[Objective] : To explore the clinical characteristics and methods for syndrome differentiation prediction, as well as to construct a predictive model for Qi deficiency and blood stasis syndrome in patients with acute ischemic stroke (AIS). [Methods] : This study employed a retrospective case-control design to analyze patients with AIS who received inpatient treatment at the Neurology Department of The First Hospital of Hunan University of Chinese Medicine from January 1, 2013 to December 31, 2022. AIS patients meeting the diagnostic criteria for Qi deficiency and blood stasis syndrome were stratified into case group, while those without Qi deficiency and blood stasis syndrome were stratified into control group. The demographic characteristics (age and gender), clinical parameters [time from onset to admission, National Institutes of Health Stroke Scale (NIHSS) score, and blood pressure], past medical history, traditional Chinese medicine (TCM) diagnostic characteristics (tongue and pulse), neurological symptoms and signs, imaging findings [magnetic resonance imaging-diffusion weighted imaging (MRI-DWI)], and biochemical indicators of the two groups were collected and compared. The indicators with statistical difference (P < 0.05) in univariate analysis were included in multivariate logistic regression analysis to evaluate their predictive value for the diagnosis of Qi deficiency and blood stasis syndrome, and the predictive model was constructed by receiver operating characteristic (ROC) curve analysis. [Results] : The study included 1 035 AIS patients, with 404 cases in case group and 631 cases in control group. Compared with control group, patients in case group were significantly older, had extended onset-to-admission time, lower diastolic blood pressure, and lower NIHSS scores (P < 0.05). Case group showed lower incidence of hypertension history (P < 0.05). Regarding tongue and pulse characteristics, pale and dark tongue colors, white tongue coating, fine pulse, astringent pulse, and sinking pulse were more common in case group. Imaging examinations demonstrated higher proportions of centrum semiovale infarction, cerebral atrophy, and vertebral artery stenosis in case group (P < 0.05). Among biochemical indicators, case group showed higher proportions of elevated fasting blood glucose and glycated hemoglobin (HbA1c), while lower proportions of elevated white blood cell count, reduced hemoglobin, and reduced high-density lipoprotein cholesterol (HDL-C) (P < 0.05). Multivariate logistic regression analysis identified significant predictors for Qi deficiency and blood stasis syndrome including: fine pulse [odds ratio (OR) = 4.38], astringent pulse (OR = 3.67), superficial sensory abnormalities (OR = 1.86), centrum semiovale infarction (OR = 1.57), cerebral atrophy (OR = 1.55), vertebral artery stenosis (OR = 1.62), and elevated HbA1c (OR = 3.52). The ROC curve analysis of the comprehensive prediction model yielded an area under the curve (AUC) of 0.878 [95% confidence interval (CI) = 0.855 – 0.900]. [Conclusion] This study finds out that Qi deficiency and blood stasis syndrome represents one of the primary types of AIS. Fine pulse, astringent pulse, superficial sensory abnormalities, centrum semiovale infarction, cerebral atrophy, vertebral artery stenosis, elevated blood glucose, elevated HbA1c, pale and dark tongue colors, and white tongue coating are key objective diagnostic indicators for the syndrome differentiation of AIS with Qi deficiency and blood stasis syndrome. Based on these indicators, a syndrome differentiation prediction model has been developed, offering a more objective basis for clinical diagnosis, and help to rapidly identify this syndrome in clinical practice and reduce misdiagnosis and missed diagnosis.

Objective To observe the pharmacokinetic effect of amoxicillin and clavulanate potassium tablets on amoxicillin in Chinese healthy subjects under fasting and high fat and high calorie diet.Methods 71 healthy subjects were given a single dose of amoxicillin potassium clavulanate tablets(0.375 g)on fasting or high fat diet,and venous blood samples were collected at different time points.The concentrations of amoxicillin in human plasma were determined by HPLC-MS/MS method,and the pharmacokinetic parameters were calculated by non-atrioventricular model using PhoenixWinNonlin 8.0 software.Results The main pharmacokinetic parameters of amoxicillin potassium clavulanate tablets after fasting and high fat diet were(5 105.00±1 444.00),(4 593.00±1 327.00)ng·mL-1,and postprandial-fasting ratio 89.40％,90％confidence interval(79.55％-100.19％);t1/2 were(1.52±0.16),(1.39±0.22)h;AUC0-t were(12 969.00±1 841.00),(11 577.00±1 663.00)ng·mL-1·h,and postdietary/fasting ratio 89.20％,90％confidence interval(83.92％-94.28％);AUC0-∞ were(13 024.00±1 846.00),(11 532.00±1 545.00)ng·mL-1·h,and postprandial-fasting ratio 88.60％,90％confidence interval(83.48％-93.50％).The median Tmax(range)were 1.63(0.75,3.00)and 2.50(0.75,6.00)h,respectively,and the Tmax of postprandial medication was delayed(P＜0.01).Conclusion Compared with fasting condition,amoxicillin Tmax was significantly delayed after high fat diet,while Cmax,AUC0-t and AUC0-∞ were not significantly changed,indicating that food could delay the absorption of amoxicillin,but did not affect the degree of absorption.

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

ObjectiveThe absorption of substances into blood is mainly dependent on the mesenteric lymphatic pathway and the portal venous pathway. The substances transported via the portal venous pathway can be metabolized by the biotransformation in the liver. On the contrary, the substances in the mesenteric lymph fluid enter the blood circulation without biotransformation and can affect the body directly. Alcohol consumption is strongly linked to global health risk. Previous reports have analyzed the changes of metabolites in plasma, serum, urine, liver and feces after alcohol consumption. Whether alcohol consumption affects the metabolites in lymph fluid is still unknown. Therefore, it is particularly important to explore the changes of substances transported via the mesenteric lymphatic pathway and analyze their harmfulness after alcohol drinking. MethodsIn this study, male Wistar rats were divided into high, medium, and low-dosage alcohol groups (receiving Chinese Baijiu at 56%, 28% and 5.6% ABV, respectively) and water groups. The experiment was conducted by alcohol gavage lasting 10 d, 10 ml·kg^-1·d^-1. Then mesenteric lymph fluid was collected for non-targeted metabolomic analysis by using liquid chromatography-mass spectrometry (LC-MS) and bioinformatic analysis. Principal component analysis and hierarchical clustering were performed by using Biodeep. Meanwhile, KEGG enrichment analysis of the differential metabolites was also performed by Biodeep. MetaboAnalyst was used to analyze the relationship between the differential metabolites and diseases. ResultsThe metabolites in the mesenteric lymph fluid of the high-dosage alcohol group change the most. Based on the KEGG enrichment analysis, the pathways of differential metabolites between the high-dosage alcohol group and the control group are mainly enriched in the central carbon metabolism in cancer, bile secretion, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, etc. Interestingly, in the biosynthesis of unsaturated fatty acids category, the content of arachidonic acid is increased by 7.25 times, whereas the contents of palmitic acid, oleic acid, stearic acid, arachidic acid and erucic acid all decrease, indicating lipid substances in lymph fluid are absorbed selectively after alcohol intake. It’s worth noting that arachidonic acid is closely related to inflammatory response. Furthermore, the differential metabolites are mainly related with schizophrenia, Alzheimer’s disease and lung cancer. The differential metabolites between the medium-dosage alcohol and the control group were mainly enriched in phenylalanine metabolism, valine, leucine and isoleucine biosynthesis, linoleic acid metabolism and cholesterol metabolism. The differential metabolites are mainly related to schizophrenia, Alzheimer’s disease, lung cancer and Parkinson’s disease. As the dose of alcohol increases, the contents of some metabolites in lymph fluid increase, including cholesterol, L-leucine, fumaric acid and mannitol, and the number of metabolites related to schizophrenia also tends to increase, indicatingthat some metabolites absorbed by the intestine-lymphatic pathway are dose-dependent on alcohol intake. ConclusionAfter alcohol intake, the metabolites transported via the intestinal-lymphatic pathway are significantly changed, especially in the high-dosage group. Some metabolites absorbed via the intestinal-lymphatic pathway are dose-dependent on alcohol intake. Most importantly, alcohol intake may cause inflammatory response and the occurrence of neurological diseases, psychiatric diseases and cancer diseases. High-dosage drinking may aggravate or accelerate the occurrence of related diseases. These results provide new insights into the pathogenesis of alcohol-related diseases based on the intestinal-lymphatic pathway.

Physcion (PHY) is an anthraquinone compound derived from traditional Chinese medicine such as Rhei Radix et Rhizoma. The aim of this study is to investigate the improvement of PHY on non-alcoholic fatty liver disease (NAFLD) and its underlying mechanism. NAFLD was induced in mice by feeding with the methionine- and choline-deficient diet (MCD) for 6 weeks. This experiment was approved by the Experimental Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval number: PZSHUTCM190705019). The results displayed that PHY (5 and 20 mg·kg^-1) reversed liver damage, reduced hepatic lipid accumulation and decreased the elevated NAFLD activity score (NAS) in MCD-fed NAFLD mice. Results from Western blot and enzyme activity demonstrated that PHY could enhance the protein expression and enzyme activity of carnitine palmitoyltransferase 1A (CPT1A) in the liver and L-02 cells, but it did not affect Cpt1a mRNA expression. Immunofluorescence results indicated that PHY (10 and 25 μmol·L^-1) could reduce the mitochondrial injury induced by non-esterified fatty acids (NEFA) in L-02 cells. Results from seahorse assay showed that PHY could enhance mitochondrial basic respiration, maximal respiration, ATP synthesis and reserve respiration in L-02 cells treated with NEFA, but had no effect on mitochondrial proton leakage. In summary, PHY reversed mitochondrial damage and enhanced fatty acid β-oxidation, thereby reducing hepatic steatosis and improving NAFLD.

The incidence of intrahepatic cholangiocarcinoma (ICC) continues to rise, and there are no effective drugs to treat it. The immune microenvironment plays an important role in the development of ICC and is currently a research hotspot. Icaritin (ICA) is an innovative traditional Chinese medicine for the treatment of advanced hepatocellular carcinoma. It is considered to have potential immunoregulatory and anti-tumor effects, which is potentially consistent with the understanding of "Fuzheng" in the treatment of tumor in traditional Chinese medicine. However, whether ICA can be used to treat ICC has not been reported. Therefore, in this study, sgp19/kRas, an in situ ICC mouse model with intact immune system, was selected to evaluate the efficacy of ICA in the treatment of ICC in vivo for the first time, and the effects of ICA on the tumor immune microenvironment of ICC mice were analyzed by flow cytometry. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-138). In this study, sgp19/kRas ICC mouse model was treated with oral gavage of 100 mg·kg^-1 ICA. We found that ICA significantly inhibited tumor growth and tumor cell proliferation in the sgp19/kRas ICC mouse model after 3 weeks of treatment. Flow cytometry analysis indicated that ICA treatment markedly reduced the proportion of M2 macrophages and increased the number of CD3⁺CD4⁺ T cells. In vitro experiments demonstrated that ICA promoted macrophage polarization towards the M1 phenotype while inhibiting polarization towards the M2 phenotype. Furthermore, transcriptomic analysis suggested that ICA enhanced Toll-like receptor 9 (TLR9) expression, influencing macrophage nitric oxide metabolism synthesis pathways and receptor-related activities, thereby regulating macrophage polarization. In summary, this study demonstrates that ICA treatment significantly delays tumor progression in sgp19/kRas ICC mouse models. Mechanistically, ICA may achieve its anti-ICC effects by upregulating TLR9 receptor expression levels, promoting macrophage polarization towards the M1 phenotype, and altering the tumor immune microenvironment.

ObjectiveTo identify the rate， population characteristics， and vaccination history of repeat infections among previously infected people in the current epidemic based on the rate of repeat infection and population characteristics of different mutant strains at different times in Pudong New Area of Shanghai， and to provide reference for the prevention and control strategies of novel coronavirus repeat infections. MethodsA total of 9 250 investigated subjects were randomly selected from the new cases of asymptomatic infection and confirmed cases reported by Pudong New Area from March to May 2022. The investigation mainly focused on demographic characteristics， nucleic acid or antigen test results， and symptoms after infection. The repeat infection rates among different populations were compared， and logistic regression was used to analyze the impact of gender， age， and vaccination status on repeat infections. ResultsThe survey sample of 9 250 people had a response rate of 81.85%. There were 4 043 males （53.40%） and 3 528 females （46.60%）， with a median age of 34 years old （P₂₅， P₇₅： 7， 61）. The overall vaccine uptake rate was 59.44% （4 500/7 571）. In December of 2022， there were 563 cases of repeat infection， with an infection rate of 7.44%. The lowest rate of repeat infection was seen in the 3‒ year-old group （2.86%） and the highest rate in the 30‒ year-old group （12.42%）， with significant differences between different age groups. The repeated infection rate for those who had completed their vaccinations was significantly lower （6.57%） compared to those who had not （7.11%）. The age groups of 3‒ years， 70‒79 years， as well as individuals who completed full vaccination and received booster shots were protective factors against repeat infections. ConclusionThe overall rate of reinfection among the infected in Shanghai during the spring of 2022 was low in the outbreak of the Omicron variant， and the rate of reinfection in the 3‒ year-old group was significantly lower than in other age groups. Completing the full course of vaccination significantly reduces the risk of reinfection. Although the reinfection rate is high in individuals who received booster shots， it remains a mitigating factor compared to those who do not receive the vaccine. It is recommended to continue monitoring reinfections in key populations and further strengthen immunization efforts.

Objective An isotemporal substitution model was used to explore the associations between activities including 10 minutes per day of physical activity(PA),sedentary behavior(SB),and sleep(SLP),and depressive symptoms among vocational school students with and without depressive symptoms.Methods Questionnaire survey was conducted on grade one to grade three students attending vocational schools in Shanghai and Jiangsu Province from Dec 2021 to Jan 2022.Fourteen schools were selected using the convenience cluster sampling method.The selected students were categorized into depressive symptoms group and non-depressive symptoms group according to the Centre for Epidemiologic Studies Depression Scale(CES-D)scores.Results A total of 40 339 questionnaires were collected,of which 10 086 were able to clearly remember the time of physical activity in the past week,and 8 149 were valid after data cleaning.According to the valid questionnaires,5 496 students(67.44%)were in the non-depressive symptoms group and 2 653(32.56%)were in the depressive symptoms group.The mean age of the students were(16.70±1.19)years.In the non-depressive symptoms group,substituting moderate physical activity(MPA)for all the other behaviors was negatively associated with CES-D scores,while substituting vigorous physical activity(VPA)for MPA and SB was positively associated with CES-D scores.In the depressive symptoms group,substituting walking,SB,and SLP with MPA was negatively associated with CES-D scores,respectively.The associations of MPA substituted for walking,SB,and SLP with CES-D scores were much stronger in the depressive symptoms group than in the non-depressive symptoms group.Conclusion The detection rate of depressive symptoms was high among vocational students.Substituting MPA for walking,SB,and SLP were negatively associated with CES-D scores,with a stronger association observed in the depressive symptoms group than in the non-depressive symptoms group.

Objective To investigate the safety and efficacy of totally no tube three-port thoracoscopic surgery (TNTT) for thymic tumor via lateral thoracic approach. Methods The clinical data of patients with thymoma admitted to the Department of Thoracic Surgery of the General Hospital of Northern Theater Command from November 2021 to May 2022 were retrospectively analyzed. The patients were divided into a TNTT group and a single utility port video-assisted thoracic surgery (SVATS) group according to different surgical methods. The clinical data were compared between the two groups. Results A total of 111 patients were collected. There were 44 patients in the TNTT group, including 20 males and 24 females, with an average age of 60.11±8.64 years, and 67 patients in the SVATS group, including 30 males and 37 females, with an average age of 62.40±7.92 years. There was no significant difference between the two groups in the baseline data (P>0.05). The postoperative hospital stay and intraoperative blood loss were shorter or less in the TNTT group (P<0.05), and the visual analogue scale score 48 hours after the operation was smaller in the SVATS group (P<0.05). Conclusion TNTT has a good surgical safety, and can shorten postoperative hospital stay, reduce intraoperative blood loss, and has significant advantages in enhanced recovery after surgery, but SVATS can reduce postoperative pain in patients.

Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.