ObjectiveCerebrospinal fluid (CSF) plays a crucial role in maintaining the homeostasis of the central nervous system (CNS). CSF rapidly exchanges with interstitial fluid (ISF) via the glymphatic system within the brain parenchyma. CSF-ISF circulation and its associated mechanisms are often referred to as the brain lymphatic system. This system is connected directly to meningeal lymphatic vessels (mLVs), jointly performing the function of clearing metabolic waste from the CNS. Emerging evidence indicates that this system is closely associated with the onset and progression of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD). Importantly, abnormal CSF circulation is not only a downstream consequence of AD pathology, but also a risk factor. In AD, the dynamics of CSF flow within the CNS are diminished, immune dysregulation occurs, and this may increase the risk of AD by exacerbating the burden of amyloid β-protein (Aβ). In the mouse model of AD, impaired CSF flow compromises this clearance function, leading to cognitive deficits. Clinically, acupuncture at cognition-related acupoints is commonly used for the prevention and treatment of AD. However, whether its therapeutic effects are mediated through the modulation of CSF dynamics remains unclear. This study aimed to evaluate the impact of acupuncture on CSF flow and investigate its acupoint specificity. MethodsMice were randomly assigned to experimental groups for the different electroacupuncture groups with the following acupoints: Baihui point (GV 20), Ear point, Neiguan point (PC 6), and Tianshu point (ST 25). Wild-type mice on a C57BL/6J background were used as controls. Fluorescent tracer was injected into the cisterna magna to label CSF flow. Fluorescence imaging was employed to assess the distribution of CSF within the brain before and after acupuncture stimulation. ResultsFollowing tracer injection into the cisterna magna, fluorescence signals rapidly reached the cerebellum and medulla—the regions closest to the injection site. Fluorescence intensity was higher in ventral brain regions compared to dorsal regions, likely due to greater vascular density in ventral areas facilitating CSF-ISF exchange. Electroacupuncture at the GV 20 produced the most pronounced enhancement of CSF across the whole brain, while stimulation at the ST 25 primarily augmented flow within subcortical regions. In contrast, electroacupuncture at the Ear point or the PC 6 had no observable effect on CSF in mice. ConclusionElectroacupuncture promotes CSF flow into the brain parenchyma in an acupoint-specific manner, with GV 20 exhibiting the most pronounced enhancement of CSF dynamics. These findings suggest that acupuncture-mediated facilitation of CSF flow may represent a potential therapeutic strategy for preventing or delaying age-related cognitive decline.

ObjectiveCerebrospinal fluid (CSF) plays a crucial role in maintaining the homeostasis of the central nervous system (CNS). CSF rapidly exchanges with interstitial fluid (ISF) via the glymphatic system within the brain parenchyma. CSF-ISF circulation and its associated mechanisms are often referred to as the brain lymphatic system. This system is connected directly to meningeal lymphatic vessels (mLVs), jointly performing the function of clearing metabolic waste from the CNS. Emerging evidence indicates that this system is closely associated with the onset and progression of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD). Importantly, abnormal CSF circulation is not only a downstream consequence of AD pathology, but also a risk factor. In AD, the dynamics of CSF flow within the CNS are diminished, immune dysregulation occurs, and this may increase the risk of AD by exacerbating the burden of amyloid β-protein (Aβ). In the mouse model of AD, impaired CSF flow compromises this clearance function, leading to cognitive deficits. Clinically, acupuncture at cognition-related acupoints is commonly used for the prevention and treatment of AD. However, whether its therapeutic effects are mediated through the modulation of CSF dynamics remains unclear. This study aimed to evaluate the impact of acupuncture on CSF flow and investigate its acupoint specificity. MethodsMice were randomly assigned to experimental groups for the different electroacupuncture groups with the following acupoints: Baihui point (GV 20), Ear point, Neiguan point (PC 6), and Tianshu point (ST 25). Wild-type mice on a C57BL/6J background were used as controls. Fluorescent tracer was injected into the cisterna magna to label CSF flow. Fluorescence imaging was employed to assess the distribution of CSF within the brain before and after acupuncture stimulation. ResultsFollowing tracer injection into the cisterna magna, fluorescence signals rapidly reached the cerebellum and medulla—the regions closest to the injection site. Fluorescence intensity was higher in ventral brain regions compared to dorsal regions, likely due to greater vascular density in ventral areas facilitating CSF-ISF exchange. Electroacupuncture at the GV 20 produced the most pronounced enhancement of CSF across the whole brain, while stimulation at the ST 25 primarily augmented flow within subcortical regions. In contrast, electroacupuncture at the Ear point or the PC 6 had no observable effect on CSF in mice. ConclusionElectroacupuncture promotes CSF flow into the brain parenchyma in an acupoint-specific manner, with GV 20 exhibiting the most pronounced enhancement of CSF dynamics. These findings suggest that acupuncture-mediated facilitation of CSF flow may represent a potential therapeutic strategy for preventing or delaying age-related cognitive decline.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective To evaluate the predictive value of serum microRNA-19a-3p(miR-19a-3p),microRNA-146a(miR-146a)and 25-hydroxyvitamin D3[25-(OH)D3]for the prognosis of children with respiratory syncytial virus(RSV)bronchiolitis.Methods A total of 202 children with RSV bronchiolitis were enrolled as disease group,followed up for one year after discharge,and divided into good prognosis group(n=55)and poor prognosis group(n=147).Additionally,180 healthy chil-dren matched by gender and age were selected as control group.Serum levels of miR-19a-3p,miR-146a and 25-(OH)D3 were measured in both the disease and control groups.The clinical data and the levels of serum miR-19a-3p,miR-146a and25-(OH)D3 of children in the poor prognosis group and the good prognosis group were compared.The correlations of serum miR-19a-3p,miR-146a and 25-(OH)D3 with the prognosis of children and their predictive value for poor prognosis of chil-dren were analyzed.Multivariate Logistic regression analysis was used to screen the related influen-cing factors of poor prognosis in children.Results The proportion of smoking among family mem-bers,the expression levels of serum miR-19a-3p and miR-146 in the poor prognosis group were sig-nificantly higher than those in the good prognosis group,and the level of 25-(OH)D3 was signifi-cantly lower than that in the good prognosis group(P＜0.05).The expression levels of serum miR-19a-3p and miR-146a were positively correlated with the poor prognosis of the children(r=0.408,0.332,P＜0.001),and the level of serum 25-(OH)D3 was negatively correlated with the poor prognosis of the children(r=-0.386,P＜0.001).The results of receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC)of serum miR-19a-3p,miR-146a and 25-(OH)D3 for predicting poor prognosis in children was 0.726,0.817 and 0.834,re-spectively.The AUC of the combined prediction of the three was 0.938,which was higher than that of the single prediction(Z=5.515,3.879,3.860,P＜0.001),and the sensitivity and specificity were 83.64％and 90.48％,respectively.The miR-19a-3p,miR-146a,25-(OH)D3 and smoking among family members were all influencing factors for the poor prognosis of children with RSV bron-chiolitis(P＜0.05).Conclusion Serum miR-19a-3p,miR-146a and 25-(OH)D3 all have cer-tain predictive values for the prognosis of children with RSV bronchiolitis,and the combined predic-tive value of the three is higher.

Adolescents and young adults (AYAs) are one of the major populations susceptible to tuberculosis. However, little is known about the unique characteristics and diagnostic biomarkers of tuberculosis in this population. In this study, 81 AYAs were recruited, and the high-quality serum proteome of the AYAs with tuberculosis was profiled by quantitative proteomics. The data of serum proteomics indicated that the relative abundance of hemoglobin and apolipoprotein was significantly reduced in the patients with active tuberculosis (ATB). The pathway enrichment analysis showed that the downregulated proteins in the ATB group were mainly involved in the antioxidant and cell detoxification pathways, indicating extensive oxidative stress damage. Random forest (RF) and extreme gradient boosting (XGBoost) were employed to evaluate protein importance, which yielded a set of candidate proteins that can distinguish between ATB and non-ATB. The analysis with the support vector machine algorithm (recursive feature elimination) suggested that the combination of apolipoprotein A-I (APOA1), hemoglobin subunit beta (HBB), and hemoglobin subunit alpha-1 (HBA1) had the highest accuracy and sensitivity in diagnosing ATB. Meanwhile, the levels of hemoglobin (HGB) and albumin (ALB) can be used as blood biochemical indicators to evaluate changes in the protein levels of APOA1 and HBB. This study established the serum proteome landscape of AYAs with tuberculosis and identified new biomarkers for the diagnosis of tuberculosis in this population.
Humans ; Proteomics/methods* ; Biomarkers/blood* ; Adolescent ; Young Adult ; Apolipoprotein A-I/blood* ; Machine Learning ; Tuberculosis/blood* ; Proteome/analysis* ; Male ; Hemoglobins/analysis* ; Female ; Blood Proteins/analysis* ; Adult

Objective To detect the expression changes of citrullinated histone H3(CitH3)during the development of deep vein thrombosis(DVT)in mice,and to explore its value in estimating the time to thrombosis.Methods The inferior vena cava(IVC)of mice was ligated to establish a thrombosis model induced by congestion.Mice were sacrificed under excessive anesthesia at 0 h,1 d,3 d,5 d,7 d,10 d,14 d and 21 d after the modeling,respectively.The congested IVC segments(0 h after modeling)and the thrombosed IVC segments(1-21 days after modeling)were extracted.Immunohistochemistry and double immunofluorescence staining were used to observe the number of neutrophils and the ex-pression of CitH3 during thrombosis.Western blotting was used to detect the protein expression level of CitH3.Results During thrombosis,CitH3 was mainly expressed in neutrophils within the thrombus.A small number of neutrophils and a few CitH3-positive cells were observed at 0 h after modeling in the congested IVC.Between 1 d and 21 d after modeling,the number of neutrophils reached a peak at 1 d and gradually decreased.The number of CitH3-positive cells and their ratio to neutrophils began to increase at 1 d,reached a peak at 5 d after modeling,and then decreased.The expression level of CitH3 protein began to increase at 1 d and reached a peak at 5 d after modeling.Conclusion The expres-sion of CitH3 during DVI shows temporal changes,and is expected to become a biological marker for estimating the formation time of thrombosis.

Objective:To investigate the optical coherence tomography (OCT) imaging features of bullous pemphigoid (BP) and pemphigus.Methods:A total of 23 patients with BP and 18 with pemphigus diagnosed according to clinical manifestations, histopathological and immunological features were collected from Wuhan No.1 Hospital from January to June 2024. OCT imaging was performed in 41 patients to observe the blisters at the lesion sites and their anatomic locations (intraepidermal or subepidermal), intravesicular inflammatory cells and fibrin deposits, dilated vessels in the upper dermis, as well as skin adjacent to the lesions.Results:Among the 23 patients with BP and 18 patients with pemphigus (including 12 with pemphigus vulgaris and 6 with pemphigus foliaceus), there were 20 males and 21 females, and their ages at onset ranged from 20 to 89 years. OCT imaging of blisters in patients with BP showed subepidermal oval to round hyporeflective liquid-filled areas containing highly refractive inflammatory cells and fibrin deposits, with dilated vessels in the upper dermis, while OCT imaging of blisters in patients with pemphigus showed intraepidermal blisters with a few inflammatory cells; the OCT imaging features of both BP and pemphigus were similar to their corresponding histopathological features. The detection rates of intravesicular inflammatory cells and fibrin deposition were significantly higher in the patients with BP (82.61% [19/23], 60.87% [14/23], respectively) than in those with pemphigus (44.44% [8/18], 11.11% [2/18]; χ2 = 6.54, 10.51, P = 0.011, 0.001, respectively). In the OCT images of normal skin adjacent to blisters, subclinical fissures were detected in 17.39% (8/46) of patients with BP and 25.00% (9/36) of patients with pemphigus. Conclusion:OCT imaging could accurately locate the blisters and potential subclinical lesions in normal skin adjacent to blisters in patients with BP and pemphigus, which is helpful for the early auxiliary diagnosis of these two diseases.

Purpose To investigate the clinicopathological features,immunophenotypic profile,differential diag-noses,and prognostic implications of liver metastatic solid pseudopapillary neoplasm(LMSPN).Methods A retro-spective analysis was conducted on the clinicopathological features,immunohistochemical profile,and clinical outcomes of of 15 cases of LMSPN cases,supplemented by a literature review.Results Of the 15 patients,12 were female and 3 were male,with a mean age of 43 years(range 25-67 years).Multiple hepatic lesions were observed in 9 cases,some of which were accompanied by abdominal or omental metastasis.The tumors exhibited a cystic-solid appearence on gross examination,ranging from 0.5 to 15 cm in diameter.Histologically,the tumors showed typical cystic-solid and pseudopapillary areas,with tumor cells arranged around small blood vessels forming characteristic pseudopapillary structures.Tumor cells exhibited relatively uniform morphology,however,some cases presented with tumor necrosis(5/15),cytologic/nuclear atypia(4/15),mitotic figures(5/15),lymphovascular invasion(6/15),perineural inva-sion(3/15),and lymph node metastasis(2/15).Immunohistochemically,tumor cells showed variable expression ofβ-catenin,LEF1,vimentin,CD10,α1-ACT,PR,E-cadherin,NSE,CD56,Syn and Ki67.Notably,the nuclear ex-pression level of Ki67 and PR were significantly associated with prognosis(P＜0.05).β-catenin,LEF1,PR,and Ki67 were predominantly expressed in the nuclei,while markers such as CKpan,CgA,Hep Par-1,Arginase-1,CK7,and CK19 were negative or only weakly expressed.Follow-up data were available for 11 patients(range 10-157 months).Four patients died of widespread hepatic and abdominal metastases,while 7 remained alive.Conclusion The liver is the most most frequent site of distant metastasis for solid pseudopapillary neoplasms of the pancreas.High expression of Ki67 and PR is associated with unfavorable prognosis in LMSPN.

Objective:To analyze the epidemiological characteristics of the population receiving assisted reproductive technology (ART) therapy and the health status of their offspring in Shanghai from 2011 to 2020.Methods:Based on the birth cohort of the entire population in Shanghai, the proportion and trend changes of ART offspring in the birth cohort were analyzed. The characteristics of ART and naturally conceived populations, including household registration, education level, maternal age, and reproductive history, were examined. Additionally, the health status between ART offspring and naturally conceived offspring were compared.Results:From 2011 to 2020, a total of 70 729 ART offspring were born in Shanghai, accounting for 3.69% of the total births. In 2020, this proportion reached 7.79%. The ART conception rate for primiparous women was higher than that for multiparous women, with both showing upward trends and reaching 9.87% and 2.36%, respectively, in 2020. The ART conception rate was higher in women with higher education levels and local household registration than in those with lower education levels and non-local household registration. The incidence rates of preterm birth and low birth weight in ART singleton offspring were 7.76% and 4.82%, respectively, higher than the 4.69% and 2.87% in naturally conceived offspring, but no increasing trend was observed in naturally conceived offspring. Among twin and multiple newborns, the incidence rates of preterm birth and low birth weight were 56.98% and 46.82% for ART, lower than the 58.51% and 51.32% for natural conception.Conclusions:The difference in social and demographic characteristics was obvious in population receiving ART, suggesting that the differed demand of some people for ART therapy, and it is necessary to strengthen the construction of public health services and further expand the coverage and accessibility of ART services. With technological advancements, the rates of preterm birth and low birth weight remain relatively stable, and even decrease in twin and multiple newborns.

OBJECTIVE: To investigate the correlation of seminal plasma oxidation reduction potential (ORP), normalized oxidation-reduction potential (nORP) and sperm DNA fragmentation index (DFI) to sperm motion parameters, and their clinical predictive value for oligoasthenozoospermia (OAZ). METHODS: This study included 433 male subjects visiting the Clinic of Andrology in our hospital from March to May 2024. According to sperm concentration and the percentage of progressively motile sperm (PMS), we divided them into a normal control (n = 119), an oligozoospermia (OZ, n = 118), an athenozoospermia (AZ, n = 119) and an OAZ group (n = 77). Using the electrode method, we measured the seminal plasma ORP, calculated nORP=ORP/sperm concentration (mV/［10⁶/ml］), and determined DFI and high DNA chromatin sperm (HDS) by flow cytometry based on sperm chromatin structure assay (SCSA), followed by comparison among the four groups in age, abstinence days, semen volume, total sperm count, sperm concentration, PMS, non-progressively motile sperm (NPMS), immotile sperm (IMS), curvilinear velocity (VCL), straight line velocity (VSL), average path velocity (VAP), linearity (LIN), straightness(STR), wobble (WOB), DFI, HDS, ORP and nORP. Using the receiver operating characteristic (ROC) curve, we assessed the predictive value of DFI, ORP and nORP for OAZ, and analyzed the correlation of DFI, ORP and nORP to sperm motion parameters by Pearson and Spearman analyses. RESULTS: Statistical analysis revealed statistically significant differences among the four groups in semen volume, abstinence days, total sperm count, sperm concentration, PMS, NPMS, IMS, total sperm motility, VCL, VSL, VAP, STR, DFI, HDS, ORP and nORP (P < 0.05), but not in age, LIN and WOB (P > 0.05). The area under the ROC curve (AUC) for the predictive value of DFI for OAZ was 0.880, with the critical value of 8.920, sensitivity of 74.8% and specificity of 88.2%; that of ORP for AZ was 0.698, with the critical value of 155.375, sensitivity of 70.6% and specificity of 64.7%; and that of nORP for OZ was 0.999, with the critical value of 9.844, sensitivity of 98.3% and specificity of 99.2%. Pearson and Spearman correlation analyses showed that DFI was correlated positively with age, abstinence days, semen volume, IMS, HDS and ORP, but negatively with PMS, NPMS, total sperm motility, VCL, VSL, VAP and STR; ORP positively with abstinence days, semen volume, IMS, DFI and nORP, but negatively with PMS, NPMS, total sperm motility, VSL, LIN and STR; and nORP positively with HDS, but negatively with abstinence days, total sperm count, sperm concentration, PMS and NPMS. CONCLUSION Oxidative stress (OS) may be an important pathological factor for elevated ORP, increased DFI and changes of routine sperm motion parameters, consequently leading to OAZ. As OS markers, DFI and ORP have a high predictive value for OS-induced OAZ.
Male ; Humans ; DNA Fragmentation ; Semen/metabolism* ; Sperm Motility ; Spermatozoa ; Oxidation-Reduction ; Adult ; Oligospermia ; Sperm Count ; Semen Analysis ; Asthenozoospermia