Objective To explore the differences in heartbeat-evoked response (HER) under drug-related cues and neutral cues in individuals with heroin use disorder (HUD), and analyze the correlation between HER potentials and immediate cue-induced craving scores. Methods Fifty HUD participants were recruited from the Chang’an Compulsory Isolation Drug Rehabilitation Center in Shaanxi Province from June to September 2024. Simultaneous acquisition of 64-channel electroencephalography (EEG) and electrocardiogram signals was performed. Twenty alternating segments of drug-related and neutral cue videos were presented, and participants rated their subjective craving after each segment using visual analogue scale (VAS) scores. Scalp EEG data were source analyzed to obtain cortical EEG signals and corresponding HER. Short-time Fourier transform was used to calculate the power spectral density (PSD) of EEG within a time window from 100 ms before the R-peak to 500 ms after it, using the R-peak as the time zero point. Cluster-based permutation testing was used to analyze PSD differences between drug-related and neutral cues in the HUD individuals. Pearson correlation analysis was performed to evaluate the correlation between HER potentials and VAS scores. Results In the 350–420 ms time window, HER potentials in the left posterior parietal, temporal, and posterior cingulate cortices were significantly lower under drug-related cues compared to neutral cues (P＜0.01); in the 140–210 ms time window, HER potentials in the right prefrontal cortex were significantly higher under drug-related cues compared to neutral cues (P＜0.01). Correlation analysis showed that HER potentials in the left temporal and left posterior cingulate cortices were significantly negatively correlated with VAS scores (P＜0.05). Drug-related cues enhanced PSD of γ power (30–100 Hz) in salience network (fronto-insular), parietal and occipital regions (P＜0.05). PSD integrations of low-γ power (40–60 Hz) in parietal region (350–400 ms) and high-γ power (70–100 Hz) in left salience network (fronto-parietal) and occipital regions (300–350 ms) were positively correlated with VAS scores (P＜0.05). Conclusions Drug-related cues may modulate cortical activity related to heartbeat perception in HUD individuals, and such dynamic changes in both time and frequency domains are stably associated with subjective craving.

Objective:To explore the clinical efficacy of "four-step" aortic valve anatomic repair for bicuspid aortic valve(BAV) with aortic regurgitation(AR).Methods:From August 2021 to November 2024, a total of 298 consecutive patients with BAV-AR underwent aortic valve anatomic repair(AVr) in Shanghai Zhongshan Hospital Fudan University, 266 males and 32 females, with age of 39(29.5, 48.5) years. All patients underwent " four-step" three-dimensional anatomic repair of the aortic annulus and leaflets, 129(43.3%) patients via upper mini-sternotomy and 169(56.7%) patients via conventional median sternotomy, with the main steps including: (1) deep dissecting and annuloplasty of the virtual basal ring(VBR); (2) symmetrical repairing of leaflets; (3) replacement or remodeling of the sinus of Valsalva; (4) annuloplasty of the sinotubular junction(STJ). Basal and perioperative data were retrospectively collected, and statistical analysis was performed in conjunction with follow-up data.Results:All patients successfully underwent anatomical repair without transferring to valve replacement during operation. Among them, 43 patients underwent aortic root reimplantation technique(Reimplantation group), while 255 patients underwent modified aortic root sleeve remodeling technique(Sleeve group). The median cardiopulmonary bypass time for the Reimplantation and Sleeve groups were 154(134, 169) minutes and 111(95, 129) minutes, respectively( P<0.05); the median aortic cross-clamp time were 112(100, 131) minutes and 80(67, 94) minutes, respectively( P<0.05). Preoperative TEE showed 35 patients(81.4%) and 229 patients(89.8%) with moderate and severe AR in Reimplantation and Sleeve groups, respectively. Postoperative TEE showed 41 patients(95.3%) with no/trace AR and 2 patients(4.7%) with central mild AR in Reimplantation group, while 212 patients(83.1%) with no/trace AR and 43 patients(16.9%) with central mild AR in Sleeve group. Follow-up was completed in all patients, with a median follow-up of 12.9(4.7, 21.2) months. Echocardiography was obtained in 271 patients(90.9%) at the latest follow-up, including no/trace AR in 167 patients(56.0%), mild AR in 89 patients(29.9%), moderate AR in 14 patients(4.7%), and severe AR in 1 patient(0.3%). Conclusion:Aortic valve anatomic repair by standardized "four-step" approach is safe and reproducible. Satisfied short- and mid-term outcome have obtained in selected BAV-AR patients.

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Objective:To explore the clinical efficacy of "four-step" aortic valve anatomic repair for bicuspid aortic valve(BAV) with aortic regurgitation(AR).Methods:From August 2021 to November 2024, a total of 298 consecutive patients with BAV-AR underwent aortic valve anatomic repair(AVr) in Shanghai Zhongshan Hospital Fudan University, 266 males and 32 females, with age of 39(29.5, 48.5) years. All patients underwent " four-step" three-dimensional anatomic repair of the aortic annulus and leaflets, 129(43.3%) patients via upper mini-sternotomy and 169(56.7%) patients via conventional median sternotomy, with the main steps including: (1) deep dissecting and annuloplasty of the virtual basal ring(VBR); (2) symmetrical repairing of leaflets; (3) replacement or remodeling of the sinus of Valsalva; (4) annuloplasty of the sinotubular junction(STJ). Basal and perioperative data were retrospectively collected, and statistical analysis was performed in conjunction with follow-up data.Results:All patients successfully underwent anatomical repair without transferring to valve replacement during operation. Among them, 43 patients underwent aortic root reimplantation technique(Reimplantation group), while 255 patients underwent modified aortic root sleeve remodeling technique(Sleeve group). The median cardiopulmonary bypass time for the Reimplantation and Sleeve groups were 154(134, 169) minutes and 111(95, 129) minutes, respectively( P<0.05); the median aortic cross-clamp time were 112(100, 131) minutes and 80(67, 94) minutes, respectively( P<0.05). Preoperative TEE showed 35 patients(81.4%) and 229 patients(89.8%) with moderate and severe AR in Reimplantation and Sleeve groups, respectively. Postoperative TEE showed 41 patients(95.3%) with no/trace AR and 2 patients(4.7%) with central mild AR in Reimplantation group, while 212 patients(83.1%) with no/trace AR and 43 patients(16.9%) with central mild AR in Sleeve group. Follow-up was completed in all patients, with a median follow-up of 12.9(4.7, 21.2) months. Echocardiography was obtained in 271 patients(90.9%) at the latest follow-up, including no/trace AR in 167 patients(56.0%), mild AR in 89 patients(29.9%), moderate AR in 14 patients(4.7%), and severe AR in 1 patient(0.3%). Conclusion:Aortic valve anatomic repair by standardized "four-step" approach is safe and reproducible. Satisfied short- and mid-term outcome have obtained in selected BAV-AR patients.

Objective To isolate and culture neural crest cells(NCCs)from lung tissue of mice and to identify the characteristics of the cells in order to provide a new cell model for studying lung injury and injure repair.Methods The mT/mG dual-fluorescence reporter mice and Wnt1-Cre transgenic mice were hybridized,and mT/mG;Wnt1-Cre transgenic mice were screened to obtain enhanced green fluorescent protein(EGFP)permanently labeled NCCs.Cell suspension of mouse lung tissue was prepared by enzymolysis.EGFP+cells(namely NCCs)were har-vested by flow cytometry.Primary culture was performed with DMEM/F12 culture medium optimized in the labora-tory,NCCs was characterized by immunofluorescence microscopy.Then NCCs differentiation was directed by mouse bone marrow mesenchymal stem cells osteogenic induction.Results The mT/mG of EGFP permanently labeled NCCs was successfully obtained by hybridization and high-purity NCCs were isolated from Wnt1-Cre transgenic mice lung tissue.They can be cultured in vitro and with spindle morphology which was,similar to fibroblast adherent proliferation.NCCs expressed the neural crest stem cell marker Sox10 and induced to differentiate into osteoblasts.Conclusions NCCs isolated and cultured from lung tissue of mT/mG;Wnt1-Cre transgenic mice show stable prolif-eration and have the characteristics of neural crest stem cells,which may function as a potential cell model for re-search on lung tissue injury and the mechanism of repair.

Objective:To explore the surgical technique and results of three-dimensional aortic valve anatomic repair for bicuspid aortic valve (BAV) with aortic regurgitation (AR).Methods:This is a retrospective case series study. From August 2021 to December 2023, 130 consecutive patients with BAV-AR underwent aortic valve anatomic repair at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University,and the data were retrospectively analyzed. There were 115 males and 15 females, aged (38.6±11.7) years (range: 15 to 67 years). All patients received modified aortic root reconstruction, to do three-dimensional root remodeling, including the basal ring, sinus of Valsalva and sino-tubular junction simultaneously. Perioperative and follow-up data were collected and analyzed. Comparisons between groups were performed using independent samples t-test, Wilcoxon paired signed-rank test, or χ2 test. Results:No patient transferred to valve replacement during the operation. The cardiopulmonary bypass time ( M(IQR)) was 109(34) minutes (range:67 to 247 minutes), and the aortic cross-clamp time was 76(26) minutes (range: 32 to 158 minutes). Preoperative transesophageal echocardiography showed 123 patients (94.6%) presented with moderate or severe regurgitation. Immediately postoperative transesophageal echocardiography showed no regurgitation in 22 patients (16.9%), trace regurgitation in 81 patients (62.3%) and mild regurgitation in 27 patients (20.8%). Follow up was completed in all patients, with a follow-up of 5.5(9.4) months (range: 0.1 to 27.6 months). No mortality was observed during follow-up. Echocardiography was obtained in 112 patients at the latest follow-up, including no regurgitation in 4 patients (3.6%), trace regurgitation in 58 patients (51.8%), mild regurgitation in 45 patients (40.2%), moderate regurgitation in 4 patients (3.6%), and severe regurgitation in 1 patient (0.9%). Conclusion:For patients with BAV-AR who have good valve quality and no severe aortic sinus dilation, the recent outcomes of three-dimensional anatomical repair technique, focusing on overall remodeling of the aortic root, are satisfactory.

Objective:To explore the surgical technique and results of three-dimensional aortic valve anatomic repair for bicuspid aortic valve (BAV) with aortic regurgitation (AR).Methods:This is a retrospective case series study. From August 2021 to December 2023, 130 consecutive patients with BAV-AR underwent aortic valve anatomic repair at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University,and the data were retrospectively analyzed. There were 115 males and 15 females, aged (38.6±11.7) years (range: 15 to 67 years). All patients received modified aortic root reconstruction, to do three-dimensional root remodeling, including the basal ring, sinus of Valsalva and sino-tubular junction simultaneously. Perioperative and follow-up data were collected and analyzed. Comparisons between groups were performed using independent samples t-test, Wilcoxon paired signed-rank test, or χ2 test. Results:No patient transferred to valve replacement during the operation. The cardiopulmonary bypass time ( M(IQR)) was 109(34) minutes (range:67 to 247 minutes), and the aortic cross-clamp time was 76(26) minutes (range: 32 to 158 minutes). Preoperative transesophageal echocardiography showed 123 patients (94.6%) presented with moderate or severe regurgitation. Immediately postoperative transesophageal echocardiography showed no regurgitation in 22 patients (16.9%), trace regurgitation in 81 patients (62.3%) and mild regurgitation in 27 patients (20.8%). Follow up was completed in all patients, with a follow-up of 5.5(9.4) months (range: 0.1 to 27.6 months). No mortality was observed during follow-up. Echocardiography was obtained in 112 patients at the latest follow-up, including no regurgitation in 4 patients (3.6%), trace regurgitation in 58 patients (51.8%), mild regurgitation in 45 patients (40.2%), moderate regurgitation in 4 patients (3.6%), and severe regurgitation in 1 patient (0.9%). Conclusion:For patients with BAV-AR who have good valve quality and no severe aortic sinus dilation, the recent outcomes of three-dimensional anatomical repair technique, focusing on overall remodeling of the aortic root, are satisfactory.

Smoking is a major concern in today's society,and the nicotine in tobacco is the major cause of addiction and difficulty in withdrawal.Long-term use of nicotine not only results in abnormal neural oscillations in the brain,but also impairs reward circuits as well as emotion regulation,thus reducing neuroplasticity and increasing susceptibility to addiction.As electrophysiological signals,electroencephalogram(EEG)signals are associated with a variety of states including cognitive function,emotion regulation,inhibitory control,and sleep.The researches on nicotine addiction reveal that changes in EEG signals are associated with abnormalities in cognitive function and inhibitory control in nicotine addicts.Therefore,exploring the abnormal neural oscillation patterns of nicotine addicts through EEG-related techniques can deepen the understanding of the intrinsic neural mechanisms of nicotine addiction and provide a scientific basis for the intervention and treatment of nicotine addiction.Herein the study summarizes the research achievements of scholars at home and abroad in recent years from the aspects of the application status of EEG in nicotine addiction researches as well as the current technology.It is found that nicotine addicts have obvious abnormalities in sleep quality,cognitive function and inhibitory control.In addition,the functional brain connectivity,event-related potentials and EEG power spectra of addicts are significantly changed.Finally,an outlook on the research prospects of EEG signals in nicotine addiction is provided,emphasizing the potential applications of EEG signals in addiction mechanisms,withdrawal responses,and assessment of treatment efficacy.

Smoking is a major concern in today's society,and the nicotine in tobacco is the major cause of addiction and difficulty in withdrawal.Long-term use of nicotine not only results in abnormal neural oscillations in the brain,but also impairs reward circuits as well as emotion regulation,thus reducing neuroplasticity and increasing susceptibility to addiction.As electrophysiological signals,electroencephalogram(EEG)signals are associated with a variety of states including cognitive function,emotion regulation,inhibitory control,and sleep.The researches on nicotine addiction reveal that changes in EEG signals are associated with abnormalities in cognitive function and inhibitory control in nicotine addicts.Therefore,exploring the abnormal neural oscillation patterns of nicotine addicts through EEG-related techniques can deepen the understanding of the intrinsic neural mechanisms of nicotine addiction and provide a scientific basis for the intervention and treatment of nicotine addiction.Herein the study summarizes the research achievements of scholars at home and abroad in recent years from the aspects of the application status of EEG in nicotine addiction researches as well as the current technology.It is found that nicotine addicts have obvious abnormalities in sleep quality,cognitive function and inhibitory control.In addition,the functional brain connectivity,event-related potentials and EEG power spectra of addicts are significantly changed.Finally,an outlook on the research prospects of EEG signals in nicotine addiction is provided,emphasizing the potential applications of EEG signals in addiction mechanisms,withdrawal responses,and assessment of treatment efficacy.

Objective: To establish a convenient non-invasive tracheal perfusion method for constructing a mouse model of silicosis-induced pulmonary fibrosis. Methods: The specific pathogen-free C57BL/6 mice were randomly divided into control group and model group, with 15 mice in each group. After anesthesia, a 22G arteriovenous indwelling needle was used to inset into the trachea through the mice's mouth. The model group mice were perfused with 0.1 mL of silica suspension with a mass concentration of 25 g/L, and the mice in the control group were perfused with an equal volume of 0.9% sodium chloride solution. On the 7th, 14th, and 30th day after modeling, the body weight of the mice was measured, and the lung tissue morphology and pathological changes were observed. The expression of α-smooth muscle actin (α-SMA) and collagen type 1 alpha 1 (COL1A1) protein in lung tissue of mice was detected by immunofluorescence on the 30th day after modeling. Results: There was no death of mice in the two groups during the experiment. There was no significant difference in body weight between the two groups (P>0.05). The lung tissues of the mice in the model group were pinkish-gray and uneven in color on the 7th and 14th days after dust exposure. On the 30th day after dust exposure, the lung tissue of the mice in the model group was gray and hard, and unevenly distributed silicon nodules were visible by the naked eyes. The histopathology results of lung tissue showed that compared with the mice in control group, the model group mice exhibited persistent aggravation of pulmonary inflammation, thickening of alveolar septum, infiltration of inflammatory cells gradually clustering into clumps, and an increasing number of fibrous foci.On the 30th day after dust exposure, the relative expression of α-SMA and COL1A1 proteins in the lung of the model group was higher than those in the control group (median： 72.59 vs 5.91, 35.62 vs 10.07, both P<0.05). Conclusion: The method of tracheal perfusion silica suspension of mice using 22G arteriovenous indwelling needle can successfully construct an animal model of silicosis fibrosis. This method is convenient, safe and effective, and is worth promoting.