Objective To evaluate the bioequivalence of test and reference mirabegron sustained release tablets under fasting/postprandial conditions.Methods A randomized,open,single dose,four cycle,two sequence,self-crossover trial design was used.32 healthy subjects respectively for fasting and fed study were enrolled,who were randomized to a single oral dose of 50 mg of either reference or test preparation of mirabegron sustained release tablets.The plasma concentration of mirabegron in healthy subjects after oral administration was detected by liquid chromatography tandem mass spectrometry,and Phoenix WinNonlin 8.2 software was used to calculate pharmacokinetic parameters and perform bioequivalence analysis.Results Subjects received a single oral dose of the reference and test formulations of mirabegron.The main pharmacokinetic parameters of mirabegron in the fasting study were asfollows:Cmaxwere(43.91±21.40)and(40.82±24.94)ng·mL-1,AUC0-t were(464.45±149.01)and(452.67±157.63)h·ng·mL-1,AUC0-∞were(501.64±162.39)and(488.70±173.81)h·ng·mL-1.The main pharmacokinetic parameters of mirabegron in the fed study were as follows:Cmax were(16.90±8.94)and(16.90±9.66)ng·mL-1,AUC0-t were(247.09±82.53)and(243.22±78.20)h·ng·mL-1,AUC0-∞ were(269.58±86.52)and(265.66±81.89)h·ng·mL-1.The 90％confidence intervals for the geometric means of Cmax,AUC0-t and AUC0-∞ for reference and test preparations in the fasting and fed groups were in the range of 80.00％to 125.00％.Conclusions The test and reference formulation of mirabegron sustained release tablets were bioeguivalence.

Myeloid neoplasms (MNs) belong to a group of hematological malignancies characterized by the abnormal biological functions of hematopoietic stem progenitor cells. The abnormal immune and hematopoietic microenvironment of patients with MN interact with malignant clonal hematopoietic stem cells, promoting the occurrence and development of their diseases. MN large granular lymphocyte proliferation (MN-LGLP) is a special and rare clinical phenomenon in this type of disease. Currently, research on this disease in domestic and international cohorts is limited. This study analyzes the clinical and laboratory characteristics of this type of patient and explores the impact of LGLP on the clinical characteristics and survival of patients with MN. Patients with MN-LGLP are prone to neutropenia and splenomegaly. The presence of LGLP is not a risk factor affecting the survival of patients with MN-LGLP. STAG, ASXL1, and TET2 are the most common accompanying gene mutations in MN-LGLP, and patients with MN-LGLP and STAG2 mutations have poor prognoses.

Purpose::To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis.Methods::A total of 282 healthy young male volunteers aged 18 -20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries. The occurrence of training injuries is monitored and diagnosed by physicians and treated accordingly. The body composition was measured using the BodyStat QuadScan 4000 multifrequency Bio-impedance system at 5, 50, 100 and 200 kHz to obtain 4 impedance values. The Shapiro-Wilk test was used to check whether the data conformed to a normal distribution. Data of normal distribution were shown as mean ± SD and analyzed by t-test, while those of non-normal distribution were shown as median (Q 1, Q 3) and analyzed by Wilcoxon rank sum test. The receiver operator characteristic curve and logistic regression analysis were performed to investigate risk factors for developing training-related lower extremity injuries and accuracy. Results::Among the 282 subjects, 78 (27.7%) developed training injuries. Lower extremity training injuries revealed the highest incidence, accounting for 23.4% (66 cases). These patients showed higher percentages of lean body mass ( p = 0.001), total body water (TBW, p=0.006), extracellular water ( p=0.020) and intracellular water ( p=0.010) as well as a larger ratio of basal metabolic rate/total weight ( p=0.006), compared with those without lower extremity muscle injuries. On the contrary, the percentage of body fat ( p=0.001) and body fat mass index ( p=0.002) were lower. Logistic regression analysis showed that TBW percentage > 65.35% ( p=0.050, odds ratio =3.114) and 3rd space water > 0.95% ( p=0.045, odds ratio =2.342) were independent risk factors for lower extremity muscle injuries. Conclusion::TBW percentage and 3rd space water measured with bio-impedance method are potential risk factors for predicting the incidence of lower extremity muscle injuries in young males following training.

Objective:To construct a whole course management and follow-up platform, named Care Plan, for patients undergoing breast reconstruction surgery, and to evaluate its initial clinical applications.Methods:From June 2023 to January 2024, patients who underwent breast reconstruction surgery at Peking Union Medical College Hospital were selected as the study subjects and enrolled in the Care Plan platform for whole course management. The platform comprised five modules: patient education, self-assessment, medical assessment, medical follow-up, and doctor-patient dialogue, each with corresponding sub-modules and specific components. Each patient was assigned to a case manager who provided one-on-one assessment, sent patient education materials, and conducted follow-ups. The preliminary application of the Care Plan platform was evaluated based on the completeness of patient data, patient education material reading status, doctor-patient dialogue topics, and follow-up responses. At 3 months postoperatively, patients were followed up and further divided into patient education group(reading at least an article on patient educational materials) and control group based on their reading status of educational materials. Patients rated their satisfaction with the surgery using a 5-point questionnaire, including five indicators: expected breast reconstruction outcome, expected surgical type, completeness of information acquisition, breast symmetry, and breast softness. Statistical analysis was performed using SPSS 27.0.1 software, with count data expressed as frequencies and (or) percentages, normally distributed measurement data expressed as Mean±SD, intergroup comparisons conducted using t-test, and P<0.05 indicating statistical significance. Results:A total of 147 female patients aged 16 to 63 years with a body mass index of 16.6 to 31.3 kg/m 2 were ultimately included. All 147 patients completed the content of the self-assessment and medical assessment modules, with relatively complete data. Of the 133 patients who received patient education materials sent through the platform, 38 (28.6%) read the materials, with the sub-module on the introduction and choices of the reconstruction surgery (37.3%, 94/252 ) being the most frequently viewed. A total of 24 patients (16.3%, 24/147 ) raised 45 questions using the doctor-patient dialogue module, with the highest proportion related to consultation issues and complications, each accounting for 22.2% (10/45). Twenty-three patients completed the 3-month follow-up, with 12 in the patient education group and 11 in the control group. The patient education group scored higher than the control group in terms of completeness of information acquisition [(4.58±0.51) points vs. (3.91±0.70) points, t=-2.65, P=0.015], while scoring lower in breast symmetry [(3.92±0.79) points vs. (4.63±0.67) points, t=2.33, P=0.030]. There was no significant difference between the two groups in terms of expected breast reconstruction outcome, expected surgical type, and breast softness scores ( P>0.05 for all). Conclusion:The Care Plan platform for whole course management and follow-up of breast reconstruction can assist medical staff in formulating patient-centered management plans, improve patients’ understanding of surgical information, and aid patients in making decisions regarding breast reconstruction methods.

italic>Lonicera Linn. is the largest genus of family Caprifoliaceae, which has a long history and abundant resources in China. Due to its ornamental and medicinal properties, the species of Lonicera shows outstanding economic value. However, affected by the huge demand and high price stimulation, there is a serious mixing phenomenon on the market. In this study, high-throughput sequencing technology was used to analyze the analysis of L. angustifolia Wallich ex Candolle var. myrtillus (Hook. f. & Thomson) Q. E. Yang, L. myrtillus Hook. f. et Thoms. var. cyclophylla Rehd, L. szechuanica Batal and L. tangutica Maxim to sequence and assemble their chloroplast (CP) genomes, and to conduct structural comparisons and phylogenetic studies. The results showed that the chloroplast genomes of the four species showed a typical circular tetrad structure, with a total length of 154 608-163 413 bp and a total GC content of 37.93%-38.42%. A total of 128-129 genes were annotated, including 83-84 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. A total of 53-68 SSRs and 133-745 long repeats were detected by chloroplast repeat structure analysis. Phylogenetic studies showed that 21 species of Lonicera medicinal plants could be significantly clustered into one branch, among which the relatives of L. angustifolia and L. szechuanica were close, and the kinship of L. myrtillus and L. tangutica was close. This study is the first comprehensive study of the chloroplast genome and phylogenetic relationship of Loicera species, and the experimental results provide a scientific basis for revealing the genetic information, species evolution and genetic diversity of Lonicera species.

Objective:To construct a whole course management and follow-up platform, named Care Plan, for patients undergoing breast reconstruction surgery, and to evaluate its initial clinical applications.Methods:From June 2023 to January 2024, patients who underwent breast reconstruction surgery at Peking Union Medical College Hospital were selected as the study subjects and enrolled in the Care Plan platform for whole course management. The platform comprised five modules: patient education, self-assessment, medical assessment, medical follow-up, and doctor-patient dialogue, each with corresponding sub-modules and specific components. Each patient was assigned to a case manager who provided one-on-one assessment, sent patient education materials, and conducted follow-ups. The preliminary application of the Care Plan platform was evaluated based on the completeness of patient data, patient education material reading status, doctor-patient dialogue topics, and follow-up responses. At 3 months postoperatively, patients were followed up and further divided into patient education group(reading at least an article on patient educational materials) and control group based on their reading status of educational materials. Patients rated their satisfaction with the surgery using a 5-point questionnaire, including five indicators: expected breast reconstruction outcome, expected surgical type, completeness of information acquisition, breast symmetry, and breast softness. Statistical analysis was performed using SPSS 27.0.1 software, with count data expressed as frequencies and (or) percentages, normally distributed measurement data expressed as Mean±SD, intergroup comparisons conducted using t-test, and P<0.05 indicating statistical significance. Results:A total of 147 female patients aged 16 to 63 years with a body mass index of 16.6 to 31.3 kg/m 2 were ultimately included. All 147 patients completed the content of the self-assessment and medical assessment modules, with relatively complete data. Of the 133 patients who received patient education materials sent through the platform, 38 (28.6%) read the materials, with the sub-module on the introduction and choices of the reconstruction surgery (37.3%, 94/252 ) being the most frequently viewed. A total of 24 patients (16.3%, 24/147 ) raised 45 questions using the doctor-patient dialogue module, with the highest proportion related to consultation issues and complications, each accounting for 22.2% (10/45). Twenty-three patients completed the 3-month follow-up, with 12 in the patient education group and 11 in the control group. The patient education group scored higher than the control group in terms of completeness of information acquisition [(4.58±0.51) points vs. (3.91±0.70) points, t=-2.65, P=0.015], while scoring lower in breast symmetry [(3.92±0.79) points vs. (4.63±0.67) points, t=2.33, P=0.030]. There was no significant difference between the two groups in terms of expected breast reconstruction outcome, expected surgical type, and breast softness scores ( P>0.05 for all). Conclusion:The Care Plan platform for whole course management and follow-up of breast reconstruction can assist medical staff in formulating patient-centered management plans, improve patients’ understanding of surgical information, and aid patients in making decisions regarding breast reconstruction methods.

Objective To investigate the age-related changes of the mandibular third molar root pulp visibility in individuals in East China,and to explore the feasibility of applying this method to deter-mine whether an individual is 18 years or older.Methods A total of 1 280 oral panoramic images were collected from the 15-30 years old East China population,and the mandibular third molar root pulp visibility in all oral panoramic images was evaluated using OLZE 0-3 four-stage method,and the age distribution of the samples at each stage was analyzed using descriptive statistics.Results Stages 0,1,2 and 3 first appeared in 16.88,19.18,21.91 and 25.44 years for males and in 17.47,20.91,22.01 and 26.01 years for females.In all samples,individuals at stages 1 to 3 were over 18 years old.Conclusion It is feasible to determine whether an individual in East China is 18 years or older based on the mandibular third molar root pulp visibility on oral panoramic images.

OBJECTIVE: Jiedu Recipe (JR), a Chinese herbal remedy, has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma (HCC). This work investigated the mechanism of JR in HCC treatment. METHODS: The chemical constituents of JR were detected using liquid chromatography-mass spectrometry. The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid (mRNA) microarray chip assay, followed by experimental validation in human HCC cells (SMMC-7721 and Huh7) in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo. HCC cell characteristics of proliferation, migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide, wound healing and Transwell assays, respectively. Image-iT™ Hypoxia Reagent was added to reveal hypoxic conditions. Stem cell sphere formation assay was used to detect the stemness. Epithelial-mesenchymal transition (EMT) markers like E-cadherin, vimentin and α-smooth muscle actin, and pluripotent transcription factors including nanog homeobox, octamer-binding transcription factor 4, and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction. Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/β-catenin pathway. RESULTS: According to network pharmacology and mRNA microarray chip analysis, JR may potentially act on hypoxia and inhibit the Wnt/β-catenin pathway. In vitro and in vivo experiments showed that JR significantly decreased hypoxia, and suppressed HCC cell features of proliferation, migration and invasion; furthermore, the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR. Results based on the co-administration of JR and an agonist (LiCl) or inhibitor (IWR-1-endo) verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/β-catenin pathway. CONCLUSION JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/β-catenin pathway under hypoxic conditions. Please cite this article as: Guo BJ, Ruan Y, Wang YJ, Xiao CL, Zhong ZP, Cheng BB, Du J, Li B, Gu W, Yin ZF. Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/β-catenin pathway under hypoxia. J Integr Med. 2023; 21(5): 474-486.
Animals ; Mice ; Humans ; Carcinoma, Hepatocellular/genetics* ; beta Catenin/pharmacology* ; Liver Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; RNA, Messenger/therapeutic use* ; Cell Line, Tumor ; Cell Proliferation ; Cell Movement ; Gene Expression Regulation, Neoplastic

β-Thalassemia caused by abnormal coding of the β-globin gene is the most common hemoglobinopathy in many Asian countries. The in-depth study of the molecular basis and epigenetic mechanism of globin gene expression is the key to explore a new treatment for thalassemia. In this study, FAIRE (formaldehyde-assisted isolation of regulatory elements), 3C (chromosome conformation capture) and ChIP (Chromatin Immunoprecipitation) were used to investigate the three-dimensional interaction network of β-globin family gene loci and the molecular mechanism of functional regulation of gene expression during rapamycin-induced chromatin remodeling in CD4+ T cells. The results showed that the opening degree of globin gene chromatin, the interaction frequency between the gene promoter region and the regulatory element LCR (Locus control regions), and the enrichment efficiency of CTCF (CCCTC-binding factor) in the gene promoter region changed differently during the change of rapamycin treatment concentration from low to high, which led to the same change trend of the gene expression pattern. At the 10 nmol/ L concentration, chromatin accessibility and gene expression decreased (P < 0. 05). At 20 nmol/ L and 50 nmol/ L concentrations, chromatin accessibility increased and gene expression was up-regulated (P < 0. 05). In this study, the molecular mechanism of gene expression regulation of the β-globin family was expounded through this dynamic change process. Our work provides a theoretical and clinical practice basis for clinical precision treatment.

Objective:To explore the value of high-resolution CT (HRCT) visual scores and quantitative analysis in assessing pulmonary Langerhans cell histiocytosis (PLCH) in adults.Methods:In total 51 adult patients with PLCH confirmed by pathology in Peking Union Medical College Hospital from August 2014 to December 2021 were retrospectively analyzed. All patients underwent HRCT and pulmonary function tests (PFT). The involvement of the nodular and cystic lesions were evaluated by two experienced radiologists using CT visual scores. The cases were divided into three groups based on the nodular scores, and into four groups based on the cystic scores, respectively. Ratio of low attenuation areas (LAA%) was measured by an automatic post-processing software. Pulmonary function indices including forced expiratory volume in the first second (FEV 1), forced vital capacity (FVC), FEV 1/FVC, diffusion capacity for carbon monoxide of lung (D LCO), alveolar ventilation (V A), D LCO/V A, D LCO corrected for hemoglobin (D LCOc), D LCOc/V A were collected. FEV 1/FVC was expressed as measured values and other indices were expressed as percent predicted (%pred). Spearman correlation analysis was used to evaluate the correlation between HRCT visual scores, LAA% and PFT. The lung function indices among different nodular groups as well as among different cystic groups were compared using the Kruskal‐Wallis test. Results:Both nodular and cystic lesions were found on HRCT images of all 51 patients. There were no correlation between the visual scores of nodular lesions and lung function indices (all P>0.05). There were no significant differences in lung function indices among different nodular groups (all P>0.05). The visual scores of cystic lesions were negatively correlated with FEV 1/FVC, D LCO%pred, D LCO/V A%pred, D LCOc%pred, D LCOc/V A%pred ( r=-0.491, -0.347, -0.330, -0.373, -0.346, respectively, all P<0.05); the pulmonary function indices among different cystic groups had significant difference (all P<0.05). LAA% were negatively correlated with FEV 1/FVC, D LCO%pred, D LCO/V A%pred, D LCOc%pred, D LCOc/V A%pred ( r=-0.278, -0.378, -0.418, -0.395, -0.451, respectively, all P<0.05). Conclusion:HRCT visual scores of nodular lesions do not correlate with lung function in patients with PLCH. Visual scores and quantitative analysis of the cystic lesions can reflect the impairment degree of pulmonary ventilation and diffusion function to a certain extent, and may be used in assessment of patients with PLCH.