Early-onset caloric restriction alleviates ageing-associated steatohepatitis in male mice via restoring mitochondrial homeostasis.

Non-alcoholic fatty liver disease is associated with ageing, and impaired mitochondrial homeostasis is the main cause for hepatic ageing. Caloric restriction (CR) is a promising therapeutic approach for fatty liver. The purpose of the present study was to investigate the possibility of early-onset CR in decelerating the progression of ageing-related steatohepatitis. The putative mechanism associated with mitochondria was further determined. C57BL/6 male mice at 8 weeks of age were randomly assigned to one of three treatments: Young-AL (AL, ad libitum), Aged-AL, or Aged-CR (60% intake of AL). Mice were sacrificed when they were 7 months old (Young) or 20 months old (Aged). Aged-AL mice displayed the greatest body weight, liver weight, and liver relative weight among treatments. Steatosis, lipid peroxidation, inflammation, and fibrosis coexisted in the aged liver. Mega mitochondria with short, randomly organized crista were noticed in the aged liver. The CR ameliorated these unfavourable outcomes. The level of hepatic ATP decreased with ageing, but this was reversed by CR. Ageing caused a decrease in mitochondrial-related protein expressions of respiratory chain complexes (NDUFB8 and SDHB) and fission (DRP1), but an increase in proteins related to mitochondrial biogenesis (TFAM), and fusion (MFN2). CR reversed the expression of these proteins in the aged liver. Both Aged-CR and Young-AL revealed a comparable pattern of protein expression. To summarize, this study demonstrated the potential of early-onset CR in preventing ageing-associated steatohepatitis, and maintaining mitochondrial functions may contribute to CR's protection during hepatic ageing.

PRL/PRLR Can Promote Insulin Resistance by Activating the JAK2/STAT5 Signaling Pathway.

Objective: Although prolactin (PRL) is known to affect food intake, weight gain, and insulin resistance, its effects on lipid metabolism and underlying mechanisms remain underinvestigated. This study aimed to investigate the effects of PRL and its receptor (PRLR) on fat metabolism in regulating the JAK2/STAT5 signaling pathway. Methods: SW872 adipocytes were incubated with oleic acid to establish an insulin resistance (IR) model. Western blot was used to detect the expression of PRLR, JAK2, p-JAK2, STAT5, and p-STAT5. Triglyceride (TG) mass was detected by chemical colorimetry methods. Results: Fat droplets in the high-dose and medium-dose PRL groups were significantly higher than in the IR model group. TG mass in the cells was increased significantly compared with the model group. Compared with the control group, the expression of PRLR, p-JAK2, and p-STAT5 were significantly decreased in the IR model group when PRL was intervened for 24 h and 48 h. The expression of PRLR, p-JAK2, and p-STAT5 in the high-dose PRL intervention group increased significantly compared with the model group. The PRLR overexpressing group had significantly increased TG content and PRLR, and JAK2, p-JAK2, STAT5, and p-STAT5 levels compared with the IR model. Conclusion: PRL and PRLR are related to fat metabolism, and the PRL/PRLR signaling pathway can promote insulin resistance by activating the JAK2/STAT5 signaling pathway and increasing the deposition of TGs.

Drosophila CTP synthase regulates collective cell migration by controlling the polarized endocytic cycle.

Phosphatidylinositol (PI) 4,5-bisphosphate (PIP2) is involved in many biological functions. However, the mechanisms of PIP2 in collective cell migration remain elusive. This study highlights the regulatory role of cytidine triphosphate synthase (CTPsyn) in collective border cell migration through regulating the asymmetrical distribution of PIP2. We demonstrated that border cell clusters containing mutant CTPsyn cells suppressed migration. CTPsyn was co-enriched with Actin at the leading edge of the Drosophila border cell cluster where PIP2 was enriched, and this enrichment depended on the CTPsyn activity. Genetic interactions of border cell migration were found between CTPsyn mutant and genes in PI biosynthesis. The CTPsyn reduction resulted in loss of the asymmetric activity of endocytosis recycling. Also, genetic interactions were revealed between components of the exocyst complex and CTPsyn mutant, indicating that CTPsyn activity regulates the PIP2-related asymmetrical exocytosis activity. Furthermore, CTPsyn activity is essential for RTK-polarized distribution in the border cell cluster. We propose a model in which CTPsyn activity is required for the asymmetrical generation of PIP2 to enrich RTK signaling through endocytic recycling in collective cell migration.

Role of Ketogenic Diets in Multiple Sclerosis and Related Animal Models: An Updated Review.

Prescribing a ketogenic diet (KD) is a century-old dietary intervention mainly used in the context of intractable epilepsy. The classic KD and its variants regained popularity in recent decades, and they are considered potentially beneficial in a variety of neurological conditions other than epilepsy. Many patients with multiple sclerosis (MS) have attempted diet modification for better control of their disease, although evidence thus far remains insufficient to recommend a specific diet for these patients. The results of 3 pilot clinical trials of KD therapy for MS, as well as several related studies, have been reported in recent years. The preliminary findings suggest that KD is safe, feasible, and potentially neuroprotective and disease-modifying for patients with MS. Research on corresponding rodent models has also lent support to the efficacy of KD in the prevention and treatment of experimental autoimmune encephalomyelitis and toxin-induced inflammatory demyelinating conditions in the brain. Furthermore, the animal studies have yielded mechanistic insights into the molecular mechanisms of KD action in relevant situations, paving the way for precision nutrition. Herein we review and synthesize recent advances and also identify unresolved issues, such as the roles of adipokines and gut microbiota, in this field. Hopefully this panoramic view of current understanding can inform future research directions and clinical practice with regard to KD in MS and related conditions.

Breast carcinoma-amplified sequence 2 regulates adult neurogenesis via ß-catenin.

BACKGROUND: Breast carcinoma-amplified sequence 2 (BCAS2) regulates ß-catenin gene splicing. The conditional knockout of BCAS2 expression in the forebrain (BCAS2 cKO) of mice confers impaired learning and memory along with decreased ß-catenin expression. Because ß-catenin reportedly regulates adult neurogenesis, we wondered whether BCAS2 could regulate adult neurogenesis via ß-catenin. METHODS: BCAS2-regulating neurogenesis was investigated by characterizing BCAS2 cKO mice. Also, lentivirus-shBCAS2 was intracranially injected into the hippocampus of wild-type mice to knock down BCAS2 expression. We evaluated the rescue effects of BCAS2 cKO by intracranial injection of adeno-associated virus encoding BCAS2 (AAV-DJ8-BCAS2) and AAV-ß-catenin gene therapy. RESULTS: To show that BCAS2-regulating adult neurogenesis via ß-catenin, first, BCAS2 cKO mice showed low SRY-box 2-positive (Sox2+) neural stem cell proliferation and doublecortin-positive (DCX+) immature neurons. Second, stereotaxic intracranial injection of lentivirus-shBCAS2 knocked down BCAS2 in the hippocampus of wild-type mice, and we confirmed the BCAS2 regulation of adult neurogenesis via ß-catenin. Third, AAV-DJ8-BCAS2 gene therapy in BCAS2 cKO mice reversed the low proliferation of Sox2+ neural stem cells and the decreased number of DCX+ immature neurons with increased ß-catenin expression. Moreover, AAV-ß-catenin gene therapy restored neuron stem cell proliferation and immature neuron differentiation, which further supports BCAS2-regulating adult neurogenesis via ß-catenin. In addition, cells targeted by AAV-DJ8 injection into the hippocampus included Sox2 and DCX immature neurons, interneurons, and astrocytes. BCAS2 may regulate adult neurogenesis by targeting Sox2+ and DCX+ immature neurons for autocrine effects and interneurons or astrocytes for paracrine effects. CONCLUSIONS: BCAS2 can regulate adult neurogenesis in mice via ß-catenin.

Peritoneal dialysis can maintain nitrogen balance with low Kt/V in anuric patients.

BACKGROUND: A big concern for continuous ambulatory peritoneal dialysis (CAPD) is dialysis adequacy in anuric patients. Some studies have even suggested that CAPD patients should be transferred to hemodialysis when they become anuric in order to achieve adequate dialysis. In the present study, we tried to find out whether anuric patients can maintain nitrogen balance with standard or even lower dialysis dose. MATERIALS AND METHODS: This was a cross-sectional single-center study. Fifteen anuric CAPD patients were selected. Their 3-day dietary records were reviewed by a dedicated dietitian to calculate their energy, protein, and nitrogen intake (NI). Nitrogen removal (NR) from urine and dialysate was measured by Kjeldahl technique. Fluid status was evaluated by bioimpedance analysis. Subjective global nutritional assessment was used to evaluate nutritional status. RESULTS: Among the 15 patients, 9 males and 6 females, mean age was 63.80 (31 - 77) years, dialysis duration 39.76 (6 - 127) months, body weight 58.70 ± 9.86 kg, and height 160.20 ± 7.93 cm. The mean dietary protein intake was 43.28 ± 7.57 g/day (0.80 ± 0.15 g/kg/d), total Kt/V was 1.59 ± 0.32 with dialysis dose of 7,904.00 ± 1,481.79 mL. However, they achieved neutral nitrogen balance (NI 6.92 ± 1.21 g/d vs. NR 6.83 ± 1.36 g/d, N balance 0.09 ± 1.00 g/d). All of them maintained good nutritional status (SGA "A", serum albumin 39.67 ± 3.58 g/L), and no symptom of nitrogen retention (serum urea 20.49 ± 3.06 mmol/L). Meanwhile, they achieved good volume control with a slightly low total fluid removal (704.00 ± 293.21 mL/d). CONCLUSION: Our study suggested that anuric patients (even with low Kt/V) can achieve nitrogen balance and stay well-nourished with appropriate dietary protein intake.

Early-onset dietary restriction maintains mitochondrial health, autophagy and ER function in the left ventricle during aging.

Dietary restriction (DR) exerts healthy benefits, including heart functions. However, the cardioprotective role of DR is till controversial among researchers due to the variation of DR conditions. The present study focuses on the protective effect of early-onset DR on cardiac injury using mitochondrial structure and expression of protein associated with mitochondrial homeostasis, autophagy and endoplasmic reticulum (ER) function as measures. 2-month-old mice were fed with a breeding diet ad libitum (AL) or DR (60% of AL) for 3 (Young) or 20 (Aged) months. Body weight increased with aging, whereas DR treatment kept body weight consistent. DR mice exhibited a higher relative heart weight than AL mice. DR mice displayed lower plasma glucose levels, compared with AL groups. Furthermore, Aged-AL, but not Aged-DR mice, had increased collagen content and morphological distortions in the left ventricle (LV). Aged-DR mice had a higher ATP and lower TBARS in the LV than Aged-AL mice. Mitochondrial morphology was detected by electron microscopy; Aged-AL mice had increased abnormal morphology of mitochondria. Treatment with DR reduced abnormal mitochondrial accumulation. Aging elevated the protein expressions of mitochondrial functions and ER-induced apoptosis. Aging downregulated autophagy related proteins and chaperones in the heart. Dietary restriction reversed those protein expressions. The present study demonstrated a beneficial effect of early onset DR on cardiac aging. The age-dependent mitochondrial dysfunction and protein quality control dysregulation was significantly reversed by long-term DR, demonstrating a concordance with the beneficial effect in the heart.

Acyl-Coenzyme A Synthetase Long-Chain Family Member 4 Is Involved in Viral Replication Organelle Formation and Facilitates Virus Replication via Ferroptosis.

Enterovirus infections can cause severe complications, such as poliomyelitis, encephalitis, myocarditis, meningitis, neurological pulmonary edema, and even death. Here, we used genome-wide CRISPR screens to gain new insight into the mechanism by which enteroviruses co-opt host pathways to potentiate replication and propagation. We found that acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) is involved in viral replication organelle formation. ACSL4 is a key component of ferroptosis, an iron-dependent, nonapoptotic programmed cell death. Our results indicated that enteroviruses and coronaviruses can induce ferroptosis via ACSL4. Most importantly, ferroptosis inhibitors, including two FDA-approved drugs, rosiglitazone (ROSI; ACSL4 inhibitor) and pioglitazone (PIO; ACSL4 inhibitor), decreased the viral load of human enteroviruses and coronaviruses, suggesting that ACSL4 is a target for counteracting viral infection. IMPORTANCE We provide the first evidence for the role of ACSL4 in enterovirus replication organelle formation. Moreover, both enteroviruses and coronaviruses induce ferroptosis via ACSL4. These findings establish a novel regulatory mechanism for viral replication. The inhibition of ACSL4 by ferroptosis inhibitors can reduce viral yields of enteroviruses and coronaviruses, including SARS-CoV-2, implying that ACSL4-mediated ferroptosis is a promising therapeutic target for viral diseases.

Challenges of Using Instant Communication Technology in the Emergency Department during the COVID-19 Pandemic: A Focus Group Study.

A record outbreak of community-spread COVID-19 started on 10 May 2021, in Taiwan. In response to the COVID-19 pandemic, care facilities have adopted various protocols using instant communication technology (ICT) to provide remote yet timely healthcare while ensuring staff safety. The challenges of patient evaluation in the emergency department (ED) using ICT are seldom discussed in the literature. The objective of this study was to investigate the factors influencing the utility of ICT for patient assessment in emergency settings during the pandemic. The patient flow protocol and the ED layout were modified and regionalized into different areas according to the patient's risk of COVID-19 infection. Nine iPads were stationed in different zones to aid in virtual patient assessment and communication between medical personnel. A focus group study was performed to assess and analyze the utility of the ICT module in the ED. Eight emergency physicians participated in the study. Of them, four (50%) had been directly involved in the development of the ICT module in the study hospital. Three main themes that influenced the application of the ICT module were identified: setting, hardware, and software. The setting theme included six factors: patient evaluation, subspecialty consultation, patient privacy and comfortableness, sanitation, cost, and patient acceptability. The hardware theme included six factors: internet connection, power, quality of image and voice, public or personal mode, portable or fixed mode, and maintenance. The software theme included six factors: platform choices, security, ICT accounts, interview modes, video/voice recording, and time limitation. Future studies should focus on quantifying module feasibility, user satisfaction, and protocol adjustment for different settings.

Dietary citrate supplementation enhances longevity, metabolic health, and memory performance through promoting ketogenesis.

Citrate is an essential substrate for energy metabolism that plays critical roles in regulating cell growth and survival. However, the action of citrate in regulating metabolism, cognition, and aging at the organismal level remains poorly understood. Here, we report that dietary supplementation with citrate significantly reduces energy status and extends lifespan in Drosophila melanogaster. Our genetic studies in fruit flies implicate a molecular mechanism associated with AMP-activated protein kinase (AMPK), target of rapamycin (TOR), and ketogenesis. Mice fed a high-fat diet that supplemented with citrate or the ketone body ß-hydroxybutyrate (ßOHB) also display improved metabolic health and memory. These results suggest that dietary citrate supplementation may prove to be a useful intervention in the future treatment of age-related dysfunction.

Diagnostic Accuracy of SARS-CoV-2 Antigen Tests for Community Transmission Screening: A Systematic Review and Meta-Analysis.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) caused the global pandemic of coronavirus disease 2019 (COVID-19). Rapid identification and isolation of infectious patients are critical methods to block COVID-19 transmission. Antigen tests can contribute to prompt identification of infectious individuals. This meta-analysis aims to evaluate the diagnostic accuracy of antigen tests for SARS-CoV-2. We conducted a literature search in PubMed, Embase, the Cochrane Library, and Biomed Central databases. Studies evaluating the diagnostic accuracy of antigen tests for SARS-CoV-2 in community participants were included. Only English-language articles were reviewed. We included eligible studies that provided available data to construct a 2 × 2 table on a per-patient basis. Overall sensitivity and specificity for antigen tests were generated using a bivariate random-effects model. Eighteen studies with 34,865 participants were retrieved. The meta-analysis for SARS-CoV-2 antigen tests generated a pooled sensitivity of 0.82 and a pooled specificity of 1.00. A subgroup analysis of ten studies that reported outcomes for 5629 symptomatic participants generated a pooled sensitivity of 0.87 and a pooled specificity of 1.00. Antigen tests might have higher sensitivity in detecting SARS-CoV-2 in symptomatic patients in the community and may be an effective tool to identify patients to be quarantined to prevent further SARS-CoV-2 transmission.

A comparative study of propofol alone and propofol combined with midazolam for dental treatments in special needs patients.

ABSTRACT: Although dental treatment with sedation is performed increasingly in special needs patients, data on adding midazolam to intravenous propofol sedation are very limited for this group. The purpose of this study was to identify the factors and procedure time associated with the use of intravenous sedation with propofol alone or propofol combined with midazolam in dental patients with special needs.This was a retrospective data analysis. The sedation medications and relevant covariates, including demographic parameters, disability levels, oral health conditions, dental procedures, treatment time, and side effects, of 718 patients with special needs were collected between April 2013 and September 2014. The unfavorable side effects by sedation types were reported. Factors associated with procedure time and the sedation medications were assessed with multiple logistic regression analyses.Of 718 patients, 8 patients experienced unfavorable side effects (vomiting, sleepiness, or emotional disturbance) after the dental procedures; the rate was 0.6% in the 509 patients who received propofol only. In 209 patients who received propofol and midazolam, 2.4% experienced the side effects. Sedation time was associated with body mass index (BMI) < 25 (adjusted odds ratio [aOR] = 1.45, 95% confidence interval [CI]: 1.04-2.04) and the performance of multiple dental procedures (aOR = 1.44, 95% CI: 1.06-1.97) but not associated with the sedation types. A significant odds ratio for the combined use of propofol and midazolam was shown for adolescents (aOR = 2.22, 95% CI: 1.28-3.86), men (aOR = 2.05, 95% CI: 1.41-2.98), patients with cognitive impairment (aOR = 1.99, 95% CI: 1.21-3.29), and patients undergoing scaling procedures (aOR = 1.64, 95% CI: 1.13-2.39).With the acceptable side effects of the use of propofol alone and propofol combined with midazolam, multiple dental procedures increase the sedation time and the factors associated with the combined use of propofol and midazolam are younger age, male sex, recognition problems, and the type dental procedure in the dental treatment of patients with special needs.

4-Ethylguaiacol modulates neuroinflammation and Th1/Th17 differentiation to ameliorate disease severity in experimental autoimmune encephalomyelitis.

BACKGROUND: Multiple sclerosis (MS) is a progressive autoimmune disease characterized by the accumulation of pathogenic inflammatory immune cells in the central nervous system (CNS) that subsequently causes focal inflammation, demyelination, axonal injury, and neuronal damage. Experimental autoimmune encephalomyelitis (EAE) is a well-established murine model that mimics the key features of MS. Presently, the dietary consumption of foods rich in phenols has been reported to offer numerous health benefits, including anti-inflammatory activity. One such compound, 4-ethylguaiacol (4-EG), found in various foods, is known to attenuate inflammatory immune responses. However, whether 4-EG exerts anti-inflammatory effects on modulating the CNS inflammatory immune responses remains unknown. Thus, in this study, we assessed the therapeutic effect of 4-EG in EAE using both chronic and relapsing-remitting animal models and investigated the immunomodulatory effects of 4-EG on neuroinflammation and Th1/Th17 differentiation in EAE. METHODS: Chronic C57BL/6 EAE and relapsing-remitting SJL/J EAE were induced followed by 4-EG treatment. The effects of 4-EG on disease progression, peripheral Th1/Th17 differentiation, CNS Th1/Th17 infiltration, microglia (MG) activation, and blood-brain barrier (BBB) disruption in EAE were evaluated. In addition, the expression of MMP9, MMP3, HO-1, and Nrf2 was assessed in the CNS of C57BL/6 EAE mice. RESULTS: Our results showed that 4-EG not only ameliorated disease severity in C57BL/6 chronic EAE but also mitigated disease progression in SJL/J relapsing-remitting EAE. Further investigations of the cellular and molecular mechanisms revealed that 4-EG suppressed MG activation, mitigated BBB disruption, repressed MMP3/MMP9 production, and inhibited Th1 and Th17 infiltration in the CNS of EAE. Furthermore, 4-EG suppressed Th1 and Th17 differentiation in the periphery of EAE and in vitro Th1 and Th17 cultures. Finally, we found 4-EG induced HO-1 expression in the CNS of EAE in vivo as well as in MG, BV2 cells, and macrophages in vitro. CONCLUSIONS: Our work demonstrates that 4-EG confers protection against autoimmune disease EAE through modulating neuroinflammation and inhibiting Th1 and Th17 differentiation, suggesting 4-EG, a natural compound, could be potentially developed as a therapeutic agent for the treatment of MS/EAE.

Application of four nutritional risk indexes in perioperative management for esophageal cancer patients.

PURPOSE: The Prognostic Nutritional Index (PNI), Nutritional Risk Index (NRI), Geriatric Nutritional Risk Index (GNRI), and Controlling Nutritional Status (CONUT) score were devised for quantifying nutritional risk. This study evaluated their properties in detecting compromised nutrition and guiding perioperative management of esophageal cancer patients. METHODS: A prospective institutional database of esophageal cancer patients was reviewed and analyzed. Compromised nutritional status was defined as PNI < 50, NRI < 97.5, GNRI < 92, or CONUT score ≥ 4, respectively. The malnutrition diagnosis consensus established by the European Society of Clinical Nutrition and Metabolism (ESPEN 2015) was selected as reference. Multivariable logistic regression and receiver operating characteristic curve analysis were used. External validation was conducted. RESULTS: After reviewing the 212-patient database, 192 patients were finally included. Among the four nutritional indexes, the GNRI < 92 showed highest sensitivity (72.0%), specificity (78.9%), and consistency (AUC 0.754, 95% CI 0.672-0.836) with malnutrition diagnosed by ESPEN 2015. The GNRI < 92 showed comparable performance with ESPEN 2015 in recognizing decreased fat mass, fat-free mass, and skeletal muscle mass (all P < 0.01). Both the GNRI < 92 and ESPEN 2015 showed good property in predicting major complications, infectious complications, overall complications and delayed hospital discharge (all P < 0.01), better than PNI < 50, NRI < 97.5, and CONUT score ≥ 4. Regarding the external validation, a retrospective analysis of 155 esophageal cancer patients confirmed the better performance of GNRI < 92 in predicting perioperative morbidities than other 3 nutritional indexes. CONCLUSION: The GNRI was optimal in perioperative management of esophageal cancer patients among the four nutritional indexes and was an appropriate alternative to ESPEN 2015 for simplifying nutritional assessment.

Sarcopenia: An underlying treatment target during the COVID-19 pandemic.

The role of skeletal muscle mass in modulating immune response and supporting metabolic stress has been increasingly confirmed. Patients with sarcopenia, characterized by reduced muscle mass and muscle strength, were reported to have poor immune response and metabolic stress when facing acute infection, major surgeries, and other attacks. Based on empirical data, patients with sarcopenia are speculated to have increased infection rates and dismal prognoses amid the current 2019 novel coronavirus disease (COVID-19) epidemic. COVID-19 infection also aggravates sarcopenia because of the increased muscle wasting caused by systematic inflammation and the reduced physical activity and inadequate nutrient intake caused by social isolation. Notably, the interventions targeting skeletal muscle are anticipated to break the vicious circle and benefit the treatment of both conditions. We recommend sarcopenia assessment for populations with advanced age, inactivity, chronic disease, cancers, and nutritional deficiency. Patients with sarcopenia and COVID-19 infection need intensive care and aggressive treatments. The provision of at-home physical activities together with protein supplementation is anticipated to reverse sarcopenia and promote the prevention and treatment of COVID-19. The recommended protocols on nutritional support and physical activities are provided in detail.

Nervous System Deletion of Mammalian INDY in Mice Mimics Dietary Restriction-Induced Memory Enhancement.

Reduced expression of the Indy (I'm Not Dead Yet) gene extends life span in Caenorhabditis elegans and Drosophila melanogaster and improves the metabolic heath of Mus musculus through inducing a physiological status akin to dietary restriction (DR). Although the function of Indy in aging and hepatic metabolism has been extensively studied, its role in the mouse nervous system remains unclear. Here, we explore the effect of mammalian Indy (mIndy, SLC13A5) gene deletion on murine cognitive function. Similar to what is seen in DR animals, systemic deletion of the mIndy gene (mIndy knockout [KO]) significantly improves memory performance and motor coordination of mice. Both DR and mIndy KO mice act normally in other behavioral tasks, including emotional, social, and food-seeking behaviors. Moreover, we find that tissue-specific deletion of mIndy in the nervous system is sufficient to improve memory performance, while liver-specific deletion has no effect on memory, and results in tests of motor coordination show no changes in either mutant. Mice with systemic or nervous system deletion of mIndy also exhibit increased hippocampal neurogenesis and dendritic spine formation in dentate granule cells; these changes are well-documented contributors to enhanced memory performance. Together, our studies demonstrate a critical role for brain-derived mIndy expression in the regulation of memory function in animals.

Highlighting sarcopenia management for promoting surgical outcomes in esophageal cancers: Evidence from a prospective cohort study.

BACKGROUND: Studies have provided controversial and limited knowledge regarding the impact of sarcopenia on surgical outcomes in esophageal cancers due to retrospective study designs and single muscle-mass assessment. This prospective cohort study aimed to resolve these issues. METHODS: Bioelectrical impedance analysis, handgrip strength measurement, and the 4-m walking test were conducted before surgery. Sarcopenia was diagnosed as low appendicular skeletal muscle mass index (<7.0 kg/m2 in men and <5.7 kg/m2 in women) plus low handgrip strength (<26 kg in men and <18 kg in women) and/or low gait speed (<0.8 m/s). Presarcopenia was diagnosed as either: (1) solely low muscle mass index; or (2) solely low handgrip strength and/or gait speed. Endpoints included perioperative biochemical indicators, postoperative complications, and the recovery of postoperative quality of life (QOL). RESULTS: In total, 212 patients were enrolled, including 55 (25.9%) and 60 (28.3%) patients diagnosed with sarcopenia and presarcopenia, respectively. The presarcopenic and normal patients showed a similar risk of postoperative complications and were combined. Despite similar baseline levels, sarcopenic patients (vs. non-sarcopenic) showed decreased prealbumin on postoperative day (POD) 1, decreased albumin on PODs 1, 3, and 5, and delayed recovery of lymphocyte counts (all P < 0.05). The levels of C-reactive protein in sarcopenic patients was lower than in non-sarcopenic patients on POD 1 (P = 0.010) but higher on POD 5 (P = 0.001). Multivariate analyses demonstrated the independent predictive value of sarcopenia for overall complications (P < 0.001), major complications (Clavien-Dindo grade ≥ III, P = 0.001), and delayed hospital discharge (>12 days, P < 0.001). Sarcopenia was demonstrated as a risk factor for deteriorated global QOL (P = 0.001), physical (P = 0.001) and role functions (P = 0.006), and severe fatigue (P = 0.004) at four weeks after surgery. CONCLUSIONS: Sarcopenia was associated with poor metabolic stress and immune responses surrounding esophagectomy and was a potential target for reducing complications and promoting recovery of QOL.

[Effect of acupuncture and moxibustion at "Feishu""Dazhui"and "Fengmen"on the expression of CC chemokine ligand 1 and CC chemokine receptor 8 in lung tissue of rats with asthma].

OBJECTIVE: To investigate the protein expression of CC chemokine ligand 1 (CCL1) and CC chemokine receptor 8 (CCR8) in the lung tissue of rats and the mechanism of acupuncture and moxibustion at "Feishu"(BL13), "Dazhui" (GV14) and "Fengmen"(BL12) in the treatment of asthma. METHODS: Sprague-Dawley rats were randomly divided into blank， model, acupuncture and moxibustion groups，n=10 in each group. Ovalbumin sensitization via intraperitoneal injection was performed to establish a model of asthma. The rats in the acupuncture group and the moxibustion group were given acupuncture for 20 min or circling moxibustion for 10 min at BL13, GV14 and BL12, once a day for 7 days. H.E. staining was used to observe the morphological changes of lung tissue. Real-time fluorescence quantitative PCR was used to measure the mRNA expression of signal transducer and activator of transcription 6 (STAT6) in lung tissue and immunohistochemistry was used to measure the protein expression of CCL1 and CCR8 in lung tissue. RESULTS: H.E. staining showed that the rats in the blank group had regular bronchial lumens and alveolar arrangement, with no inflammatory cell infiltration and aggregation around the bronchi; the rats in the model group had the infiltration and aggregation of a large number of inflammatory cells around the bronchi, stenosis of bronchial lumens, wall thickening, and alveolar structural disorder; compared with the model group, the acupuncture group and the moxibustion group had lower degrees of inflammatory cell infiltration and aggregation around the bronchi, stenosis of bronchial lumens, and wall thickening, as well as regular alveolar arrangement. The model group had significantly higher protein expression of CCL1 and CCR8 and mRNA expression of STAT6 than the blank group (P<0.05), and the acupuncture group and the moxibustion group had significantly lower protein expression of CCL1 and CCR8 and mRNA expression of STAT6 (P<0.05). CONCLUSION: Acupuncture and moxibustion can intervene against airway inflammation by inhibiting the protein expression of CCL1 and CCR8 and STAT6 signal transduction in lung tissue, which may be one of the mechanisms of acupuncture and moxibustion in the treatment of asthma.