Objective To evaluate the characteristics of the mass balance and pharmacokinetics of[14 C]birociclib in Chinese male healthy volunteers after a single oral administration.Methods This study used a 14 C labeled method to investigate the mass balance and biological transformation of birociclib in human.Subjects were given a single oral dose of 360 mg/50 pCi of[14 C]birociclib suspension after meals.The blood,urine,and fecal samples were collected at specified time points/intervals after administration.The radiation levels of 14 C labeled birociclib-related compounds in the blood,plasma,urine,and feces were analyzed using liquid scintillation counting.In addition,a combination of high-performance liquid chromatography and on-line/off-line isotope detectors was used to obtain radioactive isotope metabolite spectra of plasma,urine,and fecal samples,and high-resolution mass spectrometry was used to identify the main metabolites.Results A total of 6 healthy male subjects were enrolled in this study.The median peak time of radioactive components in plasma was 5.00 h and the average terminal elimination half-life was 43.70 h after administration.The radioactive components were basically excreted and cleared from the body within 288.00 hours after administration,and average cumulative recovery rate of radioactive drugs was(94.10±8.19)％.The radioactive drugs were mainly excreted through feces,accounting for(84.60±7.10)％of the dose of radioactive drugs administered.Urine was the secondary excretory pathway,accounting for 9.41％of the dose of radioactive drugs administered.Metabolic analysis indicated that the prototype drug was the main radioactive components in plasma samples.The main metabolites in plasma were RM4(XZP-5286),RM6(XZP-3584),and RM7(XZP-5736).The drugs were mainly cleared from the body in the form of prototype drugs and metabolites.In addition to prototype drugs,a total of 9 metabolites were identified and analyzed in plasma,urine,and fecal samples,all of which were phase 1 metabolites.The main metabolic and clearance pathways of drugs in the body were deethylation,diisopropylat ion,oxidation,etc.Conclusion After a single oral administration of[14C]birociclib suspension to healthy subjects,it was mainly cleared from the body in the form of prototype drugs and metabolites,with feces as the main excretory pathway and urine as the secondary excretory pathway.Drugs mainly undergo metabolic reactions in the body,such as deethylation,diisopropylation,and oxidation.The subjects were well tolerance after administration.

Objective To investigate the value of serum microRNA (miRNA)-184 and miR-451a expression in predicting recurrent metastasis after radical resection of stage Ⅰ to ⅡA non-small cell lung cancer (NSCLC). Methods A total of 203 patients with radical resection of stage Ⅰ to ⅡA NSCLC in the hospital from January 2020 to October 2021 were selected as NSCLC group. According to the recurrence and metastasis status during the 2-year follow-up, they were divided into recurrence and metastasis group with 30 cases and non-recurrence and metastasis group with 173 cases. Additionally, 87 healthy volunteers with physical examinations in the same period were selected as control group. Real-time quantitative polymerase chain reaction was used to detect serum expression of miR-184 and miR-451a. Multivariate Logistic regression model was used to analyze the factors affecting recurrence and metastasis after radical resection of stage Ⅰ to ⅡA NSCLC. Receiver operating characteristic (ROC) curve was used to analyze the value of serum miR-184 and miR-451a expression in predicting recurrence and metastasis. Results Compared with the control group, the expression of serum miR-184 and miR-451a in the NSCLC group decreased significantly (P < 0.05). After 2 years of follow-up, the recurrence and metastasis rate of 203 patients with stage Ⅰ to ⅡA NSCLC was 14.78% (30/203). Compared with the non-recurrence and metastasis group, the expression of serum miR-184 and miR-451a in the recurrence and metastasis group decreased significantly (P < 0.05). The independent risk factors for recurrence and metastasis after radical resection of stage Ⅰ to ⅡA NSCLC were stage ⅡA, poor differentiation and postoperative adjuvant chemotherapy, while the independent protective factors were increased miR-184 and miR-451a expression (P < 0.05). The area under the curve (AUC) of the combined prediction of serum miR-184 and miR-451a expression for recurrence and metastasis after radical resection of stage Ⅰ to ⅡA NSCLC was 0.868, which was greater than 0.784 and 0.781 of serum miR-184 and miR-451a expression alone (P < 0.05). Conclusion The serum miR-184 and miR-451a expression in patients with stage Ⅰ to ⅡA NSCLC is low and closely related to recurrence and metastasis after radical resection. The combined detection of serum miR-184 and miR-451a has a high predictive value for recurrence and metastasis after radical resection of stage Ⅰ to ⅡA NSCLC.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Molecular mass distribution of Astragalus polysaccharides is wide. Astragalus polysaccharides prepared by conventional water extraction and alcohol precipitation are mostly mixture of macromolecules. Although studies have shown that Astragalus polysaccharides have two-sided immunomodulation, the relationship between anti-inflammatory components and molecular mass distribution of Astragalus polysaccharides is not clear. Therefore, Astragalus polysaccharides were extracted by water extraction and alcohol precipitation. The relative molecular weight of them was determined by high performance gel permeation chromatography (HPGPC). Astragalus polysaccharides with different molecular weights were separated and prepared by membrane separation. RAW 264.7 cells were induced by lipopolysaccharide (LPS) to establish an inflammatory cell model in vitro and the anti-inflammatory polysaccharide were screened. The anti-inflammatory regulation mechanism of Astragalus polysaccharides was analyzed by the LC-MS/MS metabonomics technology. The results showed that APS was composed of APS-Ⅰ ( > 2 000 kDa) and APS-Ⅱ (10 kDa). APS-Ⅰ was composed of mannose, rhamnose, galacturonic acid, glucose, galactose, arabinose and the molar ratios of these monosaccharide of APS-I were 0.54∶0.26∶12.24∶17.24∶8.46∶1. APS-II was composed of rhamnose, galacturonic acid, glucose, galactose, arabinose and the molar ratios of these monosaccharide of APS-II were 0.26∶0.14∶24.04∶0.62∶1. APS-Ⅰ and APS-Ⅱ had no cell toxicity to RAW 264.7 macrophage in the range of 0-100 μg·mL^-1. Compared with the model group, APS-I at a concentration of 0-100 μg·mL^-1could significantly inhibit the secretion of NO and TNF-α by RAW 264.7, and can significantly promote the secretion of IL-10. APS-I had better anti-inflammatory activity than APS-II in vitro. The metabolomics results showed that 32 different metabolites were found between the model group and blank group; APS-I group can significantly callback 18 different metabolites; mainly related to arginine biosynthesis, arginine and proline metabolism, pyrimidine metabolism, citric acid cycle (TCA cycle), cysteine and methionine acid metabolism, tryptophan metabolism. This study found that APS-I had better anti-inflammatory activity than APS-II in vitro, and its mechanism may be closely related to amino acid metabolism and energy metabolism, which indicated the direction for further clarifying the pharmacodynamic material basis of Astragalus polysaccharides.

The paper introduces the clinical experience of GAO Hong in treatment of tic disorder. GAO Hong believes that tic disorder results from the primary qi deficiency and mind disturbance. Acupuncture for cultivating the primary and regulating the mind is proposed specially for tic disorder. This acupuncture technique focuses on harmonizing and regulating governor vessel and conception vessel. In clinical practice, the conception vessel acupoints on the abdomen and the governor vessel acupoints on the head are selected particularly, e.g. Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6) and Guanyuan (CV 4) on the abdomen; Baihui (GV 20), Shenting (GV 24), Benshen (GB 13) and Yintang (GV 24⁺) on the head. The needling sequence and the insertion depth are emphasized, which affect the curative effect and GV 20 is generally punctured first. Besides, considering to the type of disorder and the affected site, tic disorder is treated in view of both syndrome/pattern differentiation and symptom differentiation.
Abdominal Cavity ; Acupuncture Points ; Acupuncture Therapy/methods* ; Humans ; Tic Disorders/therapy*

Objective:To characterize proteomic profile in aqueous humor of patients with high myopia using quantitative proteomic analysis.Methods:Sixty-eight age-related cataract patients were divided into high myopic cataract group and simple cataract group according to that they had high myopia or not, with 34 patients (34 eyes) in each group.Aqueous humor samples (100 μl/patient) were collected from each patient using a 1 ml tuberculin syringe during cataract surgery at Tianjin Medical University Eye Hospital from January 2019 to August 2019.Sixteen samples from each group were selected for protein quantification and comparison by BCA method.The differentially expressed proteins between the two groups were analyzed using label-free liquid chromatography tandem mass spectrometry.The function and signal transduction pathways of differentially expressed proteins were further analyzed by Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes.Eighteen aqueous humor samples from each group were selected to verify the results of mass spectrometry by enzyme-linked immunosorbent assay (ELISA). This study protocol adhered to the Declaration of Helsinki.The use of human samples was approved by an Ethics Committee of Tianjin Medical University Eye Hospital (No.2020KY[L]-40). Written informed consent was obtained from each patient prior to surgery.Results:The mean protein mass concentration of aqueous humor sample in the high myopic cataract group was (1 134.91±104.78) ng/L, which was significantly higher than that in the simple cataract group (706.71±85.43) ng/L, showing statistically significant difference ( t=11.977, P<0.01). A total of 463 proteins were identified and 86 proteins were found to be differentially expressed, including 49 up-regulated proteins and 37 down-regulated proteins in the two groups.These differentially expressed proteins were mainly protein-binding activity modulator, extracellular matrix protein, carrier protein, intercellular signal molecule, protein modifying enzyme and so on, accounting for 32.70%, 14.50%, 9.10%, 9.10% and 7.30%, respectively.Bioinformatics analysis showed that 86 differentially expressed proteins were mainly related to biological processes such as complement activation and regulation, acute inflammatory response, and extracellular matrix tissue remodeling.Among them, 21 differentially expressed proteins were enriched in the complement and coagulation cascades pathways, 15 in the extracellular matrix-receptor interaction pathway, and 8 in the PI3K-Akt signaling pathway.ELISA results showed that the expression trends of three randomly selected differentially expressed proteins of the two groups were consistent with the results of label-free quantitative proteomic analysis. Conclusions:There are significant changes in proteomic profiles of aqueous humor between the high myopia cataract patients and simple cataract patients.High myopia is closely associated with inflammation and immune interactions, and remodeling of extracellular matrix.

Xiexin decoctions (XXDs) display beneficial anti-inflammatory and anti-diabetic effects, which raises interests on this group of formulae for broad clinical applications. However, there was no report about systematic analysis of XXDs to elucidate the constitution of chemical components, which hampers further investigations on the therapeutic values of XXDs. In this work, crude herbs were extracted and prepared to obtain the XXDs for systemic analysis on their chemical compositions, according to the information described in the ancient Zhang Zhongjing's herbal formulae. LC-MS analysis of five XXDs was carried out to facilitate recognition of the source herbs for compounds in the mixture. A total number of 93 compounds were identified through our methods and their chemical classes encompassed five major groups, including protoberberine alkaloids, flavonoids, stilbenes, anthraquinones and saponins. Our current work provided important information about material basis for pharmacological studies on XXDs and would help shed light on relationships between chemical compositions and therapeutic effects.

Objective:To explore the diagnosis and treatment of the multi-segment injury of brachial plexus and provide reference for diagnosis and treatment in clinical practice.Methods:From October, 2012 to January, 2015, 24 patients (21 males and 3 females, aged 7-46, average at 25.06±13.01 years) who suffered multi segments injury of brachial plexus were treated by surgical operations. Time from injury to surgery was 7 days to 7 months, with (2.43±2.15) months in average. The general data, injuries and surgical procedures of the patients were recorded. Muscle strength grading was used to evaluate and analyse the curative effect.Results:Twenty-four cases were followed-up for 3.1-7.2 years, with 4.3 years in average. Of the patients, 58.3% of the injuries were caused by mechanical traction. Combined injuries were counted for 83.3%, of which 62.5% combined with ipsilateral limb fractures, 20.8% (5/24) involved in the root of brachial plexus, 79.2% (19/24) with upper part of the clavicle, 91.6% (22/24) with lower part of the clavicle, 16.7% (4/24) with branches of the brachial plexus and 91.7% (22/24) with injuries of 2 segments, 8.3% (2/24) with injuries of 3 segments. At the last followed-up, 55.0% of the patients achieved better than M 3 in total muscle strength. The excellent and good rate was 70.8% in neurolysis group and 42.9% in multiple segment injury group. Conclusion:The mechanism of multi segments injury of brachial plexus is special, and the actual injury is difficult to be located. For patients with multi segments injury, surgical operation should be carried out as early as possible, and the correct surgical procedure can only be determined after the exploration of all sections of the brachial plexus.

BACKGROUND: Knee osteoarthritis (OA) is a major cause of disability among the older adults. Few treatments are safe and effective. Moxibustion is commonly used in treating knee OA in Chinese medicine (CM). CO Laser moxibustion device is a substitute for traditional moxibustion, which mimics the effects of traditional moxibustion. More data are needed to support its application in knee OA. OBJECTIVE: ObjectiveThe trial aims to assess the effect and safety of CO laser moxibustion in patients with knee osteoarthritis compared with a sham control. METHODS: This is a protocol for a multicenter, randomized, double-blind, placebo-controlled trial. A total of 392 participants were recruited and assigned to the CO laser moxibustion group and sham laser moxibustion group with a 1:1 ratio at 6 outpatient clinics in Shanghai, China. Participants in both groups received treatment at the affected knee(s) at the acupuncture point Dubi (ST 35) and an Ashi point. There were 3 sessions per week for 4 weeks, and an additional 20-week follow-up. Primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores at week 4. Secondary outcomes were WOMAC function score, stiffness score and overall score, VAS pain, Short-Form heath survey (SF-36), and patients' global assessment. The serum levels of cytokines involved in progress of knee OA were explored. Safety was assessed during the whole trial. Masking effectiveness was assessed by both participants and treatment providers.This is a protocol for a multicenter, randomized, double-blind, placebo-controlled trial. A total of 392 participants were recruited and assigned to the CO laser moxibustion group and sham laser moxibustion group with a 1:1 ratio at 6 outpatient clinics in Shanghai, China. Participants in both groups received treatment at the affected knee(s) at the acupuncture point Dubi (ST 35) and an Ashi point. There were 3 sessions per week for 4 weeks, and an additional 20-week follow-up. Primary outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores at week 4. Secondary outcomes were WOMAC function score, stiffness score and overall score, VAS pain, Short-Form heath survey (SF-36), and patients' global assessment. The serum levels of cytokines involved in progress of knee OA were explored. Safety was assessed during the whole trial. Masking effectiveness was assessed by both participants and treatment providers. DISCUSSION CO laser moxibustion device, designed as a substitute for CM moxibustion, is easy to use and control with no choking smoke and smell, and is a plausible method for double-blind research. This study would provide rigorous evidence for the effect and safety of CO laser moxibustion in treating knee OA (Trial registration No.: ISRCTN15030019).

Objective To evaluate the prognostic value of a novel prediction model based on fibrinogen concentration in combination with neutrophil-to-lymphocyte ratio (F-NLR score) in patients with esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant therapy and investigate their relationship with pathologic complete response (pCR).Methods Clinical data of 218 eligible ESCC patients treated with neoadjuvant therapy in the Affiliated Cancer Hospital of Zhengzhou University between 2012 and 2015 were retrospectively analyzed.The cut-off values for fibrinogen and neutrophil-to-lymphocyte ratio (NLR)were defined by the receiver operating characteristic (ROC) curve.The effects of different F-NLR scores on survival and pCR were evaluated.The survival rate was analyzed using the Kaplan-Meier method.The relationship among fibrinogen,NLR and pCR was analyzed by using Wilcoxon rank sum test.Results The 3-year overall survival (OS) rates with F-NLR scores of 0,1 and 2 were 72.1％,66.5％ and 50.2％(P=0.010),respectively.The corresponding 3-year disease-free survival (DFS) rates were 64.1％,60.2％ and 45.4％ (P=0.012),respectively.The clinical prognosis of patients with an F-NLR score of 2 was significantly worse compared with those of their counterparts with an F-NLR score of 0-1 (P=0.003).Multivariate analysis demonstrated that the F-NLR score (P=0.004) and TNM stage (P=0.000) were the independent prognostic factors.Conclusions The F-NLR score can be used as an independent prognostic factor for ESCC patients treated with neoadjuvant therapy,which is promising supplement to current TNM staging system,thereby facilitating more accurate risk stratification analysis and achieving individualized multidisciplinary treatment for ESCC patients.