Volunteer-led physical activity interventions to improve health outcomes for community-dwelling older people: a systematic review.

BACKGROUND: Physical activity (PA) is important for older people to maintain functional independence and healthy ageing. There is strong evidence to support the benefits of physical activity interventions on the health outcomes of older adults. Nonetheless, innovative approaches are needed to ensure that these interventions are practical and sustainable. AIM: This systematic review explores the effectiveness of volunteer-led PA interventions in improving health outcomes for community-dwelling older people. METHODS: Five databases (MEDLINE, Embase, CINAHL, PEDro, Cochrane library) were systematically searched for studies using trained volunteers to deliver PA interventions for community-dwelling older people aged ≥ 65 years. Meta-analysis was not conducted due to included study heterogeneity. RESULTS: Twelve papers describing eight studies (five papers reported different outcomes from the same study) were included in the review. All eight studies included strength and balance exercises and frequency of PA ranged from weekly to three times a week. Volunteer-led exercises led to improvements in functional status measured using the short physical performance battery, timed up and go test, Barthel Index, single leg stand, step touch test, chair stand test, and functional reach. Frailty status identified by grip strength measurement or the use of long-term care insurance improved with volunteer-led exercises. Interventions led to improvement in fear of falls and maintained or improved the quality of life. The impact on PA levels were mixed. CONCLUSION: Limited evidence suggests that volunteer-led PA interventions that include resistance exercise training, can improve outcomes of community-dwelling older adults including functional status, frailty status, and reduction in fear of falls. More high-quality RCTs are needed to investigate the effects of volunteer-led PA interventions among older people.

[A cohort study on plasma uric acid levels and the risk of type 2 diabetes mellitus among the oldest old in longevity areas of China].

Objective: To investigate the effect of plasma uric acid level on the incident risk of type 2 diabetes mellitus (T2DM) among the oldest old (those aged ≥80 years). Methods: Participants were recruited from the Healthy Aging and Biomarkers Cohort Study (HABCS), which conducted a baseline survey in 2008-2009 and follow-up of 3 times in 2011-2012, 2014, and 2017-2018, respectively. A total of 2 213 oldest old were enrolled in this study. The general demographic, socioeconomic, lifestyle and disease data of the oldest old were collected, and physical measurements were made for the oldest old. Fasting venous blood was collected for uric acid and blood glucose detection. Information on the incident and death of T2DM were collected through the follow-up. Cox proportional hazard regression model was used to explore the association of hyperuricemia and plasma uric acid level with the incidence of T2DM. Restricted cubic spline (RCS) function was used to explore the dose-response relationship of plasma uric acid levels with the risk of T2DM. Results: The age of participants was (93.2±7.6) years old, and 66.7% of the participants (1 475) were female. The plasma uric acid level at baseline was (289.1±88.0)µmol/L, and the prevalence of hyperuricemia was 13.3% (294 cases). During 9 years of cumulative follow-up of 7 471 person-years (average of 3.38 years for each), 122 new cases of T2DM occurred and the incidence density was 1 632.98/105 person year. Cox proportional hazards regression analysis showed that per 10µmol/L increase in plasma uric acid level, the risk of T2DM increased by 1.1% [HR (95%CI): 1.011 (1.004, 1.017)]. Compared with the participants with the lowest quintile of plasma uric acid (Q1), the risk of diabetes increased by 20.7 % among the oldest old with uric acid in the highest quintile (Q5) [HR (95%CI):1.207 (1.029, 1.416)]. The risk of T2DM was 19.2% higher in the hyperuricemia group than that in the oldest old with normal plasma uric acid [HR (95%CI): 1.192 (1.033, 1.377)]. RCS function showed that the risk of T2DM increased with the increase in plasma uric acid levels in a nonlinear dose-response relationship (P=0.016). Conclusion: The incident risk of T2DM increases with the elevates of plasma uric acid levels in the oldest old.

[Association of blood oxidative stress level with hypertriglyceridemia in the elderly aged 65 years and older in 9 longevity areas of China].

Objective: To investigate the association of blood oxidative stress level with hypertriglyceridemia in the elderly aged 65 years and older in China. Methods: A total of 2 393 participants aged 65 years and older were recruited in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study, during 2017 to 2018. Information on demographics characteristic, life style and health status were collected by questionnaire and physical examination, and venous blood was collected to detect the levels of blood oxidative stress and hypertriglyceridemia. The linear or non-linear association between oxidative stress and hypertriglyceridemia was described by restrictive cubic splines (RCS) fitting multiple linear regression model. The generalized linear mixed effect model was conducted to assess the association between oxidative stress and hypertriglyceridemia. Results: A total of 2 393 participants, mean age was 84.6 years, the youngest was 65 and the oldest was 112, the male was 47.9%(1 145/2 393), the triglyceride level was (1.4±0.8) mmol/L. The hypertriglyceridemia detection rate was 9.99%(239/2 393). The results of multiple linear regression model with restrictive cubic spline fitting showed that MDA level was linear association with triglyceride level; SOD level was nonlinear association with triglyceride level. MDA level had significantly association with hypertriglyceridemia, and the corresponding OR value was 1.063 (95%CI: 1.046,1.081) with 1 nmol/ml increment of blood MDA; SOD level had significantly association with hypertriglyceridemia, and the corresponding OR value was 0.986(95%CI: 0.983,0.989) with 1 U/ml increment of blood SOD. Conclusion: Among the elderly aged 65 and older in 9 longevity areas in China, MDA and SOD levels were associated with the risk of hypertriglyceridemia.

[Association of blood lead level with cognition impairment among elderly aged 65 years and older in 9 longevity areas of China].

Objective: To investigate the association between blood lead concentrations and cognition impairment among Chinese older adults aged 65 or over. Method: Data was collected in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study between 2017 and 2018. This study included 1 684 elderly aged 65 years and older. Information about demographic characteristics, socioeconomic factors, health status and cognitive function score of respondents were collected by questionnaire survey and physical examination. Venous blood of the subjects was collected to detect the blood lead concentration. Subjects were stratified into four groups (Q1-Q4) by quartile of blood lead concentration. Multivariate logistic regression model was used to analyze the association between blood lead concentration and cognitive impairment. The linear or non-linear association between blood lead concentration and cognitive impairment were described by restrictive cubic splines (RCS). Results: Among the 1 684 respondents, 843 (50.1%) were female and 191 (11.3%) suffered from cognition impairment. After adjusting for confounding factors, the OR value and 95%CI of cognition impairment was 1.05 (1.01-1.10) for every 10 µg/L increase in blood lead concentration in elderly; Compared with the elderly in Q1, the elderly with higher blood lead concentration had an increased risk of cognitive impairment. The OR value and 95%CI of Q2, Q3 and Q4 groups were 1.19 (0.69-2.05), 1.45 (0.84-2.51) and 1.92 (1.13-3.27), respectively. Conclusion: Higher blood lead concentration is associated with cognitive impairment among the elderly aged 65 years and older in 9 longevity areas in China.

[Analysis of pregnancy outcome of single and double blastocysts in the freeze-thaw cycle].

Objective: To compare the clinical outcomes of one and two blastocysts in the freeze-thaw transplantation cycle. Methods: Totally 3 675 cycles of frozen thawed blastocyst transplantation in Reproductive Medical Center of the Second Nanning People's Hospital from January 2012 to December 2016 were analyzed retrospectively. According to the quantity and quality of transferred blastocysts, all the patient were divided into two groups: (1) one embryo group, including the single excellent group (one high quality blastocyst) and the single non excellent group (one non high quality blastocyst); (2) two embryo groups, including the double excellent group (two high quality blastocysts), the one excellent and one non excellent group (one high quality blastocyst+one non high quality blastocyst), and the two non excellent group (two non high quality blastocysts were transplanted). Then the patients were divided into subgroups according to their ages: less than 35 years old, 35-40 years old and over 40 years old. On this basis, the implantation rate, clinical pregnancy rate, multiple birth rate and live birth rate were compared. Results: (1) The implantation rate, clinical pregnancy rate, multiple birth rate, preterm birth rate and live birth rate were all significantly increased, while the abortion rate was significantly reduced in the double blastocyst group (all P<0.05). (2) In the group of<35 years old, the rates of multiple birth and preterm birth in the double blastocyst group were significantly higher than those in the single optimal group (P<0.01). (3) In the 35-40 years old group, the clinical pregnancy rate, multiple birth rate and live birth rate of the double excellent group were significantly higher than those of the single excellent group (P<0.01); while the clinical pregnancy rate and live birth rate of the one excellent and one non excellent group and the double non excellent group were not significantly different from those of the single excellent group (P>0.05), but the multiple birth rate and preterm birth rate were significantly increased (P<0.01). The clinical pregnancy rate, live birth rate and multiple birth rate of double non optimal group were significantly higher than those of single non optimal group (P<0.01). (4) In the group>40 years old, there were no significant differences in clinical pregnancy rate and live birth rate between the two groups (P>0.05). There were no significant differences in implantation rate, clinical pregnancy rate and live birth rate between double non optimal group and single non optimal group (P>0.05). Conclusion: No matter the age of the patients, if the couple have high quality blastocysts, we should give priority to single high quality blastocyst transplantation; even if they have no high quality blastocysts, we should also consider single blastocyst transplantation, in order to reduce the risk of multiple pregnancy and improve the cumulative live birth rate, so as to improve the pregnancy outcome.

[Application of restricted cube spline in cox regression model].

Restricted cubic spline Cox proportional hazard regression model analysis is an important method of epidemiological multivariate survival analysis. By comparing the typical Cox regression model and the restricted cubic spline Cox regression model, this study expounds the limitations of the typical Cox regression model, and explains the basic principles and implementation process of the restricted cubic spline Cox proportional hazard regression model. When the follow-up data does not meet the application conditions of the typical Cox regression model, this method can be used to realize the correlation analysis between continuous exposure and outcomes.

[The role of the traditional surgical procedures for gastroesophageal reflux disease cannot be ignored].

Gastroesophageal reflux disease (GERD) is a common digestive disease with characteristics of a multitude of pathogenesis, a variety of clinical manifestations and a strong negative impact on physical and mental health of the patients. GERD is classified into non-erosive reflux disease and reflux esophagitis in terms of absence or presence of mucosal damage at endoscopic findings. Proton pump inhibitors (PPI) are widely used in the treatment of GERD, especially for patients with non-erosive reflux disease or mild reflux esophagitis. However, PPI do not affect pathophysiologic mechanisms of GERD or reduce the number of reflux events. When PPI fails to adequately control the symptoms of GERD as a result of gastroesophagel junction structural defects, the antireflux surgical procedures are indicated to create a mechanical barrier to reflux. The laparoscopic fundoplication remains the most commonly performed and is the current "gold-standard" anti-reflux procedure. The outcomes of the antireflux surgical procedures are superior to medical therapy for GERD in light of subjective symptoms, objective examinations, quality of life and patient satisfaction. As of now, enough attention has not been paid to the traditional surgical procedures of GERD in China. It is controversial about which is optimal among the three major types of procedures, selection should be tailored to classification, mechanism, age, mental status and esophageal motility. GERD is a chronic disease and either medical or surgical therapy may put the patient at different risk, therefore the patient's preferences should be considered adequately before choosing the treatment protocols.

[Suggestions for thoracic surgery clinical practice in non-epidemic area of 2019 coronavirus disease].

In this paper, the mechanism of destroying human alveolar epithelial cells and pulmonary tissue by 2019 novel coronavirus (2019-nCoV) was discussed firstly. There may be multiple mechanisms including killing directly the target cells and hyperinflammatory responses. Secondly, the clinical features, CT imaging, short-term and long-term pulmonary function damage of the 2019 coronavirus disease (COVID-19) was analyzed. Finally, some suggestions for thoracic surgery clinical practice in non-epidemic area during and after the epidemic of COVID-19 were provided, to help all the thoracic surgery patients receive active and effective treatment.

Cartilage-specific deletion of Alk5 gene results in a progressive osteoarthritis-like phenotype in mice.

OBJECTIVE: Previous studies have shown that Transforming growth factor-ß (TGF-ß)/TGFßRII-Smad3 signaling is involved in articular cartilage homeostasis. However, the role of TGF-ß/ALK5 signaling in articular cartilage homeostasis has not been fully defined. In this study, a combination of in vitro and in vivo approaches was used to elucidate the role of ALK5 signaling in articular cartilage homeostasis and the development of osteoarthritis (OA). DESIGN: Mice with inducible cartilage-specific deletion of Alk5 were generated to assess the role of ALK5 in OA development. Alterations in cartilage structure were evaluated histologically. The expressions of genes associated with articular cartilage homeostasis and TGF-ß signaling were analyzed by qRT-PCR, western blotting and immunohistochemistry. The chondrocyte apoptosis was detected by TUNEL staining and immunohistochemistry. In addition, the molecular mechanism underlying the effects of TGF-ß/ALK5 signaling on articular cartilage homeostasis was explored by analyzing the TGF-ß/ALK5 signaling-induced expression of proteoglycan 4 (PRG4) using specific inhibitors. RESULTS: Postnatal cartilage-specific deletion of Alk5 induced an OA-like phenotype with degradation of articular cartilage, synovial hyperplasia, osteophyte formation, subchondral sclerosis, as well as enhanced chondrocyte apoptosis, overproduction of catabolic factors, and decreased expressions of anabolic factors in chondrocytes. In addition, the expressions of PRG4 mRNA and protein were decreased in Alk5 conditional knockout mice. Furthermore, our results showed, for the first time, that TGF-ß/ALK5 signaling regulated PRG4 expression partially through the protein kinase A (PKA)-CREB signaling pathway. CONCLUSIONS: TGF-ß/ALK5 signaling maintains articular cartilage homeostasis, in part, by upregulating PRG4 expression through the PKA-CREB signaling pathway in articular chondrocytes.

Retraction Note: Study on the functions and mechanism of immune functions of human telomerase reverse transcriptase regulating dendritic cells treating sepsis.

The article "Study on the functions and mechanism of immune functions of human telomerase reverse transcriptase regulating dendritic cells treating sepsis", by H.-M. Chen, L.-Q. Wang, H.-P. Wan, H.-Z. Wei, L.-C. Ke, C.-Y. Liu, Q.-Y. Tan, published in Eur Rev Med Pharmacol Sci 2016; 20 (21): 4500-4507-PMID: 27874963 has been retracted by the Editor in Chief for the following reasons. Some concerns were raised on PubPeer (https://pubpeer.com/publications/3604386A706802443E51758A893D6F) about Figures 3, 4, and 5 showing some overlaps and similar bands in Western blots figures. Furthermore, there is a lack of information regarding the ethics approval for the study involving rats. The journal contacted the authors to request the original raw data and information regarding the ethical approval of the manuscript but never received a reply. Therefore, due to major concerns detected, the Editor in Chief mistrusts the results presented and decided to withdraw the manuscript. The corresponding author has been informed about the retraction. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/11476.

Expression of breast cancer anti-estrogen resistance 1 in relation to vascular endothelial growth factor, p53, and prognosis in esophageal squamous cell cancer.

The purpose of this study was to clarify the role of breast cancer anti-estrogen resistance 1 (BCAR1) expression in relation to vascular endothelial growth factor (VEGF), p53, and proliferation in esophageal squamous cell cancer (ESCC). Expression of BCAR1, VEGF, p53, and the ki-67 proliferative index were examined by tissue microarray and immunohistochemistry in 106 specimens with ESCC and matched adjacent normal tissues. Among them, 40 cases were simultaneously examined by Western blot. Both Western blot and immunohistochemistry showed that BCAR1 expression was substantially higher in ESCC than in adjacent normal tissues (P < 0.001). BCAR1 expression was significantly connected with degree of tumor differentiation, with poorly differentiated tumors showing higher BCAR1 expression (P < 0.001). BCAR1 expression was significantly and positively correlated with VEGF and p53 expression levels (r= 0.541, P < 0.001; r= 0.374; P < 0.001) but not proliferative index (r= 0.44; P= 0.066). Additionally, a significant relationship was also observed between VEGF and p53 (r= 0.321; P= 0.001). Kaplan-Meier survival analysis revealed that patients with high BCAR1 expression had significantly shorter survival times than those with low BCAR1 expression levels (median survival 40 months vs. 27 months, P= 0.09). Multivariate analysis also revealed that levels of BCAR1 expression (hazard ratio 2.250, P= 0.015) was a significant and independent prognostic indicator. High expression of BCAR1 is associated with elevated VEGF and p53 expression levels, as well as poor prognosis in ESCC. Therefore, BCAR1 may be a potential candidate for predicting prognosis and a new therapy target for ESCC.

Preparation and characterization of poly(lactic acid) nanoparticles for sustained release of pyridostigmine bromide.

A novel pyridostigmine bromide poly (lactic acid) nanoparticles (PBPNPs) was prepared to obtain sustained release characteristics of PB. A central composite design approach was employed for process optimization. The in vitro release studies were carried out by dialysis method and conducted using four different dissolution media. Similar factor method was investigated for dissolution profile comparison. Multiple linear regression analysis for process optimization revealed that the optimal PBPNPs were obtained where the values of the amount of PB (X1, mg), PLA concentration (X2, % w:v), and PVA concentration (X3, % w:v) were 49.20 mg, 3.31% and 3.41%, respectively. The average particle size and zeta potential of PBPNPs with the optimized formulation were 722.9 +/- 4.3 nm, and -25.12 +/- 1.2 mV, respectively. PBPNPs provided an initial burst of drug release followed by a very slow release over an extended period of time (72 h). Compared with free PB, PBPNPs had a significantly lower release rate of PB in vitro. The in vitro release profile of the PBPNPs could be described by Weibull models, regardless of type of dissolution medium. Statistical significance of similarity between every two dissolution profiles of PBPNPs in different dissolution media was found, and the difference between the curves of PBPNPs and pure PB was statistically significant.

A review of the Turned-down Onto Pericapsular-tissue Hemisectioned Amputated Toe (TOPHAT) flap for wound coverage during ray amputations of the toes.

INTRODUCTION: Exposure of the adjacent Metatarsal-Phalangeal Joint (MTPJ) commonly occurs after application of Topical Negative Pressure Wound Therapy (TNPWT) for a ray amputation wound. This is due to mechanical soft tissue erosion or trauma to the adjacent digital artery from direct pressure effect. This results in toe gangrene requiring a ray amputation and ultimately a larger wound bed. We describe the use of the Turned-down Onto Pericapsular-tissue Hemisectioned Amputated Toe (TOPHAT) flap - a filleted toe flap to protect the adjacent MTPJ capsule combined with a novel Negative Pressure Wound Therapy with instillation and dwell-time (NPWTi-d) dressing technique. The flap protects the adjacent joint capsule and reduces the wound burden whilst allowing the wound to benefit from TNPWT, thereby accelerating wound healing. MATERIAL AND METHODS: A retrospective review was conducted of patients with toe gangrene requiring ray amputation that underwent the TOPHAT flap on in our institution from 2019 and 2020. Complications such as wound dehiscence, hematoma, flap necrosis and secondary infection were recorded. Other outcomes recorded were time taken to final skin grafting and time taken for complete wound epithelialization. RESULTS: 9 patients underwent treatment with the TOPHAT flap. 2 patients had flap necrosis. 7 patients progressed to definitive skin coverage with skin grafting. One patient subsequently had progressive arterial disease despite successful skin grafting and required above knee amputation. The mean time to final skin grafting and complete wound epithelialization was 49.5 days and 107.5 days respectively. All patients were satisfied with the outcomes and were able to return to their pre-morbid function. CONCLUSIONS: The TOPHAT flap has a consistent vascular supply that provides durable soft tissue coverage. It is a robust and easily reproducible technique to accelerate wound healing after ray amputations even in patients with peripheral vascular disease.

Can probiotics, prebiotics and synbiotics improve functional outcomes for older people: a systematic review.

PURPOSE: Research evaluating the effect of probiotics, prebiotics and synbiotics (PPS) on laboratory markers of health (such as immunomodulatory and microbiota changes) is growing but it is unclear whether these markers translate to improved functional outcomes in the older population. This systematic review evaluates the effect of PPS on functional outcomes in older people. METHODS: We conducted a systematic review of the effect of PPS in older adults on functional outcomes (physical strength, frailty, mood and cognition, mortality and receipt of care). Four electronic databases were searched for studies published since year 2000. RESULTS: Eighteen studies (including 15 RCTs) were identified. One of five studies evaluating physical function reported benefit (improved grip strength). Two analyses of one prebiotic RCT assessed frailty by different methods with mixed results. Four studies evaluated mood with no benefit reported. Six studies evaluated cognition: four reported cognitive improvement in participants with pre-existing cognitive impairment receiving probiotics. Seven studies reported mortality as a secondary outcome with a trend to reduction in only one. Five studies reported length of hospital stay but only two peri-operative studies reported shorter stays. CONCLUSION: There is limited evidence that probiotics may improve cognition in older people with pre-existing cognitive impairment but no clear evidence of benefit of PPS on physical function, frailty, mood, length of hospitalisation and mortality. Larger studies with more homogenous interventions, accounting for confounding factors, such as diet, co-morbidities and medications, are required. There is currently inadequate evidence to recommend PPS use to older people in general. PROSPERO REGISTRATION NUMBER: PROSPERO registration number is CRD42020173417. Date of PROSPERO registration: 01/05/20.

Management of delayed intrathoracic esophageal perforation with modified intraluminal esophageal stent.

In this article, we reviewed our experience of treatment of the delayed intrathoracic nonmalignant esophageal perforation employing modified intraluminal esophageal stent. Between February 1990 and August 2006, eight patients were included in this study. Five patients experienced sepsis. The interval time between perforation and stent placement ranged from 36 h to 27 days (average, 8.6 days). Esophageal stenting and throracotomy for foreign body removal were performed in four patients. The remaining four patients underwent stent placement and thoracostomy. Nutrition was initiated through gastrostomy after 7 to 10 days after the stenting. The stent was removed after the patients resumed oral intake of food and the esophagogram showed that perforation was closed. There was no death in this group. Signs of sepsis remitted 1 week after stent placement. Complications included stress ulcer, stimulative cough, and pneumonia each. Stent removal ranged 32 to 120 days (average 66.7) after its placement. The stent was kept in place for 4 months to prevent formation of esophageal stricture in one patient with caustic esophageal burns. The follow-up was completed in all the patients. The mean follow-up period was 59 months (range 12-180). One patient with caustic esophageal burn underwent cicatricial esophagectomy and gastric transposition 3 years later due to the esophageal stricture. Barium swallow demonstrated that there was a diverticulum-like outpouching in one patient and slight esophageal stricture at T2 and T3 level in another. One patient developed reflux esophagitis 5 years after stent removal. All the patients finally had a normal intake of food. Modified esophageal stenting is an effective method to manage the delayed intrathoracic esophageal perforation. Prevention of stent migration and its convenient adjustment might be the major advantages of this method.

Prevention and management of complications after colon interposition for corrosive esophageal burns.

We present our experience in the management of complications after a colon interposition for corrosive esophageal burns. From April 1976 to December 2006, 85 patients with caustic esophageal burns were included in this study. The superior belly median incision with an anterior border incision of the left sternocleidomastoid was used. Anastomosis between the colon and the cervical esophagus was performed in 68 and between the colon and pharyngeal portion in 14 patients. An esophageal scar part resection and gastric-esophageal anastomosis was performed in one patient who had been given an unsuccessful colon and jejunum interposition at another institute. An anastomotic modeling operation was performed in one patient with anastomotic stricture who had been managed with colon interposition at another institute. Exploratory thoracotomy and gastrostomy was performed in one patient who had an unsuccessful colon interposition at another institute. Seven of 14 patients (8.5% of 17.1%) died with serious complications such as aspirated pneumonia, interposition colon necrosis, abdominal wound dehiscence and degradation of swallowing and concordance function. However, others with such serious complications survived and were discharged for rehabilitation after corresponding treatment. The 25 patients (30.1%) with other mild complications were discharged for rehabilitation and corresponding management. Two patients from other institutes were discharged for rehabilitation and one was lost to follow-up. The most dangerous complication of this procedure is colon necrosis, and the stomach is the best organ for re-operation. Otherwise, aspiration in infants due to hypoplasia and degradation of swallowing co-ordination needs attention. Peri-operative management is very important, including the control of mediastinal and pulmonary infection and systemic nutritional support to avoid abdominal wound dehiscence. The platysma flap is an excellent method for the treatment of anastomotic stricture.

Therapeutic efficacy of atypical antipsychotic drugs by targeting multiple stress-related metabolic pathways.

Schizophrenia (SZ) is considered to be a multifactorial brain disorder with defects involving many biochemical pathways. Patients with SZ show variable responses to current pharmacological treatments of SZ because of the heterogeneity of this disorder. Stress has a significant role in the pathophysiological pathways and therapeutic responses of SZ. Atypical antipsychotic drugs (AAPDs) can modulate the stress response of the hypothalamic-pituitary-adrenal (HPA) axis and exert therapeutic effects on stress by targeting the prefrontal cortex (PFC) and hippocampus. To evaluate the effects of AAPDs (such as clozapine, risperidone and aripiprazole) on stress, we compared neurochemical profile variations in the PFC and hippocampus between rat models of chronic unpredictable mild stress (CUMS) for HPA axis activation and of long-term dexamethasone exposure (LTDE) for HPA axis inhibition, using an ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS)-based metabolomic approach and a multicriteria assessment. We identified a number of stress-induced biomarkers comprising creatine, choline, inosine, hypoxanthine, uric acid, allantoic acid, lysophosphatidylcholines (LysoPCs), phosphatidylethanolamines (PEs), corticosterone and progesterone. Specifically, pathway enrichment and correlation analyses suggested that stress induces oxidative damage by disturbing the creatine-phosphocreatine circuit and purine pathway, leading to excessive membrane breakdown. Moreover, our data suggested that the AAPDs tested partially restore stress-induced deficits by increasing the levels of creatine, progesterone and PEs. Thus, the present findings provide a theoretical basis for the hypothesis that a combined therapy using adenosine triphosphate fuel, antioxidants and omega-3 fatty acids as supplements may have synergistic effects on the therapeutic outcome following AAPD treatment.

Study on the functions and mechanism of immune functions of human telomerase reverse transcriptase regulating dendritic cells treating sepsis.

OBJECTIVE: We analyzed the functions and mechanisms of immune functions of human telomerase reverse transcriptase regulating dendritic cells (DC) treating sepsis of mice models. MATERIALS AND METHODS: Eighty clean grade Balb/c animals aged from 6 to 8 weeks, weighted from 18 g to 22 g were selected for this study. The DC cells were harvested from the animals and cultivated to transfect with the recombinant eukaryotic expression plasmid hTERT-IRES2-EGFP construct. The LPS (E. coli 0111:B4, 5 mg/kg) was injected into the abdominal cavity of mice to establish sepsis models. Afterwards, animals were divided randomly into the sepsis group (A group), the group of hTERT transfecting DC (B group), the group of DC un-transfected (C group) with 25 mice in each group. 5 mice were in the normal control group (D group), without any treatment. An equivalent volume of normal saline was injected into the abdominal cavity of A group. Subsequently, 1 ml of cell suspension (105/ml) was transfected into B and C groups respectively. Five animals from A, B, C groups and one animal from group D were sacrificed after 24h, 48h, 72d, 7d and 10d respectively. RESULTS: It was found that median survival time of the group of hTERT transfecting DC was remarkably higher than that of the untransfected group and the sepsis group. The average scores of the pathology of kidney and intestine at each time were significantly lower than that of the other two groups (p<0.05). At each time point, in the group of hTERT transfecting DC, levels of CRP and Cr were remarkably lower than that of the other two groups; HLA-DR, CD40 of immune phenotype and the expression level of peripheral blood T cells MHC-II molecules were significantly higher than that of the other two groups; the expression level of IL-12 and TNF-a were significantly lower than that of the other two groups; apoptosis rate of DC were significantly lower than that of the other two groups; the content and activity of NF-κB were significantly higher than that of the other two groups (p<0.05). CONCLUSIONS: The telomerase reverse transcriptase gene can raise the expression and maturity of DC, reduce apoptosis, induce cytokine secretion, reduce the inflammatory response and increase the survival time.

A potential mechanism underlying atypical antipsychotics-induced lipid disturbances.

Previous findings suggested that a four-protein complex, including sterol-regulatory element-binding protein (SREBP), SREBP-cleavage-activating protein (SCAP), insulin-induced gene (INSIG) and progesterone receptor membrane component 1 (PGRMC1), within the endoplasmic reticulum appears to be an important regulator responsible for atypical antipsychotic drug (AAPD)-induced lipid disturbances. In the present study, effects of typical antipsychotic drug and AAPDs as well as treatment outcome of steroid antagonist mifepristone (MIF) on the PGRMC1/INSIG/SCAP/SREBP pathway were investigated in rat liver using real-time quantitative polymerase chain reaction (qPCR) and western blot analysis. In addition, serum triacylglycerol, total cholesterol, free fatty acids and various hormones including progesterone, corticosterone and insulin were measured simultaneously. Following treatment with clozapine or risperidone, both lipogenesis and cholesterogenesis were enhanced via inhibition of PGRMC1/INSIG-2 and activation of SCAP/SREBP expressions. Such metabolic disturbances, however, were not demonstrated in rats treated with aripiprazole (ARI) or haloperidol (HAL). Moreover, the add-on treatment of MIF was effective in reversing the AAPD-induced lipid disturbances by upregulating the expression of PGRMC1/INSIG-2 and subsequent downregulation of SCAP/SREBP. Taken together, our findings suggest that disturbances in lipid metabolism can occur at an early stage of AAPD treatment before the presence of weight gain. Such metabolic defects can be modified by an add-on treatment of steroid antagonist MIF enhancing the PGRMC1 pathway. Thus, it is likely that PGRMC1/INSIG-2 signaling may be a therapeutic target for AAPD-induced weight gain.