DNA double-strand break repair capacity and its pathway gene variants predict the risk and prognosis of lung cancer.

OBJECTIVES: This study aims to investigate the association between DNA double-strand breaks (DSBs) repair capacity, variations in DSBs-related genes, and the occurrence and prognosis of lung cancer in the Chinese population. METHODS: Peripheral blood mononuclear cells (PBMC) were collected from 98 lung cancer patients and 60 healthy individuals. The individual DSBs repair capacity was assessed by measuring changes in γ-H2AX levels after treatment with etoposide. Exonic sequencing of 45 DSBs-related genes was performed on PBMC DNA. Logistic regression analysis was conducted to examine the relationship between lung cancer risk and DSBs repair capacity as well as germlines gene variations. Survival analysis employed the Cox proportional hazards regression model, Kaplan-Meier method, and Log-rank test. RESULTS: Lower DSBs repair capacity predicted an increased risk of developing lung cancer (OR = 0.94, 95 %CI = 0.917-0.964, P＜0.001). Among lung cancer patients, higher DSBs repair capacity was associated with shorter progression-free survival (PFS) during first-line treatment (HR = 1.80, 95 %CI = 1.10-3.00, P = 0.031). Patients with BRCA1 mutations had shorter overall survival (OS) (HR = 1.92, 95 %CI = 1.12-3.28, P = 0.018). Patients with FOXO3 mutations had shorter PFS (HR = 4.23, 95 %CI = 1.44-12.36, P = 0.009). Analysis of patients treated with immune checkpoint inhibitors (ICIs) indicated that LIG4 mutations were associated with shorter PFS (HR = 2.90, 95 %CI = 1.00-8.10, P = 0.041). CONCLUSIONS: This study concludes that assessing DSBs repair capacity holds promise for predicting both lung cancer risk and prognosis in the Chinese population. Further large-scale studies and functional validation of specific gene mutations related to double-strand breaks are necessary for confirmation.

Assessment of lisdexamfetamine on executive function in rats: A translational cognitive research.

Executive function, including working memory, attention and inhibitory control, is crucial for decision making, thinking and planning. Lisdexamfetamine, the prodrug of d-amphetamine, has been approved for treating attention-deficit hyperactivity disorder and binge eating disorder, but whether it improves executive function under non-disease condition, as well as the underlying pharmacokinetic and neurochemical properties, remains unclear. Here, using trial unique non-matching to location task and five-choice serial reaction time task of rats, we found lisdexamfetamine (p.o) enhanced spatial working memory and sustained attention under various cognitive load conditions, while d-amphetamine (i.p) only improved these cognitive performances under certain high cognitive load condition. Additionally, lisdexamfetamine evoked less impulsivity than d-amphetamine, indicating lower adverse effect on inhibitory control. In vivo pharmacokinetics showed lisdexamfetamine produced a relative stable and lasting release of amphetamine base both in plasma and in brain tissue, whereas d-amphetamine injection elicited rapid increase and dramatical decrease in amphetamine base levels. Microdialysis revealed lisdexamfetamine caused lasting release of dopamine within the medial prefrontal cortex (mPFC), whereas d-amphetamine produced rapid increase followed by decline to dopamine level. Moreover, lisdexamfetamine elicited more obvious efflux of noradrenaline than that of d-amphetamine. The distinct neurochemical profiles may be partly attributed to the different action of two drugs to membranous catecholamine transporters level within mPFC, detecting by Western Blotting. Taken together, due to its certain pharmacokinetic and catecholamine releasing profiles, lisdexamfetamine produced better pharmacological action to improving executive function. Our finding provided valuable evidence on the ideal pharmacokinetic and neurochemical characteristics of amphetamine-type psychostimulants in cognition enhancement.

Implementation of surveillance,prevention and control of healthcare-asso-ciated infection in maternal and child healthcare institutions:A nation-wide investigation report / 中国感染控制杂志

Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24％of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66％,85.96％,80.77％,and 74.19％,respectively.51.22％MCH institutions adopted information surveillance system on HAI cases.94.31％MCH institutions carried out surveillance on hand hygiene compliance.Over 90％MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54％MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90％MCH insti-tutions established three-level pre-examination triage systems.86.18％set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50％.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.

Renal impairment in mice induced by environmental high concentration of polyionized drinking water and high temperature exposure / 环境与职业医学

Background The burden of chronic kidney diseases (CKD) is continuously increasing in the globe. Environmental factors are one of the trigger factors for chronic kidney diseases of unknown etiology (CKDu). However, the current toxicological evidence on the renal effects induced by environmental high concentrations of multiple ions in drinking water and high temperature exposure is very limited. Objective To preliminary investigate the renal effects of exposure to drinking water with environmental high concentrations of fluoride, calcium, sodium, and bromide ions alone or in combination with high temperature in mice. Methods A mouse drinking water exposure model was established using ICR male mouse (8 weeks old) with exposure to 3 mg·L−1 fluoride ions, 250 mg·L−1 calcium ions, 400 mg·L−1 sodium ions, and 1 mg·L−1 bromide ions (to mimic the high concentration of ions in the groundwater in the areas with a high prevalence rate of CKDu in Sri Lanka) and high temperature of 32 ℃. ICR male mice were randomly divided into a mixed fluoride-calcium-sodium-bromide ion and high temperature exposure group, exposure groups of each ion and high temperature alone, a fluoride-calcium-sodium ion exposure group, and a fluoride-calcium-sodium-bromide ion exposure group. In the control group, the animals were given normal purified water at room temperature of (23±2) ℃. After 12 consecutive weeks of exposure, body weights and liver (kidney) organ coefficients were determined. Assessment of renal histopathologic damage was performed by hematoxylin-eosin staining and pathology scoring. At the end of the 12-week exposure period, 24 h urine samples were collected for the measurements of creatinine (UCr), albumin (ALB), neutrophil gelatinase-associated lipocalin (NGAL), and β2-microglobulin (β2-MG) levels. Cell apoptosis was assessed by TUNEL assay. Results The mice in the mixed exposure group showed a significant decrease in body weight and marked increases in the scores of renal histopathological injuries and the urinary levels of β2-MG compared to those of the control mice (P<0.05). Compared with the control group, the differences in body weight and urinary renal injury indexes of the mice in the fluoride-calcium-sodium and the fluoride-calcium-sodium-bromide ion groups (except for the decrease of the β2-MG levels in urinary in the latter group) were not statistically significant (P>0.05), but the renal histopathological injury scores were significantly increased (P<0.05). By contrast, body weights, liver (kidney) organ coefficient, and renal histopathological injury scores were comparable in the control mice and the mice fed with drinking water containing high levels of a single ion alone or housed at high temperature alone (P>0.05). Furthermore, the renal histopathological injury score showed no significant differences between the fluoride-calcium-sodium ion exposure group and the fluoride-calcium-sodium-bromide ion exposure group (P>0.05). The interaction between bromide ions and fluoride-calcium-sodium ions on renal tissue pathological damage was not statistically significant (P>0.05). Results from the TUNEL assay showed a significant increase in renal cell apoptosis in the fluoride-calcium-sodium ion exposure group (P<0.05). Conclusions Environmental high levels of mixed fluoride, calcium, and sodium ions in drinking water induce renal pathological damage in mice, which are exacerbated in combination with high temperature environment. High temperature exposure alone does not affect the pathological damage of renal tissue,

Inhibition of GSDMD-mediated pyroptosis triggered by Trichinella spiralis intervention contributes to the alleviation of DSS-induced ulcerative colitis in mice.

BACKGROUND: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing worldwide. Although there is currently no completely curative treatment, helminthic therapy shows certain therapeutic potential for UC. Many studies have found that Trichinella spiralis (T.s) has a protective effect on UC, but the specific mechanism is still unclear. METHODS: Balb/c mice drank dextran sulfate sodium (DSS) to induce acute colitis and then were treated with T.s. In vitro experiments, the LPS combination with ATP was used to induce the pyroptosis model, followed by intervention with crude protein from T.s (T.s cp). Additionally, the pyroptosis agonist of NSC or the pyroptosis inhibitor vx-765 was added to intervene to explore the role of pyroptosis in DSS-induced acute colitis. The degree of pyroptosis was evaluated by western blot, qPCR and IHC, etc., in vivo and in vitro. RESULTS: T.s intervention significantly inhibited NLRP3 inflammasome activation and GSDMD-mediated pyroptosis by downregulating the expression of pyroptosis-related signatures in vitro (cellular inflammatory model) and in vivo (DSS-induced UC mice model). Furthermore, blockade of GSDMD-mediated pyroptosis by the caspase-1 inhibitor vx-765 has a similar therapeutic effect on DSS-induced UC mice with T.s intervention, thus indicating that T.s intervention alleviated DSS-induced UC in mice by inhibiting GSDMD-mediated pyroptosis. CONCLUSION: This study showed that T.s could alleviate the pathological severity UC via GSDMD-mediated pyroptosis, and it provides new insight into the mechanistic study and application of helminths in treating colitis.

Does good governance promote sustainable tourism? A systematic review of PESTEL analysis.

This paper aims to analyze the articles regarding the role of good governance in sustainable tourism for China. Following the PRISMA guidelines, a systematic literature review approach has been conducted in this paper. A total number of 100 peer-reviewed journal papers have been critically evaluated. Our review analysis shows that taking necessary steps under good governance can promote sustainable tourism development in China. Few policy recommendations and future research aspects have also been included in the paper. Supplementary Information: The online version contains supplementary material available at 10.1007/s43546-022-00408-x.

Treatment of the aged patients with unstable proximal humeral fracture with a locking plate and an intramedullary titanium mesh / 中华创伤骨科杂志

Objective:To evaluate the radiological and clinical outcomes of the aged patients with unstable proximal humeral fracture (UPHF) treated with a locking plate and an intramedullary titanium mesh.Methods:A retrospective study was conducted to analyze the 43 aged patients with UPHF who had been admitted to Department of Orthopedics, Zhongda Hospital Affiliated to Southeast University from January 2017 to July 2019. There were 13 males and 30 females with an age of (71.3±10.3) years (from 60 to 83 years). All patients were treated with a locking plate and an intramedullary titanium mesh to support. The postoperative imaging measurements included changes in humeral head height (HHH) and neck-shaft angle (NSA) (the difference between 3 years after surgery and the second day after surgery, taken as an absolute value); the postoperative clinical measurements included visual analogue scale (VAS), range of shoulder motion, Constant-Murley shoulder functional score (Constant score), American Shoulder and Elbow Surgeons (ASES) score, and incidence of complications.Results:All patients were followed up for (39.2±2.3) months after surgery. The change in HHH at 3 years after surgery was (1.5±1.1) mm, and the change in NSA at 3 years after surgery 3.3°±2.6°. At 3 years after surgery, the VAS score was (2.2±1.3) points, the Constant score (79.2±9.1) points, and the ASES score (78.9±9.2) points; the range of forward extension was 143.2°±20.8°, the range of outward extension 139.3°±23.1°, and the range of outward rotation 55.1°±4.7°. Complications after surgery were found in 6 patients, including humeral head necrosis in 2 cases, ectopic ossification in 1 case, and infection in 3 cases.Conclusion:In the treatment of the aged patients with UPHF, a locking plate combined with an intramedullary titanium mesh can help to restore the medial column support, leading to fine radiological and clinical outcomes.

Research progress of anti-inflammatory therapy for atherosclerosis / 中华神经科杂志

Atherosclerosis is a chronic inflammatory disease. In clinical practice, the main intervention target is to reduce low density lipoprotein cholesterol. Recent clinical data of several new lipid lowering drugs in the "post statin era" show that despite the use of high-intensity lipid lowering therapy, a large number of patients still have "residual inflammatory risk". In fact, in recent years, a large number of clinical studies have shown that anti-inflammatory treatment can effectively reduce the clinical complications of atherosclerosis, but it is also found that directly targeting/blocking inflammation may lead to increased immunosuppression or infection probability. Inflammation is a complex network involving the activation of multiple inflammatory cells, the release of inflammatory factors and the activation of inflammatory pathways. Therefore, it is necessary and significant to find effective and safe anti-inflammatory targets. Existing clinical evidence shows that targeting NOD-like receptor thermal protein domain associated protein 3/interleukin-1β/interleukin-6/hypersensitive-C-reactive protein pathway is an effective intervention target. In addition, targeted adaptive immunity, chemokines, and the release of proinflammatory regression mediators also show anti atherosclerosis effects. This article will summarize the latest progress in anti-inflammatory treatment of atherosclerosis in recent years, including the latest clinical research and the important progress still in the basic research stage, and look forward to the broad prospects of anti-inflammatory treatment of atherosclerosis.

Non-canonical STING-PERK pathway dependent epigenetic regulation of vascular endothelial dysfunction via integrating IRF3 and NF-κB in inflammatory response

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.

Intrinsic "self-consistent" phenomenon based on holistic view of traditional Chinese medicine / 中国中药杂志

The fundamental principle of traditional Chinese medicine(TCM) is holism, and it is crucial for TCM to address the key issue of the "holistic view" of Chinese herbal medicine. While the overall regulatory effects of Chinese herbal medicine have been widely recognized, the holistic internal logic of individual ingredients of Chinese herbal medicines require further clarification. In order to comprehensively understand the mechanism of action of Chinese herbal medicine, this paper combined the holistic view of Chinese herbal medicine with differentiation thinking to explore the intrinsic logical relationships within Chinese herbal medicine. Starting from the perspective of the coexistence of multiple components in Chinese herbal medicine, this paper systematically examined the "self-consistent" phenomenon within single Chinese herbal medicine. This phenomenon refers to the consistent or opposing actions of various components in terms of their physical and chemical properties, pharmacokinetic effects, biological effects, flavors and properties, and TCM efficacy. The paper summarized various logical relationships of syndrome differentiation exhibited by the same Chinese herbal medicine, analyzed the underlying reasons, and focused on analyzing external factors affecting the "self-consistent" phenomenon in the efficacy of Chinese herbal medicine, aiming to better elucidate the theoretical basis of the pharmacological effects of Chinese herbal medicine, further enrich the scientific connotation of the holistic view of Chinese herbal medicine, and provide theoretical guidance for the preparation process, compatibility patterns, and formulation design of Chinese herbal medicine.

Clinical significance and risk factors of redundant nerve root in patients with lumbar spinal stenosis / 中国骨伤

OBJECTIVE@#To investigate the clinical significance and screen the risk factors of redundant nerve roots(RNRs) in patients with lumbar spinal stenosis.@*METHODS@#The clinical data of 196 patients with lumbar spinal stenosis in the department of Spinal Surgery, Yijishan Hospital, Wannan Medical College from April 1, 2015 to November 30, 2020 were retrospectively analyzed. All patients were divided into RNRs positive group and RNRs negative group according to the presence of RNRs. The differences in general clinical data, imaging parameters, visual analogue scale(VAS), Oswestry disability index(ODI), and other indicators between the two groups were compared. The risk factors which are highly correlated with RNRs were screened by binary Logistic regression analysis.@*RESULTS@#There were 59 cases in the RNRs positive group, with an occurrence rate of 29.95% (59/137), and 137 cases in the RNRs negative group. The incidence rate of RNRs in 196 patients with lumbar spinal stenosis was 30.10% (59/196). VAS and ODI scores of patients in the two groups were statistically significant (P<0.05), and clinical symptoms of patients in the RNRs positive group were more severe than those in the RNRs negative group. There were significant differences in age, number of stenosis segments, average area of lumbar dural sac, area of the narrowest segment and the narrowest segment(P<0.05). Binary logistic regression analysis showed that the number of stenosis segments, the average median sagittal diameter of spinal canal, and the average area of dural sac in lumbar intervertebral space were correlated with the generation of RNRs (P<0.05). The regression coefficient of the number of stenosis segments was -1.115, the regression coefficient of the median sagittal diameter of the spinal canal was -1.707, and the regression coefficient of the mean dural sac area of the lumbar intervertebral space was 7.556.@*CONCLUSION@#The clinical symptoms of patients with lumbar spinal stenosis accompanied by RNRs are more severe than those without them. The number of narrow segments, median sagittal diameter of the spinal canal, and the area of the lumbar intervertebral dural sac are the high-risk factors for RNRs, with the area of the lumbar intervertebral dural sac has the highest correlation.

Investigation on the history of low-energy fractures and analysis of risk factors in elderly patients with hip fractures at the local / 中华老年医学杂志

Objective:To analyze the characteristics and risk factors of previous low-energy fractures in elderly patients with hip fractures admitted to our hospital.Methods:The data for this study was collected from 596 hip fracture patients admitted to Zhongda Hospital Affiliated to Southeast University between January 2018 and December 2021.Out of these patients, there were 404 females and 192 males.Based on the history of low-energy fracture before hip fracture, the patients were divided into two groups: a low-energy fracture group and a non-low-energy fracture group.A comparison was made between the two groups in terms of gender, age, fracture type, BMI, number of combined medical diseases, ASA score, and other characteristics.Results:The study included a total of 596 patients, with 368 patients having no history of low-energy fractures and 228 patients with low-energy fractures.Among the patients with low-energy fractures, there were 118 vertebral fractures, 69 hip fractures, 57 rib fractures, 19 radial fractures, 14 humerus fractures, and 12 patella fractures.Univariate analysis revealed significant differences in age, gender, fracture type, number of combined medical diseases, and ASA score between the two groups( P<0.05 for all). The results of multivariate Logistic analysis indicated that age( OR=1.046, 95% CI: 1.022-1.070), female sex( OR=1.474, 95% CI: 1.011-2.148), and the number of comorbid medical diseases( OR=1.211, 95% CI: 1.113-1.318)were independent risk factors for patients with a history of low-energy fractures. Conclusions:Our findings provide evidence that vertebral, hip, and rib fractures were the three most common previous low-energy fractures in elderly patients with hip fractures.We identified age, female gender, and number of medical diseases as independent risk factors for prior low-energy fractures in this population.

Effects of different environmental intervention durations on the intestinal mucosal barrier and the brain-gut axis in rats with colorectal cancer.

An enriched environment (EE) is a promising strategy for protecting the intestinal mucosal barrier and regulating the brain-gut axis, but the optimal EE intervention duration is unknown. Here, different EE intervention durations were applied to assess the optimal intervention duration in rats with colorectal cancer. We used a rat model of 1, 2-dimethylhydrazine-induced colorectal cancer. The rats were housed in an EE for 0, 2, 4, 8 weeks and 8-week blank group. The intestinal mucosa and serum TNF-α, IL-6, IL-10, ATP, CRF, and occludin levels and bacterial translocation (BT) were measured, and the intestinal mucosa morphology was evaluated. In 8 weeks, the effect of tumor on intestinal mucosal barrier was not obvious and the EE had a greater impact on it. Eight weeks of EE was more beneficial to the intestinal mucosal mechanical barrier than 2 or 4 weeks of intervention. A significant difference in BT was found between the 4- and 8-week groups. Overall, the analysis of inflammatory factor regulation revealed that the two blank groups exhibited the worst effect, and the intervention effect at 8 weeks was better than that at 2 and 4 weeks. CRF at 4 weeks was higher than that at 8-week blank group. The effect of 8-week intervention duration on the intestinal mucosal barrier was generally better than that of 2- and 4-week durations and intervention within 4 weeks can help to stabilize and promote the secretion of brain gut peptide, but the effect of different intervention durations on the brain-gut peptide levels was not obvious. In the future, we can further explore the molecular biological mechanism of the effect of different EE intervention durations on the intestinal mucosal barrier and analyze the effect of an EE on other brain-gut peptides.

Epitope vaccine design for Toxoplasma gondii based on a genome-wide database of membrane proteins.

BACKGROUND: There is presently no effective and safe vaccine for Toxoplasma gondii for humans. The study described here was designed to search for a novel group of optimal B cell and T cell epitopes from Toxoplasma membrane proteins using genome-wide comprehensive screening. METHODS: The amino acid sequences of membrane proteins of T. gondii were obtained from the UniProt database. The ABCPred and BepiPred servers were employed to predict the linear B cell epitopes. The Immune Epitope Database (IEDB) online service was utilized to forecast T cell epitopes within T. gondii membrane proteins that bind to human leukocyte antigen (HLA) class I (HLA-I) or HLA-II molecules. RESULTS: From the 314 membrane proteins of T. gondii, a total of 14 linear B cell epitopes embedded in 12 membrane proteins were identified. Eight epitopes for major histocompatibility complex (MHC) class I (MHC-I) molecules and 18 epitopes for MHC-II molecules were ultimately selected, for which world population coverage percentiles were 71.94% and 99.76%, respectively. The top rated combinations of linear B cell epitopes and T cell epitopes covering both BALB/c mice and a majority of the human population were identified for the development of a protective vaccine. CONCLUSIONS: The ultimate vaccine construct described here, which comprises B cells, MHC-I and MHC-II epitopes, might protect individuals against T. gondii infection by inducing humoral and cellular immune responses.

Hepatopulmonary metastases from papillary thyroid microcarcinoma: A case report.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Papillary thyroid microcarcinoma (PTMC) accounts for the majority of PTC cases. However, concurrent pulmonary and hepatic metastases of PTMC are rarely seen. Here, we present a patient with coexisting liver and lung metastases from PTMC. CASE SUMMARY: We describe a 26-year-old woman with PTMC with multiple concurrent metastases. After 3 d of unexplained fever, she was admitted to our hospital. Her thyroid functional tests were abnormal. Her positron emission tomography (PET)/magnetic resonance imaging (MRI) examination showed increased fluorodeoxyglucose (FDG) metabolism and space-occupying lesions in the left lobe of the thyroid. Additionally, PET/MRI images revealed multiple nodules in the lung and liver with increased FDG metabolism. Chest computer tomography (CT) showed multiple pulmonary metastases. Abdominal ultrasound and liver MRI showed multiple space-occupying lesions in the liver. The patient underwent total thyroidectomy and central lymph node dissection. Postoperative pathological analysis showed a papillary microcarcinoma multiplex in the left lobe of the thyroid. A diagnosis of hepatopulmonary metastases from papillary thyroid microcarcinoma was made. The patient was given iodine-131 treatment one year after the surgery. She recovered well after the operation, and the incision healed well. After discharge, she was treated with oral levothyroxine sodium tablets, and symptomatic and supportive treatments were also given to promote radioactive excretion and prevent bone marrow suppression by iodine-131 treatment. CONCLUSION: Since patients with thyroid cancer concurrent with hepatopulmonary metastases have rarely been reported, our case will highlight the clinical and pathological profiles of these patients.

Effects of Lisdexamfetamine, a Prodrug of D-Amphetamine, on Locomotion, Spatial Cognitive Processing and Neurochemical Profiles in Rats: A Comparison With Immediate-Release Amphetamine.

D-amphetamine has been used to enhance cognitive performance over the last few decades. Due to the rapid absorption after administration, d-amphetamine shows narrow effective window and severe abuse potential. Lisdexamfetamine, a prodrug of d-amphetamine, reduces the magnitude of plasma d-amphetamine concentration and prolongs the action duration when compared with immediate-release d-amphetamine at equimolar doses. However, the differences of these two drugs, which produce distinct pharmacokinetic characteristics, in cognition improvement still unclear. In present study, we compared the effects of d-amphetamine (i.p) and lisdexamfetamine (p.o) at equimolar doses (0.2, 0.5, 1.5, 4.5, and 13.5 mg/kg of d-amphetamine base) on locomotion, spatial working memory and recognition memory in rats. Given the crucial involvement of dopamine neurotransmitter system within the medial prefrontal cortex (mPFC) in cognitive processing, microdialysis was conducted to profile the difference in neurochemical characteristics between the two drugs. In our results, d-amphetamine ranges from 0.5 to 1.5 mg/kg significantly increased locomotor activity. However, d-amphetamine ranges from 0.2 to 13.5 mg/kg failed to improve spatial working memory and recognition memory in Y-maze-based spontaneous alternation and two-trial delayed alternation tasks of rats, respectively. In contrast, lisdexamfetamine with 4.5 mg/kg significantly increased the locomotion and improved both spatial working and recognition memory. Further, microdialysis showed that lisdexamfetamine induced lower magnitude and longer duration of extracellular dopamine increase than that of d-amphetamine. These results suggest that lisdexamfetamine was more effective than d-amphetamine in improving spatial cognitive performance, which was attributed to the steady and lasting dopamine release pattern within the mPFC.

A preliminary systematic review and meta-analysis on the effects of heart rate variability biofeedback on heart rate variability and respiration of athletes.

To date, there is no quantitative review examining the influence of heart rate variability biofeedback (HRV BFB) on the athlete population. Such an undertaking may provide valuable information on the autonomic and respiration responses of athletes when performing HRV BFB. Thus, purpose of this preliminary systematic review and meta-analysis on the effects of HRV BFB on HRV and respiration of athletes. Searches of Springerlink, SportDiscus, Web of Science, PROQUEST Academic Research Library, Google Scholar, and ScienceDirect were conducted for studies that met the following criteria: (1) experimental studies involving athletes that underwent randomized control trial; (2) availability of HRV BFB as a treatment compared with a control (CON)/placebo (PLA); (3) any pre and post HRV variable and/or breathing frequency as dependent variable/s; and, (4) peer-reviewed articles written in English. Four out of 660 studies involving 115 athletes (25 females and 90 males) ages 16-30 years old were assessed in this review. Preliminary findings suggest the promising ability of HRV BFB to improve respiratory mechanics in athlete population. More work is needed to determine the autonomic modulatory effect of HRV BFB in athletes.

Effect of preoperative waiting time on prognosis of elderly patients with hip fracture / 中国骨伤

OBJECTIVE@#To investigate the relationship between preoperative waiting time and prognosis of elderly patients with hip fracture.@*METHODS@#From January 2014 to December 2018, 333 elderly hip fracture patients undergoing surgery were retrospectively analyzed, including 104 males and 229 females, aged from 60 to 99 years with an average of (77.93±8.49) years, and 183 patients were femoral neck fracture, 150 patients were femoral intertrochanteric fracture. Among them, 269 patients (80.78%) had a clustered preoperative waiting time of 2 to 8 days, and then divided into within 4-day group(91 cases) and over 4-day group(242 cases) according to their preoperative waiting time. The survival situation was followed by telephone, and follow-up time started from fracture admission to the death event, or to the research deadline (December 31, 2019). The Kaplan-Meier method was used for survival analysis, and Cox risk proportion model was used to analyze the independent risk factors of hip fracture in elderly patients.@*RESULTS@#All patients were followed up for 12 to 75 months(means 35 months), 59 patients died and the mortality rate was 17.72%(59/333). Compared with within 4-day group, the mortality rate was higher in over 4-day group[20.66%(50/242) vs. 9.89%(9/91), χ2=5.263, P=0.022]. Multiariable Cox regression analysis showed that preoperative waiting time, age, male and Charlson comorbidity index were independent risk factors for the prognosis of hip fracture in elderly patients (all P<0.05), and every 1-day delay was associated with 5% increase of the risk of death[HR=1.05, 95%CI(1.00-1.10), P=0.045]. Subsequent analyse was stratified according to the Charlson comorbidity index (CCI), and found that over 4-day group had a higher mortality rate in patients with CCI<2, with statistically significant difference(P<0.05).@*CONCLUSION@#For elderly patients with hip fracture, most of hospitals could not complete the hip fracture surgery within 48 hours, we also need to shorten the waiting time before surgery, and thereby improve their prognosis.

Autophagy enhanced by curcumin ameliorates inflammation in atherogenesis via the TFEB-P300-BRD4 axis

Disturbance of macrophage-associated lipid metabolism plays a key role in atherosclerosis. Crosstalk between autophagy deficiency and inflammation response in foam cells (FCs) through epigenetic regulation is still poorly understood. Here, we demonstrate that in macrophages, oxidized low-density lipoprotein (ox-LDL) leads to abnormal crosstalk between autophagy and inflammation, thereby causing aberrant lipid metabolism mediated through a dysfunctional transcription factor EB (TFEB)-P300-bromodomain-containing protein 4 (BRD4) axis. ox-LDL led to macrophage autophagy deficiency along with TFEB cytoplasmic accumulation and increased reactive oxygen species generation. This activated P300 promoted BRD4 binding on the promoter regions of inflammatory genes, consequently contributing to inflammation with atherogenesis. Particularly, ox-LDL activated BRD4-dependent super-enhancer associated with liquid-liquid phase separation (LLPS) on the regulatory regions of inflammatory genes. Curcumin (Cur) prominently restored FCs autophagy by promoting TFEB nuclear translocation, optimizing lipid catabolism, and reducing inflammation. The consequences of P300 and BRD4 on super-enhancer formation and inflammatory response in FCs could be prevented by Cur. Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific Brd4 overexpression or Tfeb knock-out in Apoe knock-out mice via bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.