Concepts are the cornerstone of the development of disciplines. The concepts of TCM present that a superior concept contains more subordinate concepts. The superordinate concepts are often used to refer to different subordinate concepts, which can refer to both superior concepts themselves and non-specific subordinate concepts, that is, the characteristics of subordinate coverage and indefinite reference, which cause confusion in concept meaning, concept relationships, reasoning logic, and other problems. Nowadays, the TCM scholars pay little attention to this characteristic. Therefore, this article analyzed this characteristic, discussed its impact on the inheritance and development of TCM, and proposed that starting from the anchoring of concepts and entities to clarify the connotation of concepts, looking forward to provide new ideas for the definition of the concepts of TCM and the development of the discipline.

Objective To investigate the mechanism by which Biejiajian Pill(BJJP)regulates ferroptosis in hepatocellular carcinoma(HCC)cells through the p62/Keap1/NRF2 pathway and to provide an experimental basis for its application in the prevention and treatment of HCC.Methods Huh7 HCC cells were divided into a normal control group,a BJJP drug serum group,an erastin(a ferroptosis inducer)group,a BJJP drug serum+erastin group,and BJJP drug serum+ferrostatin-1(Fer-1)(a ferroptosis inhibitor)group.BJJP drug serum was prepared with animals treated with BJJP and CCK-8 assay was performed to determine the optimal concentration and duration of BJJP intervention.The levels of intracellular iron(Fe),reduced glutathione(GSH),lipid peroxides(MDA),and reactive oxygen species(ROS)were measured.Western blot was performed to determine the expression levels of FTH1,GPX4,xCT,SLC40A1,Keapl,p62,and NRF2.JC-1 staining was performed to measure mitochondrial membrane potential,and cell immunofluorescence was performed to determine the expression of p62 and Keap1.Results According to the CCK-8 assay results,the cell inhibition rate was highest when BJJP was administered at a high dose of 2.2 g/kg(P＜0.001).Furthermore,the inhibition rate of Huh7 cells was highest when Huh7 cells were treated with high-dose BJJP drug serum for 48 h.Therefore,the serum concentration of high-dose BJJP and 48 h were selected as the treatment dose and duration for the subsequent experiment.Compared with the control group,the BJJP drug serum group,the erastin group,and the BJJP drug serum+erastin group showed increased iron content,decreased GSH content,increased MDA levels,increased ROS aggregation,decreased FTH1,GPX4,xCT,SLC40A1,p62,and NRF2 contents,increased Keap1 content,and decreased mitochondrial membrane potential(P＜0.05).Conclusion BJJP regulates ferroptosis in Huh7 HCC cells by inhibiting the p62/Keap1/NRF2 pathway,demonstrating potentials as a therapeutic agent for HCC.

ObjectiveTo investigate the efficacy and safety of cinobufagin tablets combined with thalidomide/dexamethasone （TD） regimen in the treatment of newly diagnosed multiple myeloma （NDMM） with phlegm and stasis obstruction. MethodsThe clinical data of 50 patients with NDMM of phlegm and stasis obstruction who were hospitalized at the Jiangsu Province Hospital of Chinese Medicine from June 1st， 2015 to July 31th， 2019 were retrospectively analyzed， and they were divided into a control group （bortezomib/dexamethasone-containing regimen， 27 cases） and an observation group （cinobufagin tablets combined with TD regimen， 23 cases）. The clinical efficacy and safety were compared between the two groups after two or three courses of treatment. The primary outcomes were clinical remission rate including overall response rate and deep remission rate， one-year and two-year overall survival rate， and adverse effects. The secondary outcomes were the proportion of plasma cells in bone marrow， hemoglobin， β2-microglobulin， lactate dehydrogenase， serum creatinine， blood urea nitrogen， bone pain score， and KPS functional status score （KPS score） before and after treatment. ResultsIn terms of clinical efficacy， there was no statistically significant difference （P＞0.05） in the overall response rate ［the observation group 69.57%（16/23） vs the control group 70.37% （19/27）］ and deep remission rate ［the observation group 56.52% （13/23） vs the control group 55.56% （15/27）］ between groups after the treatment. The one-year overall survival rates of the observation group and the control group were 90.9% and 92.4%， and the two-year overall survival rates were 81.8% and 80.9% respectively， with no statistically significant differences between groups （P＞0.05）. During the treatment， no renal function injury occurred in both groups. The incidence of peripheral nerve injury in the observation group was 8.70%， which was lower than 48.15% in the control group （P＜0.01）. After the treatment， the proportion of myeloma plasma cells， β2-microglobulin， serum creatinine level， and bone pain score decreased， while the hemoglobin level and KPS score increased in both groups （P＜0.05 or P＜0.01）. Compared between groups after treatment， the bone pain score of the observation group was lower than that of the control group， while the KPS score was higher than that of the control group （P＜0.05）. ConclusionThe clinical efficacy of cinobufagin tablets combined with TD in the treatment of NDMM is equivalent to bortezomib/dexamethasone-containing regimen， but the former is more helpful in relieving the pain and improving the quality of life， and has better safety.

From the perspectives of traditional Chinese medicine （TCM） information knowledge base and assisted decision-making knowledge base， the construction status， quality evaluation status and existing problems of current TCM knowledge bases have been sorted out. And based on the quality evaluation strategies and dimensions of know-ledge bases in other disciplines， the evaluation indexes for TCM knowledge base is discussed， and the evaluation framework is initially formed， providing ideas for the improvement of the TCM knowledge base evaluation system. In terms of the evaluation indexes， there are basic evaluation dimensions which include data sources， data collection， and data application. The specific evaluation dimension of the information-based knowledge base is data quality， while that of the assisted decision-making knowledge base is data matching. Except for the data application dimension which counts the valid data items in the database for calculation， other indexes are scored based on the qualitative evaluation of "yes"， "no" or "unknown". The basic evaluation score and the specific evaluation score are added to obtain the total score. The knowledge base is graded according to the score， and the results are presented in the form of grade plus number.

SWOT-PEST model was used to analyze the internal advantages and disadvantages,external,opportunities and challenges of tertiary public pediatric hospitals.Based on stakeholder theory,through the literature review method,policy analysis method,combined with the actual work,and summarize its main role and demands.Put forward the development strategy of three-level public pediatric specialty hospital.Through the analysis of interest demands of stakeholders of tertiary public pediat-ric specialty hospitals,the overall development is good at present,but there are still problems that need to be solved urgently.From the perspective of internal and external stakeholders,the optimization strategy involving multiple levels,multiple angles and multiple subjects is proposed to promote the comprehensive development of tertiary public pediatric specialty hospitals.

BACKGROUND: Sarcopenia is an age-related progressive skeletal muscle disorder involving the loss of muscle mass or strength and physiological function. Efficient and precise AI algorithms may play a significant role in the diagnosis of sarcopenia. In this study, we aimed to develop a machine learning model for sarcopenia diagnosis using clinical characteristics and laboratory indicators of aging cohorts. METHODS: We developed models of sarcopenia using the baseline data from the West China Health and Aging Trend (WCHAT) study. For external validation, we used the Xiamen Aging Trend (XMAT) cohort. We compared the support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and Wide and Deep (W&D) models. The area under the receiver operating curve (AUC) and accuracy (ACC) were used to evaluate the diagnostic efficiency of the models. RESULTS: The WCHAT cohort, which included a total of 4057 participants for the training and testing datasets, and the XMAT cohort, which consisted of 553 participants for the external validation dataset, were enrolled in this study. Among the four models, W&D had the best performance (AUC = 0.916 ± 0.006, ACC = 0.882 ± 0.006), followed by SVM (AUC =0.907 ± 0.004, ACC = 0.877 ± 0.006), XGB (AUC = 0.877 ± 0.005, ACC = 0.868 ± 0.005), and RF (AUC = 0.843 ± 0.031, ACC = 0.836 ± 0.024) in the training dataset. Meanwhile, in the testing dataset, the diagnostic efficiency of the models from large to small was W&D (AUC = 0.881, ACC = 0.862), XGB (AUC = 0.858, ACC = 0.861), RF (AUC = 0.843, ACC = 0.836), and SVM (AUC = 0.829, ACC = 0.857). In the external validation dataset, the performance of W&D (AUC = 0.970, ACC = 0.911) was the best among the four models, followed by RF (AUC = 0.830, ACC = 0.769), SVM (AUC = 0.766, ACC = 0.738), and XGB (AUC = 0.722, ACC = 0.749). CONCLUSIONS: The W&D model not only had excellent diagnostic performance for sarcopenia but also showed good economic efficiency and timeliness. It could be widely used in primary health care institutions or developing areas with an aging population. TRIAL REGISTRATION Chictr.org, ChiCTR 1800018895.
Humans ; Aged ; Sarcopenia/diagnosis* ; Deep Learning ; Aging ; Algorithms ; Biomarkers

Objective:To analyze the clinical and pathological characteristics of chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) and not receiving antiviral therapy.Methods:This study retrospectively included CHB patients diagnosed by liver biopsy at the Third Hospital of Hebei Medical University from January 2008 to December 2022. According to the HBV DNA and HBeAg status of "immune tolerance period and immune control period", these patients were divided into three groups: chronic HBV carrier group, inactive HBsAg carrier group and indeterminate group including the patients that did not meet the inclusion criteria of the above two groups. Kruskal-Wallis H test was used for comparison of continuous data between multiple groups. Mann-Whitney U test was used for comparison of continuous data and ordered categorical data between two groups. Chi-square test or Fisher′s exact test was used for comparison of categorical data between two groups. Results:A total of 284 CHB patients with normal ALT were enrolled. There were 64, 88 and 132 cases in the chronic HBV carrier group, inactive HBsAg carrier group and indeterminate group, respectively. Histopathological analysis revealed that there were 182 (64.08%) cases with pathological inflammation grade (G) and/or fibrosis stage (S)≥2, 155 (54.58%) with S≥2 and 120 (42.25%) with G≥2. The proportion of patients with G and/or S≥2 in the indeterminate group [70.45% (93/132)] was higher than that in the chronic HBV carrier group [48.44% (31/64)] and inactive HBsAg carrier group [65.91% (58/88)] (both P<0.05). Patient′s age and the ratio of patients with S≥2 in the chronic HBV carrier group [33 years old, 39.06% (25/64)] were smaller than those in the inactive HBsAg carrier group [39 years old, 56.82% (50/88)] and the indeterminate group [39 years old, 60.61% (80/132)] (all P<0.05). Patients in the inactive HBsAg carrier group (19 U/L) had lower ALT levels than those in the chronic HBV carrier group (26 U/L) and the indeterminate group (23 U/L) (both P<0.05). The proportion of patients with cytoplasmic/cytoplasmic nuclear-type HBcAg was higher in patients with G and/or S≥2 than in patients with G and S<2 [73.08% (57/78) vs 32.08% (17/53), P<0.05], and the proportion of patients with cytoplasmic/cytoplasmic nuclear-type HBcAg increased gradually with age. The proportion of patients with cytoplasmic/cytoplasmic nuclear-type HBcAg was higher in patients with G and/or S≥2 than in patients with G and S<2 in the chronic HBV carrier status and indeterminate groups [93.33% (28/30) vs 43.33%(13/30), P<0.05; 59.46% (22/37) vs 12.50% (2/16); both P<0.05]. There was a statistically significant difference in the incidence of significant liver injury between patients≤ 30 years old and >30 years old [52.7% (39/74) vs 68.1% (143/210), P<0.05]. Conclusions:Significant liver injury occurred in 64.08% (182/284) of CHB patients with normal ALT not receiving antiviral therapy, which required the attention of clinicians. Among CHB patients with normal ALT, the expression site of HBcAg in hepatocytes was related to the occurrence of significant liver injury and could be expected to serve as an important indicator for predicting the patient′s status and the necessity of antiviral treatment. CHB patients with positive HBV DNA who were older than 30 years required antiviral treatment, and CHB patients≤30 years with normal ALT and significant hepatic tissue damage also required antiviral treatment.

Objective To investigate the clinical and pathological features of children with glycogen storage disease (GSD). Methods A retrospective analysis was performed for ten children with GSD who were admitted to the Third Hospital of Hebei Medical University and The Fifth Medical Center of Chinese PLA General Hospital from January 2002 to January 2022, based on medical history, liver biochemistry, and liver biopsy, and population characteristics, clinical manifestations, biochemical parameters, and liver histopathological characteristics were compared and analyzed. Results All ten children had developmental retardation and a short stature, with the manifestations of abnormal liver function, mild weakness, poor appetite, yellow urine, and yellow eyes, and four children had hepatosplenomegaly. Among the ten children, six had the clinical manifestations of hypoglycemia, and one had bilateral gastrocnemius hypertrophy and positive Gower sign. Two children had positive CMV IgG. Liver histopathological manifestations included diffuse enlargement of hepatocytes, light cytoplasm, and small nucleus in the middle like plant cells, with or without fibrous tissue proliferation. Conclusion Most patients with GSD have developmental retardation and abnormal aminotransferases, and liver pathological examination shows specific pathological features.

【Objective】 To evaluate the efficacy and safety of human coagulation factor Ⅷ developed by Shenzhen Weiguang Biological products Co, Ltd in the treatment of patients with hemophilia A. 【Methods】 A prospective, multi-center, open, single-group clinical study was conducted. A total of 65 subjects with hemophilia A were enrolled, and human coagulation factor Ⅷ(FⅧ) was injected according to the patients’ bleeding severity. The improvement score of bleeding symptoms and signs after the first infusion of the first bleeding event and the transfusion efficiency of FⅧ activity at 10 min and 1 hour after infusion were taken as the main efficacy indexes. The improvement scores of bleeding symptoms and signs after the first infusion and the increase of FⅧ activity at 10 min and 1 hour after infusion were the secondary efficacy indexes. 【Results】 The 65 subjects were enrolled in safety analysis set (SS) and full analysis set (FAS), and 58 of them were enrolled in protocol analysis set (PPS). Ten minutes and one hour after the first infusion, the level of factor Ⅷ activity in the subjects increased significantly, and the FⅧ activity increased by 100% or more in more than 79% of the subjects. The average infusion efficiency of FⅧ activity in all subjects was more than 100%. In 70% of the subjects, the pain was relieved rapidly and /or the bleeding symptoms were significantly improved 8 hours after each bleeding infusion, and the improvement rate of bleeding symptoms and signs reached 100% 72 hours after infusion. 【Conclusion】 After infusion of human coagulation factor Ⅷ, the activity level of factor Ⅷ in patients with hemophilia A significantly increased. The infusion efficiency can reach a optimal level, and the bleeding symptoms can be significantly improved.

【Objective】 To evaluate the clinical efficacy and safety of one kind of human prothrombin complex concentrate in treatment of patients with hemophilia B. 【Methods】 The clinical data of 36 patients with hemophilia B treated with human prothrombin complex concentrate produced by Shenzhen Weiguang Biological Products Co. Ltd. from May 2018 to April 2019 were retrospectively analyzed, and its clinical efficacy and safety were analyzed. 【Results】 A total of 35 subjects entered the full analysis set (FAS)and safety set (SS), 33 subjects entered the per protocol Set (PPS). Thirty minutes after the first infusion of FAS subjects, the activity of coagulation factor Ⅸ increased from (3.93±0.975) IU/dL to (25.61±9.337) IU/dL, and the infusion efficiency was (96.43±22.007)%. The increased value of coagulation factor Ⅱ activity was (73.25±14.874) IU/dL. The activity of coagulation factor Ⅶ was (42.79±16.847) IU/dL. The increased value of coagulation factor Ⅹ activity was (65.29±17.042) IU/dL. The increased value of coagulation factor Ⅸ activity was (21.68±9.434%) IU/dL. Twenty-four hours after the first infusion of FAS subjects, the improvement of bleeding symptoms and signs was excellent in 21 cases (60%), improved in 14 cases (40.0%), and the effective rate was 100%. The incidence of adverse reactions was 2.9%(1/35), and there was no antibody to human coagulation factor Ⅸ and new virus infection. 【Conclusion】 Infusion of human prothrombin complex concentrate produced by Shenzhen Weiguang Biological Products Co. Ltd. in the treatment of hemophilia B has significant clinical efficacy and good safety.