ObjectiveTo sort out the historical evolution， prescription evolution and modern clinical application of Huagaisan. MethodHuagaisan and its synonym Huagaitang are used as keywords to search the databases of Traditional Chinese Medicine Think Tank， Chinese Medical Dictionary， Airusheng Chinese Medical Database and China National Knowledge Infrastructure（CNKI）. According to the inclusion and exclusion criteria， we obtained the information of ancient books and modern clinical research literature related to Huagaisan， and systematically reviewed and analyzed the historical origin， prescription composition， preparation method， dosage， efficacy， medicinal material origin， processing method and modern clinical application of Huagaisan. ResultA total of 198 pieces of ancient book information were included， involving 93 ancient Chinese medicine books. Huagaisan was composed of fried Perillae Fructus， red Poria， fried Mori Cortex， Citri Eoxcarpium Rubrum， stir-fried Armeniacae Semen Amarum， Ephedrae Herba and fried Glycyrrhizae Radix et Rhizoma， which had the efficacy of promoting the lungs and relieving epidemiological symptoms， expelling phlegm and relieving cough， and treating cough with wind-cold bundled epidemiological symptoms and stagnation of phlegm and Qi. The preparation method was suggested as boiling powder， crushing the seven herbs into coarse particles， the dosage of each drug was fried Perillae Fructus of 1.27 g， red Poria of 1.27 g， fried Mori Cortex of 1.27 g， Citri Eoxcarpium Rubrum of 1.27 g， stir-fried Armeniacae Semen Amarum of 1.27 g， Ephedrae Herba of 1.27 g and fried Glycyrrhizae Radix et Rhizoma of 0.64 g， taking 8.26 g when decocting， adding 300 mL of water， decocting to 210 mL， removing the dregs， and taking it warmly after meals. Twenty-one clinical research papers were included to analyze the modern clinical application of Huagaisan， which was mainly used in the treatment of respiratory diseases such as pneumonia， asthma， bronchitis and so on. ConclusionThis paper has verified and summarized the key information of the famous classical formula Huagaisan， which can provide a detailed reference basis for the development and clinical application of its compound preparation.

Long non-coding RNAs(lncRNAs)play an indispensable role in the occurrence and development of ovarian cancer(OC).However,the potential involvement of lncRNAs in the progression of OC is largely unknown.To investigate the detailed roles and mechanisms of RAD51 homolog B-antisense 1(RAD51B-AS1),a novel lncRNA in OC,reverse transcription-quantitative polymerase chain reaction(RT-qPCR)was performed to verify the expression of RAD51B-AS1.Cellular proliferation,metastasis,and apoptosis were detected using the cell counting kit-8(CCK-8),colony-formation,transwell,and flow cytometry assays.Mouse xenograft models were established for the detection of tumorigenesis.The results revealed that RAD51B-AS1 was significantly upregulated in a highly metastatic human OC cell line and OC tissues.RAD51B-AS1 significantly increased the proliferation and metastasis of OC cells and enhanced their resistance to anoikis.Biogenetics prediction analysis revealed that the only target gene of RAD51B-AS1 was RAD51B.Subsequent gene function experiments revealed that RAD51B exerts the same biological effects as RAD51B-AS1.Rescue experiments demonstrated that the malignant biological behaviors promoted by RAD51B-AS1 overexpression were partially or completely reversed by RAD51B silencing in vitro and in vivo.Thus,RAD51B-AS1 promotes the malignant biological behaviors of OC and activates the protein kinase B(Akt)/B cell lymphoma protein-2(Bcl-2)signaling pathway,and these effects may be associated with the positive regulation of RAD51B expression.RAD51B-AS1 is expected to serve as a novel molecular biomarker for the diagnosis and prediction of poor prognosis in OC,and as a potential therapeutic target for disease management.

Objective To conduct bibliometric visualization analyses of the literature domestic and overseas on active surveillance of post-marketing safety of drugs,aiming to display the current status and trend of hotspots in this field and to provide references for future research and the improvement of the Chinese management system of active surveillance.Methods The English and Chinese literature on active surveillance of post-marketing safety of drugs were searched in Web of Science and CNKI respectively and imported into CiteSpace 6.3.R2 software for the analysis of the number of publications,authors,institutions,and national cooperative networks,and the analysis of keyword co-occurrence,clustering and emergence.Results 415 Chinese and 676 English literature were included,with an overall increasing trend in annual publication volume.The author collaboration network of Chinese literature was smaller than that of English literature,and the partnership network was sparse,with no strong centralized institution.Domestic drug regulatory agencies played an important role in the field,while drug companies'monitoring research on their own products was still relatively scarce.The research topic covered active surveillance systems,technical method research,and drug safety active surveillance practice research for specific drugs and diseases.Conclusion Countries worldwide have widely considered active surveillance of post-marketing drug safety.The heat of research activities in China has shown a significant growth trend.However,there is still a significant gap compared with the international frontiers.Further cooperation needs to be strengthened to promote the improvement of the active surveillance management system in China.

Single-cell sequencing is a new technology for high-throughput sequencing analysis of the genome, transcriptome, and epigenome at the single-cell level. Currently, single-cell sequencing technology has been widely used in bladder cancer research, opening up new ways to understand the biology of subtle bladder tumors by identifying different cell subpopulations, immune microenvironment, and single-cell technology is expected to make important changes in bladder diagnosis and treatment by identifying new biomarkers and using targeted therapies. This paper discussed the application of single-cell sequencing in bladder cancer research and clinical practice by summarizing recent advances in heterogeneous cell subpopulations, developmental patterns, and immune microenvironment and drug resistance in bladder cancer.

Objective To investigate the changes of functional brain connectivity over multiple frequency bands in resting-state electroencephalography (EEG) for lower limb amputation patients. Methods Resting-state EEG was collected from 18 lower limb amputees and 22 healthy controls from November, 2020 to June, 2021. Functional connectivity matrix was constructed with phase-locked values (PLV), and compared between groups. Results The functional connectivity was weaker in the amputees than in the controls on α band (t = 3.433, P = 0.001) and β band (t = 3.806, P = 0.001), and there was no significant difference on δ band (t = 1.429, P = 0.161) and θ band (t = 1.211, P = 0.233). Conclusion EEG functional connectivity weakens in lower limb amputees in on the α and β band, which results in neuroplasticity of multiple brain regions, not only for limb-respond cortex, but also for frontal, temporal and occipital cortices.

Objective:To investigate the predictive value of diffusion tensor imaging (DTI) parameters in upper extremity motor function recovery after surgery in patients with acute cervical spinal cord injury (CSCI).Methods:Twenty-three patients with acute CSCI who received postoperative systemic rehabilitation therapy in Department of Neurosurgery, 900 th Hospital of Joint Logistics Team of People's Liberation Army from May 2019 to July 2021 were selected as an experimental group, and 22 healthy subjects (healthy control group) matched with age and gender were selected from Physical Examination Center of the same hospital at the same period. Routine MRI sequence and DTI scan of the cervical spinal cord, scale of American Association for Spinal Cord Injury (ASIA) and modified Barthe index (mBI) were performed in patients of the experimental group 1 d and 3 months after surgery. Routine MRI sequence and DTI scan of the cervical spinal cord were performed in healthy subjects after enrollment. The DTI parameters in different regions between the two groups were compared, and the differences in DTI parameters, ASIA scores and mBI in patients of the experimental group before and after surgery were compared. Correlations of preoperative DTI parameters with preoperative upper extremity motor ASIA scores and upper extremity motor recovery rate 3 months after surgery were analyzed by Pearson correlation analysis. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of preoperative fractional anisotropy (FA) in upper extremity motor function recovery in CSCI patients 3 months after surgery. Results:As compared with the healthy control group, the experimental group had significantly lower preoperative FA in the injury area and distal injury area, and statistically higher preoperative apparent diffusion coefficient (ADC, P<0.05). In patients of the experimental group, preoperative FA in the injury area was significantly lower and ADC in the injury area was significantly higher as compared with those in the distal injury area ( P<0.05); patients of the experimental group had significantly higher FA in these two regions, upper extremity motor ASIA scores and mBI, and significantly lower ADC 3 months after surgery as compared with those 1 d before surgery ( P<0.05). The preoperative FA in the injury area and distal injury area in CSCI patients were positively correlated with preoperative upper extremity motor ASIA scores and upper extremity motor recovery rate 3 months after surgery ( P<0.05). ROC curve results showed that the area under the curve (AUC) of preoperative FA in injury area in predicting upper extremity motor function recovery 3 months after surgery was 0.912 ( 95%CI: 0.783-1.000, P<0.001); that of preoperative FA in the distal injury area was 0.842 ( 95%CI: 0.682-1.000, P<0.001). Conclusion:DTI parameters FA and ADC are sensitive indicators for detecting CSCI; preoperative FA in the injury area and distal injury area can be used to predict the upper extremity motor function recovery, but the efficacy of the former is superior to that of the later.

Objective:To investigate the effect of 125I-RSOAds-hTERT/PSA oncolytic adenovirus on targeted therapy of prostate cancer and its effect on tumor microenvironment. Methods:125I-RSOAds-hTERT/PSA ( 125I-virus complex) oncolytic adenovirus was constructed by PCR amplification and double restriction enzyme ligation. TUNEL staining, flow cytometry and Caspase-3 immunoblotting assay were used to detect the killing effect of 125I-RSOAds-hTERT/PSA oncolytic adenovirus on prostate cancer cells in vitro and in vivo, respectively. To explore the effect of 125I-virus complex on tumor tissue cytokine secretion levels, interleukin 2 (IL-2), IL-10, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in the culture supernatant of human prostate cancer cell line PC3, mouse prostate adenocarcinoma cell line RM-1, and mice serum were detected by ELISA. We explored the regulation of 125I-virus complex on the expression of CD24, CD44 and prostate stem cell antigen (PSCA) in prostate tumor tissues and tumor cells through immunohistochemistry. Meanwhile, the expression levels of CD32 and vascular endothelial growth factor (VEGF), as well as CD4+ , CD8+ and macrophage infiltration in tumor tissue were detected through immunofluorescence experiments. Results:125I-virus complex oncolytic adenovirus significantly increased tumor cell apoptosis in vitro and in vivo that was significantly higher than that of 125I group and virus complex group. Meanwhile, IL-2 ( t=-183.30, -38.20, P<0.05), IL-10 ( t=113.80, 92.71, P<0.05), TNF-α ( t=-73.20, -73.91, P<0.05), IFN-γ ( t=-65.37, -139.70, P<0.05) increased in vitro and in vivo. 125I-virus complex reduced the expression of CD24, CD44 and PSCA in tumor cells and tumor tissue, reduced the weight of tumor tissue, inhibited angiogenesis of tumor tissue ( t=8.55, P<0.05), and regulated the immune response in tumor tissue. Conclusions:125I-virus complex targeting prostate cancer can significantly kill cancer cells, reduce the weight and angiogenesis of tumor, and improve tumor microenvironment.

Objective To evaluate the safety of morphine hydrochloride injection. Methods Ear verin injection was used to evaluate the vascular irritation using the comparison of left side with right side in rabbits. Quadriceps femoris injection was used to evaluate the muscle irritation using the comparison of left side with right side in rabbits. Guinea pigs were intravenously injected with morphine hydrochloride injection at a dose of 2.8 mg·kg-1 once daily 3 times, stimulation was performed on 14 d after the last sensitization and the booster dose was 2 times the sensitization dose. The allergic reactions were observed. The different concentrations of morphine hydrochloride injection were placed in 2％ rabbit erythrocyte suspension, and then the hemolyzation and agglutination were observed. Results There were no significant vascular or muscular irritation and injury effects of morphine hydrochloride injection in rabbits. There were no evidenceof hemolyzation and agglutination in rabbit erythrocytes in vitro. No allergic reactions on guinea pigs in vivo were observed. Conclusion After treatment of morphine hydrochloride injection, neither obvious vascular /muscle stimulation or sensitization, nor hemolyzation or agglutination appeared in rabbits. The research results provide basic reference for the clinical rational and safe application of morphine hydrochloride injection.

Objective To investigate the effect of ERH gene knockdown on the proliferation and apoptosis of human bladder cancer T24 cells. Methods T24 cells infected by lentivirus with interference on ERH gene sequence were cloned to establish stable T24 cells clone in ERH gene suppression. The expression of ERH mRNA gene in bladder cancer was detected by using quantitative real time polymerase chain reaction (qPCR). The effects of ERH knockout on the cell proliferation and apoptosis were examined by using methylthiazolyl tetrazolium (MTT) assay, colony formation assay and flow cytometry. The effect of ERH knockout on the tumorigenic effect of T24 cells in vivo was verified by subcutaneous tumor formation in nude mice. Results After lentiviral transfection, qPCR results showed that the knockdown effect of ERH mRNA in ERH normal group (untreated T24 cells) was better than that in ERH gene knockdown group, and the difference was statistically significant [(1.006±0.126) vs. (0.079±0.007); t=12.72, P=0.0002]. After knocking out ERH gene, MTT assay showed that the proliferation ability of T24 cells in ERH gene knockdown group was weakened compared with ERH normal group, and the difference was statistically significant [A490 value: (0.13±0.00) vs. (0.66±0.01);t=104.61, P<0.0001]. Colony formation assay indicated that the ability of clone in ERH normal group was weakened compared with ERH gene knockdown group [(10.5 ±1.2) vs. (196.4 ±4.0); t= 73.63, P< 0.0001]. Flow cytometry showed that the cell apoptosis rate in ERH gene knockdown group was higher than that in ERH normal group [(11.0 ±0.5) ％ vs. (4.2 ±0.5) ％; t= 16.06, P<0.0001]. Imaging results of subcutaneous tumor formation in nude mice showed that the total fluorescence intensity of the tumor area in ERH gene knockdown group was (4.67 ±0.59) × 1010 μW/cm2, and the corresponding part in ERH normal group was (9.54±4.20) × 1010μW/cm2 (t=3.64, P=0.0051);tumor weight in ERH gene knockdown group was (0.80±0.62) g, and in ERH normal group was (1.79±0.71) g (t=3.33, P=0.0037). Conclusion ERH gene knockout can inhibit the proliferation of human bladder cancer T24 cells, and promote the cell apoptosis.

Objective To explore the diagnostic value of dynamic contrast-enhanced MRI (DCE-MRI) in evaluation of hemodynamic parameters of lesions and background parenchyma in benign and malignant breast lesions.Methods Breast DCE-MRI data were collected from 41 patients,including 21 benign lesions (benign group) and 24 malignant lesions (malignant group).Volume transfer constant (K),rate constant (Kep) and plasma fraction (Vp) of lesions and background parenchyma were measured,and the parameters of both groups were statistically analyzed.Taking pathological diagnosis as the gold standards,the efficacy of parameters in diagnosis of malignant breast lesions was evaluated.Results Ktrans and Kep of lesions and background parenchyma in the malignant group were higher than those in benign group (all P＜0.05).There was no significant difference between Vp of lesions and background parenchyma in both groups (both P＞0.05).In the diagnosis of malignant lesions,AUC of Ktrans of background parenchyma was the best,the sensitivity and specificity was 87.50％ and 76.19％,respectively.All parameters combined Logistic regression model had the highest AUC value (0.86,P＜0.001).Conclusion Among DCE-MRI related parameters,K of background parenchyma has the highest diagnostic value.Quantitative analysis of DCE-MRI data can help to identify benign and malignant breast lesions,and the hemodynamic characteristics of the background parenchyma are expected to be new methods for non-invasive diagnosis of breast lesions.