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.

ObjectiveTo investigate the role of paraventricular nucleus (PVN) corticotropin releasing hormone (CRH) neurons in chronic restraint stress (CRS)-induced anxiety-like behavior. And whether exercise relieves chronic restraint stress-induced anxiety through PVN CRH neurons. MethodsTwenty 8-week-old male C57BL/6J mice were randomly divided into control (Ctrl) group and chronic restraint stress (CRS) group. The open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behavior of the mice. Food intake was recorded after CRS. Immunofluorescence staining was used to label the expression of c-Fos expression in PVN and calculate the co-expression of c-Fos and CRH neurons. We used chemogenetic activation of PVN CRH neurons to observed the anxiety-like behavior. 8-week treadmill training (10-16 m/min, 60 min/d, 6 d/week) were used to explore the role of exercise in ameliorating CRS-induced anxiety behavior and how PVN CRH neurons involved in it. ResultsCompared with Ctrl group, CRS group exhibited significant anxiety-like behavior. In OFT, the mice in CRS groups spent less time in center area (P<0.001). In EPM, the time in open arm in CRS group were significantly decreased (P<0.001). Besides, food intake was also suppressed in CRS group compared with Ctrl group (P<0.05). Compared with Ctrl group, CRS significantly increase c-Fos expression in PVN and most of CRH neurons co-express c-Fos (P<0.001). Chemogenetic activation of PVN CRH neurons induced anxiety-like behavior (P<0.05) and inhibited feeding behavior (P<0.01). Exercise relieves chronic restraint stress-induced anxiety (P<0.001) and relieved the anorexia caused by chronic restraint stress (P<0.05). Aerobic exercise inhibited the CRS labeled c-Fos in PVN CRH neurons (P<0.001). Furthermore, ablation of PVN CRH neurons attenuated CRS induced anxiety-like behavior. ConclusionCRS activated PVN CRH neurons, induced anxiety-like behavior and reduced food intake. 8-week exercise attenuated CRS-induced anxiety-like behavior through inhibiting PVN CRH neuron. Ablation of CRH PVN neurons ameliorated CRS-induced anxiety-like behavior. These finding reveals a potential neural mechanism of exercise-relieving CRS-induced anxiety-like behavior. This provides a new idea and theoretical basis for the treatment of anxiety and related mental disorders.

Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

Objective:To develop an artificial intelligence (AI)-based platelet review strategy to identify abnormal platelet histograms with no significant difference between initial impedance platelet count (PLT-I) and PLT-F results.Methods:This study included 5 119 routine blood analysis in Nanfang Hospital of Southern Medical University and its Ganzhou branch from July 2023 and March 2024. Specimens exhibiting abnormal platelet histograms and an initial platelet count >40×10?/L underwent review using the fluorescent platelet count (PLT-F) channel. Consistency of the results was defined as a difference between impedance platelet count (PLT-I) and PLT-F less than ±20% of the PLT-F results. A deep learning model was developed using platelet and red blood cell histogram data from a training set of 3 807 specimens. The model′s diagnostic performance was evaluated on an independent external validation set ( n=805) using receiver operating characteristic (ROC) curve analysis. Changes in the number of reviewed samples and sample turnaround time were analyzed to assess its clinical utility. Results:The deep learning model based on platelet and red blood cell histograms achieved an area under the ROC curve (AUC) of 0.854 in the training set. At a cutoff value of 0.1, the sensitivity was 0.954 and specificity was 0.358. The model could reduce review by 16.80% (190/1 131). In the validation set, the AUC was 0.805, with a sensitivity of 0.955 and specificity of 0.307, corresponding to a reduction of 17.41% (47/270) in reviewed specimens.Conclusion:The platelet review prediction model developed based on deep learning technology can efficiently identify samples with consistent results before and after review, reducing unnecessary reviews and shortening specimen testing time, thereby improving the efficiency of platelet test.

[Purpose]To analyze the trends of incidence and mortality of malignant tumors in Linzhou City of Henan Province from 2010 to 2019.[Methods]The incidence and mortality data of malignant tumors of Linzhou cancer registration areas from 2010 to 2019 were collected and evaluated for data quality.The crude incidence/mortality rates and age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)were calculated by sex,age and can-cer type.Joinpoint software was used to calculate the average annual percentage change(AAPC)to analyze the trends from 2010 to 2019.[Results]From 2010 to 2019,the crude incidence of malig-nant tumors in Linzhou City showed an upward trend,with an AAPC of 2.09％(95％CI:0.58％～3.63％),while the ASIRC tended to be stable.The incidence of malignant tumors showed a signifi-cant upward trend in the 15～29 and 60～69 age groups,and a significant downward trend in the 70～79 age group.From 2010 to 2019,the ASIRC of esophageal cancer and stomach cancer in both men and women showed a significant downward trend,while that of lung cancer and prostate cancer increased in men,and the incidences of thyroid cancer,uterus cancer,cervical cancer,lung cancer and breast cancer increased significantly in women.From 2010 to 2019,the crude mortality of malignant tumors in Linzhou showed a significant upward trend,with an AAPC of 1.18％(95％CI:0.88％～1.48％),while ASMRC showed a significant downward trend,with an AAPC of-1.63％(95％CI:-1.86％～-1.40％).The mortality increased in the group aged 80 and above,while the other age groups remained in a downward or stable state.From 2010 to 2019,the ASMRC of stomach cancer and esophageal cancer in both men and women showed a down-ward trend,while those of prostate cancer,and malignant tumors of the lip,oral cavity and pha-ryngeal in men increased,and that of ovarian cancer in women increased significantly.[Conclu-sion]The disease burden of malignant tumors in Linzhou City is still heavy.The incidence of common cancer types such as thyroid cancer,prostate cancer and lung cancer shows a significant-ly increasing trends from 2010 to 2019.

AIM:This study aims to investigate the mechanism by which Qingfei-Jiedu-Huatan Formula(QJHF)regulates autophagy in alveolar macrophages through mTOR in the treatment of severe pneumonia(SP)in rats.METHODS:Sixty SPF-grade male rats were randomly assigned to six groups:control,model,QJHF,moxifloxacin(MOX),rapamycin(RAPA),and QJHF+RAPA,with ten rats in each group.An SP rat model was established using Klebsiella pneumoniae.After seven days of treatment,changes in IL-33 and IFN-γ levels in bronchoalveolar lavage fluid(BALF)were measured using ELISA.Histopathological alterations in lung tissue were assessed via HE staining,and the autophagy of alveolar macrophages was detected using immunofluorescence co-localization methods.The expression levels of mTOR,beclin-1,and LC3 mRNA in lung tissue were analyzed using qPCR,while Western blot was employed to assess the protein levels of p-mTOR/mTOR,beclin-1,and LC3-II/LC3-I.RESULTS:Compared to the control group,the model group exhibited a deteriorated condition,characterized by alveolar wall rupture and thickening,significant inflammatory cell infiltration in the alveolar cavity,and extensive lung tissue damage(P<0.01).Elevated levels of IL-33 and IFN-γ in BALF were also observed(P<0.01),along with increased colocalization of CD68 and LC3 in immunofluorescence analy-sis.The mTOR mRNA expression in lung tissue decreased(P<0.01),while LC3 and beclin-1 mRNA expressions in-creased(P<0.01).Additionally,the protein expression ratio of p-mTOR/mTOR decreased(P<0.01),whereas LC3-II/LC3-I and beclin-1 protein levels increased(P<0.01).In comparison to the model group,significant improvements were noted after treatment with QJHF and MOX(P<0.01),while RAPA treatment led to a worsening of these indicators(P<0.05).A slight improvement was observed with the QJHF combined with RAPA intervention,though this was not statisti-cally significant.No significant differences were found between the MOX and QJHF groups.However,the QJHF+RAPA group displayed notable improvements in various indicators compared to the RAPA group(P<0.05).CONCLUSION:The QJHF can mitigate the inflammatory response associated with severe pneumonia,potentially by activating mTOR phos-phorylation activity,which in turn inhibits excessive autophagy in alveolar macrophages.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

Objective:To understand the usage situation of e-cigarettes among residents aged 18-65 in Beijing, explore the relationship between e-cigarette use and cigarette smoking as well as smoking cessation behaviors, and provide scientific support for the developing and improving policies and measures related to e-cigarettes.Methods:Using 19 684 residents data from the Beijing Non-communication Chronic Disease and Risk Factors Surveillance in 2022, complex sampling weighted methods were used to estimate proportions, and complex sampling logistic regression analysis was applied to explore the relationship between e-cigarette use, cigarette smoking, and smoking cessation.Results:Among all study participants, the proportion of those who had ever used e-cigarettes was 3.36%, with the current e-cigarette use at 1.26%. The proportion of current e-cigarette users (1.87%) and the former e-cigarette users (3.47%) were higher ( χ2=64.70, P<0.001) among males compared to females (0.60% and 0.64% respectively). The top three reasons for using e-cigarettes were wanting to quit smoking, perceiving e-cigarettes as less harmful, and enjoying the flavors of e-cigarettes. 83.54% of e-cigarette users started with cigarettes. The results of the complex sampling multivariable logistic regression analysis showed that current smoking ( OR=61.35, 95% CI: 36.98-101.76) and former smoking ( OR=31.20, 95% CI: 15.52-62.71) were positively associated with e-cigarette, while current e-cigarette use ( OR=0.13, 95% CI: 0.04-0.39) was negatively associated with quitting cigarette smoking. Conclusions:The proportion of e-cigarette use in Beijing was relatively low. E-cigarette use was associated with cigarette use and was not conducive to smoking cessation. Therefore, stronger regulatory measures and health education campaigns regarding the risks of e-cigarettes should be implemented.

Sepsis is a systemic inflammatory response caused by severe infection or trauma, and is one of the common causes of acute lung injury(ALI) and acute respiratory distress syndrome(ARDS). Sepsis-acute lung injury(SALI) is a critical clinical condition with high morbidity and mortality. Its pathogenesis is complex and not yet fully understood, and there is currently a lack of targeted and effective treatment options. Pyroptosis, a novel form of programmed cell death, plays a key role in the pathological process of SALI by activating inflammasomes and releasing inflammatory factors, making it a potential therapeutic target. In recent years, the role of traditional Chinese medicine(TCM) in regulating signaling pathways related to pyroptosis through multi-components and multi-targets has attracted increasing attention. TCM may intervene in pyroptosis by inhibiting the activation of NLRP3 inflammasomes and regulating the expression of Caspase family proteins, thus alleviating inflammatory damage in lung tissues. This paper systematically reviews the molecular regulatory network of pyroptosis in SALI and explores the potential mechanisms and research progress on TCM intervention in cellular pyroptosis. The aim is to provide new ideas and theoretical support for basic research and clinical treatment strategies of TCM in SALI.
Pyroptosis/drug effects* ; Humans ; Sepsis/genetics* ; Acute Lung Injury/physiopathology* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Inflammasomes/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics*

OBJECTIVE: To investigate the accuracy and safety of pedicle screw placement using 3D-printed auxiliary guides in scoliosis correction surgery for adolescents. METHODS: A retrospective analysis was conducted on the clinical data of 51 patients who underwent posterior scoliosis correction surgery from January 2020 to March 2023. Among them, there were 35 cases of adolescent idiopathic scoliosis and 16 cases of congenital scoliosis. The patients were divided into two groups based on the auxiliary tool used:the 3D-printed auxiliary guide screw placement group (3D printing group) and the free-hand screw placement group (free-hand group, without auxiliary tools). The 3D printing group included 32 patients (12 males and 20 females) with an average age of (12.59±2.60) years;the free-hand group included 19 patients (7 males and 12 females) with an average age of (14.58±3.53) years. The two groups were compared in terms of screw placement accuracy and safety, spinal correction rate, intraoperative blood loss, number of intraoperative fluoroscopies, operation time, hospital stay, and preoperative and last follow-up scores of the Scoliosis Research Society-22 (SRS-22) questionnaire. RESULTS: A total of 707 pedicle screws were placed in the two groups, with 441 screws in the 3D printing group and 266 screws in the free-hand group. All patients in both groups successfully completed the surgery. There was a statistically significant difference in operation time between the two groups (P<0.05). The screw placement accuracy rate of the 3D printing group was 95.46% (421/441), among which the Grade A placement rate was 89.34% (394/441);the screw placement accuracy rate of the free-hand group was 86.47% (230/266), with a Grade A placement rate of 73.31% (195/266). There were statistically significant differences in the accuracy of Grade A, B, and C screw placements between the two groups (P<0.05), while no statistically significant differences were observed in intraoperative blood loss, number of fluoroscopies, correction rate, or hospital stay (P>0.05). In the SRS-22 questionnaire scores, the scores of functional status and activity ability, self-image, mental status, and pain of patients in each group at the last follow-up were significantly improved compared with those before surgery (P<0.05), but there were no statistically significant differences in all scores between the two groups (P>0.05). CONCLUSION In scoliosis correction surgery, compared with traditional free-hand screw placement, the use of 3D-printed auxiliary guides for screw placement significantly improves the accuracy and safety of screw placement and shortens the operation time.
Humans ; Male ; Scoliosis/surgery* ; Female ; Adolescent ; Printing, Three-Dimensional ; Retrospective Studies ; Pedicle Screws ; Child