Da Chaihutang from the Treatise on Febrile Disease （Shanghanlun） has the function of harmonizing lesser Yang and discharging internal heat. It is formulated by ZHANG Zhongjing for the concurrent diseases of lesser Yang and Yang brightness and has been widely used in the treatment of digestive system diseases， especially malignant tumors. By review of the articles published in the last 20 years， this paper summarizes the application of Da Chaihutang in treating digestive system tumors from syndrome analysis， clinical research， and mechanism research. Da Chaihutang can treat the syndrome involving lesser Yang and Yang brightness in the digestive system， release interior and exterior to expel pathogen， and remove obstruction by conforming to the descending nature of the six fu-organs. In clinical practice， Da Chaihutang can directly treat digestive system malignant tumors such as liver cancer， pancreatic cancer， intestinal cancer， gastric cancer， and gallbladder cancer. In addition， it can relieve common complications of digestive system malignant tumors， such as cancerous fever， malignant obstructive jaundice， and constipation. Moreover， it can alleviate the adverse reactions caused by Western medical treatment， such as post-embolization syndrome， side effects of chemotherapy， and incomplete postoperative obstruction. Da Chaihutang is effective when used alone as it can relieve clinical symptoms， improve prognosis， and prolong survival of advanced patients and is safe and non-toxic， suitable for long-term use by tumor patients. Regarding the mechanism， Da Chaihutang can promote the apoptosis and inhibit the proliferation of tumor cells， reduce inflammation and inflammatory injury， and improve the liver function. The clear effect and mechanism confirms the anti-tumor effect of Da Chaihutang. This paper comprehensively describes the current research status of Da Chaihutang in the treatment of digestive system tumors and puts forward the deficiencies and improvement measures for the current research， aiming to provide reference for the application of this formula in treating digestive system tumors， the establishment of Chinese and Western medicine treatment schemes of tumors， and the research and development of anti-tumor drugs.

Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.

Breast cancer is the most common cancer in women and one of the deadliest cancers worldwide.According to the distribution of tumor tissue,breast cancer can be divided into invasive and non-invasive forms.The cancer cells in invasive breast cancer pass through the breast and through the immune system or systemic circulation to different parts of the body,forming metastatic breast cancer.Drug resistance and distant metastasis are the main causes of death from breast cancer.Research on breast cancer has attracted extensive attention from researchers.In vitro construction of tumor models by tissue engineering methods is a common tool for studying cancer mechanisms and anticancer drug screening.The tumor microenvironment consists of cancer cells and various types of stromal cells,including fibroblasts,endothelial cells,mesenchymal cells,and immune cells embedded in the extracellular matrix.The extracellular matrix contains fibrin proteins(such as types Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅵ,and Ⅹcollagen and elastin)and glycoproteins(such as proteoglycan,laminin,and fibronectin),which are involved in cell signaling and binding of growth factors.The current traditional two-dimensional(2D)tumor models are limited by the growth environment and often cannot accurately reproduce the heterogeneity and complexity of tumor tissues in vivo.Therefore,in recent years,research on three-dimensional(3D)tumor models has gradually increased,especially 3D bioprinting models with high precision and repeatability.Compared with a 2D model,the 3D environment can better simulate the complex extracellular matrix components and structures in the tumor microenvironment.Three-dimensional models are often used as a bridge between 2D cellular level experiments and animal experiments.Acellular matrix,gelatin,sodium alginate,and other natural materials are widely used in the construction of tumor models because of their excellent biocompatibility and non-immune rejection.Here,we review various natural scaffold materials and construction methods involved in 3D tissue-engineered tumor models,as a reference for research in the field of breast cancer.

As the severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)pandemic continues to spread globally,its genome is undergoing mutations and evolution,giving rise to various strains such as α,β,γ,and δ.Therefore,the continuous development of drugs and vaccines targeting the various strains has become pivotal to addressing the COVID-19 pandemic.Establishing animal models of SARS-CoV-2 enables study of the pathogenesis of the virus and is crucial for evaluating the efficacy of drugs and vaccines against SARS-CoV-2.However,commonly used animal models such as mice exhibit limited susceptibility to wildtype SARS-CoV-2 infection,underscoring the urgent need for animal models that can be infected with the novel coronavirus and better simulate the human pathological and physiological conditions.This review summarizes the animal models used to study SARS-CoV-2 infection and transmission,and their progress in characterizing the viral immunopathology.

With the enormous resources having been invested in oncology drugs development in China in recent years, the Center for Drug Evaluation (CDE) of National Medical Products Administration has been issuing a number of technical guidelines to further standardize the requirements on implementation and registration of domestic oncology clinical trials. As data is the cornerstone of clinical trials, data integrity and quality will directly decide the outcome of clinical studies. Given the specific characteristics of oncology therapeutic clinical trials, and combined with the clinical data standards established by the Clinical Data Interchange Standards Consortium (CDISC) and the issued industrial guidelines, this article introduces the general considerations of clinical data management for oncology clinical trials, with the aim of emphasizing normative data collection and timely data monitoring to ensure the data quality and reliability of results of the study. This article discusses the impact of complex study design on CRF, design CRF according to CDASH, develop DVP scientifically, rolling submissions and data cut-off.

The present study explored the effect and mechanism of repeatedly steamed and sundried Rehmanniae Radix Praeparata(RRP) in delaying brain aging in ovariectomized mice. After ovariectomy, the mice were randomly divided into a model group, an estradiol valerate group(0.3 mg·kg~(-1)), and low-(1.0 g·kg~(-1)), medium-(2.0 g·kg~(-1)), and high-dose(4.0 g·kg~(-1)) RRP groups, and a sham operation group was also set up, with 15 mice in each group. One week after the operation, intragastric administration was carried out for 15 consecutive weeks. The step-down test and Morris water maze test were used to detect the behavioral changes of mice. HE staining and Nissl staining were used to observe the morphological changes of mouse brain tissues. Immunohistochemistry was used to detect the expression of Aβ and ER_β in mouse brain tissues. The serum estrogen levels and cholinesterase and cholinesterase transferase levels in brain tissues of mice were detected by assay kits. The extracted hippocampal protein was detected by the Nano-ESI-LC-MS system, identified by the Protein Discovery, and analyzed quantitatively and qualitatively by the SIEVE. The PANTHER Classification System was used for GO analysis and KEGG pathway enrichment analysis of the differential proteins. Compared with the sham operation group, the model group showed decreased learning and memory ability, shortened step-down latency(P<0.05), prolonged escape latency(P<0.05), reduced platform crossings and residence time in the target quadrant, scattered nerve cells in the hippocampus with enlarged intercellular space, increased expression of Aβ-positive cells(P<0.05), declining expression of ER_β-positive cells and estrogen level(P<0.05), and weakened cholinergic function(P<0.05). Compared with the model group, the RRP groups showed improved learning and memory ability, prolonged step-down latency(P<0.05), increased estrogen level(P<0.05), neatly arranged nerve cells in the hippocampus with complete morphology, declining Aβ-positive cells, and elevated expression of ER_β-positive cells. A total of 146 differential proteins were screened out by proteomics, and KEGG pathway enrichment yielded 75 signaling pathways. The number of proteins involved in the dopaminergic synapse signaling pathway was the largest, with 13 proteins involved. In summary, RRP can delay brain aging presumedly by increasing the level of estrogen, mediating the dopaminergic synapse signaling pathway, and improving cholinergic function.
Aging ; Animals ; Female ; Hippocampus/metabolism* ; Learning ; Mice ; Plant Extracts ; Proteomics ; Rehmannia

Objective: To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection. Methods: Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval. Results: 132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death. Conclusion Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.

Objective To systematically evaluate the biomechanical recovery of drilled holes in the femur in SD rats.Methods Eighteen female SD rats were randomized into 3 even groups (n =6).Models of 2-mm drilled holes in bilateral femurs were established in groups A and B with 2 holes on each side while no drilling was performed in group C.Samples were harvested in group A at postoperative 4 weeks,in group B at postoperative 8 weeks while at both 4 and 8 weeks in group C.The samples were evaluated in terms of linear elasticity (compression test),viscoelasticity (relaxation and creep tests) and durability (fatigue failure test).Micro-CT scan was performed to measure the bone volume fraction (BV/TV) and bone mineral density (BMD) of new bone.Sirus red staining was performed to measure regeneration of type Ⅰ collagen of new bone.Results The elasticity modulus,maximum load,compression strength and conditional yield limit in groups A were significantly lower than those in group B which were also significantly lower than those in group C (P ＜ 0.05).At 7,200 s,the relaxation (14.56 ±0.69 MPa) and creep variation (11.37％ ± 0.70％) in group A were significantly higher than those in group B (11.06 0.63 MPa and 8.98％ ± 0.40％) which were also significantly higher than those in group C (6.99 ±0.56 MPa and 5.10％ ±0.23％) (P ＜ 0.05).At the constant amplitude loads from 20 N to 200 N,from 20 N to 300 N and from 20 N to 400 N,the recycling numbers in group A (6,044.3 ±879.7,4,093.3 ±628.5 and 1,919.3 ±847.5) were significantly lower than those in group B (10,192.3 ± 1,109.1,6,750.6 ± 818.0 and 3,376.6 ± 671.3) which were also significantly lower than those in group C (28,068.3 ±2,702.6,11,788.3 ± 1,141.6 and 5,296.3 ± 735.0) (P ＜ 0.05).By micro-CT scan,the BVT and BMD in group A were significantly lower than those in group B which were also significantly lower than those in group C (P ＜ 0.05).The sirus red staining showed the type Ⅰ collagen in the bone defect area was completely regenerated in group B.Conclusion Systematic biomechanical measurements may actually detect the characteristics of biomechanical recovery of bone holes in SD rats,enriching the basic research on the bone damage repairing progress.

PURPOSE: c-Met and its ligand, hepatocyte growth factor (HGF), play a critical role in oncogenesis and metastatic progression. The aim of this study was to identify inhibited enzymogram and to test the antitumor activity of SIM-89 (a c-Met receptor tyrosine kinase inhibitor) in non-small cell lung cancer. MATERIALS AND METHODS: Z′-LYTE kinase assay was employed to screen the kinase enzymogram, and mechanism of action (MOA) analysis was used to identify the inhibited kinases. Cell proliferation was then analyzed by CCK8 assay, and cell migration was determined by transwell assay. The gene expression and the phosphorylation of c-Met were examined by realtime-PCR and western blotting, respectively. Finally, the secretion of HGF was detected by ELISA assay. RESULTS: c-Met, activated protein kinase (AMPK), and tyrosine kinase A (TRKA) were inhibited by SIM-89 with the IC₅₀ values of 297 nmol/L, 1.31 µmol/L, and 150.2 nmol/L, respectively. SIM-89 exerted adenosine triphosphate (ATP) competitive inhibition on c-Met. Moreover, the expressions of STAT1, JAK1, and c-Met in H460 cells were decreased by SIM-89 treatment, and c-Met phosphorylation was suppressed in A549, H441, H1299, and B16F10 cells by the treatment. In addition, SIM-89 treatment significantly decreased the level of HGF, which accounted for the activation of c-Met receptor tyrosine kinase. Finally, we showed cell proliferation inhibition and cell migration suppression in H460 and H1299 cells after SIM-89 treatment. CONCLUSION: In conclusion, SIM-89 inhibits tumor cell proliferation, migration and HGF autocrine, suggesting it's potential antitumor activity.
Adenosine Triphosphate ; Blotting, Western ; Carcinogenesis ; Carcinoma, Non-Small-Cell Lung* ; Cell Movement ; Cell Proliferation ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Hepatocyte Growth Factor ; Lung Neoplasms ; Phosphorylation ; Phosphotransferases ; Protein Kinases ; Protein-Tyrosine Kinases

Objective To investigate the effect of prevascularized tissue-engineered bone graft on regeneration of femoral bone defects in rats.Methods Models of femoral bone defect were created at the bilateral hind limbs of 20 healthy female 10 week-old rats which were divided into 2 even groups randomly (n =10).In group A,conventional tissue-engineered bone grafts were transplanted into the femoral bone defects;in group B,tissue-engineered bone grafts and vascular bundles were implanted into the femoral defects.At 1,4 and 8 weeks after operation,3 rats were sacrificed each time in each group to harvest samples.The remaining one in each group served as a spare animal.Regeneration of bone defects and degradation of scaffolds were assessed by radiologic modality and hematein eosin staining.Results At week 1,the new bone ratio (BV/TV) was 5.47％ ± 1.90％ in group A and 8.49％ ± 1.26％ in group B,showing no significant difference (P ＞ 0.05);at weeks 4 & 8,the BV/TV were 17.54％ ±2.04％ and 39.73％ ± 4.01％ in group A,significantly lower than those in group B (25.32％ ± 2.15％ and 53.22％ ± 2.94％) (P ＜ 0.05).At weeks 1 & 4,the scaffold degradation ratios (RSV/SV) were 97.33％ ± 2.52％ and 80.60％ ±4.00％,showing no significant differences from those in group B (95.67％ ±3.51％ and 75.22％ ±6.20％) (P ＞ 0.05).At week 8,the scaffold degradation ratio in group A (65.46％ ±4.51％) was significantly higher than that in group B (50.19％ ±4.91％) (P ＜ 0.05).At week 8,hematein eosin staining showed better integration of scaffolds with the femur,faster degradation of the interior scaffolds and greater osteogenetic activity in group B.Conclusion Prevascularization of tissue-engineered bone graft may increase new bone volume and scaffold degradation rate,promoting repair of femoral bone defects in rats.