ObjectiveNon-invasive magnetic stimulation technology has been widely used in the treatment of Alzheimer’s disease (AD), but there is a lack of convenient and timely methods for evaluating and providing feedback on the effectiveness of the stimulation, which can be used to guide the adjustment of the stimulation protocol. This study aims to explore the possibility of heart rate variability (HRV) in diagnosing AD and guiding AD magnetic stimulation intervention techniques. MethodsIn this study, we used a 40 Hz, 10 mT pulsed magnetic field to expose AD mouse models to whole-body exposure for 18 d, and detected the behavioral and electroencephalographic signals before and after exposure, as well as the instant electrocardiographic signals after exposure every day. ResultsUsing one-way ANOVA and Pearson correlation coefficient analysis, we found that some HRV indicators could identify AD mouse models as accurately as behavioral and electroencephalogram(EEG) changes (P<0.05) and significantly distinguish the severity of the disease (P<0.05), including rMSSD, pNN6, LF/HF, SD1/SD2, and entropy arrangement. These HRV indicators showed good correlation and statistical significance with behavioral and EEG changes (r>0.3, P<0.05); HRV indicators were significantly modulated by the magnetic field exposure before and after the exposure, both of which were observed in the continuous changes of electrocardiogram (ECG) (P<0.05), and the trend of the stimulation effect was more accurately observed in the continuous changes of ECG. ConclusionHRV can accurately reflect the pathophysiological changes and disease degree, quickly evaluate the effect of magnetic stimulation, and has the potential to guide the pattern of magnetic exposure, providing a new idea for the study of personalized electromagnetic neuroregulation technology for brain diseases.

Nine compounds were isolated and purified from 90% ethanol extract of Alstonia mairei Lévl by using various chromatographic methods, including silica gel, SephadexLH-20, MCI Gel and ODS column chromatography, combined with semi-preparative liquid phase separation methods. Modern spectroscopic methods (1D and 2D NMR, UV, IR, MS, etc.) were used to identify the structures of the isolated compounds. They were identified as mairoside A (1), 3′,6-di-O-sinaloylsucrose (2), myristic acid (3), methyl myristate (4), ethyl myristate (5), 3,4,5-trimethoxycinnamic acid (6), 3,4,5-trimethoxybenzoic acid (7), vinoline (8), kaempferol-3-O-rutinoside (9), among which compound 1 is a new glycoside, compounds 4 and 5 are new natural products, and the nuclear magnetic data of compound 4 were reported for the first time.

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Gap junction(GJ),also known as gap junction,is widely found between neurons and glial cells,and can connect neighboring cells and mediate the transmission of electrical sig-nals between neighboring cells.The GJ channel,which exists between neurons and mediates intercellular electrical signaling,is also known as an electrical synapse.Connexins(Cxs)are the molecular basis of GJ,and are expressed to different degrees in different neurons and glial cells.The presence of GJ mediates different functions among neurons and glial cells,which further influences the establishment of various mature neural circuits,re-flecting the importance of GJ in the maintenance of neural cir-cuits.This review summarizes the relationship between GJ and neural circuits in relation to the effects of GJ and different Cxs on neurons and glial cells,providing new research ideas for the treatment of neuropsychiatric disorders.

Objective To study the application value of different transbronchial biopsies in the diagnosis of central lung cancer in elderly patients.Methods The clinical data of 97 elderly patients with central lung cancer diagnosed by pathology from June 2020 to June 2023 in the 923rd Hospital of Chinese People's Liberation Army Joint Logistic Support Force were retrospectively analyzed.According to the different initial transbronchial biopsy methods,the patients were divided into the endobronchial biopsy(EBB)group(n=51)and the conventional transbronchial needle aspiration(cTBNA)group(n=46).The histopathological results were statistically analyzed,and the first biopsy positive rates of EBB and cTBNA in the diagnosis of senile central lung cancer were calculated and compared.At the same time,the differences of biopsy tolerance and complications between the two groups were evaluated.Results The squamous cell carcinoma proportions in both groups were over 50%.There was no significant difference in the first biopsy positive rate between the two groups(P>0.05).The incidence of temporary retreat of the scope due to subjective tolerance in the EBB group was higher than that in the cTBNA group,and the difference was statistically significant(P<0.05).There was a statistically significant difference in the incidence of intraoperative complications of different grades between the two groups(P<0.001).Among them,the incidence of grade 2 and above complications during surgery in the EBB group was significantly higher than that in the cTBNA group(P<0.001).Conclusion For elderly patients with central lung cancer,the success rate of the first biopsy of EBB and cTBNA is roughly equivalent,but the incidence of postoperative complications of the latter is significantly lower than that of the former.cTBNA can be used as the first biopsy method for this population.

To evaluate the effectiveness and safety of implantable D-shant atrial shunt device in patients with severe pulmonary arterial hypertension(PAH)and right heart failure.A 53-year-old female patient diagnosed with severe idiopathic PAH and right heart failure,her WHO FC grade was Ⅳ.The right heart catheter and implantation of D-shant atrial shunt device were performed under local anesthesia on November 30,2021.A 6 mm×4 cm peripheral artery balloon was selected to dilate the atrial septum and a D-shant atrial shunt device with a fixed 4 mm diameter orifice was implanted into the heart.The clinical symptoms and hemodynamics of the patient was improved after the intervention.Implantation of atrial shunt device as a palliative therapy to established a right to left shunt is another strategy for treating patients with severe PAH in late period,which has good effectiveness and safety.It could be the last replacement therapy to improve symptoms and prolonged lives to drug resistant and severe PAH patients.

The purpose of this study was to investigate the regulatory effects of biofilm associated non-coding small RNA(sRNA)00085 on the survival and environmental fitness of Listeria monocytogenes.Homologous recombination technology was used to construct a deletion mutant strain(△sRNA 00085)and a complementary strain(C △sRNA 00085)of the sRNA00085 target gene.The differences in biological characteristics were compared among the standard strain,△sRNA 00085,and C△sRNA 00085.The deletion of sRNA00085 led to a significant decrease in biofilm formation capacity and sensitivity to several antibiotics,including penicillin,piperacillin,doxycycline,tetracycline,vancomycin,and cotrimoxazole.However,only the minimum inhibitory concentration(MIC)of tetracycline exhibited a significant decrease in △sRNA00085.Meanwhile,the decreased biofilm formation and antibiotic resistance of the sRNA00085 mutant were restored in the C△sRNA00085 strain.Furthermore,we investigated the transcription levels of tetracycline resistance-related genes in L.monocytogenes.Down-regu-lated transcription of the tetS gene but no significant difference in transcription of the tetA gene were observed in △sRNA 00085 compared with the standard strain and C△sRNA00085.Moreover,the elimination of sRNA00085 did not affect bacterial growth ability or sensitivity to disinfectants.These findings highlight that sRNA00085 plays an important role in the environ-mental adaptability of L.monocytogenes by affecting bacterial biofilm formation and resistance.

This study analyzed and compared the epidemiological characteristics of foodborne listeriosis in the United States and China,to provide evidence for optimizing the listeriosis surveillance program in China.Descriptive statistical analysis was performed on the listeriosis monitoring data from 2009 to 2021 registered in the FDOSS system and the attribution estimates of Listeria monocytogenes(L.monocytogenes)from 2013 to 2021 published by IFSAC.Sporadic and outbreak data on listeriosis in China from the CNKI,Wanfang Medical,and CQVIP databases were collected.From 2009 to 2021,a total of 1 037 listeriosis cases were reported in the United States,including 902 hospitalizations and 165 deaths.The peak of cases caused by Lm con-taminated food was in July.The number of cases,hospitalizations,and deaths accounted for 18.4％(191/1 037),20.5％(185/902),and 22.4％(37/165)of the total,respectively.Most listeriosis outbreaks were attributed to three food groups:dairy products,vegetable crops,and fruits,with attribution percentages ranging from 73.8％to 89.6％.The overall incidence of list-eriosis in China was not high:619 cases were reported from 2009 to 2021,and only 177 cases were recorded in detailed inci-dence years;the maximum number of cases in 2018 was 26.A total of 220 cases were reported with detailed onset months;the highest number of cases in April was 30.Data on listeriosis cases in China are incomplete and sporadic,and only seven cases have been successfully traced to food.Listeriosis surveillance systems in the United States are relatively complete,and there are more foodborne outbreaks.Dairy products,vegetable row crops,and fruits are the most likely causes of disease outbreaks.Although only sporadic cases have been reported in China,China should take actions such as gradually improving multi-department coop-eration mechanisms,achieving data sharing and deepening data mining,and accelerating progress in the detection technology of food-borne pathogenic microorganisms,to ensure food safety and public health.

Exosomes can ameliorate neuronal cell injury induced by hypoxia-ischemia,but the relation-ship between astrocyte-derived exosomes(As-exo)and mitochondrial function,mitochondrial associated ER membrane(MAM)function and whether mitochondrial autophagy is relevant is currently unclear.The aim of this study was to investigate the role of astrocyte-derived exosomes in the regulation of mito-chondrial function,MAM and mitochondrial autophagy in PC 12 cells after oxygen and glucose depriva-tion/reoxygenation(OGD/R).Exosomes were extracted from the supernatant of the astrocyte culture me-dium by ultracentrifugation.Using the live cell imaging system,we observed that fluorescently labeled exosomes could show obvious enrichment in PC 12 cells at 24 h.Meanwhile,co-localization of exosomes with mitochondria could be observed under the laser confocal scanning microscope;mitochondrial pres-sure changes were detected using the Seahorse cellular energy metabolism fractionation instrument.The result showed that basal respiration in the OGD/R group,compared with that in the control group,proton leakage,maximal respiration and ATP-related respiration were significantly reduced(P＜0.05 or P＜0.01),and all four indexes were elevated and statistically significant in the OGD/R+exo group compared with the control group(P＜0.05 or P＜0.01).The results of the co-localization of the mitochondria and ER showed that the structure of the MAM was harmed by oxygen-sugar deprivation and then reoxygen-ation,and the structure of As-exo and the mitochondria appeared to have a distance-reduced polymeriza-tion phenomenon,while the mitochondria and ER co-localized.The co-localization results of mitochondri-a and ER showed that the structure of MAM was damaged by oxygen deprivation and reoxygenation,and the aggregation phenomenon of MAM was weakened by the treatment of As-exo;the flow-through results showed that As-exo could restore the decrease of the mitochondrial membrane potential and the elevation of the ROS by oxygen deprivation to a certain degree.Western blotting showed that As-exo could signifi-cantly inhibit the mitochondrial autophagy-associated tension protein homologue induced hypothetical ki-nase 1(PTEN induced kinase 1(PINK1)and Parkin protein(parkin RBR E3 ubiquitin protein ligase(Parkin))were elevated,and the addition of As-exo decreased LC3 Ⅱ/LC3 Ⅰ protein expression,ele-vated P62 protein expression,and reduced OGD/R-induced mitochondrial autophagy.The results showed that OGD/R treatment can cause mitochondrial dysfunction,MAM structural changes and increased mito-chondrial autophagy in PC12 cells,and As-exo treatment can improve mitochondrial function,attenuate the formation of MAM,and reduce mitochondrial autophagy in PC 12 cells,which can have the potential of preventing the reperfusion injury in ischemic stroke.

Diabetes mellitus is a metabolic disease with high incidence and many complications,among which type 2 diabetes mellitus(T2DM)accounts for a large proportion.Current studies have shown that T2DM is accompanied by damage of liver,kidney,and other organs and its complications seriously en-danger human health.Ferroptosis generates many Reactive Oxygen Species(ROS)through the Fenton reaction,and the accumulation of ROS activates Hypoxia Inducible Factor-1(HIF-1α).As a result,the level of vascular endothelial growth factor(VEGF)is increased.Ferrostatin-1(Fer-1),a ferroptosis in-hibitor,has strong antioxidant capacity.Therefore,based on the hypoxia-inducible factor-1α/vascular endothelial growth factor(HIF-1α/VEGF)signaling pathway,we explored the therapeutic effect of Fer-1 on the liver and kidney tissues of diabetic mice.db/db mice(21～22 weeks old)were used as the model of diabetes mellitus.Ferroptosis inhibitor Fer-1 was used as the intervention drug.db/m mice served as the blank control group,and body weight and blood glucose were measured for 4 weeks.Food intake and water intake were recorded in each group.The levels of Alanine aminotransferase(ALT)and Aspartate aminotransferase(AST)in the serum were measured.ROS and Glutathione(GSH)activity in liver and kidney tissues and urinary protein content were measured.Liver and kidney tissue sections were stained with Hematoxylin-Eosin(HE),and the pathological morphology was observed under a light microscope.The protein levels of HIF-1α,VEGF,and glutathione peroxidase 4(GPX4)in liver and kidney tissues were detected by Western blot.In db/db mice,Fer-1(1 mg·kg-1,ig)could significantly reduce the a-mount of food and water intake,the levels of ALT and AST in serum,the ROS production in liver and kidney tissues,and the level of urine protein,but significantly increase the activity of GSH,thus improve the pathological conditions of liver and kidney.Fer-1 also significantly inhibited HIF-1α and VEGF pro-tein indexes and increased GPX4 protein levels in liver and kidney tissues.Although Fer-1 can not change the body weight and reduce blood glucose in diabetic mice,it can play a therapeutic role in the liver and kidney tissues of diabetic mice in the middle and late stages,and its mechanism may be related to HIF-1α/VEGF and GPX4.