Parkinson's disease (PD) is a neurodegenerative disorder characterized by the aggregation of α-synuclein (α-syn) and dysregulated synaptic vesicle (SV) recycling. Emerging evidence suggests that ferroptosis is the target of PD therapy. However, the identification of effective anti-ferroptosis treatments remains elusive. This study explores the therapeutic potential of low-intensity ultrasound (US) in modulating SV recycling and anti-ferroptosis in cellular and animal models of PD. We demonstrate that optimized US stimulation (610 kHz, 0.2 W/cm²) activates Piezo1 channel-mediated fast endophilin-mediated endocytosis, which promotes SV recycling and synaptic function, presenting with increased frequency and amplitude of both spontaneous excitatory synaptic currents and miniature excitatory postsynaptic currents. Repaired SV recycling in turn reduces the accumulation of α-syn expression and ferroptotic cell death. These findings support the potential of noninvasive ultrasonic neuromodulation as a therapeutic strategy for PD and lead to meaningful health outcomes for the aging population.
Animals ; Ferroptosis/physiology* ; Synaptic Vesicles/metabolism* ; Dopaminergic Neurons/metabolism* ; Ion Channels/metabolism* ; Mice ; Ultrasonic Waves ; Humans ; Male ; Mice, Inbred C57BL ; Endocytosis/physiology* ; alpha-Synuclein/metabolism*

The traditional Chinese medicine （TCM） in pediatric care has a long history，proven efficacy，and distinctive characteristics.The China Association of Chinese Medicine has organized a series of youth salons to discuss the clinical advantages of treating diseases.Experts at this seminar proposed that the superior disease categories in pediatric TCM are significant for showcasing the unique strengths and advantages of TCM in the treatment of pediatric diseases，enhancing diagnostic and treatment levels，inheriting TCM knowledge，promoting the integration of TCM and Western medicine，and meeting patients' needs.The strengths of pediatric TCM are summed up as "having what others do not，excelling at what others have，being special in what others excel at，and ensuring safety in what others specialize in." The scope of superiority in pediatric TCM covers multiple systems，including respiratory，digestive，endocrine，psychological，and dermatological systems.This article summarized the advantages of TCM in treating 13 diseases discussed in the salon，such as upper respiratory tract infections，coughs，pneumonia，allergic rhinitis，bronchial asthma，atopic dermatitis，functional dyspepsia，functional constipation，enuresis，marginal short stature，simple obesity，attention deficit hyperactivity disorder，and tic disorders.The overall advantages were reflected in three aspects：First，the holistic concept and treatment based on syndrome differentiation in TCM highlight the advantage of treating the root causes of diseases，making the treatment methodical and precise.Second，most traditional Chinese herbs are natural and have strong safety profiles.Third，TCM treatment methods are abundant，especially the external treatment methods，which are widely used in pediatrics，highly accepted by parents，and have definite efficacy，as well as good safety and compliance.

Objective: To analyze the epidemiological and molecular characteristics of norovirus outbreaks in schools in Xicheng District of Beijing from 2017 to 2022, so as to provide evidence for the prevention and control of norovirus outbreaks in schools. Methods: Data of norovirus outbreaks in schools in Xicheng District, Beijing during 2017 to 2022 were collected and analyzed by descriptive epidemiological methods. Realtime PCR was used to detect the nucleic acid of group GⅠand GⅡnorovirus, the positive norovirus nucleic acid samples were sent to Beijing Center for Disease Control and Prevention for molecular typing. Results: From 2017 to 2022, 185 norovirus outbreaks were reported in schools in Xicheng District, including 166 cluster outbreaks and 19 outbreaks. A total of 2 044 cases were reported, with a total attack rate of 13.92%. There were two peaks in the outbreak time, which were from March to June after the spring semester and from October to December after autumn semester. Primary schools were the most common place of occurrence (101 cases), followed by nursery institutions (68 cases) and secondary schools (16 cases). There were statistically significant differences in the incidence rates among different sites(12.37%, 22.78%, 8.47%, χ2=263.34, P<0.01). There were significant differences in the incidence of vomiting, diarrhea, nausea and stomachache among different students (χ2=263.33, 90.58, 20.42, 30.29, P<0.01). Vomiting was the main symptom in primary school and nursery school children (96.41%, 98.28%), and the diarrhea rate was higher in middle school students (68.22%). The outbreaks were mainly caused by type GⅡ norovirus. The genotype from 2017 to 2021 showed the characteristics of diversity, mainly GⅡ.2[P16], but there was no significant advantage for the GⅡ.2 [P16] during 2019 to 2021. Conclusions The norovirus outbreak in schools in Xicheng district of Beijing from 2017 to 2022 are mainly caused by GⅡ type genome. The main genotype is GⅡ.2[P16]. Norovirus infection mainly occurred in primary schools and kindergartens. For the vulnerable populations, it is necessary to improve the capacity to early identification, student infectious disease management, active infection control and prevention measures, and pathogen surveillance and sporadic case monitoring.

AIM:To explore the intensity-dependent effects of exercises to alleviate fear memory generaliza-tion in post-traumatic stress disorder(PTSD)and the underlying mechanism.METHODS:Male C57 BL/6J mice were randomly divided into the control group,PTSD group,high-intensity exercise(PTSD-High)group,and low-intensity exer-cise(PTSD-Low)group.PTSD model were created via using a combination of conditioned foot shock(CF)and single-pro-longed stress(SPS).The contextual fear test was used to test the mice's ability to discriminate safety situations from fear condition.Immunofluorescence observed and quantified the newborn immature neurons in the DG area of the mice's hippo-campus.ELISA was used to determine the secretion level of serum tissue adiponectin.RESULTS:(1)The immobility times for the PTSD-High and Control groups were significantly lower than those of the PTSD group.(2)Immunofluores-cence analysis showed that the cell density,dendritic branching points and length of newborn immature neurons were ele-vated in High and Low groups compared to the PTSD group.(3)Adiponectin levels in the serum of the control and PTSD-High group were significantly higher than those in the PTSD group and PTSD-Low group.CONCLUSION:Fear memory establishment in PTSD mice is associated with decreased hippocampal neurogenesis.High-intensity exercise ameliorated fear memory by enhancing adiponectin secretion and promoting hippocampal neurogenesis.High-intensity exercise exerted better improvement of brain functions to PTSD model.

Objective:To develop a novel, flexible, dual-arm, master-slave digestive endoscopic minimally invasive surgical robot system named dual-arm robotic endoscopic assistant for minimally invasive surgery (DREAMS) and to evaluate its feasibility for endoscopic submucosal dissection (ESD) by using ex vivo porcine stomachs.Methods:A novel endoscopic robot (DREAMS) system was developed which was composed of a flexible two-channel endoscope, two flexible robotic manipulators, a master controller, a robotic arm, and a control system. A total of 10 artificial round-like lesions with diameters ranging from 15 to 25 mm were created (5 in gastric antrum and 5 in gastric body) by using fresh peeled stomach of healthy pigs as the model. Submucosal dissection was performed with the assistance of the DREAMS system by two operators. The main outcome was submucosal dissection speed, and the secondary outcomes included muscular injury rate, perforation rate, and grasping efficiency of the robot.Results:All 10 lesions were successfully dissected en bloc by using the DREAMS system. The diameter of the artificial lesions was 22.34±2.39 mm, dissection time was 15.00±8.90 min, submucosal dissection speed was 141.79±79.12 mm 2/min, and the number of tractions required by each ESD was 4.2 times. Muscular injury occurred in 4/10 cases of ESD. No perforation occurred. Conclusion:The initial animal experiment shows the DREAMS system is safe and effective.

Objective To investigate the epidemiological chatacteristics and genotypes of parechovirus A (PeV-A) from children with acute diarrhea in Beijing in 2021. Methods Fecal samples were randomly collected from outpatient children under 60 months with acute diarrhea in a sentinel hospital in Beijing from January to December of 2021. RNA was extracted and detected for PeV-A by real-time RT-PCR. Nested RT-PCR was performed to amplify the VP3/VP1 conjunction region. PeV-A genotypes were determined based on sequencing and NCBI BLAST. Group A rotavirus, norovirus, enteric adenovirus, astrovirus and sapovirus were also detected for co-infection analysis. Phylogenetic and statistical analyses were performed using bioinformatics and statistical software. Results Of the 198 stool samples, 11 were positive for PeV-A, with a detection rate of 5.56% (11/198). Among them, 2 cases were co-infected with enteric adenovirus. 81.82% (9/11) of PeV-A infected cases were under 24 months. The highest detection rate was observed in fall, which was 12.50% (7/56). 90.91%（10/11）of PeV-A infection occurred in summer and fall. Among the 11 PeV-A isolates, 9 were sequenced successfully, of which 7 belonged to PeV-A1B genotype and 2 belonged to PeV-A3 genotype. Conclusion PeV-A1B and PeV-A3 are identified in children with acute gastroenteritis in Beijing in 2021. Infants and young children under 2 years old are the high-risk population for PeV-A infection. Most infections occur in summer and fall.

Objective:To investigate the level of plasma Betatrophin in pregnant women with gestational diabetes mellitus (GDM) and its correlation with the control of blood glucose.Methods:Forty-five pregnant women with GDM(GDM group) who received regular obstetric examinations in the Huaihua First People′s Hospital from July 2019 to January 2021 and 50 pregnant women with normal glucose tolerance (NGT) (NGT group) during the same period were enrolled in this study. Blood glucose and blood lipid indicators were collected, plasma Betatrophin level was detected, Logistic regression analysis was used to screen the influencing factors of blood glucose control effect, the pregnancy outcome was followed up, the predictive value of Betatrophin level in blood glucose control and pregnancy outcome was evaluated by receiver operating characteristic (ROC) curve.Results:The levels of systolic blood pressure, diastolic blood pressure, fasting plasma glucose (FPG), 2 h postpartum blood glucose (2 h PG), glycosylated hemoglobin (HbA 1c), fasting insulin (FINS), 2 h postprandial insulin (2 h FINS), insulin resistance index (HOMA-IR), low density lipoprotein cholesterin (LDL-C) and plasma Betatrophin in the GDM group were higher than those in the NGT group, and insulin function index (HOMA-β) and high density lipoprotein cholesterin (HDL-C) were lower than those in the NGT group ( P<0.05). Pearson correlation analysis showed that plasma Betatrophin level was positively correlated with HbA 1c and HOMA-IR in pregnant women and the GDM group ( r = 0.310, 0.314, 0.341, 0.333; P<0.05). In the GDM group, 12 patients with poor glucose control, 33 patients with good glucose control, the FPG, HbA 1c, HOMA-IR and plasma Betatrophin levels in poor glucose control patients were higher than those in good glucose control patients, HOMA-β was lower than that in the good glucose control patients: (5.82 ± 0.98)mmol/L vs. (5.04 ± 1.11) mmol/L, (9.78 ± 2.15)% vs. (8.22 ± 1.41)%, 2.71 ± 0.56 vs. 2.24 ± 0.48, (1 345.12 ± 256.32) ng/L vs. (1 165.10 ± 217.41) ng/L, 144.15 ± 22.71 vs. 158.63 ± 20.26, there were statistical differences ( P<0.05). The area under the curve of plasma Betatrophin level to predict the effect of blood glucose control was 0.775. A total of 8 pregnant women with GDM had poor pregnancy outcome, and the area under the curve predicted pregnancy outcome by plasma Betatrophin level was 0.728. Conclusions:The level of plasma Betatrophin in patients with GDM is closely related to the degree of insulin resistance and the effect of blood glucose control, and can provide some reference for clinical evaluation and therapeutic effect prediction.

Objective:To evaluate the value of chemoradiotherapy and surgery in cervical esophageal cancer (CEC).Methods:Data of 459 patients with CEC from 2004 to 2017 were collected and retrospectively analyzed from the surveillance, epidemiology, and end results (SEER) database of National Cancer Institute (US). All patients were divided into the chemoradiotherapy group ( n=379) and surgery group ( n=80) according to the treatment methods. Survival analysis was performed by Kaplan-Meier method and survival curve was drawn. Multivariate survival analysis was conducted by Cox proportional hazards regression model. The death rate of different causes between two groups was calculated by cumulative incidence function (CIF). The differences of death rate between two groups were evaluated by Fine-Gray competing risk model. By analyzing the clinical characteristics and survival of CEC patients, the overall survival (OS) was compared between the surgery and chemoradiotherapy groups. Results:The 2- and 5-year survival rates in the chemoradiotherapy group were 43.1% and 22.4%, while those of the surgical group were 46.8% and 26.0%, respectively. No significant difference was observed in the OS between the chemoradiotherapy and surgery groups ( P=0.750). Cox multivariate analysis showed that treatment (surgery group vs. chemoradiotherapy group) was not an independent prognostic factor for OS. Based on the results of competing risk analysis, the risk of esophageal cancer-specific death in the chemoradiotherapy group was higher than that in the surgery group, and the difference was statistically significant between two groups ( P<0.001). The risk of other cause-specific death in the chemoradiotherapy group was lower than that in the surgery group ( P<0.001). The proportion of patients who died of oral, oropharyngeal, hypopharyngeal and laryngeal diseases in the surgery group was significantly higher than that in the chemoradiotherapy group(all P<0.001). Conclusions:No significant difference is observed in the OS of CEC patients treated with chemoradiotherapy or surgery. In the surgery group, the risk of esophageal cancer-specific death is lower, whereas the risk of other cause-specific death is higher compared with those in the chemoradiotherapy group.

Pheretima,also called"earthworms",is a well-known animal-derived traditional Chinese medicine that is extensively used in over 50 Chinese patent medicines(CPMs)in Chinese Pharmacopoeia(2020 edi-tion).However,its zoological origin is unclear,both in the herbal market and CPMs.In this study,a strategy for integrating in-house annotated protein databases constructed from close evolutionary relationship-sourced RNA sequencing data from public archival resources and various sequencing al-gorithms(restricted search,open search,and de novo)was developed to characterize the phenotype of natural peptides of three major commercial species of Pheretima,including Pheretima aspergillum(PA),Pheretima vulgaris(PV),and Metaphire magna(MM).We identified 10,477 natural peptides in the PA,7,451 in PV,and 5,896 in MM samples.Five specific signature peptides were screened and then validated using synthetic peptides;these demonstrated robust specificity for the authentication of PA,PV,and MM.Finally,all marker peptides were successfully applied to identify the zoological origins of Brain Heart capsules and Xiaohuoluo pills,revealing the inconsistent Pheretima species used in these CPMs.In conclusion,our integrated strategy could be used for the in-depth characterization of natural peptides of other animal-derived traditional Chinese medicines,especially non-model species with poorly annotated protein databases.

Obesity is one of the most serious global public health issue. In addition to advocating healthy lifestyle, scientists are devoted to developing healthy and effective ways to tackle obesity. In recent years, vagus nerve stimulation has been revealed to have potential therapeutic effect on obesity, which may be related to regulating endocrine hormones and body metabolism, affecting different nerve functions, regulating inflammatory and immune pathways, adjusting intestinal flora and circadian rhythm, and so on. Current researches focus on percutaneous stimulation(auricular vagus nerve stimulation), subcutaneous stimulation(cervical and abdominal vagus nerve stimulation), and gastrointestinal stimulation(the implantation of vagus nerve stimulation device and vagus nerve blocking device). Growing number of studies have confirmed that these stimulation methods have favorable effects on obesity with less side effects. Moreover, the mechanism of Chinese traditional acupuncture for obesity treatment is similar to that of vagus nerve stimulation. Most of vagus nerve stimulation is conveyed via physical therapy. It is highly feasible and theoretically has few side effects, therefore is easy to be accepted by obese subjects and may become a promising approach for obesity treatment.