ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

BACKGROUND: Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. METHODS: 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. RESULTS: Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. CONCLUSIONS CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.
Humans ; Lung Neoplasms ; Exome Sequencing ; Multiple Pulmonary Nodules ; Carcinoma ; DNA Repair

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

In order to make the shared traditional Chinese medicine （TCM） pharmacy develop more efficiently and normatively at the grass-roots level， using the “shared TCM pharmacy” as the retrieval word， this paper uses the literature research method to retrieve the reports， documents and policies from CNKI， the websites of people’s governments at all levels， the official websites of the State Administration of Traditional Chinese Medicine， people.com， China News Network， Xinhua News and other platforms before May 20， 2022， sort out the development mode and history of two “Internet plus” TCM pharmacies， namely “shared TCM pharmacies” and “smart TCM pharmacies”， and compare them with each other. Combined with the actual work of community hospitals and community service centers （stations）， the necessity and advantages （such as reducing the costs of the intermediate links of drug circulation and standardizing the grass-roots drug use process） of the development of “shared TCM pharmacy” are obtained from the perspective of primary medical care. Combined with the current situation of the promotion and application of shared TCM pharmacy in county medical communities， it is concluded that the shared TCM pharmacy should be further constructed from four aspects： improving the work process of drug centralized procurement under the background of normalization， improving the compatibility and synchronization of the whole process dispensing information system module， unifying pharmaceutical services and personnel training， defining the authority of data query and clarifying the boundaries of patient privacy to further build a shared TCM pharmacy. Finally， it integrates information technology， summarizes the definition of shared TCM pharmacy and its future construction direction， and provides reference for the next development of shared TCM pharmacy at the grass-roots level.

Objective: By detecting the expression of interleukin-13 (IL-13) and periostin in the airway of asthmatic patients, the pathological changes and pulmonary functions of airway tissues in asthmatic patients were evaluated, and the role of IL-13 and periostin airway remodeling in bronchial asthma was preliminarily explored. Methods: The bronchial tissues adjacent to tumor nest were obtained from 12 patients with lung cancer complicated with bronchial asthma (asthmatic group) and 12 lung cancer patients without bronchial asthma (non-asthmatic group) after lung cancer resection. Pulmonary function was measured for all subjects before surgery. Pathological changes of airway tissues and degree of airway remodeling were assessed by hematoxylin-eosin (H&E) staining, masson′s trichrome staining, and periodic acid-silver methenamine (PASM) staining of paraffin-embedded sections. The expression of IL-13 and periostin in bronchial tissues were evaluated by immunohistochemistry. Results: Values of the forced expiratory volume in 1 second of the predicted value (FEV1% pred) and FEV1/forced vital capacity (FEV1/FVC%) in asthmatic patients were significantly decreased compared with the non-asthmatic patients (P<0.05), indicating that lung function was impaired in asthmatic patients. There was more severe airway remodeling representing as thickening of basement membranes, collagen deposition, and increasing of goblet cells and fibroblasts in asthmatic patients than in non-asthmatic patients (all P<0.05). The expression of IL-13 and periostin were higher in asthmatic tissues than in non-asthmatic tissues (P<0.05). The immunohistochemical expression of IL-13 and periostin in bronchial tissues were positively correlated with the degree of airway remodeling in asthmatic patients, and the expression of IL-13 and periostin in bronchial tissues were positively correlated with each other. Conclusions The expression of IL-13 and periostin were increased in bronchial tissue in patients with asthma. They work together to promote the occurrence of airway remodeling, which eventually lead to a decline in lung function.

OBJECTIVETo identify potential serum biomarkers for distinguishing between latent tuberculosis infection (LTBI) and active tuberculosis (TB).

METHODSA proteome microarray containing 4,262 antigens was used for screening serum biomarkers of 40 serum samples from patients with LTBI and active TB at the systems level. The interaction network and functional classification of differentially expressed antigens were analyzed using STRING 10.0 and the TB database, respectively. Enzyme-linked immunosorbent assays (ELISA) were used to validate candidate antigens further using 279 samples. The diagnostic performances of candidate antigens were evaluated by receiver operating characteristic curve (ROC) analysis. Both antigen combination and logistic regression analysis were used to improve diagnostic ability.

RESULTSMicroarray results showed that levels of 152 Mycobacterium tuberculosis (Mtb)-antigen- specific IgG were significantly higher in active TB patients than in LTBI patients (P < 0.05), and these differentially expressed antigens showed stronger associations with each other and were involved in various biological processes. Eleven candidate antigens were further validated using ELISA and showed consistent results in microarray analysis. ROC analysis showed that antigens Rv2031c, Rv1408, and Rv2421c had higher areas under the curve (AUCs) of 0.8520, 0.8152, and 0.7970, respectively. In addition, both antigen combination and logistic regression analysis improved the diagnostic ability.

CONCLUSIONSeveral antigens have the potential to serve as serum biomarkers for discrimination between LTBI and active TB.

Adolescent ; Adult ; Aged ; Antibodies, Bacterial ; Antibody Specificity ; Antigens, Bacterial ; Biomarkers ; blood ; Female ; Humans ; Latent Tuberculosis ; blood ; diagnosis ; Logistic Models ; Male ; Middle Aged ; Mycobacterium tuberculosis ; Protein Array Analysis ; methods ; Proteome ; genetics ; Proteomics ; methods ; ROC Curve ; Young Adult

Objective: To explore the evaluation of joint injury by HEAD-US-C (Hemophilic Early Arthropathy Detection with UltraSound in China, HEAD-US-C) in patients with moderate or severe hemophilia A treated with prophylaxis vs on-demand. Methods: The patients from June 2015 to July 2017 with moderate or severe hemophilia A were examined by ultrasound imaging of the elbows, knees and ankles; Meanwhile the HEAD-US-C ultrasound assessment scale and hemophilia joint health score scale 2.1 (HJHS2.1) were used to score the joint status. The correlation between the HEAD-US-C and HJHS score was performed in prophylaxis group and on-demand group patients, respectively. Results: A total of 925 cases of joint ultrasonography were conducted in 70 patients with moderate or severe hemophilia A. Among patients with moderate hemophilia, the median (IQR) of HEAD-US-C score and HJHS score in on-demand group were significantly higher than those in the prophylaxis group[1 (0, 6) vs 0.5 (0, 3) , z=0.177, P=0.046],[2 (0, 4) vs 2 (0, 3) z=0.375, P=0.007], even though there was no significant difference of the median (IQR) number of annualized target joints bleeding episodes between on-demand and prophylaxis groups[1 (0, 7) vs 1 (0, 5) , z=1.271, P=0.137]. Unlike in moderate cases, on-demand treatment group had more annualized target joints bleeding episodes than prophylaxis group among patients with severe hemophilia[3 (0, 8) vs 2 (0, 8) , z=0.780 P=0.037]. The prophylaxis group compared favorably with on-demand therapy group in terms of HEAD-US-C score[1 (0, 6) vs 4 (0, 7) , z=2.189, P=0.008], and HJHS score[2 (0, 5) , 4 (1, 6) , z=3646, P<0.001]for the severe hemophilia patients. The positive correlation between HEAD-US-C score and HJHS score was identified (P<0.05) , whether on-demand treatment or prophylaxis groups. The correlation coefficient between HEAD-US-C score and HJHS score in on-demand treatment and prophylaxis groups were 0.739 (95% CI 0.708-0.708) , 0.865 (95% CI 0.848-0.848) respectively, and 95% CI didn’t overlap (P<0.05) , indicating that the correlation coefficient in prophylaxis group had stronger correlation than that in on-demand group. Conclusions Clinical effects of prophylaxis were significantly better than those of on-demand treatment in patients with moderate or se-vere haemophilia A. HEAD-US-C scoring system could effectively evaluate joints damage in hemophilia A patients treated with on-demand or prophylaxis, companied by significantly positive correlation with HJHS clinical evaluation system, and provided objective index for clinical effect assessment.

Objective: To assess the feasibility of HEAD-US scale in the clinical application of hemophilic arthropathy (HA) and propose an optimized ultrasound scoring system. Methods: From July 2015 to August 2017, 1 035 joints ultrasonographic examinations were performed in 91 patients. Melchiorre, HEAD-US (Hemophilic Early Arthropathy Detection with UltraSound) and HEAD-US-C (HEAD-US in China) scale scores were used respectively to analyze the results. The correlations between three ultrasound scales and Hemophilia Joint Health Scores (HJHS) were evaluated. The sensitivity differences of the above Ultrasonic scoring systems in evaluation of HA were compared. Results: All the 91 patients were male, with median age of 16 (4-55) years old, including 86 cases of hemophilia A and 5 cases hemophilia B. The median (P₂₅, P₇₅) of Melchiorre, HEAD-US and HEAD-US-C scores of 1 035 joints were 2(0,6), 1(0,5) and 2(0,6), respectively, and the correlation coefficients compared with HJHS was 0.747, 0.762 and 0.765 respectively, with statistical significance (P<0.001). The positive rates of Melchiorre, HEAD-US-C and HEAD-US scale score were 63.0% (95%CI 59.7%-65.9%), 59.5% (95%CI 56.5%-62.4%) and 56.6% (95%CI 53.6%-59.6%) respectively, and the difference was statistically significant (P<0.001). Even for 336 cases of asymptomatic joints, the positive rates of Melchiorre, HEAD-US-C and HEAD-US scale score were 25.0% (95%CI 20.6%-29.6%), 17.0% (95%CI 12.6%-21.1%) and 11.9% (95%CI 8.4%-15.7%) respectively, and the difference was statistically significant (P<0.001). There were significant changes (P<0.05) in the ultrasonographic score of HA before and after onset of hemorrhage in 107 joints of 40 patients. The difference in variation amplitude of HEAD-US-C scores and HEAD-US scores before and after joint bleeding was statistically significant (P<0.001). Conclusion Compared with Melchiorre, there were similar good correlations between HEAD-US, HEAD-US-C and HJHS. HEAD-US ultrasound scoring system is quick, convenient and simple to use. The optimized HEAD-US-C scale score is more sensitive than HEAD-US, especially for patients with HA who have subclinical state, which make up for insufficiency of sensitivity in HEAD-US scoring system

Objective To observe the pathological response in the tumor tissue and the changes of serum level of vascular endothelial growth factor ( VEGF) in esophageal cancer patients receiving concurrent chemoradiotherapy, in order to study the impacts of these two factors on the prognosis of patients. Methods One hundred pathologically confirmed esophageal cancer patients were treated with radiotherapy including 72 patients with concurrent chemoradiotherapy. After 4 weeks, gastroscopy was performed to collect tumor biopsies for examination of pathological changes. The responses to radiotherapy were classified into three degrees: mild, moderate and intensive. Moreover, serum samples were collected from the patients prior to, at the fourth week during radiotherapy, and one week after radiotherapy, and serum VEGF level was determined. The changes of serum VEGF were classified as increased, unchanged and decreased. Serum samples from 30 healthy subjects were collected and represented as VEGF healthy control. Results Among the eighty?nine patients evaluable, the 1? and 3?year overall survival ( OS) rates were 70.8% and 33.3%, respectively;1?year and 3?year progression?free survival ( PFS) rates were 61.8% and 28.2%, respectively;and 1?year and 3?year local control ( LC) rates were 76.9% and 50.0%, respectively. The 1?year OS rates in the patients with mild, moderate and intensive pathological responses were 50. 0%, 76. 9% and 78. 0%, respectively. The 1?year OS rate in the mild response group was significantly lower than that in the intensive response group ( P<0.05) . The 1?year and 3?year PFS rates in the three groups were 36.4%, 73.1%, 68.3%, and 0. 0%, 40.0% and 38. 9%, respectively, showing that the rate in the mild response group was significantly lower than that in the moderate and intensive response groups ( P<0.05 for both) . The PFS rate in the mild response group was significantly lower than that in the moderate and intensive response groups ( P<0.05 for both) . Moreover, the 1?year local control ( LC) rates in the three groups were 52.9%, 83.3%and 83.8%, and the three?year LC rates were 0. 0%, 64. 3% and 64. 0%, respectively, showing that the lowest LC rates in the mild response group were significantly lower than that in the moderate and intensive response groups (P<0.05 for both). The average serum VEGF levels in the patients prior to, during and after radiotherapy were (109.6±33.7) ng/L, (101.2±24.3) ng/L and (99.5±22.9) ng/L, respectively, all significantly higher than that in the healthy subjects [(79.6±39.2) ng/L, P<0.05 for both]. The level of serum VEGF was decreased during and after radiotherapy compared with that before radiotherapy ( F=6.124, P=0.004). The 1?year OS rates in the VEGF?increased, unchanged and decreased groups were 50.0%, 67.4% and 86.7%, respectively, and the 3?year OS rates in these three groups were 15. 4%, 27. 0% and 50.0%, respectively. The OS rates in the increased group were significantly lower than that in the VEGF?decreased group (P<0.05). Moreover, the 3?year PFS rates in the three groups were 7.7%, 21.6% and 46.4%, respectively, and the rate in the VEGF?increased group was significantly lower than that in the VEGF?decreased group ( P<0.05) . The multi?variate analysis showed that TNM stage, pathological response and serum VEGF were independent factors affecting the survival in the non?surgical patients with esophageal cancer (P<0.05 for all). Conclusions Tumor tissue pathological response and variation of serum VEGF level in response to chemoradiotherapy can be used to predict the efficacy of chemoradiotherapy in non?surgical patients with esophageal cancer. Hence, monitoring the pathological response and VEGF changes during the course of therapy is of utmost importance to evaluate and perform an individualized therapy in clinical practice.