Oroxylin A (OA) is a natural flavonoid primarily derived from the plants Oroxylum indicum and Scutellaria baicalensis. Currently, OA is obtainable through chemical synthesis and exhibits polypharmacological properties, including anti-cancer, anti-inflammatory, anti-microbial, and multi-organ protective effects. The first-in-class drug OA tablets are presently undergoing phase Ib/IIa clinical trials for hepatocellular carcinoma (HCC) treatment. Substantial evidence suggests that OA demonstrates therapeutic potential against various hepatic and gastrointestinal (GI) disorders, including HCC, hepatic fibrosis, fatty liver disease, hepatitis, liver injury, colitis, and colorectal cancer (CRC). OA exerts its therapeutic effects primarily by modulating several crucial signaling pathways, including those associated with apoptosis, oxidative stress, inflammation, glucolipid metabolism, and fibrosis activation. The oral pharmacokinetics of OA is characterized by phase II metabolism, hydrolysis, and enterohepatic recycling. This review provides a comprehensive overview of the critical stages involved in the development of OA tablets, presenting a holistic perspective on the progression of this first-in-class drug from preclinical to clinical phases. It encompasses the synthesis of active pharmaceutical ingredients, pharmacokinetics, pharmacological efficacy, toxicology, drug delivery, and recent advancements in clinical trials. Importantly, this review examines the potential mechanisms by which OA may influence the gut-liver axis, hypothesizing that these interactions may confer health benefits associated with OA that transcend the limitations posed by its poor bioavailability.
Humans ; Flavonoids/pharmacokinetics* ; Tablets ; Animals ; Gastrointestinal Diseases/drug therapy* ; Liver Diseases/drug therapy* ; Drug Development ; Clinical Trials as Topic ; Scutellaria baicalensis/chemistry*

OBJECTIVE To explore the role of Yes-associated protein(YAP)in epidermal stem cell(EPSC)differentiation after ionizing radiation(IR).METHODS ① A punch was used to induce skin injuries on the back of mice.The IR group received localized irradiation with 60 Co γ-rays,while the normal control group did not.Samples were collected at 0,1,3,6,9,and 12 d for RNA and protein extraction.Western blotting was used to detect changes in YAP protein expressions during wound healing.Real-time quantitative polymerase chain reaction(RT-qPCR)was performed to assess the mRNA levels of Yap and its downstream target genes,connective tissue growth factor(Ctgf),and cysteine-rich protein 61(Cyr61).② EPSCs were exposed to 60 Co γ at a dose of 4 or 8 Gy,while the control group was not irradiated.Cells were collected to detect the levels of YAP protein via Western blotting.Cells were collected at 4,12,24,and 36 h post-IR to assess the levels of YAP mRNA by RT-qPCR.③ Short hairpin RNA(shRNA)was used to establish stable YAP knockdown cell lines,and the knockdown efficiency of sh YAP was verified by Western blotting.RT-qPCR was then performed to detect the impact of YAP knockdown on mRNA levels of K1 and K10 after IR.RESULTS① Compared with the control group,the YAP protein level in the IR group during wound healing was significantly reduced(P<0.05,P<0.01),so were the mRNA levels of Yap and its downstream target genes Ctgf and Cyr61(P<0.05,P<0.01).② Compared to the cell control group,the mRNA and protein levels of YAP in the IR group cells were significantly reduced(P<0.01).③ In the sh YAP cells,the YAP protein level was significantly reduced(P<0.01).Furthermore,the mRNA levels of K1 and K10 were significantly decreased after IR in sh YAP cells(P<0.01).CONCLUSION YAP can regulate EPSC differentiation in wound healing after IR.

Objective:To explore the value of diffusion tensor imaging (DTI) in evaluating the effects of hyperbaric oxygen therapy (HOT) in treating spinal cord injury.Methods:The modified Allen′s method was used to induce a traumatic spinal cord injury in 30 rats who were then divided randomly into an injured group and a treatment group, each of 15. The treatment group was given HOT twice a day for 3 days, then once a day for a total of 4 weeks. The injured group did not receive HOT. DTI was performed (along with Basso-Beattie-Bresnahan (BBB) evaluation) at 0h, 6h, 24h, as well as 3, 7, 14, 21 and 28 days after the operation. Two-factor repeated measures ANOVA was conducted to analyze any differences in the DTI results: the fractional anisotropy, mean apparent diffusivity, radial diffusivity and axial diffusivity, as well as the BBB scores. LSD t-tests were performed to analyze the significance of the differences at different time points.Results:At each time point after 24h the average FA value of the treatment group was significantly higher than the injured group′s average, while its average MD and RD values were significantly lower. Beyond 14 days the average AD value of the treatment group was significantly higher than that of the injured group. The treatment group′s average BBB score was also significantly higher at all the time points beyond 3 days.Conclusions:DTI results can evaluate spinal cord function and provide valuable information for the dynamic assessment of hyperbaric oxygen therapy after a traumatic spinal cord injury, and the therapy promotes the recovery of motor function, at least in rats.

Objective To investigate the correlation between the expression of Hsa_circ_0026352 and the clinical characteristics of breast cancer(BC) patients, to evaluate the value of Hsa_circ_0026352 as a diagnostic marker of breast cancer. Methods Human circRNA microarray was used to screen the different expression of circRNAs in BC tissues. qRT-PCR was used to verify the expression of Hsa_circ_0026352 in BC tissue and peripheral blood. CircRNA structure were performed by circPrimer1.2 software. T-test, ANOVA analysis, curve regression analysis and ROC curve analysis were performed to determine the diagnostic values of Hsa_circ_0026352. Results Hsa_circ_0026352 was significantly down-regulated in both breast cancer tissues and peripheral blood (P < 0.01). The AUC of Hsa_circ_0026352 were 0.881 in tissues and 0.826 in peripheral blood (both P < 0.01). The relative expression of Hsa_circ_0026352 in peripheral blood of BC cancer patients was negatively correlated with CA153 level (P < 0.05). The AUC of Hsa_circ_0026352 in peripheral blood of patients with ER positive, early stage breast cancer and breast neoplasm metastasis were 0.710, 0.771 and 0.722 (all P < 0.01), respectively. Conclusion Hsa_circ_0026352 could be a novel predictive biomarker for diagnosis of BC.

Objective:To explore multidisciplinary team (MDT) for the treatment of hip fracture in the elderly.Methods:A retrospective analysis was done of the 196 elderly patients who had been admitted to Department of Joint Surgery, Beijing Shijitan Hospital from September 2017 to December 2018 for hip fractures. They were divided into 2 groups depending on whether MDT had been applied or not. In the MDT group of 102 patients, there were 43 males and 59 females with an age of 81.9±8.4 years, and 63 femoral neck fractures and 39 intertrochanteric fractures. In the traditional treatment group of 94 patients, there were 37 males and 57 females with an age of 81.3±8.6 years, and 55 femoral neck fractures and 39 intertrochanteric fractures. The 2 groups were compared in terms of complications and mortality during hospitalization, interval from admission to surgery, total hospital stay, and Harris hip scores at 6 months after surgery.Results:There were no statistically significant differences in general data before surgery between the 2 groups, indicating comparability ( P>0.05). Eighty-four patients (89.4%) in the traditional treatment group and 98 patients (96.1%) in the MDT group underwent surgery, showing no significant difference between the groups ( χ2=3.327, P=0.068). In the patients undergoing surgery in the MDT group, the incidences of postoperative delirium [12.2% (12/98)], pulmonary infection [11.2% (11/98)], cardiogenic disease [13.3%(13/98)], electrolyte disturbance[12.2%(12/98)] and deep venous thrombosis of lower extremity [6.1% (6/98)] were significantly lower, the interval from admission to surgery (1.9 d±0.9 d) and total hospital stay (10.2 d±0.9 d) significantly shorter, and Harris hip scores (81.3±6.2) at 6 months after surgery significantly higher than those in the patients undergoing surgery in the traditional treatment group [31.0%(26/84), 22.6% (19/84), 25.0% (21/84), 28.6% (24/84), 16.7%(14/84); 3.1 d±1.6 d and 14.1 d±6.2 d; 75.4±7.8; respectively] (all P<0.05). Conclusion:In the treatment of hip fracture in the elderly, multidisciplinary team is effective in reducing complications during hospitalization, shortening the interval from admission to surgery and total hospital stay, and promoting functional recovery of the hip.

Objective: To evaluate the efficacy and prognostic factors of comprehensive treatment of undifferentiated high grade pleomorphic sarcoma (UHGPS) in extremities and trunk, including surgery, radiotherapy and chemotherapy. Methods: A retrospective analysis and follow-up of 131 UHGPS cases with clinical stage Ⅱ or Ⅲ in extremities and trunk soft tissue was performed to analyze the prognostic factors. Survival data were collected through follow-up. The survival rate was calculated with life table method and Kaplan-Meier survival curves were drawn. Survival rate between the two groups was compared using Log rank test. The multivariate analysis was performed using Cox regression model. Results: The median survival time of 131 patients was 41.6 months. The 1-year, 3-year and 5-year survival rates were 95.0%, 82.0%, and 77.0%, respectively. The 5-year recurrence-free survival rate was 81.0%, and the 5-year metastasis-free survival rate was 72.0%. Univariate analysis showed that the tumor size, initial or recurrence, surgical margin, AJCC stage, and with/without standard treatment were associated with overall survival (all P<0.05). Stratification analysis according to the American Joint Committee of Cancer (AJCC) stage showed that 5-year survival rate of stage Ⅱ patients with radiotherapy was 100.0%, which was higher than that of patients without radiotherapy (79.6%) and the difference was statistically significant (P=0.010); but no statistical significance of radiotherapy for stage Ⅲ and chemotherapy for stage Ⅱ or Ⅲ patients (all P>0.05). The multivariate analysis showed surgical margin (HR=4.220, P=0.002), with/without standard treatment (HR=4.040, P=0.030) were independent risk factors associated with prognosis of UHGPS patients. Conclusions For UHGPS with stage Ⅱ or stage Ⅲ in extremities and trunk soft tissue, patients with complete resection and standard treatment have improved prognosis. Therefore, standard treatment, including extensive resection for the first surgery, should be performed according to expert consensus in order to increase the long-term survival rate. Adjuvant radiotherapy should be performed for stage Ⅱ patients.

Objective: To establish and optimize the HPLC fingerprints of Angelica sinensis medicinal material and determine the ligustilide content to improve the quality standard for Angelica sinensis and improve the quality control level of Chinese angelica medici-nal material and preparations. Methods: A method for the determination of ligustilide was optimized by HPLC. The column was eluted on an Agilent ZORBAX SB C18(250 mm×4. 6 mm, 5 μm) column with acetonitrile-water (60 ∶ 40) as the mobile phase. The flow rate was 1. 0 ml·min-1, the detection wavelength was 326 nm, and the column temperature was at 35 ℃. The HPLC fingerprints of 13 batches of Angelica sinensis from different origins and methodological investigations were established and validated to set up an HPLC fingerprinting evaluation method for Angelica sinensis. Acetonitrile-0. 1% formic acid was used as the mobile phase with gradient elu-tion. The flow rate was 1. 0 ml·min-1, the detection wavelength was 280nm, and the column temperature was at 25℃. Results: The results showed that under the above HPLC conditions, ligustilide had good linearity within the range of 0. 032 3-0. 645 5 mg·ml-1(r=0. 999 9), and the average recovery was 100. 5% (RSD=1. 61% ,n=6). The quality fraction of ligustilide in Angelica sinensis was 0. 885 6%-2. 382 2% . Through the establishment of HPLC fingerprints of Angelica sinensis, the characteristic profiles with better peak shape and degree of separation and 18 common peaks with better resolution were obtained. The similarities of the 13 batches of angelica were all between 0. 9 and 1. 0. Conclusion: According to the methodological investigation, the HPLC fingerprints and ligustilide con-tent determination method of Angelica sinensis are simple, reliable, stable and feasible.

Objective To explore the value of DTI quantitative parameters in evaluating neurological function changes of acute traumatic spinal cord injury (TSCI)in rat models.Methods The modified Allen's dropping weight technique was used to establish TSCI rat models.Then the rats were divided into mild injury group,moderate injury group and severe injury group (each n=10).DTI examination and Basso-Beattie-Bresnahan (BBB) score were performed pre-TSCI and 0 h,6 h,24 h,3 day,7 day and 14 day post-TSCI,respectively.The BBB scores and DTI parameters,including FA,mean apparent diffusivity (MD),radial diffusivity (RD) and axial diffusivity (AD) were measured and compared among groups.The correlation between BBB scores and the parameters was evaluated.Results The differences of FA,MD and RD value were statistically significant among varying injury degree groups and different time points after TSCI (all P＜0.05).AD value had statistical difference among different time points (F=12.720,P＜0.001),whereas no difference was found among varying injury degree groups (F=0.469,P=0.630).FA and MD values decreased while RD increased 0 h post-TSCI.Then RD and MD increased continuously,whereas FA decreased continuously until 24 h post TSCI (all P＜0.05),and the parameters kept stable after 24 h post-TSCI (all P＞ 0.05).The BBB scores were lowest on 0 h post-TSCI,then maintained increasing (all P＜0.05).In addition,the BBB scores and MD values had good correlation (r=0.958,P＜ 0.01).Conclusion DTI can quantitatively evaluate function changes of TSCI in rat models.Moreover,treatment within 24 h post-TSCI might be recommended for TSCI therapy.

Objective: To evaluate the clinical value of preoperative ¹⁸F-Fludeoxyglucose (¹⁸F-FDG PET-CT) in lymphatic metastasis diagnosis of cutaneous melanoma on extremities and trunk. Methods: 112 patients with cutaneous melanoma pathologically of extremities and trunk from January 2006 to December 2016, who received ¹⁸F-FDG PET-CT examination preoperatively, were retrospectively reviewed. The correlations between the maximal diameters of lymph nodes, the maximal standard uptake value (SUV) and the diagnostic impression grades of PET-CT examination, and the final pathological diagnosis were analyzed. The correlations between Breslow thickness of primary lesions and the diagnostic impression of PET-CT examination were also analyzed. All the above were analyzed with Receiver Operating Characteristic (ROC) curve to get the cut-off value. Based on the final results of pathological diagnosis of lymph nodes as the golden standard, the statistically significant indicators of ROC curve analysis were used to evaluate the diagnostic effect, as well as to calculate the sensitivity, specificity and accuracy. With gender, age, maximal diameter of lymph nodes, maximal SUV, diagnosis impressions, and Breslow thickness as the independent variables and pathological diagnosis results of lymph nodes as the dependent variable, two-class stepwise Logistic regression analysis was used to determine the independence of diagnostic indicators. ROC curve analysis and log rank test were used to analyze the relationship between Breslow thickness and patient survival. Results: To evaluate melanoma patients′ lymph node status, the results of ROC curve analysis showed that the area under the curve of lymph node maximal diameter, maximal SUV, diagnosis impression of PET-CT examinations were 0.789, 0.786 and 0.816, respectively (all P<0.05). The cut-off values were 0.85 cm, 1.45 and 2.5, respectively. The sensitivity of the cut-off values to determine the status of lymph nodes in melanoma patients were 71.4%, 64.9% and 72.1% respectively, and the specificities were 85.2%, 88.7% and 87.0% respectively. Multivariate Logistic regression analysis showed that PET-CT diagnosis impressions had independent diagnostic significance for the lymph node status of melanoma patients (OR=11.296, 95%CI: 2.550~50.033). The area under the curve of Breslow thickness evaluating PET-CT diagnostic impression is 0.664 (P=0.042) and the cut-off value was 4.25 mm. The survival rate of the patients with Breslow thickness ≥ 4.25 mm was lower than that in the group <4.25 mm (P=0.006). Conclusions ¹⁸F-FDG PET-CT can help to evaluate metastases and make treatment decisions for cutaneous melanoma of extremities and trunk, especially for patients whose primary lesion′s Breslow thickness has reached more than 4.25 mm. For the patients whose maximal SUV of regional lymph node is higher than 1.45 and short diameter of the largest lymph node is larger than 0.85cm, the possibility of metastases should be considered.

Objective To probe the relationship between the expression of TL1A and the level of IFN-γ secreted by T cells in the acute stage of Guillain-Barre syndrome (GBS). Methods ① Six-week female Bal b/c mice were immunized by purified recombinant human soluble TNF-like molecular 1A (rhsTL1A) protein. The polyclonal antibody against rhsTL1A was identified by immunofluorescence using human umbilical vein epithelial cells (HUVEC). ② To detect the biologic activity of rhsTL1A, the peripheral blood mononuclear cells (PBMC) from the healthy donors were separated by Ficoll gradient centrifugation and were seeded on 96-well plates with medium containing 2 μg/ml PHA (control group), 2 μg/ml PHA + 25 ng/ml rhsTL1 A, 2 μg/ml PHA + 100 ng/ml rhsTL1A and 2 μg/ml PHA + 400 ng/ml rhsTLlA respectively. T cell proliferation assay was carried out using ~3H-TdR. ③ IFN-γ productions in the sera of the children with GBS in the acute stage were detected by ELISA. ④ The ratio of CD_3~+ TL1A~+ T cells to CD_3~+ T cells in the peripheral blood of the children with GBS in acute stage was detected with flow, cytometry. ⑤PBMC from the children in acute GBS were separated and cultured in the environment adding 2 μg/ml PHA and 400 ng/ml rhsTL1A in vitro. Then, the IFN-γ in the supernatant was determined by ELISA kit after 72 hours. Results ① hTL1A A expressed by eukaryotic HUVECs was recognized by rhsTL1 A polyclonal antiserum. ② The result of T cell proliferation assay showed that SI of 25 ng/ml rhTL1A, 100 ng/ml rhTL1A A and 400 ng/ml rhTL1A group was increased compared with control group. The SI of 2 μg/ml PHA +400 ng/ml rhsTL1 A group was the highest (2. 65) among them. ③ IFN-γ productions in the sera of the children with GBS in the acute stage ((102. 25±22. 17) pg/ml) were increased significantly compared with healthy control ((28.75 ± 1.31) pg/ml, t = 3. 309, P < 0. 05). ④ The ratio of CD_3~+ TL1A~+ T cells to CD_3~+ T cells in the peripheral blood of the children with GBS in acute stage (18.22%± 1.83%) was enhanced significantly compared with healthy control (5. 17% ±0. 48%, t = 6. 884, P < 0. 01). ⑤ PBMC both in healthy control and the acute GBS secreted more IFN-γ markedly ((43.56± 4.41) pg/ml and (180.64 ± 38.39) pg/ml) after being incubated in 2 μg/ml PHA and 400 ng/ml rhsTL1A (t =4. 523 and 2. 600, P <0. 01 and 0. 05 respectively). Moreover, PBMC in acute GBS secreted more IFN-γ, than that of the healthy group markedly (t = 3. 545, P < 0. 05). Conclusions ① The mouse antiserum recognizing rhsTL1A is successfully obtained. ② In this study, 400 ng/ml rhsTL1A promotes the proliferation of T cells activated by 2 μg/ml PHA, indicating that rhsTL1A has biological activity. ③ The expression of hTL1A of activated T cells in the peripheral blood of the children with acute GBS is up-regulated. These TL1A proteins promote the secretion of IFN-γ through binding to their receptors DR_3.