Objective To study the pharmacokinetics and bioequivalence of two formulations of rasagiline mesylate tablets in healthy subjects under fasting and fed conditions.Methods The two-period,two-sequence,crossover study design was adopted in the fasting study.Thirty-six subjects were enrolled and given either test preparation or reference preparation 1 mg respectively in two periods.After collecting plasma samples,the plasma concentration of rasagiline was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)and the bioequivalence was evaluated using the average bioequivalence(ABE)method.The four-period,two-sequence,fully replicate crossover study design was adopted in the fed study.Forty-eight subjects were enrolled and given the test preparation or the reference preparation at a dose of 1 mg twice respectively in four periods.According to the degree of intra-individual variation of Cmax,AUC0-t and AUC0-∞,the equivalence was evaluated using the reference-scaled average bioequivalence and ABE method,respectively.Results In the fasting study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(9.70±3.14)and(9.62±3.85)ng·mL-1,AUC0-t were(6.03±1.47)and(6.02±1.95)ng·h·mL-1,AUC0-∞ were(6.13±1.51)and(6.12±1.97)ng·h·mL-1.The 90％confidence interval(CI)of the geometric mean ratio(GMR)were 94.11％-118.06％,99.22％-107.74％and 99.16％-107.44％for Cmax,AUC0-t and AUC0-∞,respectively,which were within the acceptance criteria of 80.00％-125.00％.In the fed study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(3.00±1.92)and(3.52±1.77)ng·mL-1,AUC0_t were(5.02±1.20)and(5.06±1.20)ng·h·mL-1,AUC0-∞ were(5.11±1.23)and(5.14±1.22)ng·h·mL-1.The 90％CI of GMR were 96.99％-101.19％and 97.17％-101.41％for AUC0-t and AUC0-∞,which were within the acceptance criteria of 80.00％-125.00％.The 95％upper confidence bound of Cmax for were less than"0",and the point estimate of GMR were within the acceptance criteria of 80.00％-125.00％.The incidence of adverse events in fasting and fed studies was 22.86％and 22.92％,respectively,and all adverse events were moderate to mild.Conclusion The two rasagiline mesylate tablets were bioequivalent,and both the formulations were well tolerated.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota. Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336-0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34-0.55),which were mainly involved in neurodevelopment. Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

Through a compound induction method, combined with neurobehavioral, macroscopic characterization and objective pathological evaluation indicators, a murine depression model of liver depression transforming into fire syndrome was constructed and confirmed. The model was constructed using a combination of sleep deprivation, light exposure, and alternate-day food deprivation. Evaluation was conducted at three levels: face validity, constructs validity, and predictive validity. The establishment of the liver depression transforming into fire syndrome depression model was further validated through the counterproof of traditional Chinese medicine formulas. In terms of face validity, compared to the control group, mice in the model group exhibited typical depressive symptoms in neurobehavioral assessments; the general observation of the model group mice reveals disheveled and lackluster fur, along with delayed and easily agitated responses. Additionally, there is a substantial increase in water consumption. In the sleep phase detection of mouse, the model group showed a significant increase in the proportion of time spent in the wake phase during sleep, accompanied by a significant decrease in the proportions of time spent in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep phases. There are significant differences in physiological indicators such as average blood flow velocity, blood flow rate, tongue, urine, and claw color (r values) in the internal carotid artery. Structural validity demonstrated that levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and γ-aminobutyric acid (GABA) in the hippocampus of model mice decreased significantly, while acetylcholine (ACh), tryptophan (Try), and glutamic acid (Glu) levels increased significantly. Treatment with Danzhi Xiaoyao San led to varying degrees of restoration in the aforementioned neurotransmitters. In terms of predictive validity, the antidepressant paroxetine effectively ameliorated depressive behaviors in the model mice, and the classic formula Danzhi Xiaoyao San demonstrated varying degrees of improvement in depression-related indicators. In conclusion, this study has established a novel animal model of liver-stagnation with the fire depression, thereby expanding the repertoire of traditional Chinese medicine depression models. This development contributes to the diversification of melancholic syndrome models in Chinese medicine, offering a broader spectrum of options for scientific exploration, efficacy evaluation, and drug screening in the future prevention and treatment of depression with traditional Chinese medicine. Animal experiments were conducted with the approval and supervision of the Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine (ethics number: 20230313040).

Combined radiation and burn injury (CRBI) is a severe syndrome, which is induced by the simultaneous or successive radiation and burn; but no appropriate clinical therapies are available. Loong oil (LO) is a traditional Chinese medicine oil composed of the oil extracts of cuttlebone, safflower, walnut oil, and rapeseed oil, which has been demonstrated to own anti-radiation and tissue healing functions. In this study, glyceryl monostearate (GMO) was used for the preparation of lyotropic liquid crystals that loaded LO to obtain Loong oil-lyotropic liquid crystals (LOL) for the treatment of skin CRBI. The hexagonal phase structure of LOL was proved by small X-ray scattering (SAXS) analysis with an approximate 7:9:11 ratio of peaks and under the polarizing microscope with the birefringence phenomenon. LOL had a high LO loading capacity (4%) and good bio-adhesive force, favoring skin administration. Animal experiments were approved by the Ethics Committee of the Beijing Institute of Radiation Medicine, Academy of Military Medical Sciences and the experiments were conducted in accordance with relevant guidelines and regulations (approval number: IACUC-DWZX-2022-834). Compared to triethanolamine creams, LOL had higher skin permeability with total skin penetration within 1 h, benefiting the treatment of deep CRBI. A deep II degree burn CRBI mouse model was established after whole-body irradiation with 5 Gy ⁶⁰Co γ-ray and the next 6-second 100 ℃ burn injury. LOL promoted LO skin penetration, improved epithermal cell proliferation and the formation of hair follicles, accelerated wound healing, and inhibited scarring, which benefitted the therapy of CRBI. In this study, LO application fields are expanded and LO is a promising medication for the treatment of CRBI.

Objective:To explore the impact of rehabilitation exercise intervention mode based on cardiac function classification on clinical effect and quality of life(QOL)in patients with chronic heart failure(CHF).Methods:A total of 160 CHF patients who visited our hospital from Dec 2021 to Jan 2023 were selected,and 154 cases were fi-nally enrolled.According to the random number table method,patients were divided into study group and control group with 77 cases in each group.Control group received routine nursing program,while the study group received rehabilitation exercise intervention based on cardiac function classification on the basis of control group,both groups were intervened for three months.Clinical total effective rate,and cardiopulmonary function,serum oxidative stress indicators and MLHFQ score before and after intervention were compared between two groups.Results:Total effective rates of study subgroups of class Ⅱ and Ⅲ were significantly higher than those of control group(class Ⅱ:100.00％vs.83.78％;class Ⅲ:97.37％vs.80.00％)(P＜0.05 both).Compared with control subgroup of classⅢ after intervention,there were significant rise in peak VO2[(16.98±2.03)ml·min-1·kg-1 vs.(18.61±2.41)ml·min-1·kg-1],LVEF[(41.73±4.53)％vs.(48.03±5.22)％]and 6MWD[(351.34±61.00)m vs.(391.53±64.42)m](P＜0.01 all);and significant reductions in LVEDd[(57.55±3.91)mm vs.(53.18±3.07)mm],LVESd[(35.90±2.91)mm vs.(30.50±2.67)mm],levels of LPO[(6.00±0.99)mg/L vs.(3.95±0.61)mg/L],MPO[(3.83±0.58)mg/L vs.(2.03±0.28)mg/L],and MLHFQ total score[(57.05±4.57)points vs.(45.29±3.94)points]in study subgroup of class Ⅲ(P=0.001 all).Compared with control subgroup of class Ⅱ after intervention,there were significant rise in peak VO2,LVEF and 6MWD,and significant reductions in LVEDd,LVESd,levels of LPO,MPO and MLHFQ score in study subgroup of class Ⅱ,P＜0.05 or＜0.01.There was no significant difference in the incidence rate of adverse events during follow-up between two groups(3.90％vs.6.49％,P=0.717).Conclusion:Rehabilitation exercise intervention based on cardiac function classifi-cation can significantly improve cardiopulmonary function,inhibit oxidative stress response in vivo and improve quality of life in CHF patients,which is worthy of promotion and application in clinical practice.

In the study of age estimation in living individuals,a lot of data needs to be analyzed by mathematical statistics,and reasonable medical statistical methods play an important role in data design and analysis.The selection of accurate and appropriate statistical methods is one of the key factors af-fecting the quality of research results.This paper reviews the principles and applicable principles of the commonly used medical statistical methods such as descriptive statistics,difference analysis,consistency test and multivariate statistical analysis,as well as machine learning methods such as shallow learning and deep learning in the age estimation research of living individuals,and summarizes the relevance and application prospects between medical statistical methods and machine learning methods.This paper aims to provide technical guidance for the age estimation research of living individuals to obtain more scientific and accurate results.

Objective:To investigate the relationship between the inflammatory cytokines level in the plasma of nasopharyngeal carcinoma patients before radiotherapy and acute radiotherapy adverse reactions, and to establish a preliminary model for predicting the risk of severe acute adverse reactions during radiotherapy.Methods:A cross-sectional study was conducted. A total of 85 nasopharyngeal carcinoma patients who received radical radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from May 2016 to March 2019 were retrospectively collected. The highest grade adverse reactions of radiation oral mucositis, radiation dermatitis and xerostomia during radiotherapy were evaluated according to the American Cancer Radiotherapy Collaboration (RTOG) acute radiation injury evaluation criteria, and the above adverse reactions ≥ grade 3 were treated as the severity. Olink proteomics technology was used to detect the level of 92 inflammatory cytokines (the standardized protein expression values) in the plasma of patients before radiotherapy for the first time. Single factor analysis of variance and independent sample t-test were used to analyze the relationship between inflammatory cytokines and clinical factors, as well as acute adverse reactions during radiotherapy. Based on inflammatory cytokines and/or the clinical factors, binary logistic regression was used to construct a predictive model for the risk of severe acute radiotherapy adverse reactions. Whether the most severe adverse reactions assessed by the American RTOG acute radiation injury evaluation criteria during radiotherapy were severe or not were taken as the gold standard. Receiver operating characteristic (ROC) curve was used to analyze the effectiveness of the established models for judging the severe acute adverse reactions. Results:Among the 85 patients, 68 were males and 17 were females, with the median age [ M ( Q1, Q3)] of 49 years (43 years, 60 years). All patients received radical radiotherapy, of which 64 cases were treated with combination chemotherapy or targeted therapy. A total of 19 cases (22.1%) experienced severe acute radiotherapy adverse reactions. There were statistically significant differences in the levels of interleukin (IL)-22 receptor A1 (IL-22RA1), IL-18 receptor 1(IL-18R1), eotaxin-1 (CCL11), tumor necrosis factor ligand superfamily member 14 (TNFSF14), FMS-like tyrosine kinase 3 ligand (Flt3L), and monocyte chemotactic protein 2 (MCP-2) in the plasma of patients with grade 1, 2, 3 acute radiation oral mucositis before radiotherapy; there were statistically significant differences in the levels of CD244 (all P < 0.05); there were statistically significant differences in the levels of CD244, CC chemokines ligand 20 (CCL20), leukemia inhibitory factor ligand (LIF-R) and IL-4 in the plasma of patients with grade 1, 2, 3 acute radiation dermatitis before radiotherapy (all P < 0.05); there were statistically significant differences in the levels of IL-12B, CXC chemokines ligand 11 (CCL11), LIF-R and IL-33 in the plasma between patients with grade 1 and grade 2 xerostomia before radiotherapy (all P<0.05). The result of single factor analysis of variance showed that the clinical factors were not associated with severe acute radiation adverse reactions (all P > 0.05). Binary logistic regression model M1 was established by selecting 6 clinical factors including age, T staging, N staging, clinical staging, whether to receive chemotherapy or not and whether to suffer from diabetes or not in the literatures. Based on cytokine function and previous literatures, the binary logistic regression model M2 was established by selecting IL-22RA1, IL-18R1, MCP-2, CCL11, CD244, CCL20 and IL-33 from the differential cytokines. A binary logistic regression model M3 was established by combining the above clinical factors with cytokines. The ROC curve analysis showed that the area under the curve of the M1, M2, M3 predictive models for judging the severe acute radiation adverse reactions was 0.781, 0.841, 0.868, respectively. Conclusions:There were differences in the expression levels of various inflammatory cytokines in plasma before radiotherapy among patients with different grades of acute radiotherapy adverse reactions. Building the models based on plasma inflammatory cytokine levels combined with clinical factors before the first radiotherapy could effectively predict the risk of severe acute radiotherapy adverse reactions in patients with nasopharyngeal carcinoma.

Objective To investigate the effect of human platelet-rich plasma-derived exosomes(PRP-exos)on the proliferation of Schwann cell(SC)cultured in vitro. Methods PRP-exos were extracted by polymerization-precipitation combined with ultracentrifugation.The morphology of PRP-exos was observed by transmission electron microscopy,and the concentration and particle size distribution of PRP-exos were determined by nanoparticle tracking analysis.Western blotting was employed to determine the expression of the marker proteins CD63,CD81,and CD9 on exosome surface and the platelet membrane glycoprotein CD41.The SCs of rats were isolated and cultured,and the expression of the SC marker S100β was detected by immunofluorescence staining.The fluorescently labeled PRP-exos were co-cultured with SCs in vitro for observation of their interaction.EdU assay was employed to detect the effect of PRP-exos on SC proliferation,and CCK-8 assay to detect the effects of PRP-exos at different concentrations(0,10,20,40,80,and 160 μg/ml)on SC proliferation. Results The extracted PRP-exos appeared as uniform saucer-shaped vesicles with the average particle size of(122.8±38.7)nm and the concentration of 3.5×10¹² particles/ml.CD63,CD81,CD9,and CD41 were highly expressed on PRP-exos surface(P<0.001,P=0.025,P=0.004,and P=0.032).The isolated SCs expressed S100β,and PRP-exos could be taken up by SCs.PRP-exos of 40,80,and 160 μg/ml promoted the proliferation of SCs,and that of 40 μg/ml showed the best performance(all P<0.01). Conclusions High concentrations of PRP-exos can be extracted from PRP.PRP-exos can be taken up by SCs and promote the proliferation of SCs cultured in vitro.
Humans ; Rats ; Animals ; Exosomes/metabolism* ; Platelet-Rich Plasma ; Schwann Cells ; Coculture Techniques ; Cell Proliferation ; Cells, Cultured

OBJECTIVE: To evaluate the effect of transcutaneous acupoint electrical stimulation (TEAS) at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy. METHODS: A total of 66 patients of primary lung cancer undergoing thoracoscopic lobectomy were divided to an observation group (33 cases, 1 case discontinued) and a control group (33 cases). In the observation group, TEAS at Neiguan (PC 6) was used 30 min before anesthesia induction till the end of surgery. The surgery time, maximum value of partial pressure of end-tidal carbon dioxide (P_ETCO₂) and minimum value of oxygen saturation (SpO₂) of the two groups were recorded. The dosage of propofol, sufentanil, remifentanil and dexmedetomidine were analyzed. Separately, before induction (T₀), at the start of surgery (T₁), thoracic exploration (T₂) and lobectomy (T₃), as well as 30 min (T₄) and 60 min (T₅) after lobectomy, the mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), serum cortisol (Cor) and norepinephrine (NE) were measured. The time of post anesthesia care unit (PACU) stay, ambulation, flatus, chest drainage and the incidence of nausea and vomiting were compared between the two groups. RESULTS: The maximum value of P_ETCO₂, the dosage of propofol and remifentanil in the observation group were lower than those in the control group (P < 0.05, P < 0.01), the minimum value of SpO₂ in the observation group was higher than that of the control group (P < 0.01). At T₁-T₅, the MAP, HR, serum Cor and NE levels in the observation group were all lower than those in the control group (P < 0.05). The ambulation time, the time for the flatus, chest drainage time, and the incidence of nausea and vomiting in the observation group were all lower than those in the control group (P<0.001, P < 0.01). CONCLUSION For the general anesthesia under preserving spontaneous breathing in thoracoscopic surgery, TEAS at Neiguan (PC 6) relieves stress response, reduces opioids dosage and promotes postoperative recovery.
Humans ; Acupuncture Points ; Carbon Dioxide ; Flatulence ; Propofol ; Remifentanil ; Anesthesia, General ; Nausea ; Norepinephrine ; Electric Stimulation