Parkinson’s disease (PD) is a common neurodegenerative disorder with profound impact on patients’ quality of life and long-term health, and early detection and intervention are particularly critical. In recent years, the search for precise and reliable biomarkers has become one of the key strategies to effectively address the clinical challenges of PD. In this paper, we systematically evaluated potential biomarkers, including proteins, metabolites, epigenetic markers, and exosomes, in the peripheral blood of PD patients. Protein markers are one of the main directions of biomarker research in PD. In particular, α‑synuclein and its phosphorylated form play a key role in the pathological process of PD. It has been shown that aggregation of α-synuclein may be associated with pathologic protein deposition in PD and may be a potential marker for early diagnosis of PD. In terms of metabolites, uric acid, as a metabolite, plays an important role in oxidative stress and neuroprotection in PD. It has been found that changes in uric acid levels may be associated with the onset and progression of PD, showing its potential as an early diagnostic marker. Epigenetic markers, such as DNA methylation modifications and miRNAs, have also attracted much attention in Parkinson’s disease research. Changes in these markers may affect the expression of PD-related genes and have an important impact on the onset and progression of the disease, providing new research perspectives for the early diagnosis of PD. In addition, exosomes, as a potential biomarker carrier for PD, are able to carry a variety of biomolecules involved in intercellular communication and pathological regulation. Studies have shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide a new breakthrough for early diagnosis. It has been shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide new breakthroughs in early diagnosis. In summary, through in-depth evaluation of biomarkers in the peripheral blood of PD patients, this paper demonstrates the important potential of these markers in the early diagnosis of PD and in the study of pathological mechanisms. Future studies will continue to explore the clinical application value of these biomarkers to promote the early detection of PD and individualized treatment strategies.

Objective To investigate the preventive effects of lidocaine administered through different routes on cardiovascular stress responses during anesthesia tracheal intubation. Methods Total 120 patients scheduled for elective surgery under general anesthesia were randomly divided into three groups: intravenous injection group （group IV）, throat spray group （group LJ）, and control group （group CT）, with 40 patients in each. Group IV received 50 mg of lidocaine via intravenous injection 1 minute before tracheal intubation. Group LJ received 50 mg of lidocaine sprayed into the pharyngeal cavity, glottis, and subglottic area. Group CT did not receive any treatment, and the remaining procedures were performed following the routine general anesthesia induction protocol. Heart rate （HR）, systolic blood pressure （SBP）, diastolic blood pressure （DBP）, and mean arterial pressure （MAP） were recorded at four time points: T₀ （before tracheal intubation）, T₁ （immediately after tracheal intubation）, T₂ （3 minutes after intubation）, and T₃ （5 minutes after intubation）. Statistical analysis of the data was performed using SPSS 22.0. Results There were no significant differences in HR at various time points within the group LJ. The changes in HR in the group IV and group CT were different statistically from those in the throat spray group. The blood pressure of patients in all three groups increased to varying degrees immediately after tracheal intubation, with the group CT showing particularly significant changes that differed significantly from both the group IV and the group LJ. The group LJ rapidly returned to levels close to those before intubation. Conclusion The preventive effects of lidocaine on stress responses during tracheal intubation were different depending on the route of administration. The inhibitory preventive effect of the throat spray method was superior to that of intravenous lidocaine, especially in preventing changes in heart rate.

ObjectiveTo explore the effects of astragalin （AST） on autophagy and apoptosis of astrocytes in the L_4-5 dorsal horn of the spinal cord in mice with inflammatory pain induced by complete Freund's adjuvant （CFA）. MethodsTwenty-four male C57BL/6 mice， aged six months， were randomly assigned to four groups： control group， saline group， CFA model group， and CFA+AST group， six mice in each group. The inflammatory pain model was established by injection of 10 µL CFA into the right lateral malleolus fossa. The saline group were injected with an equal amount of normal saline at the same site. The inflammatory pain mice in CFA+AST group were further treated with AST （60 mg/kg） intraperitoneally once a day for 21 consecutive days. Multiplex immunofluorescence staining was used to detect the coexpression of autophagy-related factors including ATG 12 and Beclin-1， apoptosis-related factors including Cleaved-Caspase3 and Caspase9， and the astrocyte marker such as GFAP in the L_4-5 spinal dorsal horn of the mice in each group. Western blot was used to examine the protein expression levels of autophagy-related proteins（ATG12， Beclin-1） and apoptosis-related proteins（Caspase 3， Caspase 9） in the L_4-5 spinal dorsal horn of mice. ResultsImmunofluorescent staining showed that in the L_4-5 dorsal horn of the spinal cord， the fluorescence intensity of ATG12 （P<0.000 1） and Beclin-1 （P<0.000 1） was significantly increased， while that of Cleaved-Caspase 3 （P<0.001） and Caspase 9 （P<0.000 1） was decreased in the CFA+AST group when compared to the CFA model group. Furthermore， AST could inhibit the activation of astrocytes. Western blot further confirmed that AST significantly upregulated the expression of ATG12 （P<0.000 1） and Beclin-1 （P<0.000 1） in the L_4-5 spinal cord of CFA mice， and downregulated the expression of Caspase 3 （P<0.01） and Caspase 9 （P<0.001）. ConclusionsAST promotes autophagy of astrocytes and inhibits their apoptosis in the L_4-5 spinal dorsal horn of CFA mice.

ObjectiveTo explore the effect of different drying conditions on the appearance and intrinsic quality indicators of Pinelliae Rhizoma for screening suitable drying conditions， so as to provide reference for its standardized production and quality evaluation. MethodsDifferent dried samples of Pinelliae Rhizoma were prepared by lime-assisted sweating method and intermittent drying method. Visual analysis was employed to measure the color brightness values（L^*） of the surface， cross-section and powder of the samples， texture analyzer was used to determine the hardness of the samples under different drying conditions. The total starch content was calculated by measuring the contents of amylose and amylopectin in the samples with ultraviolet-visible spectroscopy. High performance liquid chromatography（HPLC） was used to determine the contents of seven nucleoside components（uracil， hypoxanthine， uridine， inosine， guanosine， β-thymidine and adenosine） in the samples. Pearson correlation analysis was conducted to explore the correlation between the external characteristics and intrinsic indicators of the different dried samples. Principal component analysis（PCA） was used to comprehensively rank the data of various indicators， and partial least squares-discriminant analysis（PLS-DA） was used to screen differential components with variable importance in the projection（VIP） value>1. Furthermore， the difference between the optimal drying condition for Pinelliae Rhizoma and the traditional sun-drying method was explored by independent samples t-test. ResultsWith the increase of temperature， the color of the intermittently dried samples gradually deepened， while their hardness gradually decreased. Concurrently， the contents of extract， total starch， uridine and adenosine exhibited an upward trend， whereas the contents of uracil， hypoxanthine and inosine displayed a downward trajectory. Compared with the intermittent drying group， the content of extract in the samples subjected to lime-assisted sweating increased. With the increase of lime dose， the hardness and the total content of nucleoside components in the samples showed a downward trend， while the total starch content showed an upward trend. Correlation analysis showed that the comprehensive score of L^* was negatively correlated with the contents of uracil， hypoxanthine and inosine， and positively correlated with the contents of uridine， guanosine and adenosine. Hardness was negatively correlated with adenosine content， and positively correlated with the contents of inosine， uracil and hypoxanthine. Through comprehensive consideration and comprehensive score of principal components， the method of 5% lime-mixed sweating for 6 days emerged as the top-ranking approach. Except for the extract， the results of independent samples t-test showed that there was no significant difference between the 5% lime-mixed sweating for 6 days and the traditional sun-drying in terms of other content indicators. ConclusionThe whiteness and firmness of Pinelliae Rhizoma exhibit significant correlations with its chemical composition， while uridine， uracil， guanosine， adenosine and inosine are the key constituents responsible for the quality difference of Pinelliae Rhizoma under different drying conditions. The lime-assisted sweating method optimized in this study can be proposed as a viable alternative to the traditional sun-drying method. This method not only ensures the quality of the medicinal material but also effectively reduces the drying time and prevents mold contamination， which provides a valuable reference for the standardization of drying conditions and the establishment of quality evaluation criteria for Pinelliae Rhizoma.

Objective: To retrospectively analyze the clinical data of 474 newborns with hyperbilirubinemia, and to investigate the clinical characteristics of hyperbilirubinemia caused by ABO hemolytic disease of the fetus and newborn (ABO-HDFN) and factors influencing the phototherapy duration. Methods: A total of 474 neonates with hyperbilirubinemia treated in the First Hospital of Lanzhou University from January 2019 to January 2023 were enrolled. Blood type identification and the standard serological tests (direct antiglobulin test, serum free antibody test, and antibody elution test) were performed for all neonates. Baseline clinical data were collected and analyzed. According to the results of the hemolysis tests, neonates were divided into hemolytic jaundice group and non-hemolytic jaundice group. Clinical indicators, including hemoglobin levels, length of hospital stay, and phototherapy duration, were compared between the two groups. A multiple linear regression model was used to explore clinical factors influencing the duration of phototherapy. Results: Among the 474 neonates with hyperbilirubinemia, 354 were diagnosed with ABO-HDFN (hemolytic group), while 120 were without ABO-HDFN (non-hemolytic group). The incidence of ABO-HDFN in neonates with blood type A (55.93%, 198/354) was significantly higher than those with blood type B (44.07%, 156/354) (P<0.05). Furthermore, neonates born to multiparous women had a significantly higher ABO-HDFN incidence (81.56%, 146/179) than first-born neonates (70.51%, 208/295) (P<0.05). Neonates in the hemolytic group had significantly lower hemoglobin levels (170.67±21.86 g/L vs 178.99±22.05 g/L, P<0.001), lower red blood cell counts (4.66±0.63×10 /L vs 4.89±0.59×10 /L, P<0.05), and lower hematocrit (50.05±6.56% vs 52.61±6.75%, P<0.05) compared to the non-hemolytic group. Additionally, the hemolytic group had significantly longer hospital stays (6 [5, 9] days vs 6 [4, 8] days), longer phototherapy duration (62 [38, 84.25] h vs 53 [34.25, 64.77] h), and higher frequency of jaundice episodes (9 [7, 13] times vs 8 [6, 12] times] compared to the non-hemolytic group (all P<0.05). Regression analysis indicated that a positive indirect Coombs test and multiparity were independent risk factors associated with prolonged phototherapy duration (P<0.05). Conclusion: ABO incompatibility is the leading cause of hemolytic disease in neonates, particularly in cases where the mother has blood type O and the neonate has blood type A. In such cases, close monitoring of bilirubin levels is strongly recommended. Multiparous pregnancies increase the risk of alloimmune hemolysis. Therefore, neonates born to multiparous women may require more frequent bilirubin monitoring and appropriate prenatal interventions when necessary. Additionally, changes in indicators such as hemoglobin level and red blood cell count should be closely monitored as early warning indicators for hemolytic anemia and bilirubin elevation.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.
Animals ; Haplorhini ; Axons ; Motor Neurons ; Interneurons ; Macaca ; Dependovirus/genetics* ; Genetic Vectors

The goal of achieving elimination of schistosomiasis across all endemic counties in China by 2030 was proposed in the Outline of the Healthy China 2030 Plan. On June 16, 2023, the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023—2030) was jointly issued by National Disease Control and Prevention Administration and other 10 ministries, which deployed the targets and key tasks of the national schistosomiasis elimination programme in China. This article describes the progress of the national schistosomiasis control programme, analyzes the opportunities to eliminate schistosomiasis, and proposes targeted recommendations to tackle the challenges of schistosomiasis elimination, so as to accelerate the process towards schistosomiasis elimination and facilitate the building of a healthy China.

AIM: To explore the mechanism of osthole on elderly spontaneously hypertensive rats. METHODS: 20-month-old spontaneously hypertensive rats (SHRs) and healthy Wistar-Kyoto (WKY) rats were purchased. SHRs were treated with osthole (i.g.) for 8 weeks. The systolic blood pressure and diastolic blood pressure of rats were monitored. Hematoxylin-eosin staining (H&E), periodic acid-schiff staining (PAS) and Masson staining were used to observe the pathological changes of rat kidney tissues. The activity of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) in rat kidney was detected by ELISA kit. PI3K/Akt/mTOR signaling pathway related proteins were detected by western blot. RESULTS: Osthole reduced the systolic and diastolic blood pressure of SHRs, improved the histopathological changes of SHRs kidney, reduced the activity of MDA in SHRs kidney, and increased the activity of SOD and GSH. Osthole reduced the levels of p-PI3K, p-Akt and p-mTOR. CONCLUSION: Osthole reduces the activity of PI3K/Akt/mTOR signaling pathway and exerts a protective effect on renal oxidative stress injury in aged spontaneously hypertensive rats.

Two methods including gas chromatography tandem mass spectrometry (GC-MS/MS) and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were established to detect common alkyl sulfonates and aryl sulfonates genotoxic impurities. Four alkyl sulfonates and methyl benzenesulfonate were determined by GC-MS/MS using butyl methanesulfonate as the internal standard, the chromatographic column was HP-5MS UI (30 mm × 0.25 mm, 0.25 µm), the carrier gas was helium, the flow rate was 1.0 mL·min^-1 in a constant flow mode, the sample inlet temperature was set to 250 ℃, the split ratio was 10∶1, and the initial temperature of the heating program was 80 ℃, maintained for 1 minute, and then increased to 240 ℃ at a heating rate of 30 ℃·min^-1 for 2 minutes. The mass spectrometry detector was an electron bombardment ion source (EI source), the data collection condition was multi reaction monitoring mode (MRM), and method validation using the raw material of clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of four alkyl sulfonates and methyl benzenesulfonate were good at 3-50 ng·mL^-1 and 9-150 ng·mL^-1, with a correlation coefficient of r > 0.999, The spiked recovery was 80%-120%. The detection limits were 1 and 3 ng·mL^-1; Ten aryl sulfonates determined by LC-MS/MS, the chromatographic column was CSH Fluoro phenyl (100 mm × 2.1 mm, 1.7 µm), the mobile phase was methanol (B)-5 mmol·L^-1 ammonium formate (D), with a flow rate of 0.2 mL·min^-1, and gradient elution was performed. The gradient program (T/% B) was set as 0/20, 25/90, 35/90, 42/20. The mass spectrometer detector was electro spray ionization with positive ionization mode (ESI⁺), the data collection was in dynamic multi reaction monitoring mode (dMRM), and the method was validated using the raw material of the clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of aryl sulfonates were good at 9-2 000 ng·mL^-1, 3-100 ng·mL^-1 and 0.9-30 ng·mL^-1, respectively. The correlation coefficient r > 0.999, the spiked recovery was 80%-120%. The detection limits were 30, 1 and 0.3 ng·mL^-1. Two detection methods did not detect potential sulfonate genotoxicity impurities in the above APIs. The established analytical methods are reliable and effective, which can provide reference for drug quality control and detection.