OBJECTIVES: To investigate the effect of orexin-A-mediated regulation of ionotropic glutamate receptors for promoting motor function recovery in rats with spinal cord injury (SCI). METHODS: Thirty-six newborn SD rats (aged 7-14 days) were randomized into 6 groups (n=6), including a normal control group, a sham-operated group, and 4 SCI groups with daily intrathecal injection of saline, DNQX, orexin-A, or orexin-A+DNQX for 3 consecutive days after PCI. Motor function of the rats were evaluated using blood-brain barrier (BBB) score and inclined plane test 1 day before and at 1, 3, and 7 days after SCI. For patch-clamp experiment, spinal cord slices from newborn rats in the control, sham-operated, SCI, and SCI+orexin groups were prepared, and ventral horn neurons were acutely isolated to determine the reversal potential and dynamic indicators of glutamate receptor-mediated currents under glutamate perfusion. RESULTS: At 3 and 7 days after SCI, the orexin-A-treated rats showed significantly higher BBB scores and grip tilt angles than those with other interventions. Compared with those treated with DNQX alone, the rats receiving the combined treatment with orexin and DNQX had significantly higher BBB scores and grip tilt angles on day 7 after PCI. In the patch-clamp experiment, the ventral horn neurons from SCI rat models exhibited obviously higher reversal potential and greater rise slope of glutamate current with shorter decay time than those from sham-operated and orexin-treated rats. CONCLUSIONS Orexin-A promotes motor function recovery in rats after SCI possibly by improving the function of the ionotropic glutamate receptors.
Animals ; Spinal Cord Injuries/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Receptors, Ionotropic Glutamate/metabolism* ; Recovery of Function/drug effects* ; Orexins/pharmacology* ; Male ; Female ; Animals, Newborn ; Neuropeptides/pharmacology* ; Intracellular Signaling Peptides and Proteins/pharmacology*

Objective:To explore the current situation of ageism among older adults in megacity communities and analyze its influencing factors.Methods:From November to December 2023, convenience sampling was used to select 200 older adults who visited the Niujie Community Health Service Center in Xicheng District, Beijing as the research subject. A survey was conducted on older adults using the General Information Questionnaire, Barthel Index, 15-Item Geriatric Depression Scale, Family Adaptation, Partnership, Growth, Affection and Resolve Scale (Family APGAR Scale), Rosenberg Self-Esteem Scale, Social Support Rating Scale, Lubben Social Network Scale, and Ageism Questionnaire. Multiple linear regression was used to analyze the influencing factors of ageism among older adults in the community.Results:A total of 200 questionnaires were distributed and 200 valid questionnaires were collected, with a valid response rate of 100.00% (200/200). The total score of ageism among 200 older adults in the community was (3.55±0.31), with objective and subjective scores of (3.59±0.28) and (3.50±0.48), respectively. Multiple linear regression showed that occupational status, pre-retirement or current work, family care, self-esteem, and social support were the influencing factors of ageism among older adults in the community ( P<0.05) . Conclusions:Ageism among older adults is influenced by various factors. Medical and nursing staff should focus on older adults who are retired, mainly engaged in physical work, and have poor family and social support when formulating intervention strategies. Community health workers should regularly organize activities to encourage older adults to actively participate, enhance their sense of social participation, reduce ageism, so as to promote healthy aging.

OBJECTIVES: Several countries have successfully eliminated measles, and China is making significant strides toward achieving this goal. This study focused on investigating the patterns of measles infections in Zhejiang Province, China, as well as control measures. The objective was to provide valuable insights that could contribute to the development of nationwide elimination strategies. METHODS: We analyzed measles surveillance data from 2005 to 2022 in Zhejiang Province. We utilized a joinpoint regression model to examine trends in measles. Additionally, we employed SaTScan version 9.5 to identify spatial-temporal clusters. Finally, we used an age-period-cohort model to assess the effects of age, period, and cohort. RESULTS: The age-standardized incidence rate (ASIR) of measles infection in Zhejiang Province from 2005 to 2022 was 5.24 per 100,000, showing a consistent and significant downward trend with an annual percentage change of -24.93% (p<0.05). After 2020, the ASIR for measles infection fell to below 0.1 per 100,000. The majority of measles cases occurred in individuals either without an immunization history or with an unknown immunization status, representing 41.06% and 41.40% of the cases from 2010 to 2022, respectively. According to data from the National Measles Surveillance System, the annual rate of discarded measles cases from 2009 to 2014, and the annual rate of discarded measles and rubella cases from 2015 to 2022, were both above 2 per 100,000, indicating the high sensitivity of the measles surveillance system. CONCLUSIONS The significant reduction in measles incidence from 2005 to 2022 demonstrates substantial progress in Zhejiang Province towards the elimination of measles.

OBJECTIVES: Several countries have successfully eliminated measles, and China is making significant strides toward achieving this goal. This study focused on investigating the patterns of measles infections in Zhejiang Province, China, as well as control measures. The objective was to provide valuable insights that could contribute to the development of nationwide elimination strategies. METHODS: We analyzed measles surveillance data from 2005 to 2022 in Zhejiang Province. We utilized a joinpoint regression model to examine trends in measles. Additionally, we employed SaTScan version 9.5 to identify spatial-temporal clusters. Finally, we used an age-period-cohort model to assess the effects of age, period, and cohort. RESULTS: The age-standardized incidence rate (ASIR) of measles infection in Zhejiang Province from 2005 to 2022 was 5.24 per 100,000, showing a consistent and significant downward trend with an annual percentage change of -24.93% (p<0.05). After 2020, the ASIR for measles infection fell to below 0.1 per 100,000. The majority of measles cases occurred in individuals either without an immunization history or with an unknown immunization status, representing 41.06% and 41.40% of the cases from 2010 to 2022, respectively. According to data from the National Measles Surveillance System, the annual rate of discarded measles cases from 2009 to 2014, and the annual rate of discarded measles and rubella cases from 2015 to 2022, were both above 2 per 100,000, indicating the high sensitivity of the measles surveillance system. CONCLUSIONS The significant reduction in measles incidence from 2005 to 2022 demonstrates substantial progress in Zhejiang Province towards the elimination of measles.

OBJECTIVES: Several countries have successfully eliminated measles, and China is making significant strides toward achieving this goal. This study focused on investigating the patterns of measles infections in Zhejiang Province, China, as well as control measures. The objective was to provide valuable insights that could contribute to the development of nationwide elimination strategies. METHODS: We analyzed measles surveillance data from 2005 to 2022 in Zhejiang Province. We utilized a joinpoint regression model to examine trends in measles. Additionally, we employed SaTScan version 9.5 to identify spatial-temporal clusters. Finally, we used an age-period-cohort model to assess the effects of age, period, and cohort. RESULTS: The age-standardized incidence rate (ASIR) of measles infection in Zhejiang Province from 2005 to 2022 was 5.24 per 100,000, showing a consistent and significant downward trend with an annual percentage change of -24.93% (p<0.05). After 2020, the ASIR for measles infection fell to below 0.1 per 100,000. The majority of measles cases occurred in individuals either without an immunization history or with an unknown immunization status, representing 41.06% and 41.40% of the cases from 2010 to 2022, respectively. According to data from the National Measles Surveillance System, the annual rate of discarded measles cases from 2009 to 2014, and the annual rate of discarded measles and rubella cases from 2015 to 2022, were both above 2 per 100,000, indicating the high sensitivity of the measles surveillance system. CONCLUSIONS The significant reduction in measles incidence from 2005 to 2022 demonstrates substantial progress in Zhejiang Province towards the elimination of measles.

OBJECTIVES: Several countries have successfully eliminated measles, and China is making significant strides toward achieving this goal. This study focused on investigating the patterns of measles infections in Zhejiang Province, China, as well as control measures. The objective was to provide valuable insights that could contribute to the development of nationwide elimination strategies. METHODS: We analyzed measles surveillance data from 2005 to 2022 in Zhejiang Province. We utilized a joinpoint regression model to examine trends in measles. Additionally, we employed SaTScan version 9.5 to identify spatial-temporal clusters. Finally, we used an age-period-cohort model to assess the effects of age, period, and cohort. RESULTS: The age-standardized incidence rate (ASIR) of measles infection in Zhejiang Province from 2005 to 2022 was 5.24 per 100,000, showing a consistent and significant downward trend with an annual percentage change of -24.93% (p<0.05). After 2020, the ASIR for measles infection fell to below 0.1 per 100,000. The majority of measles cases occurred in individuals either without an immunization history or with an unknown immunization status, representing 41.06% and 41.40% of the cases from 2010 to 2022, respectively. According to data from the National Measles Surveillance System, the annual rate of discarded measles cases from 2009 to 2014, and the annual rate of discarded measles and rubella cases from 2015 to 2022, were both above 2 per 100,000, indicating the high sensitivity of the measles surveillance system. CONCLUSIONS The significant reduction in measles incidence from 2005 to 2022 demonstrates substantial progress in Zhejiang Province towards the elimination of measles.

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and is characterized by primary left ventricular hypertrophy usually caused by mutations in sarcomere genes. The mechanism underlying cardiac remodeling in HCM remains incompletely understood. An investigation of HCM through integrative analysis at multi-omics levels will be helpful for treating HCM. DNA methylation and chromatin accessibility, as well as gene expression, were assessed by nucleosome occupancy and methylome sequencing (NOMe-seq) and RNA-seq, respectively, using the cardiac tissues of HCM patients. Compared with those of the controls, the transcriptome, DNA methylome, and chromatin accessibility of the HCM myocardium showed multifaceted differences. At the transcriptome level, HCM hearts returned to the fetal gene program through decreased sarcomeric and metabolic gene expression and increased extracellular matrix gene expression. In the DNA methylome, hypermethylated and hypomethylated differentially methylated regions were identified in HCM. At the chromatin accessibility level, HCM hearts showed changes in different genome elements. Several transcription factors, including SP1 and EGR1, exhibited a fetal-like pattern of binding motifs in nucleosome-depleted regions in HCM. In particular, the inhibition of SP1 or EGR1 in an HCM mouse model harboring sarcomere mutations markedly alleviated the HCM phenotype of the mutant mice and reversed fetal gene reprogramming. Overall, this study not only provides a high-precision multi-omics map of HCM heart tissue but also sheds light on the therapeutic strategy by intervening in the fetal gene reprogramming in HCM.
Cardiomyopathy, Hypertrophic/metabolism* ; Humans ; Animals ; DNA Methylation ; Mice ; Transcriptome ; Chromatin/genetics* ; Early Growth Response Protein 1/metabolism* ; Male ; Epigenome ; Nucleosomes/genetics* ; Female ; Middle Aged ; Disease Models, Animal ; Adult

Objective:To evaluate the efficacy of esketamine combined with fascia iliaca compartment-subarachnoid block in optimizing anesthesia in elderly patients undergoing hip fracture surgery.Methods:Sixty-two American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ elderly patients of either sex, aged 60-85 yr, with body mass index of 18.5-30.0 kg/m 2, were divided into 2 groups ( n=31 each) using a random number table method: fascia iliaca compartment-subarachnoid block group (FS group) and esketamine combined with fascia iliaca compartment-subarachnoid block group (ES group). In FS group, patients underwent ultrasound-guided fascia iliaca compartment block at 30 min before the operation of subarachnoid anesthesia on the surgical side. In ES group, esketamine 0.25 mg/kg was intravenously administered at 5 min before skin incision based on the fascia iliaca compartment-subarachnoid block. Patient-controlled intravenous analgesia was used for postoperative analgesia, and tramadol 1 mg/kg was intravenously given for rescue analgesia when numerical rating scale score > 4. The pressing times of patient-controlled analgesic pump, the number of rescue analgesia and consumption of tramadol were recorded within 48 h after operation. The occurrence of postoperative adverse reactions (respiratory depression, nausea and vomiting, dizziness, drowsiness, pruritus, illusion, nightmares) was recorded. Results:Compared with FS group, the consumption of postoperative tramadol was significantly decreased, and the pressing times of patient-controlled analgesic pump and the number of rescue analgesia were reduced in ES group ( P<0.05). There were no significant differences in the incidence of postoperative adverse reactions between the two groups ( P>0.05). Conclusions:Combination of esketamine with fascia iliaca compartment-subarachnoid block for hip fracture surgery can raise postoperative analgesia and optimize clinical management strategies in elderly patients.

Objective:To evaluate the effect of ultrasound-guided single fascia iliaca compartmentblock (FICB) combined with esketamine on postoperative delirium (POD) in elderly patients undergoing hip fracture surgery.Methods:Sixty-two patients of either sex, aged 60-85 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing hip fracture surgery under subarachnoid anesthesia, were divided into 2 groups ( n=31 each) using a random number table method: single FICB group (group FICB) and single FICB combined with esketamine group (group FICB+ E). Ultrasound-guided FICB was performed on the operated side at 30 min before subarachnoid anesthesia. In FICB+ E group, esketamine was intravenously injected as a bolus of 0.3 mg/kg at 5 min before skin incision followed by an infusion of 0.25 mg·kg -1·h -1 until 30 min before the end of procedure. Patient-controlled intravenous analgesia was used for postoperative analgesia, and tramadol 1 mg/kg was given for rescue analgesia. The pressing times of patient-controlled analgesia, the number of rescue analgesia, and consumption of tramadol were recorded within 48 h after operation. The Ramsay sedation score was used to assess the degree of sedation at skin incision, 30 min after the start of surgery, 30 min before the end of surgery, at the end of surgery, and at discharge from the post-anesthesia care unit. Postoperative delirium (POD) occurred within 7 days after surgery was assessed using the Confusion Assessment Method. The serum concentrations of tumor necrosis factor-alpha, interleukin-6, S100β and glial fibrillary acidic protein (GFAP) were detected by enzyme-linked immunosorbent assay on admission to the operating room and at 3 and 7 days after surgery. The occurrence of adverse drug reactions (respiratory depression, nausea and vomiting, dizziness, somnolence, urinary retention) was recorded. Results:Compared with group FICB, the incidence of POD was significantly decreased within 3 days after surgery, the consumption of tramadol, pressing times of patient-controlled analgesia and the number of rescue analgesia were reduced, Ramsay sedation score was increased at each time point, and the serum concentrations of tumor necrosis factor-alpha, interleukin-6, S100β and glial fibrillary acidic protein were decreased after surgery ( P<0.05), and no significant change was found in the total incidence of POD at 7 days after surgery in group FICB+ B ( P>0.05). Conclusions:Ultrasound-guided single FICB combined with esketamine can provide adequate analgesia and sedation in the perioperative period for elderly patients with hip fractures, reducing the risk of early postoperative (within 3 days) POD.

Objective:To study the protective effects and mechanisms of melatonin (MTn) on lipopolysaccharide (LPS) and hypoxic-ischemic(HI) induced white matter damage (WMD) in neonatal rats.Methods:Seventy-two 3-day-old newborn Sprague-Dawley (SD) rats were randomly assigned into sham operation group (the sham group), model group (the HI group) and MTn intervention group (the HI+MTn group) ( n=24 for each group). For the sham group, only dissection of the right common carotid artery was performed without ligation. Animal models of WMD were established using LPS pretreatment and HI method in both the HI group and HI+MTn group. The HI+MTn group received MTn intraperitoneal injection (15 mg/kg, 1 h before LPS injection and then once daily). The HI group and the sham group received equal volume of normal saline containing 1% ethanol intraperitoneal injection. The rats were sacrificed on d7 of experiment and periventricular white matter (PVWM) was collected for hematoxylin-eosin (HE) and TUNEL staining to determine WMD and apoptosis. The distribution and morphology of microglial cells in the PVWM were studied using IBA1 immunofluorescence staining. Reactive oxygen species (ROS) kit was used to detect ROS. The expression of nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasomes, interleukin (IL)-1β, IL-18 and mitochondrial autophagy markers (pink1 and parkin) were determined using real-time quantitative PCR. Results:Compared with the sham group, the HI group showed WMD, cell degeneration and necrosis,increased cell apoptosis and increased expressions of NLRP3 inflammasomes and downstream inflammatory factors (IL-1β and IL-18) in PVWM. Compared with the HI group,the HI+MTn group showed reduced WMD, cell apoptosis, microglia infiltration and inflammatory factors expression. MTn increased pink1 and parkin expression and reduced ROS production in PVWM.Conclusions:MTn reduces ROS production by enhancing mitochondrial autophagy and inhibits NLRP3 inflammasomes hyperactivation to alleviate endotoxin- and HI-induced WMD in neonatal rats.