Objective: To confirm the therapeutic efficacy of the ginkgo biloba extract EGb761 on ischemic stroke and elucidate its underlying mechanism. Methods: Male Sprague-Dawley rats were divided into three groups: sham, model, and EGb761 (ginkgo biloba extract). Ischemic stroke was then simulated in rats via embolic middle cerebral artery occlusion surgery, with the extract administered half an hour before surgery. Neurological deficit scores, infarct volume, cerebral edema rate, and inflammatory factors served as the primary metrics for drug efficacy. Serum metabolites were analyzed using 1H-nuclear magnetic resonance to elucidate the operative mechanism. Results: Treatment with the ginkgo biloba extract EGb761 significantly ameliorated the neurological deficit scores (P = .0343), diminished the cerebral infarct volume (P = .0001) and cerebral edema rate (P = .0030), and alleviated neuroinflammation (all P < .05) in middle cerebral artery occlusion rats. In addition, it significantly altered the contents of various metabolites, such as 2-hydroxybutyrate, isoleucine, isopropanol, isobutyric acid, N6-acetyllysine, glutamate, glutamine, methionine, and N,N-dimethylglycine (all P < .05). Enrichment analysis of the differential metabolites indicated that EGb761 may be involved in the regulation of amino acid metabolism, betaine metabolism, glucose-alanine cycle, Warburg effect, and urea cycle. Conclusion The ginkgo biloba extract EGb761 demonstrates anti-ischemic stroke effect on ischemic stroke model rats by regulating amino acids and amino acid derivatives, such as isoleucine, N6-acetyllysine, glutamate, methionine, and N,N-dimethylglycine.

OBJECTIVE: Based on the PTEN-induced hypothetical kinase 1 (PINK1)/Parkin pathway, the effect of acupuncture pretreatment on the expression of mitochondrial autophagy-related proteins in gastrocnemius muscle tissue of rats with exercise-induced muscle damage (EIMD) was observed, and the underlying mechanism of acupuncture pretreatment for the prevention and treatment of EIMD was explored. METHODS: Of 88 SD male rats, aged 6 weeks, 8 rats were randomly selected as a blank group, and the remaining 80 rats were randomized into a model group and an acupuncture pretreatment group, with 40 rats in each group. Either the model group or the acupuncture pretreatment group was subdivided randomly into 5 subgroups with 8 rats in each one according to the time points of sample collection, 0 h, 12 h, 24 h, 48 h and 72 h after modeling. An intermittent downhill running centrifugal exercise was carried out on an animal experimental treadmill to establish the EIMD model in the model group and the acupuncture pretreatment group. The rats in the acupuncture pretreatment group received acupuncture at "Guanyuan" (CV6) and bilateral "Zusanli" (ST36), once a day for 20 min each time, for 7 consecutive days before EIMD model preparation. Transmission electron microscopy was used to observe the ultrastructure of gastrocnemius muscle tissue in each group. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were detected by ELISA. Western blot was used to detect the protein expression of PINK1, Parkin, sequestosome 1 (p62) and microtubule-associated protein light chain 3B (LC3B) in rat gastrocnemius muscle tissue. Real-time PCR was adopted to detect the mRNA expression of PINK1, Parkin, p62 and LC3B in rat gastrocnemius muscle tissue. RESULTS: Compared with the blank group, the mitochondria of gastrocnemius muscles showed obvious swelling in the 0 h, 12 h, 24 h, and 48 h model subgroups , autophagosomes were formed in the 12 h and 24 h model subgroups, and the mitochondrial morphology returned to normal gradually in the 72 h model subgroup. The serum MDA contents of rats in 5 model subgroups increased (P<0.01, P<0.05). The contents of SOD and CAT in the subgroups of 0 h, 12 h, 24 h and 48 h decreased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1, Parkin and LC3B in gastrocnemius muscle tissue of rats in 0 h, 12 h and 24 h subgroups were elevated (P<0.01); and the protein and mRNA expression levels of p62 in the 0 h, 12 h, 24 h and 48 h subgroups were reduced (P<0.01, P<0.05). Compared with the model subgroup at the same time point, the myofibril damage and the degree of mitochondrial swelling were mild in each acupuncture pretreatment subgroup, and the numbers of autophagosomes were fewer. The contents of MDA in the acupuncture pretreatment subgroups decreased at 0 h, 12 h, 24 h, and 48 h (P<0.05, P<0.01). The contents of SOD and CAT in the 12 h acupuncture pretreatment subgroup increased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1 and Parkin in the 0 h, 12 h, and 24 h acupuncture pretreatment subgroups decreased (P<0.01, P<0.05). The protein and mRNA expression levels of LC3B in the 12 h acupuncture pretreatment subgroup decreased (P<0.01), and that of p62 in the 0 h and 24 h acupuncture pretreatment subgroups increased (P<0.01, P<0.05). CONCLUSION The intermittent downhill running centrifugal exercise induces the excessive mitochondrial autophagy. Acupuncture pretreatment may attenuate EIMD, and the underlying mechanism is related to the regulation of PINK1/Parkin signaling pathway expression, reducing oxidative stress damage in skeletal muscle cells, and inhibiting mitochondrial autophagy overactivation.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Male ; Rats ; Acupuncture Therapy ; Protein Kinases/genetics* ; Rats, Sprague-Dawley ; Mitophagy ; Humans ; Muscle, Skeletal/metabolism* ; Physical Conditioning, Animal ; Muscular Diseases/physiopathology* ; Signal Transduction

Paclitaxel (PTX), a valuable natural product derived from Taxus species, exhibits remarkable anti-cancer properties. It penetrates nanopores in microtubule walls, interacting with tubulin on the lumen surface and disrupting microtubule dynamics, thereby inducing cytotoxic effects in cancer cells. PTX and its derivatives have gained approval for treating various diseases due to their low toxicity, high efficiency, and broad-spectrum application. The widespread success and expanding applications of PTX have led to increased demand, raising concerns about accessibility. Consequently, researchers globally have focused on developing alternative production methods and applying nanocarriers in PTX delivery systems to enhance bioavailability. This review examines the challenges and advancements in PTX sourcing, production, physicochemical properties, anti-cancer mechanisms, clinical applications, trials, and chemo-immunotherapy. It aims to provide a comprehensive reference for the rational development and effective utilization of PTX.
Humans ; Paclitaxel/pharmacology* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Neoplasms/drug therapy* ; Animals ; Taxus/chemistry*

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

ObjectiveThis nested case-control study, based on the Shanghai Birth Cohort (SBC), aimed to explore the impact of early pregnancy exposure to organophosphorus flame retardants (OPFRs) on attention deficit hyperactive disorder (ADHD)-like symptoms in 4-year-old children, so as to provide epidemiological evidence regarding the health effects of emerging contaminant OPFRs in children. MethodsStrengths and Difficulties Questionnaire (SDQ) was used to assess ADHD like symptoms in 4-year-old children. Children with an SDQ hyperactivity subscale score ≥6 points were defined as cases, while those with a score <5 points were considered as controls. The case and control groups were matched at 1∶1 based on the child’s age (±6 months), sex, and parental or primary caregiver’s education level. A total of 105 cases and 112 controls were included eventually. Concentrations of eight OPFRs metabolites in early pregnancy urine samples were measured using ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), including di-phenyl phosphate (DPHP), di-m-cresylphosphate (DmCP), di-o-cresylphosphate (DoCP), di-p-cresylphosphate (DpCP), di-n-butyl phosphate (DnBP), di-iso-butyl phosphate (DiBP), bis(2-butoxyethyl) phosphate (BBOEP), and bis(2-ethylhexyl) phosphate (BEHP). Basic demographic information of mothers and children were collected through questionnaire surveys and medical records extraction. Binary logistic regression models were used to analyze the effect of individual OPFRs exposure during early pregnancy on ADHD-like symptoms, while a quantile g-computation (Qgcomp) regression model was employed to assess the effects of mixed OPFRs exposure (with detection rates >75%) on ADHD-like symptoms in 4-year-old children. ResultsIn this study, the detection rates of DPHP, DoCP, and the DmCP&DpCP in the urine of early pregnancy women were higher than 75%, with DPHP having the highest detection rate (86.18%). The median concentrations of DPHP were highest in both the case and control groups (0.396 μg·L^-1 and 0.305 μg·L^-1, respectively). Binary logistic regression analyses revealed that exposure to DPHP during early pregnancy increased the risk of ADHD-like symptoms in 4-year-old children (OR=1.262, 95%CI: 1.017‒1.565). The mixed exposure model analyses showed that early pregnancy co-exposure to OPFRs increased the risk of ADHD-like symptoms (OR=1.508, 95%CI: 1.012‒2.258), with DPHP being the primary contributor to the association. ConclusionEarly pregnancy exposure to DPHP is positively associated with an increased risk of ADHD-like symptoms in 4-year-old children. Additionally, DPHP contributed the most to the adverse effects of mixed OPFRs exposure on ADHD-like symptoms. However, these findings require further validation through other large-scale prospective cohort studies.

Objective To determine the median effective concentration(EC50)of ropivacaine at the volume of 0.5 mL/kg for ultrasound-guided interscalene brachial plexus block in children aged 6 to 10 years.Methods A prospective dose-finding trial was conducted based a sequential Dixon up-and-down allocation.We recruited children aged 6 to 10 years who were scheduled for unilateral surgery on upper extremity regions in our hospital from April to December 2022.All of them were subjected to general intravenous anaesthesia combined with ultrasound-guided interscalene brachial plexus block.The ropivacaine volume for each patient was 0.5 mL/kg.The concentration of 0.2%for the first patient,subsequent concentrations were adjusted based on the block effect of previous patient,increase or decrease by 0.02%.The trial was stopped when there were 7 turning points.Isotonic regression and Bootstrap were used to calculate the values of EC50 and 95%effective concentration(EC95),along with their 95%confidence intervals(CI).General data,incidence of adverse events,and score of postoperative pain were recorded.Results A total of 26 children aged 6 to 10 years were included.The EC50 of ultrasound-guided interscalene brachial plexus block was determined to be 0.091%(95%CI:0.077%～0.105%),and the EC95 was estimated to be 0.117%(95%CI:0.110%～0.118%).Successful blockade was achieved in 16 cases(61.5%),while 10 cases(38.5%)failed.No statistical differences existed between successful and failed cases regarding sex,age,body weight,surgical site,surgical laterality,operative time,or anesthesia duration.None of the patients experienced adverse events such as pneumothorax,vascular injury,or Horner's syndrome,and the score of postoperative pain were all<6 by modified Children's Hospital of Eastern Ontario Pain Scale.Conclusion In children aged 6 to 10 years,the EC50 of ropivacaine is 0.091%at a volume of 0.5 mL/kg for ultrasound-guided interscalene brachial plexus block,and this low dose of regional anesthetic can reduce the risks such as systemic toxicity and direct neurotoxicity.

Objective This research was performed to identify rodent-borne pathogens in Hekou Port,Yunnan Province.Methods Rodents were captured using cages and dissected to collect their lungs,liver,spleen,and other viscera.Eight pathogens,including Yersinia pestis,Leptospira,Bartonella,and Anaplasmataceae,were identified using polymerase chain reaction amplification.Amplified pathogen sequences from positive samples were sequenced,and BLAST homology searches were conducted using GenBank to confirm pathogen identities.A phylogenetic tree of the identified pathogens was constructed using the neighbor joining method.Results The total of 31 rodents,identified as Rattus tanezumi,R.norvegicus,and Mus musculus,were captured.Among these,R.tanezumi was the dominant species,accounting for 64.52％of the total.Two pathogens,Leptospira interrogans and Neoehrlichia mikurensis,were detected,with positivity rates of 9.68％and 29.03％,respectively.No other pathogens were detected.The overall positivity rate for rodent-borne pathogens was 35.48％.Conclusions The single 16S rRNA gene fragment is insufficient for the molecular identification of all Neoehrlichia species.Accurate species identification should be based on a combined analysis of multiple genes.The prevalence of rodent-borne pathogens in Hekou Port indicates the necessity for enhanced surveillance of rodent-borne diseases and implementation of additional prevention and control measures in border ports.

Objective To explore the impact of enteral nutrition formula containing slow-release starch on blood glucose variability and prognosis in patients with severe acute pancreatitis(SAP).Methods A total of 204 SAP patients were enrolled and randomly divided into control group and ob-servation group using a random number table method,with 102 patients in each group.The control group received early enteral nutrition support with a standard enteral nutrition formula,while the ob-servation group received early enteral nutrition support with an enteral nutrition formula containing slow-release starch.Blood glucose variability indicators[largest amplitude of glycemic excursions(LAGE),standard deviation of blood glucose(SDBG),blood glucose coefficient of variation(BGCV),mean blood glucose(MBG),mean amplitude of glycemic excursions(MAGE),and time in range(TIR)]were compared between the two groups after treatment,along with clinical indicators during hospitalization,inflammatory markers[procalcitonin,C-reactive protein,interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)],and nutritional indicators(albumin,prealbumin)levels.Kaplan-Meier analysis was conducted to assess the prognosis of the two groups,and multivariate Cox regression analysis was performed to identify factors influencing prognosis.Results After treat-ment,the observation group exhibited lower levels of MBG,LAGE,SDBG,BGCV,MAGE,and a higher TIR compared with the control group(P＜0.05).During hospitalization,the observation group had a shorter duration of enteral nutritiontherapy,lower insulin usage,and lower incidence rates of multiple organ failure and infectious pancreatic necrosis compared with the control group(P＜0.05).After treatment,the observation group had lower levels of procalcitonin,C-reactive protein,IL-6,and TNF-α compared with the control group(P＜0.05);however,there were no statistically significant differences in albumin and prealbumin levels between the two groups(P＞0.05).Kaplan-Meier analysis showed that the cumulative mortality rate in the observation group was 12.75％,which was lower than the 17.65％in the control group(Log-rank x2=4.361,P=0.037).Multivariate Cox regression analysis revealed that TIR after treatment(HR=0.920;95％CI,0.869 to 0.974)was an independent protective factor for prognosis in SAPpatients(P＜0.05),while infectious pancreatic necrosis(HR=4.269;95％CI,1.922 to 9.482)was an inde-pendent risk factor for prognosis in SAP patients(P＜0.05).Conclusion Enteral nutrition formu-la containing slow-release starch helps stabilize blood glucose variability,control inflammatory mark-er levels,improve nutritional status,and prognosis in SAP patients.Both TIR and infectious pancre-atic necrosis are closely related to the prognosis of SAP patients.

Colorectal cancer(CRC) is a common malignant tumor worldwide. Due to the treatment intolerance and side effects, CRC rank the top among various cancers regarding the incidence and mortality rates. Therefore, exploring new therapies is of great significance for the treatment of CRC. Aerobic glycolysis(AEG) plays an important role in the microenvironment formation, proliferation, metastasis, and recurrence of CRC and other tumor cells. It has been confirmed that intervening in the AEG pathway can effectively curb CRC. The active ingredients and compound prescriptions of traditional Chinese medicine(TCM) can effectively inhibit the proliferation, metastasis, and drug resistance and regulate the apoptosis of tumor cells by modulating AEG-associated transport proteins [eg, glucose transporters(GLUT)], key enzymes [hexokinase(HK) and phosphofructokinase(PFK)], key genes [hypoxia-inducible factor 1(HIF-1) and oncogene(c-Myc)], and signaling pathways(MET/PI3K/Akt/mTOR). Accordingly, they can treat CRC, reduce the recurrence, and improve the prognosis of CRC. Although AEG plays a key role in the development and progression of CRC, the specific mechanisms are not yet fully understood. Therefore, this article delves into the intrinsic connection of the targets and mechanisms of the AEG pathway with CRC from the perspective of tumor cell glycolysis and explores how active ingredients(oxymatrine, kaempferol, and dioscin) and compound prescriptions(Quxie Capsules, Jiedu Sangen Decoction, and Xianlian Jiedu Prescription) of TCM treat CRC by intervening in the AEG pathway. Additionally, this article explores the shortcomings in the current research, aiming to provide reliable targets and a theoretical basis for treating CRC with TCM.
Humans ; Colorectal Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Glycolysis/drug effects* ; Animals ; Medicine, Chinese Traditional ; Signal Transduction/drug effects*

Fuxiong has a long history of cultivation. Since its first record in the Beneficial Formulas from the Taiping Imperial Pharmacy of the Song Dynasty, Fuxiong had always been used by ancient physicians and became a preponderant variety for some reasons during the periods of the Ming Dynasty, Qing Dynasty, and Republic of China. However, as for modern use, only Chuanxiong Rhizoma is valued, and the medicinal value of Fuxiong is gradually being overlooked. This article systematically researches the nomenclature, producing area, origin, and efficacy of Fuxiong, proving that the planting technology of Fuxiong matured in the Song Dynasty at the latest, slightly later than the emergence of Chuanxiong Rhizoma in the Sui and Tang Dynasties. Over the years, the producing area of Fuxiong has not undergone significant changes, and it is mainly cultivated within Jiangxi province. According to the analysis of the origin of Xiongqiong, combined with modern genetic research, it can be basically clarified that the early source of Xiongqiong may not be single. With the popularization of cultivation, Chuanxiong Rhizoma became a Dao-di herb earliest, gradually replacing Xiongqiong and being recognized clinically. After cultivation, the polyploidy of Chuanxiong Rhizoma varieties formed stable inheritance, forming the later Fuxiong. Medical experts have gradually deepened their understanding of the efficacy of Fuxiong. Initially, they believed that it was a substitute for Chuanxiong Rhizoma and had weaker efficacy than Chuanxiong Rhizoma. Medical experts in Jin and Yuan Dynasties such as Zhu Danxi and Dai Sigong believed that Fuxiong was good at relieving stagnation. Books and records of materia medica in the Ming and Qing Dynasties explicitly proposed the great ability of Fuxiong to relieve stagnation. Fuxiong should be distinguished from Chuanxiong Rhizoma when applied, and the application differences should be clearly reflected in medical records. Based on the comprehensive research in this article, it can be concluded that although most of ancient physicians have attached great importance to genuineness of Chuanxiong Rhizoma, Fuxiong, as a dominant variety of traditional application, has a clear historical context and significant efficacy characteristics, worthy of further in-depth study.
Drugs, Chinese Herbal/history* ; China ; Medicine, Chinese Traditional/history* ; History, Ancient ; Humans ; History, Medieval ; Plants, Medicinal/chemistry* ; Rhizome/growth & development*