ObjectivePhotoacoustic pump-probe imaging can effectively eliminate the interference of blood background signal in traditional photoacoustic imaging, and realize the imaging of weak phosphorescence molecules and their triplet lifetimes in deep tissues. However, background differential noise in photoacoustic pump-probe imaging often leads to large fitting results of phosphorescent molecule concentration and triplet lifetime. Therefore, this paper proposes a novel triplet lifetime fitting method for photoacoustic pump-probe imaging. By extracting the phase of the triplet differential signal and the background noise, the fitting bias caused by the background noise can be effectively corrected. MethodsThe advantages and feasibility of the proposed algorithm are verified by numerical simulation, phantom and in vivo experiments, respectively. ResultsIn the numerical simulation, under the condition of noise intensity being 10% of the signal amplitude, the new method can optimize the fitting deviation from 48.5% to about 5%, and has a higher exclusion coefficient (0.88>0.79), which greatly improves the fitting accuracy. The high specificity imaging ability of photoacoustic pump imaging for phosphorescent molecules has been demonstrated by phantom experiments. In vivo experiments have verified the feasibility of the new fitting method proposed in this paper for fitting phosphoometric lifetime to monitor oxygen partial pressure content during photodynamic therapy of tumors in nude mice. ConclusionThis work will play an important role in promoting the application of photoacoustic pump-probe imaging in biomedicine.

ObjectiveAs a second messenger in intracellular signal transduction, Ca²⁺ plays an important role in cell migration. Previous studies have demonstrated that extracellular Ca²⁺ influx can promote electric field-guided cell migration, known as electrotaxis. However, the effect of intracellular Ca²⁺ flow on electrotaxis is unclear. Therefore, in this study, we investigate the effect of Ca²⁺ flux on the electrotaxis of Dictyostelium discoideum. MethodsThe electrotaxis of Dictyostelium discoideum was investigated by applying a direct current (DC) electric field. Cell migration was recorded using a real-time imaging system. Calcium channel inhibitors, the extracellular Ca²⁺ chelator EGTA, Ca²⁺-free DB buffer, and caffeine were applied to investigate the impact of intra- and extracellular Ca²⁺ flow on electrotaxis. The involvement of G proteins and ERK2 in directed cell migration mediated by endoplasmic reticulum Ca²⁺ release was explored using mutants. ResultsDictyostelium discoideum migrated toward the cathode in the electric field in a voltage-dependent manner. The intracellular Ca²⁺ concentration of the cells was significantly increased in the electric field. Inhibition of both extracellular Ca²⁺ influx and intracellular Ca²⁺ release suppressed cell electrotaxis migration. Inhibition of endoplasmic reticulum Ca²⁺ release induced by caffeine significantly impaired the electrotaxis of Dictyostelium discoideum. Deletion of Gα2, Gβ, Gγ, and Erk2 notably reduced the electrotaxis of the cells. Enhancing Ca²⁺ release mediated by caffeine restored the electrotaxis of the Gα2^-, Gβ ^-, and Erk2^- mutant cells partially or completely, but did not restore electrotaxis in the Gγ^- mutant cells. ConclusionCa²⁺ release from the endoplasmic reticulum regulates electrotaxis migration in Dictyostelium discoideum and is involved in the regulation of cell electrotaxis by G proteins and ERK2.

ObjectiveTo understand the whole genome characteristics and the information for genetic evolution in the two coxsackievirus A2 (CVA2) strains isolated from patients with herpangina in Shanghai, and to provide a scientific basis for the prevention and treatment of herpetic angina. MethodsTwo CAV2 strains isolated from patients with herpetic angina in Shanghai were performed whole genome sequencing and analysis for phylogenetics, nucleotide homology, and evolution. ResultsA phylogenetic analysis of the VP1 region revealed that the two Shanghai strains both belonged to CVA2 genotype D, with the highest homology to OL357660, a strain from Yunnan. The average nucleotide identity (ANI) of the whole genome between the two Shanghai strains was 98.88%, and the ANI of the whole genome comparisons to other CVA2 genotype D strains and CVA2 genotypes A-C strains ranged from 84.64% to 97.42% and from 79.21% to 84.20%, respectively. The two Shanghai strains had low homology in the 3D region compared to the existing CVA2 strains. The phylogenetic analysis and sliding window nucleotide similarity analysis indicated that the two Shanghai strains and the Yunnan OL357660 strain might constitute a new genetic lineage. ConclusionThe two CVA2 strains isolated for the first time in Shanghai are assigned to genotype D (GenBank: PQ130039 and PQ130040), which is identical to the existing subtype prevalent in China. As represented by the Shanghai strains, a new CVA2 genetic lineage is been identified. This study has enriched the data on genetic evolution and genetic variation of CVA2 in Shanghai, indicating the requirement to strengthen surveillance for the epidemiological pattern of CVA2.

ObjectiveTo explore the pathological mechanism-syndrome-treatment patterns of approved Chinese patent medicines （CPMs） that treat collateral disorders， providing a reference for the principle of "treating different diseases with the same therapy" in collateral pathology. MethodsCPMs that apply treatment strategies based on collateral disorders were identified from the Pharmacodia database by extracting information from the "efficacy" or "indications" sections of drug package inserts. A database was established to extract the names and compositions of the CPMs， as well as their indications， related traditional Chinese medicine （TCM） symptoms， disease locations （affected areas）， and pathological factors. Frequency statistics were performed. Using the Apriori algorithm， an association rule analysis was conducted on CPMs and disease-location combinations related to the top three most frequent pathological factor combinations. Core formulas for these combinations were identified and analyzed through drug network analysis and MCODE module clustering. ResultsA total of 660 CPMs targeting collateral disorders were retrieved， involving 299 indications， 323 TCM symptoms， 21 disease locations， 19 pathological factors， and 124 pathological factor combinations. The most frequent pathological factor combinations were blood stasis （involved in 109 CPMs， 16.52%）， exogenous wind （外风） -cold-dampness （involved in 43 CPMs， 6.52%）， and qi deficiency-blood stasis （involved in 42 CPMs， 6.36%）. Analysis of the core formulas for these combinations revealed common ingredients such as Honghua （Carthami Flos）， Chuanxiong （Chuanxiong Rhizoma）， Danggui （Angelicae Sinensis Radix）， and Dilong （Pheretima）. ConclusionCollateral disorders involve a wide range of pathogenesis and represent a fundamental mechanism in the onset and development of various diseases， characterized by obstruction and stagnation. The primary therapeutic principle is unblocking of the collaterals. Blood stasis obstructing the collaterals is the core pathological basis， and the strategy of activating blood circulation and resolving stasis to unblock the collaterals should be central to the treatment. The core medication pattern involves combining blood-activating and stasis-resolving herbs with insect-derived medicinals that unblock collaterals. Exogenous wind is often the initiating patholo-gical factor in colla-teral disorders， and the appropriate addition of wind-dispelling herbs can enrich the treatment strategies for such conditions.

This article reports a case with the chief complaint of “hepatosplenomegaly to be investigated” and a confirmed diagnosis of Niemann-Pick disease type B after various tests， and a literature review was conducted to summarize the heterogeneous manifestations of liver involvement in type B Niemann-Pick disease， in order to improve the clinical management of difficult and rare liver diseases.

ObjectiveTo explore the impact of autonomic nerve function on motor function in patients with post-stroke depression (PSD) from the perspective of regional homogeneity (ReHo). MethodsFrom January to December, 2020, a total of 60 inpatients and outpatients with cerebral infarction in the Affiliated Brain Hospital of Nanjing Medical University were divided into control group (n = 30) and PSD group (n = 30). Two groups were assessed using Fugl-Meyer Assessment (FMA), modified Barthel Index (MBI) and Hamilton Depression Scale (HAMD). Heart rate variability (HRV) was measured. Ten patients in each group were selected randomly to undergo resting state functional magnetic resonance imaging (rs-fMRI) to calculate ReHo. ResultsAll HRV indices were lower in PSD group than in the control group (|t| > 2.092, P < 0.05). In PSD group, FMA and MBI scores showed positive correlations with 24-hour standard deviation of normal-to-normal R-R intervals (SDNN), the root mean square of successive differences between normal heartbeats over 24 hours (RMSSD), the percentage of differences between adjacent normal R-R intervals over 24 hours that were greater than 50 ms (PNN50), total power (TP), very low frequency power (VLF) and low frequency power (LF) (r > 0.394, P < 0.05), and showed negative correlations with HAMD scores (|r| > 0.919, P < 0.001). HAMD scores in PSD group were negatively correlated with SDNN, RMSSD, PNN50, TP and VLF (|r| > 0.769, P < 0.001). Compared with the control group, the ReHo increased in PSD group in the right rectus gyrus (142 voxels, t = 6.575), the left medial and paracingulate gyri (204 voxels, t = 4.925) (GRF correction, P_-Voxel < 0.005，P_-Cluster < 0.05); and reduced in the right cerebellum (191 voxels, t = -6.487), the left middle temporal gyrus (140 voxels, t = -5.516), and the left precentral gyrus (119 voxels, t = -4.764) (GRF correction, P_-Voxel < 0.005，P_-Cluster < 0.05) in PSD group. ConclusionAutonomic nerve function is related to motor dysfunction in patients with PSD. The modulation of emotional, cognitive and motor brain regions by the autonomic nervous system may play a role in influencing the motor function in patients with PSD.

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC₅₀ values of 3.77 μmol·L^-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

Objective:To analyze the influencing factors related to the prognosis of delayed replantation of avulsed permanent teeth.Methods:A retrospective study was conducted on the clinical data of 35 patients with 38 affected teeth underwent delayed replantation of permanent teeth.According to the prognosis after 12 to 108 months of follow-up,the replantation results of the cases were divided into-success,survival and failure groups.Survival curves were plotted using Kaplan-Meier method,Log-Rank test was used for univariate analysis,and Cox proportional risk regression models were used for multivariate analysis to assess the effects of gender,age,degree of tooth development,mode of tooth preservation and mode of endodontic treatment on the survival rate of replanted teeth.Results:Of the 38 replanted teeth,3 were successful,28 remained and 10 failed.The 9-year cumulative survival rate of the replanted teeth was 34.7％.The results showed that there were no statistically significant differences in the survival rate of the replanted teeth in the groups with different sex,age,degree of tooth development and the mode of preservation of avulsed teeth(P＞0.05).There were statistically significant differences in the cumulative survival rate of the replanted teeth among the groups with different endodontic treatment(P＜0.01),which showed that the cumulative survival rate in the root canal filling group＞continuous root canal sealing group＞pulp preserva-tion treatment group.Conclusion:For the delayed replantation of avulsed premanent teeth,survival prognosis of the teeth treated with pulp preservation is poor,early pulp extraction and root canal filling are recommended.

ObjectiveTo analyze the epidemiological distribution and temporal trends of liver cancer incidence among Luzhou residents from 2016‒2022， and to provide a theoretical basis for improving liver cancer prevention and treatment strategies in Luzhou. MethodsData on liver cancer incidence among Luzhou residents from 2016 to 2022 were collected， and the incidence rate， age-specific incidence rate， and annual percentage change （APC） were calculated. A Joinpoint regression model was used to fit a time series segment to the monthly number of new cases in each district and county of Luzhou to explore the trend of liver cancer incidence rate. ResultsThe incidence rate of liver cancer in Luzhou increased from 22.96/10⁵ in 2016 to 32.31/10⁵ in 2022. The incidence rate of liver cancer in men was higher than that in women in both 2016 and 2022， and the incidence rate of liver cancer in men increased from 34.83/10⁵ in 2016 to 47.95/10⁵ in 2022， with an APC of 3.3%； the incidence rate of liver cancer in women increased from 10.50/10⁵ in 2016 to 15.95/10⁵ in 2022， with an APC of 3.0%， and the differences in the change trends were not statistically significant （P>0.05）.The incidence of liver cancer was low in the age group of 0‒<40 years from 2016 to 2022 and increased with age； the incidence of liver cancer in the age group of 55 years and above was increasing at an average annual rate of 16.4%. ConclusionThe overall incidence of liver cancer in Luzhou is on the rise， and the incidence of liver cancer in men is higher than that in women. Middle-aged and elderly men are the key population for liver cancer prevention and treatment， and liver cancer prevention and treatment should be carried out in a targeted manner， taking into account regional development differences.

BACKGROUND:Alzheimer's disease is a degenerative neurological disorder characterized primarily by cognitive impairment.Acupuncture is a kind of traditional Chinese medicine therapy for treating Alzheimer's disease,but its mechanism is not yet clear. OBJECTIVE:To observe the effects of electroacupuncture with"Zhi San Zhen"on the Notch signaling pathway,β-amyloid protein(Aβ)and synaptic plasticity in 5xFAD mice. METHODS:Sixteen male,6-month-old 5xFAD mice,SPF-grade,were randomly divided into the electroacupuncture with"Zhi San Zhen"group(electroacupuncture group)and the model group,with eight mice in each group.Eight SPF-grade,male,6-month-old C57BL/6 mice were used as the wild control(wild)group.The electroacupuncture group received electroacupuncture with"Zhi San Zhen"intervention,5 times a week for 4 consecutive weeks.The model group and the wild group did not receive electroacupuncture intervention.The Morris water maze was used to preliminarily assess their learning and memory abilities.Thioflavin S staining was performed to detect Aβ plaque deposition.Western blot and real-time quantitative polymerase chain reaction(RT-qPCR)were used to measure the expression levels of transmembrane receptor protein Notch-1,Notch 1 intracellular domain(NICD),hairy and enhancer of split 1(Hes 1),hairy and enhancer of split 5(Hes 5),synaptophysin(SYN),postsynaptic density protein-95(PSD-95),and Aβ. RESULTS AND CONCLUSION:Compared with the model group,the wild group and the electroacupuncture group showed shortened escape latency,increased platform crossing times,and longer target quadrant dwell time(P<0.05).Compared with the wild group,the model group had significantly increased deposition of Aβ plaques,while electroacupuncture with"Zhi San Zhen"inhibited the deposition of Aβ plaques in the hippocampus of 5xFAD mice(P<0.05).Compared with the wild group,the model group had decreased mRNA levels of SYN,PSD-95,Notch 1,NICD,Hes 1,and Hes 5 in the hippocampal tissue of mice,and increased mRNA levels of Aβ(P<0.05).Electroacupuncture with"Zhi San Zhen"increased the mRNA levels of SYN,PSD-95,Notch 1,NICD,Hes 1,and Hes 5 in the hippocampal tissue,and decreased the mRNA level of Aβ(P<0.05).Compared with the Wild group,the model group had decreased protein expression levels of SYN,PSD-95,Notch 1,NICD,Hes 1,and Hes 5 in the hippocampal tissue of mice,and increased protein expression levels of Aβ(P<0.05).Electroacupuncture with"Zhi San Zhen"upregulated the protein expression levels of SYN,PSD-95,Notch 1,NICD,Hes 1,and Hes 5,and inhibited the protein expression of Aβ(P<0.05).To conclude,electroacupuncture with"Zhi San Zhen"can improve the learning and memory abilities of 5xFAD mice,possibly by inhibiting the deposition of Aβ protein and activating the Notch signaling pathway in the hippocampus to enhance synaptic plasticity.