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 effect of LAG-3 deficiency (LAG3^-/-) on natural killer (NK) cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis. Methods C57BL/6 mice, each weighing (20 ± 2) g, were divided into the LAG3^-/- and wild type (WT) groups, and each mouse in both groups was inoculated with 3 000 E. multilocularis protoscoleces via the hepatic portal vein. Mouse liver and spleen specimens were collected 12 weeks post-infection, sectioned and stained with sirius red, and the hepatic lesions and fibrosis were observed. Mouse hepatic and splenic lymphocytes were isolated, and flow cytometry was performed to detect the proportions of hepatic and splenic NK cells, the expression of CD44, CD25 and CD69 molecules on NK cell surface, and the secretion of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin (IL)-4, IL-10 and IL-17A. Results Sirius red staining showed widening of inflammatory cell bands and hyperplasia of fibrotic connective tissues around mouse hepatic lesions, as well as increased deposition of collagen fibers in the LAG3-/-group relative to the WT group. Flow cytometry revealed lower proportions of mouse hepatic (6.29% ± 1.06% vs. 11.91% ± 1.85%, P < 0.000 1) and splenic NK cells (4.44% ± 1.22% vs. 5.85% ± 1.10%, P > 0.05) in the LAG3^-/- group than in the WT group, and the mean fluorescence intensity of CD44 was higher on the surface of mouse hepatic NK cells in the LAG3^-/- group than in the WT group (t = −3.234, P < 0.01), while no significant differences were found in the mean fluorescence intensity of CD25 or CD69 on the surface of mouse hepaticNK cells between the LAG3^-/- and WT groups (both P values > 0.05). There were significant differences between the LAG3^-/- and WT groups in terms of the percentages of IFN-γ (t = −0.723, P > 0.05), TNF-α (t = −0.659, P > 0.05), IL-4 (t = −0.263, P > 0.05), IL-10 (t = −0.455, P > 0.05) or IL-17A secreted by mouse hepatic NK cells (t = 0.091, P > 0.05), and the percentage of IFN-γ secreted by mouse splenic NK cells was higher in the LAG3^-/- group than in the WT group (58.40% ± 1.64% vs. 50.40% ± 4.13%; t = −4.042, P < 0.01); however, there were no significant differences between the two groups in terms of the proportions of TNF-α (t = −1.902, P > 0.05), IL-4 (t = −1.333, P > 0.05), IL-10 (t = −1.356, P > 0.05) or IL-17A secreted by mouse splenic NK cells (t = 0.529, P > 0.05). Conclusions During the course of E. multilocularis infections, LAG3^-/- promotes high-level secretion of IFN-γ by splenic NK cells, which may participate in the reversal the immune function of NK cells, resulting in aggravation of hepatic fibrosis.

Objective To observe the clinical efficacy and safety of Sangxing Zhike Prescription in treating postinfectious cough(PIC)of warm dryness invading the lung type.Methods A total of 66 PIC patients with warm dryness invading the lung type who were admitted to the First Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2020 to June 2022 were randomly divided into a treatment group and a control group,with 33 patients in each group.The treatment group was given Sangxing Zhike Prescription combined with Compound Methoxyphenamine Capsules,and the control group was given Compound Methoxyphenamine Capsules combined with Chinese medicine placebo.The course of treatment covered 7 days.The changes in the Visual Analogue Scale(VAS)scores of the severity of cough,the scores of cough symptom,and the scores of traditional Chinese medicine(TCM)syndrome in the two groups were observed before and after the treatment.After treatment,the clinical efficacy and safety in the two groups were evaluated.Results(1)During the trial,one case fell off from the treatment group and 4 cases fell off from the control group,and eventually 61 cases completed the observation,of which 32 cases were in the treatment group and 29 cases were in the control group.(2)After 7 days of treatment,the total effective rate of the treatment group was 84.38%(27/32)and that of the control group was 58.62%(17/29),and the intergroup comparison(tested by chi-square test)showed that the therapeutic efficacy of the treatment group was significantly superior to that of the control group(P＜0.05).(3)After treatment,the VAS scores of the severity of cough,and the scores of daytime cough,nighttime cough of the Cough Symptom Score Scale as well as the overall cough scores in the two groups were significantly lower than those before treatment(P＜0.05 or P＜0.01),and the reduction of the VAS scores and the overall cough symptom scores in the treatment group was significantly superior to that in the control group(P＜0.05).(4)After treatment,obvious improvement was presented in the scores of TCM symptoms of cough,throat itching,dry throat,foreign body sensation in the throat,sore throat and pharyngeal signs as well as total TCM syndrome scores in the treatment group when compared with the pre-treatment period(P＜0.01),whereas in the control group,only the scores of cough,throat itching,dry throat,and sore throat and the total TCM syndrome scores were improved compared with the pre-treatment period(P＜0.05 or P＜0.01).The post-treatment intergroup comparison showed that the treatment group was significantly superior to the control group in improving the scores of throat itching,foreign body sensation in the throat,and pharyngeal signs as well as total TCM syndrome scores(P＜0.05 or P＜0.01).(5)During the treatment process,no significant adverse reactions occurred in both groups,or no abnormal changes were shown in the safety indexes such as blood routine test,liver and kidney functions of the patients.Conclusion Sangxing Zhike Prescription combined with Compound Methoxyphenamine Capsules exerts certain effect in treating patients with PIC of warm dryness invading the lung type,and its efficacy is significantly superior to that of Compound Methoxyphenamine Capsules treatment alone with relatively high safety profile.

Free fatty acids, as important energy metabolism substrates for the heart, play an important role in various cardiovascular diseases; ω-3 PUFA, as an important branch of free fatty acids, has been confirmed by more and more researches to be closely related to cardiovascular diseases. Heart failure, as a common cardiovascular problem, seriously affects people's quality of life. Studies have shown that ω-3 PUFA plays a significant role in the development of heart failure. In this paper, we try to review the metabolism, pathogenesis and therapeutic significance of ω-3 PUFA in heart failure.

Four pyrazines were isolated from the n-butanol fraction of Hypecoum erectum L. by using various chromatographic methods, including MCI gel, ODS, silica gel and semi-preparative HPLC. The structures of the isolated compounds were identified as hyperectpyrazin A (1), 1′S-(6-methylpyrazin-2-yl)-ethane-1′,2′-diol (2), 2-hydroxymethyl-6-methylpyrazin (3) and pyrazine-2-carboxylic acid (4) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, MS, etc.). The absolute configuration of compound 2 was determined by using the Mo₂(OAc)₄ induced CD analysis for the first time. Compound 1 was a new compound, compounds 2-4 were isolated from H. erectum for the first time. Compounds 1-4 were evaluated for their inhibition against acetylcholinesterase and nitric oxide generation induced by lipopolysaccharide-RAW264.7 macrophage cells. At a concentration of 50 μmol·L^-1, compounds 2 and 4 displayed inhibitory effects on acetylcholinesterase with the inhibition rates of 44.40% and 43.99%, respectively.

By sorting out the differences and connections between family doctor teams and specialized disease teams, role competency and mutual collaboration, and introducing the learning health system (LHS) mechanism, a comprehensive operating system for community general practice learning organizations based on LHS was constructed, focusing on five single disease types. The system includes a combination of general and specialized medicine that links three levels of medical institutions, thereby opening up the business cooperation process between professionals in different institutions, and establishing a sustainable collaboration mechanism. This allows medical institutions at three levels to continuously tap the potential of their disciplines, achieve their own ability growth and feel higher work value, and also bring better health solutions to residents, guided by the common goal of "health centered, patient centered".

Objective To explore the role of MAPK4 in cervical squamous cell carcinoma(CSCC)for the identification of candidate prognostic prediction biomarkers and molecular therapeutic targets.Methods The TCGA cohort was subjected to Kaplan-Meier survival analysis.Immunohistochemistry experiments were conducted on clinical samples to explore the correlation between MAPK4 and patient prognosis.A nomogram was constructed based on MAPK4 mRNA levels.Western blot,CCK-8,colony formation,and Transwell cell function experiments were performed to clarify the abnormal expression and role of MAPK4 in CSCC.DIA proteome sequencing was used to identify effector molecules regulated by MAPK4.Combined with the above cell function experiments,the knockdown of MAPK4 and the overexpression of effector molecules revealed that MAPK4 regulated effector molecules to mediate tumor progression.Results CSCC patients with elevated MAPK4 mRNA levels and high protein expression have a worse prognosis.The constructed nomogram based on MAPK4 can accurately predict the 1-,3-,and 5-year survival rates of patients.Compared with that in normal cervical tissues,MAPK4 protein expre-ssion was up-regulated in tumors.MAP-K4 knockdown substantially inhibited the proliferation,colony formation,mig-ration,and invasion of CSCC ME180 and SiHa cells.SLC3A2 is a downs-tream effector molecule of MAPK4.Overexpression SLC3A2 can weaken the inhibitory effect of MAPK4 knockdown on cell proliferation,colony formation,migration,and invasion.Conclusion MAPK4 is a candidate prognostic biomarker for patients with CSCC.MAPK4 positively regulates SLC3A2 protein expression and accelerates tumor progression,making it a potential molecular therapeutic target for patients with CSCC.

Objective:To investigate the sensitivity of tumor organoids derived from samples of colorectal cancer to lobaplatin and oxaliplatin hyperthermic perfusion in vitro and to assist clinical development of hyperthermic intraperitoneal chemotherapy. Method:Tumor samples and relevant clinical data were collected from patients with pathologically confirmed colorectal cancer in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2021 to December 2022. Organoids were cultured and tumor tissue were passaged. In vitro hyperthermic perfusion experiments were performed on organoids with good viability. Firstly, 10 organoids were treated with oxaliplatin and lobaplatin at the following six concentrations: 1 000, 250, 62.5, 15.6, 3.9, and 0.98 μmol/L. The organoids were exposed to oxaliplatin at 42℃ for 30 minutes and to lobaplatin at 42℃ for 60 minutes. Dose-response curves of responses to in vitro hyperthermic perfusion with these two drugs were constructed and evaluated. Clinical doses of oxaliplatin and lobaplatin were further tested on 30 organoids. This testing revealed oxaliplatin was effective at 579 μmol/L at a hyperthermic perfusion temperature of 42℃ for 30 min and lobaplatin was effective at 240 μmol/L at a hyperthermic perfusion temperature of 42℃ for 60 minutes. Result:Thirty-two tumor organoids were cultured from samples of colorectal cancer. The median concentration required for oxaliplatin to eliminate 50% of tumor cells (IC50) was 577.45 μmol/L (IQR: 1846.09 μmol/L). The median IC50 for lobaplatin was 85.04 μmol/L (IQR: 305.01 μmol/L).The difference between the two groups was not statistically significant ( Z=1.784, P=0.084). In seven of 10 organoids, lobaplatin showed a greater IC50 after in vitro hyperthermic perfusion than did oxaliplatin. Testing of 30 organoids with clinical doses of oxaliplatin and lobaplatin revealed that oxaliplatin achieved an average inhibition rate of 39.6% (95%CI: 32.1%?47.0%), whereas the average rate of inhibition for lobaplatin was 89.7% (95%CI: 87.0%?92.3%): this difference is statistically significant ( t=?15.282, P<0.001). Conclusion:The rate of inhibition achieved by hyperthermic perfusion of lobaplatin in vitro is better than that achieved by hyperthermic perfusion with oxaliplatin. Lobaplatin is more effective than oxaliplatin when administered by hyperthermic intraperitoneal perfusion and therefore has the potential to replace oxaliplatin in this setting.

ObjectiveTo observe the effect of Xiaoke drink on insulin resistance in ob/ob mice and explore the mechanism. MethodEighteen ob/ob mice were randomly assigned into model， Xiaoke drink （17.68 g·kg^-1）， and atorvastatin （0.01 g·kg^-1） groups （n=6）， and six C57BL/6 mice were selected as the normal group. Mice in the normal and model groups were administrated with the same amount of distilled water. Fasting body weight， weekly food intake， and weekly water intake were measured at a fixed time. Fasting plasma glucose （FPG） and 2-hour post-load plasma glucose （2 hPG） were measured before and after 8-week intervention. After intervention， total cholesterol （TC）， triglyceride （TG）， fasting insulin （FINS）， Homeostasis Model Assessment-Insulin Resistance （HOMA-IR）， blood routine， and alkaline phosphatase （ALP） were measured. Western blot was employed to determine the expression levels of ubiquitin-specific protease 20 （USP20） and 3-hydroxy-3-methylglutaryl coenzyme A reductase （HMGCR） in the liver. The pancreas was stained with hematoxylin-eosin for observation. ResultCompared with the model group， the Xiaoke drink group showed decreased body weight of ob/ob mice （P<0.05， P<0.01）， declined growth trend of body weight （P<0.05， P<0.01）， reduced weekly average water intake， lowered levels of FPG， 2 hPG， TC， and HOMA-IR （P<0.05， P<0.01）， and down-regulated expression level of USP20 in the liver （P<0.05）. HMGCR content was positively correlated with USP20 expression. In addition， Xiaoke drink promoted the recovery of islet tissue morphology and function in ob/ob mice. ConclusionXiaoke drink can ameliorate insulin resistance in ob/ob mice by inhibiting USP20/HMGCR expression， reversing cholesterol biosynthesis process， and reducing cholesterol level.

Background::Somatic copy number variations (SCNVs) in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys. Methods::This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detect CDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models. Results::A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69] vs. 35.0% [28/80] vs. 51.8% [29/56], P <0.001). In the univariable competing risk analysis, the cumulative regression rate was statistically significantly lower ( P = 0.008), while the cumulative progression rate was higher ( P = 0.017) in ESCdys patients with CDKN2A deletion than in those without CDKN2A deletion. CDKN2A deletion was also an independent predictor of prognosis in ESCdys ( P = 0.004) in the multivariable analysis. Conclusion::The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.