The activation of the sirtuin1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species (ROS) levels. Clinical trials have demonstrated that Zhongfeng Xingnao Liquid (ZFXN) ameliorates post-stroke cognitive impairment (PSCI). However, the underlying mechanism, particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway, remains unclear. This study employed an oxygen-glucose deprivation (OGD) cell model using SH-SY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation (2VO). The effects of ZFXN on learning and memory, neuroprotective activity, mitochondrial function, oxidative stress, and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro. Results indicated that ZFXN significantly increased the B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax) ratio, reduced terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL)⁺ cells, and markedly improved cognition, synaptic plasticity, and neuronal function in the hippocampus and cortex. Furthermore, ZFXN exhibited potent antioxidant activity, evidenced by decreased ROS and malondialdehyde (MDA) content and increased superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels. ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential (MMP), Tom20 fluorescence intensity, adenosine triphosphate (ATP) and energy charge (EC) levels, and mitochondrial complex I and III activity, thereby inhibiting mitochondrial damage. Additionally, ZFXN significantly increased SIRT1 activity and elevated SIRT1, nuclear Nrf2, and HO-1 levels. Notably, these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro. In conclusion, ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.
Sirtuin 1/genetics* ; Animals ; NF-E2-Related Factor 2/genetics* ; Cognitive Dysfunction/genetics* ; Male ; Rats, Sprague-Dawley ; Rats ; Humans ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Heme Oxygenase-1/genetics* ; Stroke/complications* ; Oxidative Stress/drug effects* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Reactive Oxygen Species/metabolism* ; Neuroprotective Agents

Triggering receptor expressed on myeloid cells 2 (TREM2)-mediated microglial phagocytosis is an energy-intensive process that plays a crucial role in amyloid beta (Aβ) clearance in Alzheimer's disease (AD). Energy metabolic reprogramming (EMR) in microglia induced by TREM2 presents therapeutic targets for cognitive impairment in AD. Jiawei Xionggui Decoction (JWXG) has demonstrated effectiveness in enhancing energy supply, protecting microglia, and mitigating cognitive impairment in APP/PS1 mice. However, the mechanism by which JWXG enhances Aβ phagocytosis through TREM2-mediated EMR in microglia remains unclear. This study investigates how JWXG facilitates microglial phagocytosis and alleviates cognitive deficits in AD through TREM2-mediated EMR. Microglial phagocytosis was evaluated through immunofluorescence staining in vitro and in vivo. The EMR level of microglia was assessed using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) kits. The TREM2/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway was analyzed using Western blotting in BV₂ cells. TREM2^-/- BV₂ cells were utilized for reverse validation experiments. The Aβ burden, neuropathological features, and cognitive ability in APP/PS1 mice were evaluated using ELISA kits, immunohistochemistry (IHC), and the Morris water maze (MWM) test. JWXG enhanced both the phagocytosis of EMR disorder-BV₂ cells (EMRD-BV₂) and increased EMR levels. Notably, these effects were significantly reversed in TREM2^-/- BV₂ cells. JWXG elevated TREM2 expression, adenosine triphosphate (ATP) levels, and microglial phagocytosis in APP/PS1 mice. Additionally, JWXG reduced Aβ-burden, neuropathological lesions, and cognitive deficits in APP/PS1 mice. In conclusion, JWXG promoted TREM2-induced EMR and enhanced microglial phagocytosis, thereby reducing Aβ deposition, improving neuropathological lesions, and alleviating cognitive deficits.
Drugs, Chinese Herbal/pharmacology* ; Microglia/drug effects* ; Phagocytosis ; Cognitive Dysfunction/drug therapy* ; Metabolic Reprogramming ; Animals ; Mice ; Cell Line ; Receptors, Immunologic/metabolism* ; Membrane Glycoproteins/metabolism* ; Signal Transduction ; Amyloid beta-Peptides/metabolism* ; Energy Metabolism

Objective:To explore the clinical data of patients with metastatic pheochromocytoma/paraganglioma (PPGL).Methods:The clinical data of 57 patients with metastatic pheochromocytoma/paraganglioma diagnosed and treated at Peking Union Medical College Hospital from January 2016 to June 2022 were reviewed, including 28 cases of pheochromocytoma(PCC) and 29 cases of paraganglioma(PGL). The clinical manifestations, biochemical indexes, tumour characteristics, and metastatic characteristics of the 57 patients were analysed.Results:There were 34 males and 23 females. The median age at the time of initial diagnosis was 34 (20, 54) years, 17 (29.3%) presented with concurrent metastases, and 40 (70.7%) with heterochronous metastases. The median time to presentation of metastases was 2.2 (0, 5.0) years (range 0-22 years). Adrenergic symptoms were present in 45 cases (78.6%) at the time of initial diagnosis, and the median size of the primary tumour was 6.7 (5.0, 9.0) cm. Excessive catecholamine secretion was present in 48 cases (81.4%). The most common locations of metastasis were lymph nodes (71.9%, 41/57), bone (47.3%, 27/57), lung (38.6%, 20/57), and liver (35.1%, 20/57). Metastatic PGL had more multifocal metastases than PCC [10 (34.5%) vs. 2 (7.1%), P=0.011)], was more frequently associated with SDHB mutations [13 (42.9%) vs. 3 (10.7%), P=0.008], and was more likely to have concurrent metastases [12 (41.3%) vs. 5 (17.9%), P=0.005]. Metastatic PCC primary tumours were larger compared to PGL [median length 8.9 (4.0, 17.0) cm vs. 6.1 (1.0, 15.8) cm, P=0.020]. Conclusions:Patients with PGL present with metastases over an extremely wide time span, and patients diagnosed with PPGL should be followed throughout their lives. PGL is more prone to multifocal metastases and simultaneous metastases than PCC, and PGL is more highly correlated with the SDHB mutation.

Objective:To investigate the behavior and emotion of trainees (residents) in the standardized residency training under the novel coronavirus pneumonia (NCP) epidemic, and adjust the training plan and mode of standardized residency training during the NCP epidemic according to the survey results.Methods:A real-name closed questionnaire survey was conducted among 40 residents (27 ultrasound majors and 13 other majors) in ultrasound department using the "Questionnaire Star" WeChat applet, including basic personal information, questions related to NCP, behavioral change survey, behavioral attitude survey and emotional status survey. All the collected data were further statistically analyzed by Chi-square test and rank sum test using SPSS 19.0Results:There were forty valid questionnaires and the participation rate was 100.0%. The accuracy of 24 NCP-related questions was not significantly different between residents majoring in ultrasound and other specialties [92.0%(596/648) vs. 93.6%(292/312), P>0.05]. All the residents had a good understanding of NCP. The main behaviors of going out were significantly reduced, while various behaviors of being at home were significantly increased. Their interest in learning declined. When the epidemic happened (or possibly) in the community or village they lived in, their negative emotions, such as nervousness, fear pessimism and depression, were obviously expressed. Network teaching and evaluation through WeChat public number were adopted and we guided residents to adjust their home behaviors and emotions according to the survey results. Conclusion:Under the NCP epidemic, the behaviors and emotions of residents had been extensively changed. The training center should adjust the teaching plan and mode of training in time, and provide more counselling service in psychology and learning for residents during the epidemic.

Objective To explore the key points of forensics appraisal of medical disputes in mental hospitals,strengthen the management of mental hospitals,prevent medical disputes and improve medical quality.Methods Using the written judgment of China Judgments Online as materials,the order multi-class Logistic regression analysis was conducted on the common faults and level of responsibility in cases of death resulting from mental hospital treatment.Results Improper nursing,improper management,insufficient knowledge of the disease,unclear information,inadequate rescue,improper medication,unclear diagnosis were the risk factors of the degree of responsibility of medical disputes,and other diseases were protective factors.Conclusion Analyzing the common faults and identification points of death disputes in mental hospitals and rectifying them from two aspects can effectively prevent the occurrence of medical disputes,improve the quality of medical treatment,and achieve a win-win situation for doctors and patients.

Objective:To analyze the mediating effects of emotional changes in self-management interventions on the relationship between behavioral management and quality of life in elderly patients with type 2 diabetes and therefore to provide a reference for improving the emotional status of elderly diabetes patients and future community-based self-management interventions.Methods:From 2016 to 2020, a total of 69 self-management groups were formed in Hangzhou, each consisting of 10-15 patients with type 2 diabetes.Based on the construction of a medical consortium and family doctors signing up to provide services, intervention teams were established to conduct a series of group self-management activities for each group.Surveys via questionnaires were conducted before and after the intervention, as well as 6 months after the intervention, to collect patient data on demographics, disease status, emotions, quality of life, and self-management behaviors.The intervention effects were evaluated, and the correlations between emotional changes, self-management behaviors, and changes in quality of life were analyzed.Bootstrap analysis was used to test the mediating effects.Results:A total of 707 elderly diabetes patients were included.There were statistically significant differences in the scores of the Self-Rating Anxiety Scale(SAS), the Self-Rating Depression Scale(SDS), physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, mental health, physical component summary, mental component summary, the dietary control dimension of the type 2 diabetes self-care scale(2-DSCS), regular exercise, medication adherence, blood glucose monitoring, foot care, the dimension of prevention and management of hyperglycemia and hypoglycemia, and the total score of 2-DSCS( P<0.05 for all).Compared with pre-intervention, changes in SAS, SDS, physical component summary and mental component summary scores were all correlated with each dimension of 2-DSCS right after intervention and 6 months after intervention( r=-0.336-0.333, P<0.05), with the exception of changes in the blood glucose monitoring dimension score and changes in the emotional status score.The direct effect of self-management behavior on the quality of life in elderly patients with type 2 diabetes was 0.159, and the indirect effect through emotions was 0.229, with the mediating effect accounting for 59.02% of the total effect. Conclusions:Community-based group self-management activities can effectively improve the emotions and management behaviors of elderly diabetes patients and enhance their quality of life, Emotional changes play a certain mediating role between self-management behaviors and improvement in quality of life.

Hepatocellular carcinoma (HCC) has been known as the second common leading cancer worldwide, as it responds poorly to both chemotherapy and medication. Triptolide (TP), a diterpenoid triepoxide, is a promising treatment agent for its effective anticancer effect on multiple cancers including HCC. However, its clinical application has been limited owing to its severe systemic toxicities, low solubility, and fast elimination in the body. Therefore, to overcome the above obstacles, photo-activatable liposomes (LP) integrated with both photosensitizer Ce6 and chemotherapeutic drug TP (TP/Ce6-LP) was designed in the pursuit of controlled drug release and synergetic photodynamic therapy in HCC therapy. The TP encapsulated in liposomes accumulated to the tumor site due to the enhanced permeability and retention (EPR) effect. Under laser irradiation, the photosensitizer Ce6 generated reactive oxygen species (ROS) and further oxidized the unsaturated phospholipids. In this way, the liposomes were destroyed to release TP. TP/Ce6-LP with NIR laser irradiation (TP/Ce6-LP+L) showed the best anti-tumor effect both

Objective:To evaluate the effect of self-management model of community diabetes patients under the guidance of general practitioners.Methods:A total of 22 communities in Hangzhou were selected as intervention pilot from 2016 to 2017, and 10-15 diabetic patients were recruited to form a self-management team in each community. Relying on the construction of medical alliance and there sources of contracted service of family doctors, intervention teams were set up to conduct regular, personalized and continuous self-management interventions on patients. Intervention continued for 4-6 months. Before, after and 6 months after the intervention, the basic information of patients, knowledge of diabetes, faith in managing disease, self-management behavior, self-management ability of patients, and quality of life were collected through questionnaire survey, body mass index (BMI), 2-hour postprandial blood glucose and glycosylated hemoglobin were detected uniformly, and statistical analysis was conducted.Results:A total of 292 patients were involved in the self-management group, the average age was (66.38±7.90) years old, most of them were female (64.73%). Six months after the intervention, the awareness rate of basic knowledge, risk factors and prevention and treatment knowledge about diabetes in patients (68.64%, 78.75%, 63.41%) were significantly higher than those before the intervention (28.08%, 48.29%, 39.38%), the proportion of patients with reasonable diet, moderate exercise, active problem-solving, management plan making and action according to the plan increased (from 65.41%, 28.76%, 39.04%, 31.85%, 27.74% to 86.76%, 60.28%, 65.16%, 78.05%, 73.17%)(all P<0.05).In terms of time effect, the scores of physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health in SF-36 after intervention and 6 months after intervention were all increased step by step (all P<0.05). Before the intervention, BMI, 2-hour postprandial blood glucose and glycosylated hemoglobin were (24.20±3.11) kg/m 2, (9.29±2.23) mmol/L, (6.81±1.01)% respectively. After the intervention, the three indexes all showed a downward trend, which were (22.89±2.98) kg/m 2, (8.81±1.61) mmol/L, (6.57±0.76)% respectively ( F=14.832, 6.828, 9.667; all P<0.05). Conclusion:Under the guidance of general practitioners, the self-management model of community diabetes patients can effectively improve the level of recognition, belief and behavior of patients, improve their self-management ability and quality of life, and improve BMI and blood glucose control level.

Moschus chrysogaster (sifanicus) viral hemorrhagic disease (McVHD) is an acute and highly lethal infectious disease caused by Moschus chrysogaster hemorrhagic disease virus (McHDV) whose genome sequence is highly homologous with rabbit hemorrhagic disease virus. To screen the protective antigen of McHDV and set the basis for study of McVHD vaccine, the antigen epitope of major structural protein VP60 of McHDV was analyzed, and the specific primers were designed to obtain three amplified DNA sequences encoding the main antigen epitope of VP60 from McHDV by using RT-PCR. Then the three DNA fragments were sequenced and cloned to prokaryotic expression vector with pET-28a(+) by using overlap extension PCR, and finally the prokaryotic expression plasmid pET-truncated-VP60 was constructed. Subsequently, the pET-truncated-VP60 was transformed into Escherichia coli BL21(DE3), and the recombinant proteins were expressed by IPTG induction. Finally, the expressed protein was purified and applied to immunize that without immunizing with RHD vaccine, then the antiserum titers were evaluated by the hemagglutination inhibition test, and the immune-protective efficacy of the recombinant proteins was observed and analyzed through animal challenge test. The results showed that the multi-epitope DNA fragments of VP60 of McHDV was successfully expressed in the form of inclusion bodies in E. coli, and the relative molecular weight of recombinant proteins is about 45 kDa. After immunized with the recombinant proteins, 100% of New Zealand white rabbits were resistant to attack of McHDV, which indicates efficient immune-protective efficacy of chosen epitope recombinant protein. The study laid a foundation for the development of the new subunit vaccines of McVHD.

Objective: To explore the effects of Shenqi Yizhi Granule on the cognitive function and the expression of MMP-2 and VEGF in serum of APP/PS1 transgenic mice. Methods: Taking APP/PS1 double transgenic mice as the research carrier, Shenqi Yizi granule was used to interven for 180 days. The learning and remembering ability was tested by Morris water maze, passive avoidance test, and open field. The pathomorphism of the hippocampus CA1 region of mice was tested by HE staining and electron microscopy. The concentration of MMP-2 and VEGF in serum was tested by ELISA. Results: Compared with the blank group, the escape latency of the model group was significantly increased (P ＜ 0.05), and the frequency of the entering medium ring was obviously decreased (P ＜ 0.05). The number of nerve cells in the hippocampal CA1 area was reduced, and the arrangement was disordered. The nuclear pyknosis was deeply stained, and the ultrastructure of nerve cells was abnormal. The concentration of MMP-2 and VEGF in serum was significantly increased (P ＜ 0.05). Compared with the model group, the escape latency of treatment group was decreased (P ＜ 0.05) and the frequency of the entering middle ring was increased (P ＜ 0.05). The concentration of MMP-2 and VEGF in serum was decreased (P ＜ 0.05). Conclusion: Shenqi Yizhi Granule could improve the ability of learning and memory of APP/ PS1 double transgenic mice, and decrease the concentration of MMP-2 and VEGF in serum.