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.

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 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.

Objective:To integrate qualitative research on the experience of type 2 diabetes patients using self-management APP, so as to provide evidence support for the design and promotion of highly accepted diabetes self-management APP.Methods:This study is a Meta-synthesis. Qualitative research on experience of type 2 diabetes patients using self-management APP was retrieved through computer in China National Knowledge Infrastructure (CNKI) , WanFang, VIP, China Biology Medicine disc Literature Database, PubMed, Web of Science, Cochrane Library, Embase, CINAHL, PsycINFO, Ovid (LWW Journals) , Scopus Chinese and English databases. The retrieval time limit was from the establishment of the database to April 30, 2022. According to the quality evaluation criteria for qualitative research of the Joanna Briggs Institute (JBI) Evidence-Based Health Care Center, the methodology of the included article was evaluated, and the included article was integrated with the method of pooled Meta-synthesis.Results:A total of 11 articles were included, 48 research findings were extracted and summarized into 3 integration results and 14 new categories. The integration results included that self-management APP promoted patients to form continuous self-management behavior and improved physical and mental health, obstacle factors that affected patients' use of APP, and patients' suggestions for improving the function of APP.Conclusions:Patients feel the benefits of self-management APP, such as correct understanding of diabetes, disease control, and improvement of psychological status. When developing relevant APP, we should pay attention to the change of patient behavior, design the APP function based on user needs, conduct cultural adjustment, improve training and technical support, and improve its acceptance and promotion.

Objective:To systematically review the risk prediction models for hypoglycemia in diabetic patients.Methods:The literatures published up to March 25, 2022 was retrieved from PubMed, Embase, Web of Science, Cochrane Library, CINAHL, MEDLINE, China National Knowledge Infrastructure, Wanfang, VIP and SinoMed. Two researchers independently screened the literatures, extracted information, and applied the PROBAST tool to evaluate the quality of the included models.Results:A total of 11 literatures and 13 models were included. The area under the receiver operating characteristic curve or C statistic of all models was 0.666-0.890, with a high risk of bias and a low risk of applicability, and the most included predictors were chronic kidney disease and age. The main reason for the bias in the model were insufficient number of events in the dependent variable, improper handling of continuous variables, and screening of predictors by single factor analysis. Conclusions:The existing hypoglycemia risk prediction models for diabetic patients are still in the development stage, and medical and nursing staff can choose the existing hypoglycemia models according to the results of this systematic review and clinical practice. In the future, we should improve the existing models based on tools or carry out large-sample, multi-center, prospective cohort studies, and build a high-quality hypoglycemia risk prediction model for diabetic patients that is more suitable for China based on more comprehensive and accurate statistical methods and clinical data.

Objective:To investigate risk factors for cognitive decline in elderly hospitalised hypertensive patients, develop a risk prediction model and validate it.Methods:By the convenient sampling method, a total of 379 elderly hypertensive patients admitted to Department of Cardiology, Department of Geriatrics (General) and Department of Endocrinology in Xuanwu Hospital of Capital Medical University from April to October 2022 were selected as the study objects. Binomial Logistic regression analysis was used to explore the risk factors of cognitive frailty in elderly hospitalized hypertensive patients and establish a prediction model. Receiver operating characteristic curve (ROC) and Hosmer-Lemeshow goodness of fit test were used to evaluate the prediction effect and calibration degree of the model, and Bootstrap method was used for internal verification.Results:Among 379 elderly hospitalized hypertensive patients, 145 (38.3%) had cognitive frailty. Binomial Logistic regression analysis showed that age, education level, drinking history, daily exercise, use of angiotensin receptor antagonists, Barthel index and nutritional status were the influential factors for cognitive frailty in elderly hospitalized hypertensive patients ( P< 0.05). The area under ROC curve of the prediction model was 0.770 (95% CI: 0.721-0.819, P< 0.001), the sensitivity was 0.607, the specificity was 0.838, and the maximum approximate entry index was 0.445. Hosmer Lemeshow goodness of fit test χ 2=3.581, P=0.893. Internal validation was conducted using the Bootstrap method to resample 1 000 times, and the results showed that the average area under the ROC curve of the prediction model was 0.737 (0.687-0.788) . Conclusions:The risk prediction model for cognitive decline in elderly hospitalized hypertensive patients can predict the risk of cognitive frailty in elderly hospitalized hypertensive patients, which can provide references for medical staff to develop corresponding intervention measures.

OBJECTIVETo explore the role of β2-nicotinic acetylcholine receptor (β2-nAChR) in the development of γ- aminobutyric acid A type receptors (GABA-Rs) in hippocampal CA1 and CA3 pyramidal neurons of mice.

METHODSThe hippocampal CA1 and CA3 pyramidal neurons were acutely isolated from β2-nAChR gene knockout (β2-KO group) mice. GABA currents in CA1 and CA3 pyramidal neurons were induced with the selective GABA-R agonist muscimol and recorded using perforated patch-clamp recording technique. The GABA currents of CA1 and CA3 pyramidal neurons were tested for their equilibrium potentials (Es) and kinetic parameters and were compared with the measurements in wild-type mice (WT group).

RESULTSThe mean E of CA1 neurons (=7) of β2-KO mice (=4) was -31.7±3.5 mV, showing an obvious depolarizing shift compared with the WT mice ( < 0.05); the mean E of CA3 neurons (=4) was -16.1±4.6 mV, also showing a depolarizing shift ( < 0.01). The difference in the Es between CA3 and CA1 neurons in β2-KO mice, but not in WT mice, was significant ( < 0.05). The GABA-R desensitization was significantly slowed down in both CA1 and CA3 neurons of β2-KO mice, with decay time of 2.2±0.2 s and 3.2±0.1 s, respectively, significantly longer than those in WT mice (1.6±0.1 s and 2.3±0.1 s, respectively; < 0.05).

CONCLUSIONSβ2-containing nAChRs may promote the functional maturation of GABA-R in CA1 and CA3 pyramidal cells in mouse hippocampus.

OBJECTIVE: To investigate the effects of etomidate on electrophysiological properties and nicotinic acetylcholine receptors (nAChRs) of ventral horn neurons in the spinal cord. METHODS: The spinal cord containing lumbosacral enlargement was isolated from 19 neonatal SD rats aged 7-12 days. The spinal cord were sliced and digested with papain (0.18 g/30 mL artificial cerebrospinal fluid) and incubated for 40 min. At the ventral horn, acute mechanical separation of neurons was performed with fire-polished Pasteur pipettes, and perforated patch-clamp recordings combined with pharmacological methods were employed on the adherent healthy neurons. In current-clamp mode, the spontaneous action potential (AP) of the ventral horn neurons in the spinal cord was recorded. The effects of pretreatment with different concentrations of etomidate on AP recorded in the ventral horn neurons were examined. In the voltage-clamp mode, nicotine was applied to induce inward currents in the ventral horn neurons, and the effect of pretreatment with etomidate on the inward currents induced by nicotine were examined with different etomidate concentrations, different holding potentials and different use time. RESULTS: The isolated ventral horn neurons were in good condition with large diverse somata and intact processes. The isolated spinal ventral horn neurons (=21) had spontaneous action potentials, and were continuously perfused for 2 min with 0.3, 3.0 and 30.0 μmol/L etomidate. Compared with those before administration, the AP amplitude, spike potential amplitude and overshoot were concentration-dependently suppressed ( < 0.01), and spontaneous discharge frequency was obviously reduced ( < 0.01, =12). The APs of the other 9 neurons were completely abolished by etomidate at 3.0 or 30 μmol/L. At the same holding potential (VH=-70 mV), pretreatment with 0.3, 3.0 or 30.0 μmol/L etomidate for 2 min concentration-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine ( < 0.01, =7). At the holding potentials of - 30, - 50, and - 70 mV, pretreatment with 30.0 μmol/L etomidate for 2 min voltage-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine ( < 0.01, =6 for each holding potential). During the 6 min of 30.0 μmol/L etomidate pretreatment, the clamped cells were exposed to 0.4 mmol/L nicotine for 4 times at 0, 2, 4, and 6 min (each exposure time was 2 s), and the nicotinic current amplitude decreased gradually as the number of exposures increased. But at the same concentration, two nicotine exposures (one at the beginning and the other at the end of the 6 min pretreatment) resulted in a significantly lower inhibition rate compared with 4 nicotine exposures ( < 0.01, =6). CONCLUSIONS etomidate reduces the excitability of the spinal ventral neurons in a concentration-dependent manner and suppresses the function of nAChR in a concentration-, voltage-, and use-dependent manner.
Animals ; Animals, Newborn ; Etomidate ; Neurons ; Patch-Clamp Techniques ; Rats ; Spinal Cord

Background Lipid metabolism in liver shows circadian-dependent profiles. The hepatotoxicity of environmental chemicals is dependent on circadian time. Objective To observe the effects of bisphenol A (BPA) exposure at different zeitgeber time (ZT) on hepatic and blood lipid metabolism and decipher the underlying mechanisms related to circadian rhythm in mice. Methods Thirty-five female C57BL/6J mice were sacrificed every 4 h in a light-dark cycle (12 h/12 h). The liver tissues were collected to describe the circadian profiles of hepatic Rev-erba, Bmal1, Clock, Srebp1c, and Chrebp mRNA expression levels within 24 h. Thirty female mice were divided into 6 groups by the timing (ZT3 represents the 3 h after light on, ZT15 represents the 3 h after light off) and dose (50 or 500 μg·kg⁻¹·d⁻¹) of BPA exposure to observe hepatotoxicity. Mice were gavaged with designed doses of BPA once per day for 4 weeks. Mice were maintained with ad libitum access to food and water and measured body weight weekly. After the experiment, mice were euthanatized and liver tissues were separated to determine the biochemical indicators of lipid metabolism and lipid metabolism- and circadian-related gene mRNA expressions. Results Hepatic Rev-erba, Bmal1, Clock, Srebp1c, and Chrebp mRNA expression levels were rhythmic during a 24 h period in mice. At ZT3 and ZT15, BPA did not alter body weight, plasma glucose, plasma total cholesterol, plasma low density lipoprotein cholesterol, and plasma triglycerides (P>0.05). The plasma high density lipoprotein cholesterol decreased in the 50 μg·kg⁻¹·d⁻¹ BPA group at ZT3 by 14.56% compared with the control group (P<0.05). The liver triglycerides increased in the 50 μg·kg⁻¹·d⁻¹ BPA group at ZT15 by 115.20% compared with the control group (P<0.05). BPA decreased Srebp1c mRNA expression level when dosing at ZT3 and increased Chrebp, Srebp1c, and Acc1 mRNA expression levels when dosing at ZT15 compared with the control group (P<0.05). BPA increased Bmal1 mRNA expression level and decreased Rev-erbα mRNA expression level at ZT3 exposure and decreased Bmal1 and increased Rev-erbα mRNA expression level at ZT15 exposure (P<0.05). Conclusion BPA exposure at light or dark period has different effects on hepatic lipid metabolism in mice. Hepatic lipid deposit appears when BPA is dosed at dark period. Rev-erbα-Bmal1 regulation circuits and the subsequent upregulation of Srebp1c and Chrebp and the target gene Acc1 may be involved.