Objective To investigate the clinical efficacy of minimally invasive mitral valvuloplasty (MVP) in the treatment of infective endocarditis (IE) with mitral regurgitation (MR). Methods A retrospective analysis was conducted on the clinical data of patients who underwent MVP for IE with MR at the Department of Cardiovascular Surgery in Zhongshan Hospital, Fudan University from 2016 to 2020. Patients were divided into two groups based on the surgical incision: those with a right mini-thoracotomy were classified as a minimally invasive surgery (MIS) group, and those with a median sternotomy (MS) were classified as an MS group. All patients had isolated mitral valve involvement. Perioperative data were analyzed, and mid- to long-term outcomes were compared between the two groups. Results A total of 86 patients were included, with 40 in the MIS group [22 males and 18 females, with a mean age of (39.78±15.36) years ranging from 14 to 75 years] and 46 in the MS group [27 males and 19 females, with a mean age of (49.94±16.13) years ranging from 14 to 71 years]. The patients in the MIS group were relatively younger (P=0.004) with better preoperative cardiac function (P=0.004). There was no statistical difference in preoperative fever, gender, or comorbidities between the two groups (P>0.05). The MIS group had shorter postoperative ventilation times, less postoperative 24-hour drainage, less blood transfusion, and shorter total hospital stays compared to the MS group (P＜0.05). There was no statistical difference in cardiopulmonary bypass times or ICU stays between the two groups (P>0.05). The perioperative complication rates and mortality rates were not significantly different between the two groups (P>0.05). Follow-up was conducted for 11-92 months, with a mean duration of (49±19) months and an overall follow-up rate of 91.9%. During the follow-up, 3 patients in each group required reoperation for mitral valve issues, with no statistical difference in incidence (7.5% vs. 6.5%, P=0.691). There were no warfarin-related complications, recurrences, or deaths in either group during follow-up. Multivariate regression analysis identified age, preoperative cardiac function, and surgeon experience as influencing factors for the choice of surgical approach. Conclusion Minimally invasive MVP for IE with MR is relatively safe in the perioperative period and shows significant efficacy, with clear mid- to long-term outcomes. It is recommended for younger patients with better preoperative cardiac function and when performed by surgeons with extensive experience in mitral valvuloplasty.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

Objective:To anatomically and phenotypically characterize the insular cortex(IC)-nucleus tractus soli-tarii(NTS)neural pathway.Methods:Adult male Sprague-Dawley rats were divided into three experimental cohorts for neural circuit tracing.Anterograde labeling was achieved by injecting anterograde self-complementary adeno-associated viruses(scAAVs)into the IC.Retrograde tracing involved NTS injections of either retrograde scAAVs or FluoroGold(FG),combined with immunofluorescence histochemical staining to identify IC-originating projection neurons.For postsynaptic neurochemical phenotype characterization,IC was injected with AAV2/1-CaMKII-Cre,while a mixture of AAV2/9-Syn-DIO-mCherry and AAV2/9-VGAT1-EGFP was injected into the NTS.The rats were allowed to survive for one week following scAAVs or FG injection or four weeks after recombinase-dependent systems injection.Then the rats were sacrificed,and serial brain sections were prepared for immunofluorescence histochemical staining(brain section containing FG)and subsequent fluorescence/confocal microscopic analysis.Results:(1)Anterograde viral tracing re-vealed dense axonal terminals from the IC projecting to the medial subnucleus of the NTS,while retrograde tracing re-vealed that IC neurons projecting to the NTS were predominantly localized within the dysgranular layer;(2)IC-NTS projection neurons were exclusive glutamatergic(100%,n=3);(3)NTS neurons receiving IC inputs were mainly lo-calized in the medial subnucleus,and were predominantly GABAergic(79.8±3.2%,n=3).Conclusion:The pres-ent results indicate that a descending pathway from excitatory neurons of the IC terminates onto inhibitory neurons of the NTS,which might represent a potential neuromodulatory target for visceral pain disorders.

Objective:To anatomically and phenotypically characterize the insular cortex(IC)-nucleus tractus soli-tarii(NTS)neural pathway.Methods:Adult male Sprague-Dawley rats were divided into three experimental cohorts for neural circuit tracing.Anterograde labeling was achieved by injecting anterograde self-complementary adeno-associated viruses(scAAVs)into the IC.Retrograde tracing involved NTS injections of either retrograde scAAVs or FluoroGold(FG),combined with immunofluorescence histochemical staining to identify IC-originating projection neurons.For postsynaptic neurochemical phenotype characterization,IC was injected with AAV2/1-CaMKII-Cre,while a mixture of AAV2/9-Syn-DIO-mCherry and AAV2/9-VGAT1-EGFP was injected into the NTS.The rats were allowed to survive for one week following scAAVs or FG injection or four weeks after recombinase-dependent systems injection.Then the rats were sacrificed,and serial brain sections were prepared for immunofluorescence histochemical staining(brain section containing FG)and subsequent fluorescence/confocal microscopic analysis.Results:(1)Anterograde viral tracing re-vealed dense axonal terminals from the IC projecting to the medial subnucleus of the NTS,while retrograde tracing re-vealed that IC neurons projecting to the NTS were predominantly localized within the dysgranular layer;(2)IC-NTS projection neurons were exclusive glutamatergic(100%,n=3);(3)NTS neurons receiving IC inputs were mainly lo-calized in the medial subnucleus,and were predominantly GABAergic(79.8±3.2%,n=3).Conclusion:The pres-ent results indicate that a descending pathway from excitatory neurons of the IC terminates onto inhibitory neurons of the NTS,which might represent a potential neuromodulatory target for visceral pain disorders.

Animal survival necessitates adaptive behaviors in volatile environmental contexts. Virtual reality (VR) technology is instrumental to study the neural mechanisms underlying behaviors modulated by environmental context by simulating the real world with maximized control of contextual elements. Yet current VR tools for rodents have limited flexibility and performance (e.g., frame rate) for context-dependent cognitive research. Here, we describe a high-performance VR platform with which to study contextual behaviors immersed in editable virtual contexts. This platform was assembled from modular hardware and custom-written software with flexibility and upgradability. Using this platform, we trained mice to perform context-dependent cognitive tasks with rules ranging from discrimination to delayed-sample-to-match while recording from thousands of hippocampal place cells. By precise manipulations of context elements, we found that the context recognition was intact with partial context elements, but impaired by exchanges of context elements. Collectively, our work establishes a configurable VR platform with which to investigate context-dependent cognition with large-scale neural recording.
Animals ; Mice ; Rodentia ; Virtual Reality ; Cognition ; Recognition, Psychology

Objective:To investigate the relationship between chronic obstructive pulmonary disease (COPD) and bone mineral density (BMD) in Chinese male and female adults.Methods:Linear regression models were used to analyze the correlations between COPD and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade concerning bone mineral density indices, including broadband ultrasound attenuation, speed of sound, and stiffness index, based on data from the second resurvey of China Kadoorie Biobank.Results:Among 23 876 participants, the prevalence of COPD was 34.3% (3 130/9 125) in males and 23.2% (3 416/14 751) in females. Compared with healthy males and healthy females, broadband ultrasound attenuation, speed of sound, and stiffness index decreased in males and females with COPD, with β values (95% CI) of -0.87 (-1.37- -0.36), -3.42 (-5.42- -1.43) and -1.53 (-2.34- -0.71) in males and -0.66 (-1.09- -0.23), -2.24 (-3.92- -0.55), -1.06 (-1.71- -0.40) in females, respectively. The decrease was greater in males than females (all P for interaction <0.05). The GOLD grade of COPD was inversely correlated with all the three indices in a dose-response manner (all P for trend <0.001). Subgroup analysis showed that patients with COPD had a greater decrease in BMD in males whose ages were ≥ 60 years, males who were less physically active, and participants who were not overweight or obese. Conclusions:COPD was negatively correlated with bone mineral density. More attention should be paid to the bone mineral density of patients with COPD, especially those with older age, less physical activity, or lower BMI.

Objective:To evaluate the effect of inhaled medication compliance intervention in elderly patients with chronic obstructive pulmonary disease (COPD) based on integrated theory of health behavior change.Methods:A total of 117 elderly COPD patients who visited Respiratory Department of Beijing Chaoyang Hospital Affiliated to Capital Medical University from July to December 2021 were selected by the convenient sampling method. According to the random number table method, they were divided into the experimental group and the control group. 7 cases fell off during follow-up, and a total of 110 cases were finally included in the study, of which 55 cases were in the experimental group and 55 cases in the control group. The control group adopted the conventional health education method, while the experimental group adopted the intervention plan of inhalation medication compliance of elderly COPD patients based on the integrated theory of health behavior change. The accuracy of inhalation device use, inhalant medication compliance, forced expiratory volume in the first second (FEV 1) and Chronic Obstructive Pulmonary Diseases Assessment Test (CAT) scores were compared between the two groups before intervention and 3 months after intervention. Results:After 3 months of intervention, the inhalation device use accuracy, inhalation medication compliance in experimental group were higher than those in the control group, the score of CAT in experimental group was lower than that in the control group, the differences were statistically significant ( P<0.05). There was no statistically significant difference in FEV 1 between two groups ( P>0.05) . Conclusions:The intervention plan for inhalation medication compliance in elderly patients with chronic obstructive pulmonary disease based on the integrated theory of health behavior changes can improve their inhalation medication compliance and improve their quality of life.

Objective    To analyze the short-term and long-term efficacy of staged coronary artery bypass grafting (CABG) and carotid artery stenting (CAS) compared with CABG alone in patients with coronary heart disease with preoperative history of stroke and carotid stenosis. Methods    We reviewed the clinical data of 55 patients (48 males, 7 females, aged 67.62±7.06 years) with coronary heart disease and carotid stenosis who had a history of stroke and underwent CABG+CAS or CABG alone in Zhongshan Hospital from 2008 to 2017. There were 13 patients in the staged CABG+CAS group and 42 patients in the CABG alone group. The differences in the incidence of perioperative adverse events and long-term survival between the two groups were studied, and univariate and multivariate analyses were carried out to determine the independent risk factors of long-term adverse events. Results     Perioperative adverse events occurred in 1 (7.69%) patient of the staged CABG+CAS group, and 4 (9.52%) patients of the CABG alone group (P=0.84). During the follow-up period (67.84±37.99 months), the long-term survival rate of patients in the staged CABG+CAS group was significantly higher than that in the CABG alone group (P=0.02). The risk of long-term adverse events in the staged CABG+CAS group was 0.22 times higher than that in the CABG alone group (95%CI 0.05-0.92, P=0.04). Conclusion    Staged CABG+CAS can significantly improve the long-term survival prognosis without increasing the perioperative risk. It is a safe and effective treatment, but prospective randomized studies are still needed to further confirm this finding.

Objective:This study aimed to establish a fourfold fluorescent quantitative RT-PCR detection method for rapid typing of Dengue virus (DENV) using Y-type primers and fluorescent quantitative RT-PCR technology.Methods:Four types of DENV were used to transcribe RNA in vitro to evaluate the sensitivity and specificity of the method and to verify it with clinical samples.Results:The minimum detection limits of DENV type I, II, III and IV were 5.01 copies/PCR, 6.16 copies/PCR, 6.35 copies/PCR, 6.39 copies/PCR, respectively and had no significant difference compared with single-plex real-time fluorescent quantitative RT-PCR. There was also no crossover with other viruses. The positive agreement rate and negative agreement rate of clinical specimens were both 100%.Conclusions:The Y-type primer quadruple fluorescence quantitative RT-PCR method established in this study could effectively avoid cross-reactions between different DENV types, and has good sensitivity and specificity, and can be used for rapid typing of DENV in relevant clinical specimens with high detection efficiency and low costs.