OBJECTIVE To investigate the effects and mechanisms of oliceridine fumarate （TRV130） in improving postoperative cognitive dysfunction （POCD） in elderly rats based on the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） pathway. METHODS Rats were randomly divided into the control group （normal saline）， the model group （normal saline）， the TRV130 group （2.8 mg/kg）， the TLR4/NF-κB pathway inhibitor （TAK-242） group （3 mg/kg）， the β -arrestin inhibitor （Barbadin） group （3 mg/kg）， and the traditional opioid drug （morphine） group （2.8 mg/kg）， with 15 rats in each group. Except for the control group， POCD models were established in all other groups. From the first day after surgery， drugs/normal saline were administered via caudal vein injection once daily for 3 consecutive days. After the last administration， the pathological damage of hippocampal tissue was observed； the cognitive function， serum inflammatory factor levels， hippocampal neurons apoptosis rate， and the expression of ionized calcium-binding adapter molecule 1 （Iba-1）， glial fibrillary acidic protein （GFAP）， and TLR4/NF-κB pathway-related mRNA and protein in hippocampal tissue were detected. RESULTS In the model group， the neurons in the CA1 region of the hippocampus were disordered and sparse， with decreased number， pyknotic and fragmented nuclei accompanied by inflammatory cell infiltration. Compared with the control group， the escape latency， serum levels of tumor necrosis factor α （TNF-α）， interleukin-6 （IL-6）， and IL-1β， hippocampal neurons apoptosis rate， average fluorescence intensities of Iba-1 and GFAP， mRNA expression levels of TLR4 and NF-κB p65， and their protein expression/phosphorylation levels in hippocampal tissue were significantly increased/elevated in the model group （ P ＜0.05）； the time spent in the target quadrant and the number of platform crossings were significantly shortened/decreased （ P ＜0.05）. Compared with the model group， the cognitive function， pathological， inflammatory， and apoptosis-related indicators were significantly improved in the TRV130 group， TAK-242 group， and Barbadin group （ P ＜0.05）； the mRNA expression levels of TLR4 and NF-κB p65 and their protein expression/phosphorylation levels were significantly decreased in the TRV130 group and TAK-242 group （ P ＜0.05）. CONCLUSIONS TRV130 may improve POCD in elderly rats by inhibiting the TLR4/NF-κB pathway and alleviating postoperative central nervous system inflammatory responses.

OBJECTIVE Exploring the specific changes in brain signal variability during healthy aging using functional near-infrared spectroscopy technology.METHODS Twenty-eight young adults and 30 elderly adults were included,and functional near-infrared spectroscopy was used to record the changes in brain blood oxygen and calculate the brain signal variability during the execution of visual-audio dual tasks.RESULTS The brain signal variability of the elderly group was significantly reduced when performing visual-audio dual tasks,especially in the bilateral dorsolateral prefrontal cortex,right Broca,bilateral primary somatosensory cortex,bilateral Wernicke area,bilateral frontopolar area,bilateral primary motor cortex,bilateral somatosensory association cortex,bilateral orbitofrontal area,bilateral pre-motor and supplementary motor cortex.The brain signal variability in the left primary somatosensory cortex(r=-0.385,P=0.043)and right primary somatosensory cortex(r=-0.386,P=0.042)of young adults was negatively correlated with visual reaction time;The brain signal variability in the right somatosensory association cortex(r=-0.371,P=0.044),left pre-motor and supplementary motor cortex(r=-0.393,P=0.032)of elderly adults was negatively correlated with visual reaction time.CONCLUSION Elderly individuals exhibit a significant reduction in neural signal variability within the prefrontal cortex and sensory related cortex,resulting in diminished neural dynamic adaptability that compromises behavioral performance during visual-audio dual tasks.

OBJECTIVE Aimed to construct a corpus for a developing auditory-verbal communication training system tailored for the elderly and to grade the difficulty of sentence materials.The ultimate goal is to meet the diverse needs of trainees with varying hearing and speech capabilities.METHODS A training corpus,encompassing 3 627 sentences across 12 distinct topics,was systematically established.During the pre-experimental phase,12 adult subjects with normal hearing were recruited.They were tasked with conducting speech recognition rate tests on 100 randomly selected test sentences under four different signal-to-noise ratio(SNR)conditions.By plotting the performance-intensity(P-I)function curve,the SNR50 value,specifically-6.5 dB,was accurately determined.In the formal experiment,17 additional subjects were recruited.All sentences within the corpus were then subjected to speech recognition rate tests in a noisy environment under the established SNR50 condition.The average recognition rate was computed,and both the recognition rate-frequency histogram and the normal distribution curve were plotted.Leveraging the area beneath the normal curve,the segmentation points of the speech recognition rate were calculated,enabling the classification of sentences into three difficulty levels:easy,medium,and difficult.RESULTS The task of classifying the difficulty of sentences within the corpus was successfully accomplished.Specifically,there were 1 144 easy sentences,constituting 33%of the total;1 099 medium sentences,accounting for 32%;and 1 212 difficult sentences,representing 35%.CONCLUSION This research has successfully concluded the establishment of a corpus for the elderly's auditory-verbal communication ability training system and its associated difficulty grading.The obtained grading results are found to be in accordance with the principle of partitioning the difficulty gradient based on area.This study explores an effective method for grading the difficulty of auditory training sentences,ensuring that the training content matches the level of the trainer's competence.This not only enhances the training effectiveness but also improves the overall user experience.

Objective:To investigate whether intermittent fasting alleviates insulin resistance in a polycystic ovary syndrome(PCOS) mouse model through the regulation of autophagy.Methods:Fifty 3-week-old female C57BL/6J mice were randomly assigned into the following groups using a random number table: normal control(NC) group( n=10), maintained on a standard chow diet; high-fat diet(HFD) group( n=10) fed a diet with 60% of calories derived from fat; and PCOS model group( n=30), established by combining a HFD with dehydroepiandrosterone(DHEA) administration. Successful modeling was confirmed by disrupted estrous cycles, hyperandrogenism, and polycystic ovarian morphology. The PCOS model mice were further divided into three groups: PCOS group( n=9), PCOS with intermittent fasting group(PCOS+ IF, n=9), and PCOS with intermittent fasting plus the autophagy inhibitor 3-methyladenine(3-MA) group(PCOS+ IF+ 3-MA, n=9). Autophagy levels were assessed by detecting markers LC3 and p62 and observing autophagosomes via transmission electron microscopy. Glucose tolerance test(GTT) and insulin tolerance test(ITT) were performed, and the area under the curve(AUC) was calculated to evaluate insulin resistance. Western blotting was used to detect phosphorylation levels of phosphatidylinositol 3-kinase(PI3K), protein kinase B(Akt), mammalian target of rapamycin(mTOR), and p70S6 kiase(p70S6K). Results:Compared with the NC group, the PCOS model group showed absent estrous cycles, significantly elevated serum testosterone, sex hormone binding globulin, and luteinizing hormone(LH) levels( P<0.001), and polycystic ovarian changes on hematoxylin-eosin staining, confirming successful model establishment. Immunohistochemistry, transmission electron microscopy, and Western blotting demonstrated that autophagy levels were increased in the PCOS+ IF group compared with the PCOS group, while 3-MA administration reduced the intermittent fasting - induced autophagy. The AUC values for both GTT and ITT were significantly lower in the PCOS+ IF group than those in the PCOS group( P<0.001, P=0.003), but increased in the PCOS+ IF+ 3-MA group compared to the PCOS+ IF group( P<0.001, P=0.020). Western blotting analysis showed that phosphorylation levels of PI3K, Akt, mTOR, and p70S6K were significantly decreased in the PCOS+ IF group compared with the PCOS group( P=0.002, P=0.001, P=0.001, and P<0.001, respectively), and increased in the PCOS+ IF+ 3-MA group compared with the PCOS+ IF group( P=0.021, P=0.041, P=0.047, and P=0.024, respectively). Conclusions:Intermittent fasting alleviates insulin resistance in a PCOS mouse model through inhibitiing PI3K/Akt/mTOR signaling pathway and promoting autophagy.

This case report describes the diagnostic and therapeutic management of a 67-year-old fe-male with a 40-year history of Sj?gren disease(SjD)who was hospitalized for evaluation of recurrent fever lasting over one month.The patient's initial diagnosis of SjD was established four decades earlier based on clinical manifestations,serological findings,and evidence of glandular damage.Her clinical presenta-tion included recurrent parotid gland enlargement accompanied by sicca symptoms,notably persistent xerostomia and xerophthalmia,followed by progressive dental caries.Serological studies demonstrated positivity for antinuclear antibodies,anti-SSA/Ro,and anti-α-fodrin antibodies.Objective assessments confirmed significant ocular involvement(Schirmer's test≤5 mm/5 min)and pulmonary interstitial changes on chest CT,consistent with the 2016 American College of Rheumatology and European League Against Rheumatism(ACR/EULAR)classification criteria for SjD.The patient's condition remained sta-ble under low-dose corticosteroids and disease-modifying anti-rheumatic drugs(DMARDs)until the re-cent onset of prolonged fever,necessitating evaluation for fever of unknown origin.Differential diagnoses considered disease flare,infection,and malignancy.The European Sj?gren's Syndrome Disease Activity Index(ESSDAI)score was 5 points,indicating moderate systemic disease activity.Initial laboratory in-vestigations revealed no evidence of infection,and empirical anti-infective therapy proved ineffective.No-tably,despite the absence of lymphadenopathy,laboratory findings including borderline positive IgM λ M-protein,elevated lactate dehydrogenase,hyperferritinemia,and increased β2-microglobulin levels raised suspicion for lymphoproliferative disorders,given the established association between SjD and lymphoma.Bone marrow aspiration showed no significant abnormalities,but PET/CT imaging detected hypermetabolic lesions in the left breast and right distal femur,suggesting potential malignancy.Subse-quent histopathological examination of the breast lesion confirmed non-Hodgkin's lymphoma(NHL),specifically diffuse large B-cell lymphoma(DLBCL)of the germinal center B-cell(GCB)subtype.Treatment with R-CHOP chemotherapy(rituximab,cyclophosphamide,doxorubicin,vincristine,and prednisone)induced complete metabolic remission after three cycles.However,she subsequently developed treatment-related complications,including myelosuppression and pulmonary infection.This case underscores the importance of maintaining a high index of suspicion for atypical site involvement in SjD patients,particularly when lymphoma risk factors are present.Comprehensive differential diagnosis should include lymphoma and other malignancies,and the diagnostic value of PET/CT and histopatholog-ical examination in disease evaluation is emphasized.SjD complicated by breast lymphoma is exceptional-ly rare,and its pathogenesis may involve lymphocytic infiltration,abnormal activation of lymphocytes,formation of ectopic germinal centers in the breast,and eventual malignant transformation.These mecha-nisms require further investigation through clinical and basic research studies.

Objective:To systematically evaluate and integrate qualitative research from nurses on perceptions and feelings of elder self-neglect, with the aim of providing a reference for early identification, prevention, and intervention of elder self-neglect by nursing staff.Methods:Qualitative research of nurses' perceptions and feelings of elder self-neglect was systematically searched in the Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biology Medicine disc by computer. The search period was from database establishment to March 31, 2024. The quality of the literature was evaluated according to the quality evaluation criteria for qualitative research of the Australia Joanna Briggs Institute Evidence-Based Health Care Center. The aggregate integration approach was used to integrate the findings of the study.Results:A total of eight papers were included to distill 30 findings, and similar findings were generalized and integrated to form 11 categories and synthesized into three integrated findings, including nurses' perception of elder self-neglect, manifestations of elder self-neglect from nurses' perspectives, and influencing factors of elder self-neglect from nurses' perspectives.Conclusions:Nurses should understand the manifestations and influencing factors of elder self-neglect, improve own professionalism, and help the elderly establish positive coping mechanisms to promote healthy aging.

Objective:To develop an artificial intelligence (AI)-guided intravitreal injection robot system to accurately detect the injection point on the ocular surface and guide the robotic arm to complete the intravitreal injection positioning task through 3D position calculation.Methods:The Dikablis subset of the TEyeD dataset was used.Training set, testing set, and validation set were constructed by using equal interval sampling strategy.The system read the ocular surface color RGB image with an RGBD camera, then used a PatchCrop-Transformer-based injection point detection algorithm to detect and locate key points such as the pupil, iris, and eyelid in the image.Next, it extracted the local 3D point cloud data near the injection point based on the depth information obtained by the camera.Through principal component analysis (PCA) of the local area point cloud data, the injection point and injection direction were determined.The key information was then passed to the robotic arm system.The end of the robotic arm adopted a remote center of motion (RCM) mechanism.After solving the forward and inverse kinematics, the joint movement path was obtained, and the robotic arm was controlled to move to 2 cm above the injection point.After confirmation by the doctor, the insertion, injection, and withdrawal operations were completed to ensure the stability and repeatability of the injection process.The mean square error (MSE) of key points localization and the success detection rate (SDR) within different pixel error ranges (2, 5, and 10 pixels) of the study method were compared with those of the NFDP, SLPT, and StarLoss methods, and the effects of random weight enhancement, fixed weight enhancement, and no enhancement methods on the MSE of key points localization were evaluated.The repeatability and absolute positioning accuracy of the robotic arm system were also evaluated.Results:After adding random weight enhancement, the model of this study outperformed the fixed weight enhancement and no enhancement methods in both MSE and SDR.The MSEs of the model proposed in this study for overall eye, pupil, and iris localization were 4.25, 2.41, and 1.54, respectively, which were lower than those of the NFDP, StarLoss, and SLPT methods.Within the error ranges of 5 and 10 pixels, the SDRs of the model proposed in this study were 72.09% and 92.68%, respectively, which were higher than those of the NFDP, StarLoss, and SLPT methods.The single-axis repeatability errors and absolute positioning errors of the robotic arm were within ±5 μm.Conclusions:The AI-guided intravitreal injection robot system integrates RGBD images to achieve automatic recognition of the ocular injection point and high-precision motion control through RCM mechanism design and corresponding kinematic solution methods.

ObjectiveTo understand the seropositivity of neutralizing antibodies (NAb) and low-level NAb against SARS-CoV-2 infection in the community residents, and to explore the impact of COVID-19 vaccination and SARS-CoV-2 infection on the levels of NAb in human serum. MethodsOn the ground of surveillance cohort for acute infectious diseases in community populations in Shanghai, a proportional stratified sampling method was used to enroll the subjects at a 20% proportion for each age group (0‒14, 15‒24, 25‒59, and ≥60 years old). Blood samples collection and serum SARS-CoV-2 NAb concentration testing were conducted from March to April 2023. Low-level NAb were defined as below the 25^th percentile of NAb. ResultsA total of 2 230 participants were included, the positive rate of NAb was 97.58%, and the proportion of low-level NAb was 25.02% (558/2 230). Multivariate logistic regression analysis indicated that age, infection history and vaccination status were correlated with low-level NAb (all P<0.05). Individuals aged 60 years and above had the highest risk of low-level NAb. There was a statistically significant interaction between booster vaccination and one single infection (aOR=0.38, 95%CI: 0.19‒0.77). Compared to individuals without vaccination, among individuals infected with SARS-CoV-2 once, both primary immunization (aOR=0.23, 95%CI: 0.16‒0.35) and booster immunization (aOR=0.12, 95%CI: 0.08‒0.17) significantly reduced the risk of low-level NAb; among individuals without infections, only booster immunization (aOR=0.28, 95%CI: 0.14‒0.52) showed a negative correlation with the risk of low-level NAb. ConclusionsThe population aged 60 and above had the highest risk of low-level NAb. Regardless of infection history, a booster immunization could reduce the risk of low-level NAb. It is recommended that eligible individuals , especially the elderly, should get vaccinated in a timely manner to exert the protective role of NAb.

Objective:To develop an artificial intelligence (AI)-guided intravitreal injection robot system to accurately detect the injection point on the ocular surface and guide the robotic arm to complete the intravitreal injection positioning task through 3D position calculation.Methods:The Dikablis subset of the TEyeD dataset was used.Training set, testing set, and validation set were constructed by using equal interval sampling strategy.The system read the ocular surface color RGB image with an RGBD camera, then used a PatchCrop-Transformer-based injection point detection algorithm to detect and locate key points such as the pupil, iris, and eyelid in the image.Next, it extracted the local 3D point cloud data near the injection point based on the depth information obtained by the camera.Through principal component analysis (PCA) of the local area point cloud data, the injection point and injection direction were determined.The key information was then passed to the robotic arm system.The end of the robotic arm adopted a remote center of motion (RCM) mechanism.After solving the forward and inverse kinematics, the joint movement path was obtained, and the robotic arm was controlled to move to 2 cm above the injection point.After confirmation by the doctor, the insertion, injection, and withdrawal operations were completed to ensure the stability and repeatability of the injection process.The mean square error (MSE) of key points localization and the success detection rate (SDR) within different pixel error ranges (2, 5, and 10 pixels) of the study method were compared with those of the NFDP, SLPT, and StarLoss methods, and the effects of random weight enhancement, fixed weight enhancement, and no enhancement methods on the MSE of key points localization were evaluated.The repeatability and absolute positioning accuracy of the robotic arm system were also evaluated.Results:After adding random weight enhancement, the model of this study outperformed the fixed weight enhancement and no enhancement methods in both MSE and SDR.The MSEs of the model proposed in this study for overall eye, pupil, and iris localization were 4.25, 2.41, and 1.54, respectively, which were lower than those of the NFDP, StarLoss, and SLPT methods.Within the error ranges of 5 and 10 pixels, the SDRs of the model proposed in this study were 72.09% and 92.68%, respectively, which were higher than those of the NFDP, StarLoss, and SLPT methods.The single-axis repeatability errors and absolute positioning errors of the robotic arm were within ±5 μm.Conclusions:The AI-guided intravitreal injection robot system integrates RGBD images to achieve automatic recognition of the ocular injection point and high-precision motion control through RCM mechanism design and corresponding kinematic solution methods.

This article reports a postcraniotomy patient with renal insufficiency and electrolyte imbalance who developed ventilator-associated pneumonia caused by extensively drug-resistant Klebsiella pneumoniae.According to the patient's pathophysiological characteristics,bacterial epidemiological characteristics,and bacterial culture results,combined with the latest guidelines and the pharmacokinetic/pharmacodynamic characteristics of antibiotics,a full-dose ceftazidime/avibactam regimen was initially suggested by the clinical pharmacist,and which was adopted by doctor.When the effect of ceftazidime/avibactam was poor and no guideline-recommended alternatives were available,the clinical pharmacist,in conjunction with clinical experience,proposed a combination therapy of colistin sulfate and tigecycline,with the implementation of adverse reaction monitoring and mucin sulfate blood concentration monitoring.Finally,the pneumonia was effectively controlled,the inflammatory indicators such as temperature and the white blood cell count returned to normal,no adverse drug reactions occurred,and the patient was successfully transferred to the rehabilitation institution.Clinical pharmacists stay updated on the latest medication knowledge both domestically and internationally,recommend advanced drug treatment protocols for clinical practice,assist in managing severe infections,and play an important role in the clinical team.