Comparing efficacies of different exercises on androgen deprivation therapy adverse effects in prostate cancer patients: a network meta-analysis.

INTRODUCTION: Previous studies showed exercise have efficacies for androgen deprivation therapy (ADT) adverse effects. To compare the efficacies of different exercises on ADT adverse effects, we conducted the network meta-analysis (NMA). METHODS: Literature retrieval was performed in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL). 19 studies (1184 participants) were included. All analyses were performed in R 4.1.2 or RevMan 5.4.1. RESULTS: NMA results showed that compared with the control group, both aerobic + resistance training (ART) (MD = 5.92, 95% CI [0.38; 11.46]) and resistance exercise (RE) (MD = 5.62, 95% CI [2.70; 8.55]) improved quality of life (QoL). ART (P score: 0.72) may have superiority over RE (P score: 0.7). ART (MD = -10.89, 95% CI [-17.67; -4.11]) significantly improved the performance of 400-m test. RE could significantly improve leg strength (MD = 118, 95% CI [78.75; 157.25]) and chest strength (MD = 13.30 [4.07; 22.53]). RE ranked first for strength improvements of leg and chest. CONCLUSION: ART showed better efficacy for the QoL, and significantly improved the performance of 400-m test. RE might be superior for the strengths of leg and chest. ART may be appropriate for patients with less significant muscle strength decline but also other adverse effects of ADT, such as decreased cardiopulmonary function.

An umbrella review of the evidence associating occupational carcinogens and cancer risk at 19 anatomical sites.

Occupational exposure to carcinogens of increasing cancer risk have been extensively suggested. A robust assessment of these evidence is needed to guide public policy and health care. We aimed to classify the strength of evidence for associations of 13 occupational carcinogens (OCs) and risk of cancers. We searched PubMed and Web of Science up to November 2022 to identify potentially relevant studies. We graded the evidence into convincing, highly suggestive, suggestive, weak, or not significant according to a standardized classification based on: random-effects p value, number of cancer cases, 95% confidence interval of largest study, heterogeneity between studies, 95% prediction interval, small study effect, excess significance bias and sensitivity analyses with credibility ceilings. The quality of meta-analysis was evaluated by AMSTAR 2. Forty-eight articles yielded 79 meta-analyses were included in current umbrella review. Evidence of associations were convincing (class I) or highly suggeastive (class II) for asbestos exposure and increasing risk of lung cancer among smokers (RR = 8.79, 95%CI: 5.81-13.25 for cohort studies and OR = 8.68, 95%CI: 5.68-13.24 for case-control studies), asbestos exposure and increasing risk of mesothelioma (RR = 4.61, 95%CI: 2.57-8.26), and formaldehyde exposure and increasing risk of sinonasal cancer (RR = 1.68, 95%CI: 1.38-2.05). Fifteen associations were supported by suggestive evidence (class III). In summary, the current umbrella review found strong associations between: asbestos exposure and increasing risk of lung cancer among smokers; asbestos exposure and increasing risk of mesothelioma; and formaldehyde exposure and higher risk of sinonasal cancer. Other associations might be genuine, but substantial uncertainty remains.

Second-line treatment options in metastatic castration-resistant prostate cancer after progression on first-line androgen-receptor targeting therapies: A systematic review and Bayesian network analysis.

OBJECTIVE: To summarize and indirectly compare the efficacy and safety of different second-line systematic therapies after first-line androgen-receptor targeting therapies (ARTs) for biomarker-unselected metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: Studies published in English up to May 2023 were identified in PubMed, Web of Science and ASCO-GU 2023. Studies accessing the efficacy and safety of second-line systematic therapies after first-line ARTs for biomarker-unselected mCRPC patients were eligible for current systematic review and network meta-analysis (NMA). RESULTS: Thirty-two studies with 5388 patients and 10 unique treatment modalities met our inclusion criteria. Current evidence suggested that docetaxel (DOC) combined with the same ART as first-line (ART1) (ART1 + DOC) were associated with significantly improved PSA response, PSA progression-free survival (PFS) and clinical or radiographic PFS (rPFS) compared with other reported second-line systematic therapies, including DOC. An increase in toxicity was observed with ART1 + DOC. Our NMA indicated that DOC monotherapy was only inferior to ART1 + DOC in improvement disease outcomes. The incidence of toxicity between patients received second-line DOC and an alternative ART (ART2) was similar. CONCLUSION: The available evidence reviewed in our work suggested a clinical benefit of DOC nomotherapy and DOC plus ART1 as the second-line systematic therapy for biomarker-unselected mCRPC patients progressed on a first-line ART. More studies and RCTs are needed to evaluate the optimal second-line treatments for mCRPC patients with one prior first-line ART.

Effect of intubation in lateral position on placement of a double-lumen tube in patients undergoing unilateral video-assisted thoracic surgery: a randomied clinical trial.

Background: Approximately one-third of patients who undergo double-lumen tube (DLT) intubation in the conventional supine position experience DLT malposition. No randomized study investigates the effect of DLT intubation in the lateral position. We therefore aimed to evaluate the effect of intubation in lateral position on placement of a DLT compared to supine intubation, and to test primary hypothesis that lateral DLT intubation could reduce the incidence of DLT malposition. Methods: We randomly allocated 108 patients undergoing video-assisted thoracic surgery to receive DLT intubation in the comfortable and surgically required lateral position (lateral group) or in the supine position (supine group) from October to December 2022. The primary outcome was the incidence of DLT malposition defined as movement >1.0 cm to correct the DLT position. The secondary outcomes included intubation time, the frequency and duration of fibreoptic bronchoscopy, the need for re-intubation, intra-operative vital signs, and post-operative recovery. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2200060794). Findings: The incidence of DLT malposition was significantly lower in the lateral group (1/53 [2%]) than that in the supine group (16/53 [30%]; RR [95% confidence interval] of 0.06 [0.01-0.46]; P < 0.001). Lateral DLT intubation decreased the intubation time, the frequency and duration of fibreoptic bronchoscopy. The incidence of hypotension, post-operative sore throat, and upper-arm discomfort was lower in the lateral group. Other secondary outcomes were similar between groups. Interpretation: Lateral DLT intubation reduced the incidence of DLT malposition for patients undergoing video-assisted thoracic surgery. These results support that lateral DLT intubation offers more benefits and may be a superior option compared to conventional supine intubation. Funding: National Natural Science Foundation of China and of Zhejiang Province.

Effect of intubation in the lateral position under general anesthesia induction on the position of double-lumen tube placement in patients undergoing unilateral video-assisted thoracic surgery: study protocol for a prospective, single-center, parallel group, randomized, controlled trial.

BACKGROUND: The double-lumen tube (DLT) is an essential equipment for thoracic anesthesia and the precise position of DLT placement is particularly important for anesthesia and surgery. However, the incidence of DLT malposition remains high and it leads to lung isolation failure and hypoxemia during one-lung ventilation. This trial aims to explore the clinical application and efficacy of intubation in the lateral position under general anesthesia induction to reduce the incidence of DLT malposition in patients undergoing unilateral video-assisted thoracic surgery (VATS). METHODS: In this prospective, single-center, parallel group, randomized, controlled trial, we will recruit 108 patients, aged 18-80 years, scheduled for elective unilateral VATS with DLT intubation under general anesthesia, and they will be randomly assigned to two groups: a lateral DLT intubation group (group L) and a conventional supine DLT intubation group (group C). The left-sided DLT will be used to intubate in patients of both groups. The position of DLT will be confirmed and adjusted by using the fiberoptic bronchoscopy (FOB). The primary outcome is the incidence of DLT malposition observed via the FOB, and the secondary outcomes include the time of intubation, the frequency and duration of re-adjustments of DLT placement under FOB, whether to re-intubate, intraoperative vital signs, and postoperative recovery. DISCUSSION: Accurate DLT positioning is crucially important for thoracic surgery, but the incidence of DLT malposition is still high in the present clinical practice of thoracic anesthesia. This trial aims to investigate whether lateral DLT intubation can reduce the incidence of DLT malposition, with more stable intraoperative vital signs and less postoperative complications. TRIAL REGISTRATION: The study protocol was registered at Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) with registration number: ChiCTR2200060794 on June 11, 2022.

Which Type of Exercise During Radiation Therapy Is Optimal to Improve Fatigue and Quality of Life in Men with Prostate Cancer? A Bayesian Network Analysis.

Context: Physical exercise in men with prostate cancer (CaP) has shown benefits in improving cancer-related fatigue (CRF) and quality of life (QoL) during radiation therapy. However, types of exercises that are more effective are not well understood. Evidence acquisition: We searched PubMed, Web of Science, and ClinicalTrials.gov up to November 2021 to identify potentially relevant studies. Randomized controlled trials (RCTs) testing the effects of exercise training on CRF, QoL, and treatment-related toxicities in patients with CaP undergoing radiation therapy were included. The quality of individual studies was evaluated using the Tool for the assEssment of Study qualiTy and reporting in Exercise (TESTEX) scale. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation method. A meta-regression analysis was conducted to test the study-level covariates. A random-effect network meta-analysis was conducted based on a Bayesian model. Evidence synthesis: Eight RCTs with 466 participants were included. Exercise achieved significant improvements in CRF (standardized mean difference [SMD] = 1.24, 95% confidence interval or CI [0.43, 2.06], I2 = 93%) and QoL (SMD = 1.40, 95% CI [0.05, 2.75], I2 = 95%). Based on the meta-regression and Bayesian model, combined moderate-intensity continuous training aerobic exercise and resistance exercise (MICT/RES) showed the highest probability of ranking first in terms of CRF and QoL improvement, but the results of QoL were unstable. Exercise training also had a positive effect on urinary toxicities (SMD = -0.53, 95% CI [-0.79, -0.27], I2 = 0%). A subgroup analysis indicated that MICT/RES might be the most promising exercise modality for reducing intestinal toxicities (SMD = -1.76, 95% CI [-2.32, -1.20]). Conclusions: MICT/RES might be superior to any other types of exercise at reducing CRF. MICT/RES was more effective on significantly mitigating urinary and intestinal toxicities. Patient summary: In prostate cancer (CaP) survivors during radiation therapy, exercise training is an effective and safe intervention to reduce cancer-related fatigue (CRF) and improve quality of life (QoL), and should be prescribed as a rehabilitation option for clinical management. As for the types of exercises, moderate-intensity continuous training aerobic exercise and resistance exercise seem to be the most effective interventions to reduce CRF, improve QoL, and mitigate treatment-related symptoms.

Pathophysiology of Ischemic Stroke: Noncoding RNA Role in Oxidative Stress.

Stroke is a neurological disease that causes significant disability and death worldwide. Ischemic stroke accounts for 75% of all strokes. The pathophysiological processes underlying ischemic stroke include oxidative stress, the toxicity of excitatory amino acids, ion disorder, enhanced apoptosis, and inflammation. Noncoding RNAs (ncRNAs) may have a vital role in regulating the pathophysiological processes of ischemic stroke, as confirmed by the altered expression of ncRNAs in blood samples from acute ischemic stroke patients, animal models, and oxygen-glucose-deprived (OGD) cell models. Due to specific changes in expression, ncRNAs can potentially be biomarkers for the diagnosis, treatment, and prognosis of ischemic stroke. As an important brain cell component, glial cells mediate the occurrence and progression of oxidative stress after ischemic stroke, and ncRNAs are an irreplaceable part of this mechanism. This review highlights the impact of ncRNAs in the oxidative stress process of ischemic stroke. It focuses on specific ncRNAs that underlie the pathophysiology of ischemic stroke and have potential as diagnostic biomarkers and therapeutic targets.

Interleukins and Ischemic Stroke.

Ischemic stroke after cerebral artery occlusion is one of the major causes of chronic disability worldwide. Interleukins (ILs) play a bidirectional role in ischemic stroke through information transmission, activation and regulation of immune cells, mediating the activation, multiplication and differentiation of T and B cells and in the inflammatory reaction. Crosstalk between different ILs in different immune cells also impact the outcome of ischemic stroke. This overview is aimed to roughly discuss the multiple roles of ILs after ischemic stroke. The roles of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-16, IL-17, IL-18, IL-19, IL-21, IL-22, IL-23, IL-32, IL-33, IL-34, IL-37, and IL-38 in ischemic stroke were discussed in this review.

Recent advances in double-lumen tube malposition in thoracic surgery: A bibliometric analysis and narrative literature review.

Thoracic surgery has increased drastically in recent years, especially in light of the severe outbreak of the 2019 novel coronavirus disease (COVID-19). Routine "passive" chest computed tomography (CT) screening of inpatients detects some pulmonary diseases requiring thoracic surgeries timely. As an essential device for thoracic anesthesia, the double-lumen tube (DLT) is particularly important for anesthesia and surgery. With the continuous upgrading of the DLTs and the widespread use of fiberoptic bronchoscopy (FOB), the position of DLT in thoracic surgery is gradually becoming more stable and easier to observe or adjust. However, DLT malposition still occurs during transferring patients from a supine to the lateral position in thoracic surgery, which leads to lung isolation failure and hypoxemia during one-lung ventilation (OLV). Recently, some innovative DLTs or improved intervention methods have shown good results in reducing the incidence of DLT malposition. This review aims to summarize the recent studies of the incidence of left-sided DLT malposition, the reasons and effects of malposition, and summarize current methods for reducing DLT malposition and prospects for possible approaches. Meanwhile, we use bibliometric analysis to summarize the research trends and hot spots of the DLT research.

TUBA1C is a Prognostic Marker in Low-grade Glioma and Correlates with Immune Cell Infiltration in the Tumor Microenvironment.

TUBA1C, a microtubule component, contributes to the development of several cancers. Our purpose was to study the expression of TUBA1C, its potential prognostic value, and its effects on the infiltration of immune cells of low-grade glioma (LGG). Through applying multiple bioinformatics analyses, we extracted and analyzed datasets from TCGA, TIMER, GTEx, GEPIA, and HPA to investigate the potential oncogenic mechanisms of TUBA1C, including the correlation between TUBA1C and prognosis, immune-checkpoints, tumor microenvironment (TME), and infiltration of immune cells in LGG. GO functional annotations and KEGG pathway analyses were further applied to investigate the potential action of TUBA1C in LGG. We revealed that the mRNA levels of TUBA1C were increased in LGG tumor tissues than in normal tissues. Additionally, TUBA1C was up-regulated in the grade III of LGG than in grade II. Moreover, we found that TUBA1C may be an independent prognostic factor of LGG, and high TUBA1C expression correlated to a poor prognosis of LGG. TUBA1C expression was positively associated with the infiltration of B cells, CD8 T+ cells, CD4+ T cells, macrophages, dendritic cells, and neutrophils. TUBA1C was also verified to be co-expressed with immune-related genes and immune-checkpoints. GO and KEGG pathway analyses indicated that TUBA1C may potentially regulate the pathogenesis of LGG through immune-related pathways, including chemokine pathway; JAK-STAT pathway; natural killer cell mediated cytotoxicity; T cell receptor pathway; leukocyte migration; negative regulation of immune system process; regulation of lymphocyte activation; T cell activation and other pathways. In conclusion, TUBA1C expression is increased in LGG and high TUAB1C expression is related to a poor prognosis. TUBA1C may influence tumor development by regulating the tumor-infiltrating cells in the TME. TUBA1C may be a potential target for immunotherapy.

Metal-Free Cationic Polymerization of Vinyl Ethers with Strict Temporal Control by Employing an Organophotocatalyst.

By virtue of spatiotemporal control over the chain propagating, visible-light-regulated organocatalytic photoredox cationic polymerization provides an appealing approach for the construction of metal-free, well-defined polymers and materials. However, so far, organic photocatalysts capable of mediated cationic polymerization of vinyl ethers are quite limited, and the photocontrol or efficiency is often eroded due to the difficulty in achieving a good activation-deactivation balance, which is greatly dependent on the redox property of the catalyst. Here, we introduce a new type of organic photocatalysts, bisphosphonium salts, which show high performance in the photoregulated reversible addition-fragmentation chain transfer cationic polymerization of vinyl ethers and allow the synthesis of poly(vinyl ethers) with predictable molecular weights and narrow dispersities at low ppm catalyst loadings under visible light. In particular, the tunable redox potential and excellent stability endow the bisphosphonium salts strict temporal control, thus enabling the metal-free polymerization with a halt in a long dark period.

Individualized lung protective ventilation vs. conventional ventilation during general anesthesia in laparoscopic total hysterectomy.

Laparoscopic total hysterectomy is performed by carbon dioxide insufflation, Trendelenburg position and mechanical ventilation of patients under general anesthesia. However, this may induce pulmonary atelectasis and/or hyperdistention of the lungs. Multiple studies have indicated that mechanical ventilation with the use of low tidal volumes, moderate positive end-expiratory pressure (PEEP) and regular alveolar recruitment maneuvers may improve post-operative outcomes. However, the benefits of an individualized level of PEEP have not been clearly established. In the present study, it was hypothesized that a moderate fixed PEEP may not suit all patients and an individually-titrated PEEP during anesthesia may improve the peri-operative pulmonary oxygenation function. The aim of the present study was to compare the pulmonary oxygenation function and post-operative pulmonary complications (PPCs) in patients receiving individualized lung-protective mechanical ventilation (LPV) vs. conventional ventilation (CV) during laparoscopic total hysterectomy. The present study was a randomized double-blinded clinical trial on 87 patients who were randomly divided to receive CV or protective ventilation (PV). An optimal individualized PEEP value was determined using a static pulmonary compliance-directed PEEP titration procedure. Pulmonary oxygenation function, serum inflammatory factors, including interleukin-8 and Clara cell protein 16, the incidence of PPCs and the post-operative length of stay were also determined. Patients in the PV group exhibited improved pulmonary oxygenation function during and after the operation. The total percentage of PPCs during the first 7 days after surgery was significantly lower in the PV group compared with those in the CV group. In conclusion, as compared to CV, intra-operative individualized LPV significantly improved pulmonary oxygenation function and reduced the incidence of PPCs during the first 7 days after laparoscopic total hysterectomy (Clinical trial registration no. ChiCTR1900027738).

Dexmedetomidine attenuates lipopolysaccharide induced acute lung injury in rats by inhibition of caveolin-1 downstream signaling.

OBJECTIVE: Toll-like receptor 4(TLR-4)/nuclear factor-kappa B(NF-κB) pathway plays an important role in inducing acute lung injury (ALI). Studies have proved Dexmedetomidine (Dex) inhibits inflammatory response to mitigate lipopolysaccharide (LPS)-induced ALI and protect against multiorgan injury in various scenarios via restraining TLR-4/NF-κB signaling pathway. Many of the known downstream molecules have been orientated with a protein caveolin-1(Cav-1), which is supposed to take part in regulating TLR4-mediated inflammatory responses. However, its mechanisms have not been confirmed. The aim of this study is to evaluate the protective effects and potential mechanisms of Dex against LPS-induced ALI in male rats. METHODS: Male rats received tail-vein injection of LPS to form ALI model. Rats were administrated with intraperitoneal injection Dex0.5 h before ALI. At 6 h after LPS injection, bronchoalveolar lavage fluid (BALF) and lung tissue were harvested. We stained the lung tissue sections with hematoxylin eosin (HE) staining to observe the histopathological damage and measure the ALI pathology score. We also measured the wet-to-dry(W/D) weight ratio of lung tissue. Lung myeloperoxidase (MPO) and inflammatory cytokines in the BALF were detected by Enzyme-linked immunosorbent assay(ELISA). Protein levels of Cav-1, TLR-4 and NF-κB in lung tissue were tested by immunohistochemistry method. The mRNA expression of Cav-1, TLR4 and the NF-κB in lung tissue were measured to determine the related mechanisms by quantitative real-time polymerase chain reaction(RT-PCR). RESULTS: It was indicated that Dex pretreatment markedly mitigated pathomorphologic changes and pathological lung injury scores. Besides, Dex pretreatment obviously decreased the W/D weight ratio of lung tissue, attenuated MPO activity significantly, along with LPS-stimulated augment of lung inflammatory cells infiltration in BALF. Moreover, compared with LPS model group, Dex pretreatment apparently increased the protein levels of Cav-1 downregulated by sepsis and decreased the protein levels of TLR-4 and NF-κB in lung tissue. Furthermore, Dex pretreatment apparently upregulated the expression of Cav-1 mRNA, restrained TLR4 and NF-κB mRNA. CONCLUSION: Dex pretreatment protects against LPS-induced ALI via inhibiting the activation of the TLR-4/NF-kB signaling pathway by upregulating the expression of Cav-1 downregulated by sepsis.

Thalidomide alleviates postoperative pain and spatial memory deficit in aged rats.

Pain is a major risk factor of post-operative cognitive dysfunction (POCD) in aged population. We investigated the effects of thalidomide, an anti-inflammatory and analgesic drug, on POCD in aged rats, and also explored the underlying mechanisms. Laparotomy was performed under anesthesia in aged rats (24-25 months) to establish POCD models. Thalidomide (5-50mg/kg) was intraperitoneally administered immediately after laparotomy. Within 12h after the operation, pain symptoms were assessed by rat grimace scale (RGS). Within postoperative day (POD) 3-14, spatial memory was evaluated using performance errors in a radial arm maze. Protein levels of inflammatory cytokines and N-methyl-D-aspartate (NMDA) receptors were measured on POD 14. POCD rats treated with thalidomide showed decreased RGS and performance errors, compared with saline-treated POCD rats. Single administration of thalidomide significantly reduced production of cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1ß) in serum but not in the brain, and attenuated upregulation of NMDA receptor (NR) 2A/B subunits in the hippocampus at POD 14. MK-801 abolished thalidomide-induced attenuation of spatial memory deficits. Our results support that thalidomide could disrupt the development of post-operative memory deficit in aged rats through its long-term regulation of NMDA receptors (NRs) in the hippocampus. Therefore, thalidomide might provide a new means to prevent the development of POCD.

Coapplication of lidocaine and membrane-impermeable lidocaine derivative QX-222 produces divergent effects on evoked and spontaneous nociceptive behaviors in mice.

The present study was aimed at investigating the analgesic properties of a combination of lidocaine and QX-222 and its effects on evoked pain behavior (complete Freund's adjuvant-induced allodynia and hyperalgesia in inflammatory condition) and spontaneous pain behavior (formalin-induced acute pain) in mice. Drugs were injected adjacent to sciatic nerve or into plantar. Motor function, thermal withdrawal latency, mechanical withdrawal threshold, and licking/biting were evaluated by behavioral tests. A combination of lidocaine and QX-222 adjacent sciatic nerve injection produced the long-lasting sensory-specific nerve block, and intraplantar injection inhibited spontaneous pain in the formalin-treated mice but did not detectably attenuated hyperalgesia and allodynia in the complete Freund's adjuvant- (CFA-) treated mice. Our results suggest that a combination of lidocaine and QX-222 achieves a long-lasting differential block (sensory selective) and produces divergent effects on evoked and spontaneous pain behaviors in mice.

Skeletal muscle-specific CPT1 deficiency elevates lipotoxic intermediates but preserves insulin sensitivity.

OBJECTIVE: By specific knockout of carnitine palmitoyl transferase 1b (CPT1b) in skeletal muscles, we explored the effect of CPT1b deficiency on lipids and insulin sensitivity. METHODS: Mice with specific knockout of CPT1b in skeletal muscles (CPT1b M-/-) were used for the experiment group, with littermate C57BL/6 as controls (CPT1b). General and metabolic profiles were measured and compared between groups. mRNA expression and CPT1 activity were measured in skeletal muscle tissues and compared between groups. Mitochondrial fatty acid oxidation (FAO), triglycerides (TAGs), diglycerides (DAGs), and ceramides were examined in skeletal muscles in two groups. Phosphorylated AKT (pAkt) and glucose transporter 4 (Glut4) were determined with real-time polymerase chain reaction (RT-PCR). Insulin tolerance test, glucose tolerance test, and pyruvate oxidation were performed in both groups. RESULTS: CPT1b M-/- model was successfully established, with impaired muscle CPT1 activity. Compared with CPT1b mice, CPT1b M-/- mice had similar food intake but lower body weight or fat mass and higher lipids but similar glucose or insulin levels. Their mitochondrial FAO of skeletal muscles was impaired. There were lipids accumulations (TAGs, DAGs, and ceramides) in skeletal muscle. However, pAkt and Glut4, insulin sensitivity, glucose tolerance, and pyruvate oxidation were preserved. CONCLUSION: Skeletal muscle-specific CPT1 deficiency elevates lipotoxic intermediates but preserves insulin sensitivity.

Effects of different therapeutic methods and typical recipes of Chinese medicine on activation of c-Jun N-terminal kinase in kupffer cells of rats with fatty liver disease.

OBJECTIVE: To observe the effects of different therapeutic methods and the recipes of Chinese medicine (CM) on the activation of c-Jun N-terminal kinase (JNK) in Kupffer cells of rats with fatty liver disease and to explore the mechanisms of these therapeutic methods. METHODS: By using a random number table, 98 rats were randomly divided into 7 groups: control group, model group, and 5 treatment groups, including soothing Liver (Gan) recipe group, invigorating Spleen (Pi) recipe group, dispelling dampness recipe group, promoting blood recipe group, and complex recipe group. Rats in the control group were fed with normal food and distilled water by gastric perfusion, while rats in the model group were fed with high-fat food and distilled spirits by gastric perfusion. Rats in the 5 treatment groups were fed with high-fat food and corresponding recipes by gastric perfusion. Twelve weeks later, all rats were sacrificed and liver tissues were stained for pathohistological observation. Kupffer cells were isolated from livers of rats to evaluate JNK and phospho-JNK expressions by Western blotting. RESULTS: The grade of hepatic steatosis was higher in the model group than the control group (P<0.05). Compared with the model group, the grade of fatty degeneration in soothing Liver recipe group and invigorating Spleen recipe group were significantly ameliorated (P<0.05). Expressions of JNK and phospho-JNK in Kupffer cells were significantly higher in the model group than those in the control group (P<0.05, P<0.01). Compared with the model group, expressions of JNK in all treatment groups decreased, especially in invigorating Spleen recipe group and promoting blood recipe group (P<0.05). Compared with the model group, expressions of phospho-JNK in all treatment groups declined significantly (P<0.01), especially in soothing Live recipe group and invigorating Spleen recipe group. CONCLUSIONS: The high expressions of JNK and phospho-JNK in Kupffer cells might play an important role in the pathogenesis of fatty liver disease in rats. The recipes of CM, especially invigorating Spleen recipe and soothing Liver recipe, might protect liver against injury by reducing the total JNK protein content and inhibiting the activation of JNK protein in Kupffer cells of fatty liver model rats, which showed beneficial effects on fatty liver disease.

Effect of berberine on expressions of uncoupling protein-2 mRNA and protein in hepatic tissue of non-alcoholic fatty liver disease in rats.

OBJECTIVE: To observe the effect of berberine on uncoupling protein-2 (UCP2) mRNA and protein expressions in the hepatic tissue of non-alcoholic fatty liver disease (NAFLD) in rats, and to explore the molecular mechanism. METHODS: To establish the NAFLD rat model; the rats were fed by high fat forage and were randomly divided into four groups: normal group, model group, berberine high-dose group (324 mg/kg), and berberine low-dose group (162 mg/kg). After treatment for 12 weeks, the expression of UCP2 mRNA in the liver tissue was analyzed by semiquantitative reverse transcription polymerase chain reaction (RT-RTPCR). The expression level of UCP2 protein in the liver tissue was examined by immunohistochemistry. Total PCR). cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) contents in blood serum, and TG and TC contents in the liver were detected by an automatic biochemical analyzer. The other is to observe the axungia degree of the liver. RESULTS: The expression of UCP2 mRNA and positive cell numbers in the liver tissue were dramatically increased in the model group (P<0.01). Lipid in the serum and hepatic tissues increased significantly, and the liver was fatty. But in the treatment groups, the expression levels of mRNA and UCP2 proteins were significantly down-regulated (P<0.01). Liver steatosis was improved. CONCLUSIONS: Berberine can down-regulate the expression levels of UCP2 mRNA and UCP2 proteins of hepatic tissue in NAFLD rats. It can promote the recovery of hepatocyte steatosis and improve lipid metabolism disorder in NAFLD rats. Berberine shows a potential therapeutic effect on NAFLD.

[The effect of NaCl solution with different concentration on the resuscitation of hemorrhagic shock].

OBJECTIVE: To observe the clinical results of different concentration NaCl solution in hemorrhagic shock resuscitation. METHODS: The 75 cases with hemorrhagic shock were divided into five groups by means of random number table. Treat the cases with 0.9% (control group), 3%, 4.5%, 6% and 7.5% NaCl solution, respectively. Observe the changes of BP, HR, blood gas, renal function, electrolyte concentration of plasma, before and after treatment. RESULTS: After transfusion, compared with groups of 0.9% NS, the mean BP of patients in other four groups rise more quickly but only the group of 4.5% can last 30 minutes (P < 0.05), and K(+) of plasma in groups of 6%, 7.5% NS decline more obviously (P < 0.05), the group of 4.5% maintain the best lever. CONCLUSION: The mean BP of patients rise quickly and continue for a long time, in the group of 4.5%. Meanwhile the internal environment of the body maintain relatively stable in the group of 4.5%.