通外科杂志

Objectives To elucidate the prognostic impact of preoperative control of nutritional status (CONUT) scores on gastric cancer patients undergoing adjuvant chemotherapy after radical gastrectomy.Methods A retrospective analysis of 536 stage Ⅱ-Ⅲ gastric cancer patients undergoing adjuvant chemotherapy after radical resection from Jul 1998 to Dec 2014 was performed.Patients were divided into high (≥ 3) and low (≤ 2) CONUT groups with a CONUT score of 3 divided into critical values.Results The 5-year survival rate of the high CONUT group was significantly lower than that of the low CONUT group (37.3 ％ vs.55.7％,P ＜0.001).Univariate analysis showed that the high CONUT group was associated with larger tumors,more lymph node metastasis,lower body mass index,higher prognostic nutritional index,and preoperative anemia (all P ＜ 0.05).Multivariate analysis showed that the CONUT score was an independent prognostic factor for patients with gastric cancer (HR:1.564,95％ CI:1.090-2.321,P =0.016).The 5-year survival rate of the high CONUT group was significantly lower than that of the low CONUT group (P ＜ 0.05).Conclusion The CONUT score is an indicator for predicting the prognosis of patients with stage Ⅱ-Ⅲ gastric cancer after adjuvant chemotherapy.The nutritional evaluation is helpful to develop a plan for preoperative nutritional intervention.

Effect of Curcumin in Reversing Resistance of Human Colon Carcinoma Against Oxaliplatin Cell Line HCT-116/L-OHP / 中国实验方剂学杂志

Objective:To construct oxaliplatin (L-OHP) drug-resistant cell line HCT-116/L-OHP in human colon cancer, in order to observe the reversal effect of curcumin (cur) on its drug resistance, and preliminarily explore the possible drug resistance mechanism. Method:The concentration gradient increasing method was used to gradually increase the L-OHP concentration of HCT-116 in parental colon cancer cells, and the cell line HCT-116/L-OHP resistant to L-OHP was established. The cytotoxicity of L-OHP and curcumin to HCT-116 and HCT-116/L-OHP cells was detected by cell counting kit-8(CCK-8) method to observe whether curative resistance could be reversed. Western blot was used to detect the expressions of drug-resistance-related proteins. Real-time PCR was used to detect changes in related genes. Result:Human colon cancer cell line resistant to L-OHP were successfully established and named as HCT-116/L-OHP, with a drug resistance index of 12.6.Compared with HCT-116 cell lines, the expression levels of resected and repaired cross complementation gene 1 (ERCC1) protein and gene in HCT-116/L-OHP cell lines were significantly increased (PP-1), the expression of ERCC1 decreased (PPConclusion:HCT-116/L-OHP cell lines have a stable drug resistance, and its drug resistance mechanism may be up-regulated with the expression of ERCC1, which leads to the up-regulation of Bcl-2,GST-π,MRP,P-gp,Survivin and other related proteins, and enables tumor cells to acquire drug resistance. Curcumin can reverse the drug resistance of HCT-116/L-OHP, and its mechanism may be to reduce the expression of ERCC1, thereby down-regulating the expressions of Bcl-2,GST-π,MRP,P-gp,Survivin and other drug-resistant related genes and proteins, and increase the sensitivity of tumor to L-OHP, so as to reverse the drug resistance of tumor cells.