OBJECTIVE To investigate the efficacy and safety of metformin in the treatment of diabetes mellitus type 2 （T2DM） complicated with sarcopenia in elderly patients. METHODS From January 2022 to January 2024， clinical data from eligible patients with T2DM complicated with sarcopenia treated at the First Affiliated Hospital of Chongqing Medical and Pharmaceutical College were collected. Patients were randomly assigned into control group （70 cases） and observation group （70 cases） using a random number table. Both groups received routine interventions； control group additionally received subcutaneous injections of Insulin glargine injection before bedtime and Human insulin injection 30 minutes before breakfast， lunch and dinner every day. In addition to the same treatments as the control group， the observation group was administered 0.5 g of Metformin hydrochloride sustained-release tablets orally once daily. Both groups were treated continuously for 24 weeks. Comparisons were made between the two groups in terms of glucose metabolism indexes [fasting blood glucose （FBG）， 2 h postprandial blood glucose （2 hBG）， and glycosylated hemoglobin （HbA1c）]， homeostasis model assessment of insulin resistance （HOMA-IR）， appendicular skeletal mass muscle index （ASMI）， grip strength， walking speed， lipid metabolism indexes [serum total triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）]， serological markers [high-sensitivity C reactive protein （hs-CRP）， interleukin-6 （IL-6）， and ferritin levels] and quality of life. The occurrence of ADR was recorded in both groups. RESULTS 65 patients in the control group and 63 patients in the observation group completed this study， respectively. After treatment， the levels of FBG， 2 hBG， HbA1c， HOMA-IR，TG and TC in both groups， and the levels of hs-CRP， IL-6 and ferritin in observation group were all significantly reduced compared to those before treatment （P＜0.05）， and the HOMA-IR in observation group was significantly lower than control group （P＜0.05）； additionally， the grip strength， walking speed， and scores for daily living and activity abilities of observation group were increased than those before treatment and the control group （P＜0.05）. The incidence of adverse drug reactions in both groups was 2.86%. CONCLUSIONS Metformin can reduce inflammatory factors and ferritin levels， promote the recovery of muscle mass and strength， improve insulin resistance， and quality of life in elderly patients with T2DM complicated with sarcopenia， and does not increase the occurrence of adverse drug reactions.

The 5-hydroxytryptamine 2A receptor (5-HT_2AR) is one of the key targets in the development of novel antidepressants. To develop new antidepressants targeting the 5-HT_2A receptor, this study established a high-throughput screening method for drugs targeting the 5-HT_2A receptor based on the principle of detecting calcium flux signals. The immunofluorescence assay and western blotting were employed to evaluate receptor expression levels in the 5-HT_2AR-CHO cell line. The reaction system parameters, including cell seeding density, DMSO concentration, and dye incubation time, were optimized with Z'-factor and signal window values as evaluation indicators. The specificity, precision, stability, and applicability of the method were assessed. Results indicated that the 5-HT_2AR-CHO cell line stably expressed high levels of the 5-HT_2A receptor. The optimized screening method involved a reaction system with 10 000 cells/well, 0.2% DMSO, and 2 h incubation with Calcium 6 dye. The method demonstrated excellent specificity, with inter-batch precision below 10% for the detection of 5-hydroxytryptamine (5-HT) at low, medium, and high concentrations. Testing four compounds that target the 5-HT_2A receptor- agonists 2,5-dimethoxy-4-iodoamphetamine (DOI), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and lysergic acid diethylamide (LSD), along with the antagonist MDL100907-yielded Z'-factors (at EC₈₀) greater than 0.85 and signal window values over 0.91. The EC₅₀ values of these compounds were in the nanomolar range, and their potency rank order aligned with previously reported data, confirming the reliability of the established method. When being applied to the detection of 38 known active compounds, the method efficiently identified 5-HT_2A receptor agonists and antagonists while showing no response to non-target compounds. In conclusion, this study successfully constructs a high-throughput screening approach for 5-HT_2A receptor-targeting drugs based on calcium flux signals. The method possesses strong specificity, high sensitivity, and robust stability, being suitable for screening antidepressants targeting the 5-HT_2A receptor.
High-Throughput Screening Assays/methods* ; Receptor, Serotonin, 5-HT2A/metabolism* ; Animals ; CHO Cells ; Cricetulus ; Calcium Signaling/drug effects* ; Antidepressive Agents/pharmacology* ; Humans ; Serotonin 5-HT2 Receptor Antagonists/pharmacology* ; Calcium/metabolism*

Objective To observe the changes in functional connectivity(FC)of raphe nucleus in patients with first-episode depression complicated with suicidal ideation(SI).Methods Ninety-eight first-episode depression patients were prospectively enrolled and assigned into SI group(n=56)or non SI group(n=42)based on complicated with SI or not,while 47 healthy volunteers were recruited as control group.Resting-state functional MRI was performed.FC between dorsal raphe nucleus(DRN),median raphe nucleus(MRN)and the whole brain were analyzed and compared among 3 groups and between each 2 groups,and the correlations of FC of different brain regions with clinical data of SI group were explored.Results Compared with control group,FC between DRN and left cerebellum and left putamen in SI group and non SI group decreased(all P＜0.05),between MRN and right inferior temporal gyrus increased but between MRN and left inferior frontal gyrus,right superior occipital gyrus,left inferior parietal lobule,left putamen decreased(all P＜0.05).FC between DRN and left putamen in SI group was higher than that in non SI group(P＜0.05).FC between MRN and right central posterior gyrus of SI group increased compared with that in the rest 2 groups(both P＜0.05).FC between MRN and left putamen in SI group was positively correlated with body mass score of Hamilton depression scale-24(HAMD-24)(rs=0.297,P=0.026).Conclusion Abnormal changes of FC between raphe nucleus and cortex,also between raphe nucleus and subcortical area occurred,and FC between MRN and left putamen positively correlated with body mass score of HAMD-24 in patients with first-episode depression complicated with SI.

Objective: To investigate the impact of childhood traumatic experiences on individual risktaking decisions in early adulthood using functional nearinfrared spectroscopy (fNIRS), so as to provide the reference for clarifying the brain mechanisms underlying the impact of childhood trauma on individual risky decision. Methods: From December 2023 to March 2024, 28 children with childhood trauma experiences (trauma group) and 32 healthy college students (control group) were selected from Jining Medical University by a combination of stratified descent and convenient sampling methods. All subjects participated in the Iowa Game task fNIRS scanning. The brain activation, functional connectivity, graph theory properties (degree centrality, betweenness centrality, and local efficiency), and Receiver Operating Characteristic (ROC) analysis were performed by using preprocessing fNIRS data. Results: Compared with control group, trauma group showed significantly fewer choice times in the inferior deck (Z=-0.88), and showed significantly decreased activation levels in the right frontalpolar (Z=-2.59), as well as showed significant decreased functional connectivity between left dorsolateral prefrontal and in right dorsolateral prefrontal (Z=-3.78), and between left dorsolateral prefrontal cortex and the right frontal pole (Z=-3.68)(P<0.05). The central index of right inferior frontal gyrus in the trauma group was higher than that in the control group, while the central index of left and right dorsolateral frontal lobes was lower than that in the control group (Z=2.13, -2.53, -2.12, P<0.05). The centrality index of the right inferior frontal gyrus in the trauma group was higher than that in the control group (Z=2.47, P<0.05). The local efficiency indicators of the right inferior frontal gyrus, left and right frontal pole in the trauma group were higher than those in the control group (Z=2.51, 2.17, 2.53, P<0.05). The results of the ROC curve analysis showed that the local efficiency achieved the highest area under the curve (AUC=0.68). Conclusions Young adults with childhood trauma experience tend to choose lower loss, and the frontal pole shows a lack of activation in the whole process of risk decision performance. The abnormalities in the brain connectivity and network properties might be the neural basis of excessive defense mechanisms that childhood trauma leads to risky decisions.

Objective Using cochlear metabolomics to study the mechanisms underlying age-related hearing loss in rat.Methods A total of 30 rats with 2-month-old(young group)and 14-month-old(old group)were select-ed,with 15 rats in each group.The auditory function in each group was detected by auditory brainstem response(ABR),the morphology of cochlear tissue in both groups was observed using HE staining,and the oxidative stress status of cochlear tissue was detected by flow cytometry.Five rats/groups were selected for metabolomic examina-tion of cochlear tissue by untargeted ultra-high performance liquid chromatography-mass spectroscopy(LC-MS/MS)to analyze the metabolic differences in the aging cochlea.Results Compared with young group,ABR detection of tone burst at 8,16,and 32 kHz and click response thresholds were significantly higher in old group(P＜0.05),HE staining showed cochlear senescence-related vascular stripe atrophy(P＜0.05),and flow cytometric techniques suggested significantly higher levels of oxidative stress in old group(P＜0.05).Metabolomics detection revealed that a total of 124 differential metabolites were identified in the cochlea of the old group,of which 16 metabolites in-cluding sphingosine,all-trans-retinoic acid,and oleamide were significantly upregulated,while the levels of 108 me-tabolites such as purine,taurine,thiamine,and proline and its derivatives were significantly decreased.The results suggested that physiopathological mechanisms such as protein synthesis and catabolism,sphingolipid metabolism,purine metabolism,oxidative stress-related signaling,cell death,and coenzyme biosynthesis may be involved in co-chlear aging.Conclusion Cellular senescence and cochlear metabolic dysfunction may be important mechanisms of age-related hearing loss.

The patient, an 84-year-old man, was admitted to the hospital with "low back pain with limitation of movement for more than half a year". Admission examination: mild kyphotic deformity of the spine, significant tenderness and percussion pain in the lower back, bilateral lower limb muscle strength graded 5, normal skin sensation. Lumbar MRI and CT revealed a compressive fracture of the L 4 vertebra. Dual-energy X-ray absorptiometry (DEXA) indicated a bone mineral density T-score of -2.6, suggesting osteoporosis. Admission diagnosis: osteoporotic compressive fracture of the L 4 vertebra. The patient underwent thorough examinations to exclude surgical contraindications. On the fourth day of admission, the patient underwent percutaneous vertebroplasty of the L 4 vertebra. At the end of the operation, the patient became unresponsive, with a blood pressure drop to 94/63 mmHg and oxygen saturation falling to 80%. Cranial CT showed multiple punctate gas density shadows within the brain. Lumbar CT revealed gas accumulation in the soft tissue adjacent to the lumbar spinous processes, localized intraductal gas, and punctate gas density shadows within the vessels in both groin areas. The diagnosis was intracranial arterial gas embolism. The patient's condition deteriorated further, with loss of consciousness, neck stiffness, increased muscle tone of both lower limbs, and positive Babinski's sign on both sides. Symptomatic treatments included brain protection, maintaining cerebral perfusion, and improving collateral cerebral circulation, but the patient did not regain consciousness. The patient developed a pulmonary infection one month postoperatively and died three months postoperatively due to respiratory failure. This case highlights the potential risk of gas embolism during vertebroplasty. Measures to reduce such complications should be implemented, such as minimizing the duration of venous blood-air contact, pre-filling the cannula with saline to reduce the venous blood-air interface, and appropriately increasing venous pressure to reduce the risk of gas entry. It is recommended to use smaller diameter catheters. For patients with pre-existing cardiac conditions or elderly patients, preoperative cardiac Doppler ultrasound should be performed to exclude anatomical abnormalities such as patent foramen ovale.

Objective: To investigate the analgesic mechanism of Tuina (Chinese therapeutic massage) by observing the effect of the N-methyl-D-aspartate receptor subunit 2B (NR2B)/postsynaptic density-95 (PSD-95) pathway on the dendritic structure of spinal cord dorsal horn in rats with lumbar disc herniation. Methods: Fifty Sprague-Dawley rats were randomly divided into a blank group, a model group, a Tuina group, a blocker agent group, and a blocker agent + Tuina group. The sciatic nerve chronic constriction injury (CCI) model was prepared by the sciatic nerve ligation method. From the 4th day after modeling, rats in the Tuina group and the blocker agent + Tuina group were subject to daily Tuina intervention, and those in the blocker agent group and the blocker agent + Tuina group were daily intrathecally injected with NR2B blocker agent (MK-801). The spontaneous pain score was used to observe the pain behavior of all rats. The expression levels of NR2B and downstream PSD-95 were measured by immunohistochemistry, and the dendritic structure changes were observed by Golgi staining for rat spinal cord dorsal horn after 14 d of continuous intervention. Results: Compared with the blank group, the degree of rat spontaneous pain after CCI was elevated in both the model and the Tuina groups (P<0.01) and was reduced in the Tuina group after the Tuina intervention compared with the model group (P<0.05). Compared with the model group, the rat spontaneous pain level after blocking NR2B was reduced in both the blocker agent group and the blocker agent + Tuina group (P<0.05). The NR2B and PSD-95 protein levels were significantly higher in the model group compared with the blank group (P<0.01); the total number of dendritic branches was increased (P<0.01), and the total dendritic length became longer (P<0.01) in the spinal cord dorsal horn. The rat NR2B and PSD-95 protein levels were significantly decreased in the Tuina group compared with the model group (P<0.01); the total dendritic branch number was reduced (P<0.01) and the total length was shortened (P<0.01) in the spinal cord dorsal horn. After blocking NR2B, the expression levels of NR2B and downstream PSD-95 protein were significantly lower in both the blocker agent group and the blocker agent + Tuina group compared to the model group (P<0.01). The total branch number was significantly reduced (P<0.01), and the total length was significantly shortened (P<0.01) of the dendrites in the spinal cord dorsal horn. Conclusion: Tuina may exert an analgesic effect by remodeling the dendritic structure in the spinal cord dorsal horn in rats with lumbar disc herniation, and its mechanism may be related to the inhibition of NR2B/PSD-95 signaling pathway.

The high incidence of dual sleep and frail disorders in the elderly people, often occurring together, seriously affects the physical and mental health of the older people, effective research on the dynamics of dual sleep and frail disorders is important for improving the quality of life for the older people and responding to global ageing trend. While trajectory studies provide a unique practical scientific perspective to grasp the dynamics of development, dual trajectories unite dual barriers provide an opportunity to study the dynamic dependence of both sleep and frailty simultaneously sleep trajectories and frailty trajectories in older people are interrelated and interacted through deeper mechanisms. Therefore, it is necessary for the study not only focus on the ongoing development of health problems, but also needs to consider multiple aspects and propose targeted intervention program.
Aged ; Humans ; Frail Elderly ; Frailty ; Quality of Life ; Aging ; Sleep

Background Prolonged exposure to vibration can cause vascular endothelial injury, and inflammatory response plays an important role in vascular endothelial injury. Studies have shown that long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) is involved in regulating the expression of inflammatory injury of endothelial cells. Objective To investigate the effects of vibration on the secretion of inflammatory factors and the expression of IncRNA MEG3 by vascular endothelial cells in vitro. Methods Human umbilical vein endothelial cells (HUVEC) were divided into two categories: vibration and control. The vibration exposure included 63 Hz (6.76 m·s⁻²), 200 Hz (5.08 m·s⁻²), and 250 Hz (4.56 m·s⁻²) frequency bands, and 1 and 2 d exposure time with 1 to 4 h of daily vibration. The control treatment was the same as the vibration category except that they were not exposed to vibration. CCK-8 was used to detect the effects of different vibration frequencies and time on the viability of HUVEC. The expression levels of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-4 (IL-4), and interleukin-10 (IL-10) in the cells and supernatants were detected by enzyme-linked immunosorbent assay. The expression levels of IncRNA MEG3 were detected by real-time fluorescence quantitative PCR. Results Compared with the cells with the control treatment, the cell viability of the 1-day exposure group increased after 1.5 h and 3 h of vibration at 63 Hz, while decreased after 2 h and 2.5 h; the cell viability of the 2-day exposure group increased at the frequency of 63 Hz for 1.5 h, but decreased at 2 h and 2.5 h. At the frequency of 200 Hz, the cell viability of the 1-day exposure group increased at 2 h and 4 h, but decreased at 2.5 h and 3 h; the cell viability of the 2-day exposure group increased at 1.5 h and decreased at 2.5 h. For the vibration exposure at frequency of 250 Hz, the cell viability of the 1-day exposure group increased at 1.5 h and 2.5 h, but decreased at 3 h; of the 2-day exposure group, the cell viability increased at 1.5 h and decreased at 3 h. For the exposure settings of 63 and 200 Hz vibration for 2.5 h and 250 Hz vibration for 3 h, and with the control treatment as reference, the expression levels of TNF-α, IL-8, IL-4, and IL-10 in cells and supernatants were increased in the 1 d and 2 d exposures; the expression level of lncRNA MEG3 decreased in the 1 d exposure group; however, for the 2 d exposure, the expression level of lncRNA MEG3 decreased only in the 63 Hz vibration exposure. All of these results were statistically significant (P<0.05). Conclusion Vibration could induce an increase in the levels of inflammatory factors TNF-α, IL-8, IL-4, and IL-10 and a decrease in the expression level of lncRNA MEG3 in vascular endothelial cells in vitro.

Objective:To determine the relationship between health self-empowerment level and health self-management skill in older adults.Methods:A household survey was conducted from June 2020 to April 2021, among older adults in two communities each in Zhuzhou and Changsha selected by stratified cluster sampling. Data were collected through a general questionnaire, simplified. Elders Health Empowerment Scale, and Rating Scale of Health Self-Management Skill for Adults. A total of 444 questionnaires were distributed, of which 425 were valid. Pearson correlation and hierarchical regression analyses were used to analyze the relationship between health self-empowerment level and health self-management skill.Results:Final sample included 425 elderly people. Health self-empowerment was at medium to high level (30.9±5.6), whereas health self-management was at medium level (146.2±21.7); and the two factors were significantly correlated (Pearson coefficient was 0.724). After controlling for confounding factors (demographic characteristics), health self-empowerment independently accounted for 34.3% of the variation in health self-management ability.Conclusion:Health self-empowerment positively affects health self-management ability among older adults, which suggests the importance of stimulating health self-empowerment awareness in the process of health self-management.