BACKGROUND:Previous studies by our research group discovered that Jiawei Xiaoyao San has a significant anti-liver cancer effect,but the specific mechanism of action was unclear. OBJECTIVE:To investigate the regulatory effects of the traditional Chinese medicine formula Jiawei Xiaoyao San on the levels of miRNAs in plasma exosomes of rats with diethylnitrosamine chronically induced primary liver cancer,based on high-throughput sequencing combined with bioinformatics. METHODS:SD rats were randomly divided into a blank control group,a liver cancer model group,and a Jiawei Xiaoyao San treatment group.Liver cancer models were induced by continuous administration of diethylnitrosamine for 12 weeks.Starting from the 17th week,rats in the Jiawei Xiaoyao San treatment group were administered Jiawei Xiaoyao San once daily until the end of the 20th week,while rats in the blank control and liver cancer model groups were given an equivalent volume of saline.Anti-hepatocellular carcinoma effects were validated by assessing the morphological structure of rat liver tissues,along with the expression of the hepatocellular carcinoma markers,Glypican-3 protein and serum alpha-fetoprotein.Plasma exosomes from each group of rats were isolated using ultracentrifugation.High-throughput sequencing technology was used to screen for differentially expressed miRNAs in rat plasma exosomes.Bioinformatics was used to predict the potential biomarkers through which Jiawei Xiaoyao San exerts its anti-liver cancer effects via liver cancer-derived exosomal miRNAs,followed by functional analysis. RESULTS AND CONCLUSION:(1)Jiawei Xiaoyao San significantly improved the morphological structure of liver tissues in a rat model of liver cancer.Compared with the liver cancer model group,the expression of liver cancer markers Glypican-3 protein and serum alpha-fetoprotein was significantly reduced in the Jiawei Xiaoyao San treatment group.(2)Bioinformatics analysis showed that in the Jiawei Xiaoyao San group,upregulated miR-223-3p in the liver cancer model group had target binding sites with genes E2F1 and NCOA1,which were closely related to liver cancer survival and prognosis.Therefore,Jiawei Xiaoyao San has a therapeutic effect on liver cancer,possibly by targeting negative regulation of NCOA1/E2F1 through liver cancer plasma-derived exosomal miR-223-3p,thereby playing anti-liver cancer effect.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

This study established a high performance liquid chromatography(HPLC) fingerprint of Chuanxiong Rhizoma from different producing areas and screened its potential differential components for producing areas by chemometrics. Furthermore, the content of the above differential components in Chuanxiong Rhizoma from different producing areas was measured and compared. Then, the geoherbalism markers(geo-markers) that can be used to distinguish Dao-di and non-Dao-di Chuanxiong Rhizoma were excavated by chemometrics. In fingerprint studies, a total of 27 common peaks were determined, and the fingerprint similarity for 37 batches of Chuanxiong Rhizoma samples from different producing areas was above 0.968. The orthogonal partial least squares-discriminant analysis(OPLS-DA) was capable of distinguishing Chuanxiong Rhizoma from Sichuan and from three other provinces, as well as Dao-di Chuanxiong Rhizoma(from Dujiangyan) and non-Dao-di Chuanxiong Rhizoma(from other producing areas) in Sichuan province. Meanwhile, 14 potential differential components in Chuanxiong Rhizoma from different provinces and 16 potential differential components in Chuanxiong Rhizoma from different producing areas in Sichuan were screened by the variable importance in projection(VIP) analysis under OPLS-DA. The reference standards were used to identify 10 potential differential components in the common peaks, and subsequent content determination verified that the content of the above 10 potential differential components was different among different producing areas. Then, the OPLS-DA and VIP analysis were performed with the content of the 10 potential differential components as variables. The results showed that Z-ligustilide, chlorogenic acid, and the ratio of butylidenephthalide/senkyunolide A were the geo-markers that can distinguish Chuanxiong Rhizoma from Sichuan and Chuanxiong Rhizoma from Shaanxi, Hebei, and Jiangxi, while Z-ligustilide, n-butylphthalide, and the ratios of Z-ligustilide/senkyunolide A and butylidenephthalide/senkyunolide A were the geo-markers that can distinguish Dao-di Chuanxiong Rhizoma(from Dujiangyan) and non-Dao-di Chuanxiong Rhizoma(from other producing areas) in Sichuan province. This study elucidated the differences in material basis of Dao-di and non-Dao-di Chuanxiong Rhizoma based on fingerprinting and content determination combined with chemometrics, which provides a reference for the study of material basis of Dao-di traditional Chinese medicine.
Drugs, Chinese Herbal/chemistry* ; Rhizome/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Chemometrics/methods* ; Quality Control

Objective:This study aimed was to analyze the disease progression of postoperative recurrence/me-tastasis of pancreatic ductal adenocarcinoma(PDAC)and provide clinical evidence for evaluating the difference in prog-nosis between site and pattern of recurrence/metastasis.Methods:The clinical data of 167 patients with PDAC who underwent pancreatectomy in Panjin Liao-Oil Gem Flower Hospital from January 2011 to June 2019 were retrospec-tively analyzed.Kaplan-Meier curves and Cox-regression analyses were applied to assess survival outcomes.Results:In this study,96 patients(57.5%)recurred within 12 months after surgery,and the median recurrence time was 10.9 months.Compared to patients without recurrence,patients with recurrence/metastasis had higher baseline CA19-9>100 IU/mL and were treated more often with neoadjuvant chemotherapy(P<0.05).In the no recurrence group,patients had histopathological analyses yielded lower less poorly differentiated tumors,less positive margin,less pT3+4 stages and pN1+2 stages(P<0.05).In a multivariate Cox regression analysis,receipt of neoadjuvant chemotherapy,poor tumor differ-entiation and positive margin were independent predictors for recurrence/metastasis within 12 months after surgery(P<0.05).Neoadjuvant treated patients had less pT1+2 stages(P=0.015),a lower lymph node ratio,less perineural invasion,less positive margin,and were less likely to be treated with adjuvant chemotherapy compared to upfront surgery treated patients(P<0.05).Recurrence/metastasis rates were higher in the neoadjuvant treated cohort versus the upfront surgery cohort(P=0.014).There was no statistical difference in the recurrence/metastasis rate distribution between neoadjuvant therapy and upfront surgery,and neoadjuvant therapy exhibited no significant impact on recurrence/metastasis patterns in PDAC(P>0.05).The overall survival period of patients without recurrence/metastasis within 12 months was signifi-cantly longer than that of patients with recurrence/metastasis after PDAC resection(P<0.001).Conclusion:The varying site recurrence/metastasis rates and time to recurrence/metastasis,underline the inherent heterogeneity of PDAC and the specific interactions in the tumor microenvironments at the recurrence/metastasis sites.Further research is essential to establish optimal personalized treatment strategies for patients with recurrent PDAC.

Objective:This study aimed was to analyze the disease progression of postoperative recurrence/me-tastasis of pancreatic ductal adenocarcinoma(PDAC)and provide clinical evidence for evaluating the difference in prog-nosis between site and pattern of recurrence/metastasis.Methods:The clinical data of 167 patients with PDAC who underwent pancreatectomy in Panjin Liao-Oil Gem Flower Hospital from January 2011 to June 2019 were retrospec-tively analyzed.Kaplan-Meier curves and Cox-regression analyses were applied to assess survival outcomes.Results:In this study,96 patients(57.5%)recurred within 12 months after surgery,and the median recurrence time was 10.9 months.Compared to patients without recurrence,patients with recurrence/metastasis had higher baseline CA19-9>100 IU/mL and were treated more often with neoadjuvant chemotherapy(P<0.05).In the no recurrence group,patients had histopathological analyses yielded lower less poorly differentiated tumors,less positive margin,less pT3+4 stages and pN1+2 stages(P<0.05).In a multivariate Cox regression analysis,receipt of neoadjuvant chemotherapy,poor tumor differ-entiation and positive margin were independent predictors for recurrence/metastasis within 12 months after surgery(P<0.05).Neoadjuvant treated patients had less pT1+2 stages(P=0.015),a lower lymph node ratio,less perineural invasion,less positive margin,and were less likely to be treated with adjuvant chemotherapy compared to upfront surgery treated patients(P<0.05).Recurrence/metastasis rates were higher in the neoadjuvant treated cohort versus the upfront surgery cohort(P=0.014).There was no statistical difference in the recurrence/metastasis rate distribution between neoadjuvant therapy and upfront surgery,and neoadjuvant therapy exhibited no significant impact on recurrence/metastasis patterns in PDAC(P>0.05).The overall survival period of patients without recurrence/metastasis within 12 months was signifi-cantly longer than that of patients with recurrence/metastasis after PDAC resection(P<0.001).Conclusion:The varying site recurrence/metastasis rates and time to recurrence/metastasis,underline the inherent heterogeneity of PDAC and the specific interactions in the tumor microenvironments at the recurrence/metastasis sites.Further research is essential to establish optimal personalized treatment strategies for patients with recurrent PDAC.

The column chromatography and semi-preparative liquid phase chromatography with several chromatographic packing materials, including macroporous adsorbent resin, silica gel, ODS, and Sephadex LH-20, were used for the separation and purification of n-butanol-soluble portion of ethanol extract of Leonurus japonicus Houtt. The structures of isolates were identified by HR-MS, IR, NMR, and acid hydrolysis reaction. Six phenylethanol glycosides were obtained from L. japonicus and identified as leonoside G (1), leonoside E (2), leonoside B (3), leonoside F (4), cistanoside G (5), and salidroside (6). Compound 1 is a new phenylethanol glycoside.

Objective To study the pharmacokinetic characteristics of the test formulation of compound lidocaine cream and reference formulation of lidocaine and prilocaine cream in Chinese healthy subjects and to evaluate whether there is bioequivalence between the two formulations.Methods A single-center,single-dose,randomized,open-label,two-period,two-sequence,crossover design was used.This study included 40 healthy subjects,and in each period,test formulation or reference formulation 60 g was applied to the skin in front of both thighs(200 cm2 each side,a total of 400 cm2)under fasting conditions,and the drug was left on for at least 5 h after application.The concentrations of lidocaine and prilocaine in plasma were determined using liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.Pharmacokinetic parameters were calculated using WinNonlin 8.0 software to evaluate the bioequivalence of the two formulations.Results After the application of the test formulation compound lidocaine cream and the reference formulation lidocaine and prilocaine cream on both thighs of the subjects,the pharmacokinetic parameters of lidocaine in plasma were as follows:Cmax were(167.27±91.33)and(156.13±66.86)ng·mL-1,AUC0-t were(1 651.78±685.09)and(1 636.69±617.23)ng·mL-1·h,AUC0-∞ were(1 669.85±684.65)and(1 654.37±618.30)ng·mL-1·h,the adjusted geometric mean ratios were 104.49％,101.88％and 101.89％,respectively,with 90％confidence intervals of 98.18％-111.20％,97.80％-106.13％and 97.87％-106.07％,all within the range of 80.00％-125.00％.The pharmacokinetic parameters of prilocaine in plasma were as follows:Cmax were(95.66±48.84)and(87.52±39.16)ng·mL-1,AUC0-t were(790.86±263.99)and(774.14±256.42)ng·mL-1·h,AUC0_m were(807.27±264.67)and(792.84±254.06)ng·mL-1 h,the adjusted geometric mean ratios were 107.34％,103.55％and 102.98％,respectively with 90％confidence intervals of 101.69％-113.31％,99.94％-107.30％and 99.65％-106.43％,all within the range of 80.00％-125.00％.Conclusion The test formulation compound lidocaine cream and the reference formulation lidocaine and prilocaine cream are bioequivalent.