According to the principle and current domestic and international construction processes of core outcome set(COS) and the characteristics of post-stroke aphasia, this study built COS with evidence-based support for traditional Chinese medicine(TCM) treatment of post-stroke aphasia. Firstly, a comprehensive review was conducted on the articles about the TCM treatment of post-stroke aphasia that were published in the four major Chinese databases, three major English databases, and three clinical registration centers over the past five years. The articles were analyzed and summarized, on the basis of which the main part of the COS for clinical research on the TCM treatment of post-stroke aphasia was formed. Secondly, clinical doctors and related nursing personnel were interviewed, and important outcome indicators in the clinical diagnosis and treatment process were supplemented to form a pool of core outcome indicators. Two rounds of Delphi surveys were carried out to score the importance of the core outcome indicators in the pool. Finally, a consensus meeting of experts was held to establish the COS for clinical research on the TCM treatment of post-stroke aphasia. The final COS included a total of 268 studies [236 randomized controlled trials(RCTs), 21 Meta-analysis, and 11 clinical registration protocols] and 20 open questionnaire survey results. After two rounds of Delphi surveys, a total of 14 outcome indicators and their corresponding measurement tools were included in the expert consensus meeting. The final expert consensus meeting determined the COS for post-stroke aphasia, which included 9 indicator domains and 12 outcome indicators.
Humans ; Aphasia/therapy* ; Stroke/complications* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Treatment Outcome

This study aims to explore the scientific connotation of sinking Rehmanniae Radix has the best quality and compare the quality between floating and sinking fresh Rehmanniae Radix samples. Ultra-performance liquid chromatography tandem quadrupole electrostatic field Orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) was employed to detect the chemical components in floating and sinking fresh Rehmanniae Radix samples. The fingerprint of fresh Rehmanniae Radix was established by high performance liquid chromatography(HPLC), and four index components were determined simultaneously. The cluster analysis, principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were conducted to compare the quality of floating and sinking fresh Rehmanniae Radix samples. An evaporative light-scattering detector was used to compare the content of five sugars. The extract yield and drying rate were determined, and the quality connotation of sinking Rehmanniae Radix has the best quality was explained by multiple indicators. A total of 41 components were preliminarily identified from fresh Rehmanniae Radix by UHPLC-Q-Orbitrap HRMS, including 7 iridoid glycosides, 9 phenylethanol glycosides, 6 amino acids, 4 sugars, 3 phenolic acids, 5 nucleosides, 3 organic acids, 1 ionone, 1 furan, 1 coumarin, and 1 phenylpropanoid. The results showed that the main chemical components were consistent between floating and sinking fresh Rehmanniae Radix. Nine common peaks were identified in the fingerprints of 15 batches of floating and sinking fresh Rehmanniae Radix samples, and the similarity of fingerprints was greater than 0.9. The cluster analysis, PCA, and OPLS-DA classified floating and sinking fresh Rehmanniae Radix sasmples into two categories, indicating differences in the quality between them. The total content of catalpol, rehmannioside D, ajugol, and verbascoside in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was catalpol. The total content of fructose, glucose, sucrose, raffinose, and stachyose in sinking fresh Rehmanniae Radix samples was higher than that in floating samples of the same batch and specification, and the main differential component was stachyose. The extract yield and drying rate of the sinking samples were higher than those of floating samples. This study preliminarily showed that floating and sinking fresh Rehmanniae Radix samples had the same components but great differences in the content of medicinal substance basis. The total content of four glycosides and five sugars, extract yield, and drying rate of sinking fresh Rehmanniae Radix samples is higher than that of floating samples of the same batch and specification. These findings, to a certain extent, explains the scientificity of sinking Rehmanniae Radix has the best quality recorded in ancient books and provide a reference for the quality control and clinical application of fresh Rehmanniae Radix.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Rehmannia/chemistry* ; Chemometrics ; Mass Spectrometry/methods* ; Quality Control ; Principal Component Analysis ; Plant Extracts

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Microplastics(MPs)are emerging contaminants in aquatic environments characterized by their polar structure,small particle size(Typically less than 5 mm),large surface area,good stability,and resistance to biodegradation.They pose adverse effects on the normal physiological activities of aquatic organisms and can accumulate in biota,including humans.Therefore,there is an urgent need for rapid and accurate quantitative analysis of MPs in water environments.In this study,Raman spectroscopy combined with partial least squares(PLS)was employed for rapid and accurate quantitative analysis of polyethylene(PE)and polystyrene(PS)MPs in real water samples.Initially,33 simulated water samples containing different concentrations of MPs were prepared,and their Raman spectra were collected.Six spectral preprocessing methods(Normalization,multiplicative scatter correction,standard normal variate transformation,first derivative,second derivative,and wavelet transform)were investigated for their impact on the predictive performance of PLS calibration models.Subsequently,three variable selection methods including synergy interval partial least squares(SiPLS),variable importance in projection(VIP)and mutual information(MI)were employed to optimize the input variables of the PLS calibration model.The predictive capability of the PLS calibration model was evaluated and validated using leave-one-out cross-validation.Under the optimal conditions of spectral preprocessing,variable selection,input variables and latent variables,the wavelet transform-partial least squares(WT-PLS)calibration model based on distilled water was established,and the contents of PE and PS in real water samples were predicted with prediction correlation coefficients(R2p)of 0.9540 and 0.8472 for PE and PS,respectively,and prediction errors(Errorp)of 0.0690 and 0.1126,respectively.Furthermore,a mixed sample MI-PLS calibration model was developed,demonstrating the best predictive performance in real water samples(With R2p values of 0.9776 and 0.9755 for PE and PS,respectively,and Errorp values of 0.0360 and 0.0392,respectively).This method provided a novel approach and new methodology for quantitative analysis of MPs and other organic pollutants in real water samples.

Objective:To evaluate the efficacy of acute T-cell lymphoblastic leukemia(T-ALL)in children and explore the prognostic risk factors.Methods:The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed,and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia(B-ALL)in the same period.Kaplan-Meier analysis was used to evaluate the overall survival(OS)and event-free survival(EFS),and COX proportional hazard regression model was used to evaluate the prognostic factors.Among 116 children with T-ALL who received standard treatment,78 cases received the Chinese Childhood Leukemia Collaborative Group(CCLG)-ALL 2008 protocol(CCLG-ALL 2008 group),and 38 cases received the China Childhood Cancer Collaborative Group(CCCG)-ALL 2015 protocol(CCCG-ALL 2015 group).The efficacy and serious adverse event(SAE)incidence of the two groups were compared.Results:Proportion of male,age ≥ 10 years old,white blood cell count(WBC)≥ 50 × 109/L,central nervous system leukemia,minimal residual disease(MRD)≥ 1％during induction therapy,and MRD ≥ 0.01％at the end of induction in T-ALL children were significantly higher than those in B-ALL children(P＜0.05).The expected 10-year EFS and OS of T-ALL were 59.7％and 66.0％,respectively,which were significantly lower than those of B-ALL(P＜0.001).COX analysis showed that WBC ≥ 100 x 109/L at initial diagnosis and failure to achieve complete remission(CR)after induction were independent risk factors for poor prognosis.Compared with CCLG-ALL 2008 group,CCCG-ALL 2015 group had lower incidence of infection-related SAE(15.8％vs 34.6％,P=0.042),but higher EFS and OS(73.9％vs 57.2％,PEFS=0.090;86.5％vs 62.3％,PoS=0.023).Conclusions:The prognosis of children with T-ALL is worse than children with B-ALL.WBC ≥ 100 × 109/L at initial diagnosis and non-CR after induction(especially mediastinal mass has not disappeared)are the risk factors for poor prognosis.CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.

Immunotherapy is an important breakthrough in canc-er treatment.Unfortunately,low drug concentration in tumor sites almost ineffectively initiates immune responses and thereby severely limits immune therapy applications in clinics.Nanoma-terials are well-recognized drug delivery system in cancer thera-py.Nanographene oxide(NGO)have shown immense perti-nence for anti-cancer drug delivery owing to their ultra-high sur-face area,chemical stability,good biocompatibility and excel-lent photosensitivity.In addition,functionalized modifications on the surface of NGO increase tumor targeting and minimize cy-totoxicity.This study focuses on reviewing the literature and up-dates on NGO in drug delivery and discussing the possibilities and challenges of NGO in cancer synergetic therapy.

This study aims to explore the mechanism of Zhuanggu Jianxi Decoction in reducing synovial tissue inflammation in human knee osteoarthritis(KOA) via the liver X receptors(LXRs)/nuclear factor(NF)-κB signaling pathway. The synovial tissue samples were collected from 5 healthy volunteers and 30 KOA synovitis patients and cultured in vitro. The samples from the heathy volunteers were set as the normal group, and those from KOA synovitis patients were randomized into synovitis, Zhuanggu Jianxi Decoction, LXRα inhibitor, and N-CoR inhibitor groups. The synovitis tissue samples of the 5 groups were treated with 10% blank serum, 10% blank serum, 10% drug-containing serum, 10% drug-containing serum+LXRα inhibitor, and 10% drug-containing serum+N-CoR inhibitor, respectively, for 7 days. After intervention, the synovial tissue samples of each group were collected and stained with hematoxylin-eosin for observation and scoring of the pathological changes. The expression intensity of the fibroblast-specific marker α-smooth musle actin(α-SMA) in the synovial tissue was observed by immunofluorescence staining. The levels of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), matrix metalloproteinase-3(MMP-3), and matrix metalloproteinase-13(MMP-13) in the supernatant of synovium homogenate were determined by ELISA. The mRNA and protein levels of LXRα, N-CoR, P50, and P65 in the synovial tissue were determined by RT-qPCR and Western blot, respectively. The results showed that compared with the normal group, the synovitis group showcased obvious synovial lining cell proliferation, inflammatory cell infiltration, synovial cell disarrangement, increased histopathological score(P<0.05), enhanced α-SMA fluorescence intensity and increased number of synovial fibroblasts(P<0.05), elevated levels of IL-1β, TNF-α, MMP-3, and MMP-13 in the synovial tissue(P<0.05), down-regulated mRNA and protein levels of LXRα and N-CoR, and up-regulated mRNA and protein levels of P50 and P65(P<0.05). Compared with the synovitis group, the Zhuanggu Jianxi Decoction group showed alleviated pathological changes, declined histopathological score of the synovial tissue(P<0.05), decreased α-SMA fluorescence intensity and number of synovial fibroblasts(P<0.05), lowered levels of IL-1β, TNF-α, MMP-3, and MMP-13(P<0.05), up-regulated mRNA and protein levels of LXRα and N-CoR, and down-regulated mRNA and protein levels of P50 and P65(P<0.05) in the synovial tissue. Compared with the Zhuanggu Jianxi Decoction group, the LXRα inhibitor group and N-CoR inhibitor group showed aggravated pathological changes, risen histopathological score of the synovial tissue(P<0.05), enhanced α-SMA fluorescence intensity and increased number of synovial fibroblasts(P<0.05), elevated levels of IL-1β, TNF-α, MMP-3, and MMP-13(P<0.05), down-regulated mRNA and protein levels of LXRα and N-CoR, and up-regulated mRNA and protein levels of P50 and P65(P<0.05). The results above indicated that Zhuanggu Jianxi Decoction could alleviate the synovial tissue inflammation in KOA patients by upregulating the mRNA and protein levels of LXRα and N-CoR in the LXRs/NF-κB pathway to downregulate the mRNA and protein levels of P50 and P65 and reduce the activity of the NF-κB pathway in the synovial tissue.
Humans ; Osteoarthritis, Knee/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Male ; Liver X Receptors/immunology* ; Middle Aged ; NF-kappa B/metabolism* ; Female ; Synovial Membrane/metabolism* ; Aged ; Adult

Objective: To establish a nomogram prognostic model for predicting the 5-, 10-, and 15-year overall survival (OS) of non-metastatic renal cell carcinoma patients managed with radical nephrectomy (RN), compare the modelled results with the results of pure pathologic staging, the Karakiewicz nomogram and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score commonly used in foreign countries, and stratify the patients into different prognostic risk subgroups. Methods: A total of 1 246 non-metastatic renal cell carcinoma patients managed with RN in Sun Yat-sen University Cancer Center (SYSUCC) from 1999 to 2020 were retrospectively analyzed. Multivariate Cox regression analysis was used to screen the variables that influence the prognosis for nomogram establishment, and the bootstrap random sampling was used for internal validation. The time-receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve analysis (DCA) were applied to evaluate the nomogram. The prediction efficacy of the nomogram and that of the pure pathologic staging, the Karakiewicz nomogram and the SSIGN score was compared through the area under the curve (AUC). Finally, patients were stratified into different risk subgroups according to our nomogram scores. Results: A total of 1 246 patients managed with RN were enrolled in this study. Multivariate Cox regression analysis showed that age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological T and N stages were independent prognostic factors for RN patients (all P<0.05). A nomogram model named SYSUCC based on these factors was built to predict the 5-, 10-, and 15-year survival rate of the participating patients. In the bootstrap random sampling with 1 000 iterations, all these factors occurred for more than 800 times as independent predictors. The Harrell's concordance index (C-index) of SYSUCC was higher compared with pure pathological staging [0.770 (95% CI: 0.716-0.823) vs 0.674 (95% CI: 0.621-0.728)]. The calibration curve showed that the survival rate as predicted by the SYSUCC model simulated the actual rate, while the clinical DCA showed that the SYSUCC nomogram has a benefit in certain probability ranges. In the ROC analysis that included 857 patients with detailed pathological nuclear stages, the nomogram had a larger AUC (5-/10-year AUC: 0.823/0.804) and better discriminating ability than pure pathological staging (5-/10-year AUC: 0.701/0.658), Karakiewicz nomogram (5-/10-year AUC: 0.772/0.734) and SSIGN score (5-/10-year AUC: 0.792/0.750) in predicting the 5-/10-year OS of RN patients (all P<0.05). In addition, the AUC of the SYSUCC nomogram for predicting the 15-year OS (0.820) was larger than that of the SSIGN score (0.709), and there was no statistical difference (P<0.05) between the SYSUCC nomogram, pure pathological staging (0.773) and the Karakiewicz nomogram (0.826). The calibration curve was close to the standard curve, which indicated that the model has good predictive performance. Finally, patients were stratified into low-, intermediate-, and high-risk subgroups (738, 379 and 129, respectively) according to the SYSUCC nomogram scores, among whom patients in intermediate- and high-risk subgroups had a worse OS than patients in the low-risk subgroup (intermediate-risk group vs. low-risk group: HR=4.33, 95% CI: 3.22-5.81, P<0.001; high-risk group vs low-risk group: HR=11.95, 95% CI: 8.29-17.24, P<0.001), and the high-risk subgroup had a worse OS than the intermediate-risk group (HR=2.63, 95% CI: 1.88-3.68, P<0.001). Conclusions: Age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological stage were independent prognostic factors for non-metastasis renal cell carcinoma patients after RN. The SYSUCC nomogram based on these independent prognostic factors can better predict the 5-, 10-, and 15-year OS than pure pathological staging, the Karakiewicz nomogram and the SSIGN score of patients after RN. In addition, the SYSUCC nomogram has good discrimination, agreement, risk stratification and clinical application potential.
Humans ; Nomograms ; Retrospective Studies ; Carcinoma, Renal Cell/pathology* ; Prognosis ; Risk Factors ; Nephrectomy ; Kidney Neoplasms/pathology* ; Necrosis

Objective: This study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitor combined tyrosine kinase inhibitor (TKI) therapy versus TKI monotherapy as the second-line regimen for patients with metastatic non-clear cell renal carcinoma (nccRCC) who failed first-line TKI therapy. Methods: The clinicopathological data of 67 patients with metastatic nccRCC who failed first-line TKI therapy between October 2011 and September 2020 were retrospectively analyzed, including 22 patients who received TKI monotherapy and 45 patients who received TKI plus PD-1 inhibitor as the second-line therapy. The efficacy was assessed according to Response Evaluation Criteria in Solid Tumors version 1.0/1.1 (RECIST 1.0/1.1), the Kaplan-Meier method was used to plot the survival curves, and the Log rank test was used to analyze the differences in the survival between the two groups. Treatment-related adverse events (AEs) after treatment were observed in both groups. Results: The overall objective response rate (ORR) and disease control rate (DCR) were 37.3% (25/67) and 56.7% (38/67), respectively. The overall second-line progression-free survival (PFS) was 7.7 months and Overall Survival (OS) was 25.2 months. The ORR and DCR of patients in the combination therapy group were 48.9% (22/45) and 71.1% (32/45), respectively, which were significantly improved compared with the TKI monotherapy group [13.6% (3/22) and 27.3% (6/22), respectively] (P=0.007 and P=0.001, respectively). The median PFS of 9.2 months for second-line treatment was longer in patients in the combination therapy group than in the TKI monotherapy group (5.2 months, P=0.001), but the median OS was not statistically different between the two groups (28.2 months vs 20.8 months, P=0.068). Common treatment-related AEs included hypertension, diarrhea, fatigue, stomatitis, hand-foot syndrome, and hypothyroidism. The incidence of hypothyroidism was higher in the combination therapy group [40.0% (18/45)] than in the TKI monotherapy group [22.7% (5/22), P=0.044]; the incidence of other treatment-related AEs between the two groups were not statistically significant (all P>0.05). Conclusion: Immune-targeted combination therapy was more effective than TKI monotherapy alone and was well tolerated in the treatment of metastatic nccRCC patients who failed first-line TKIs.
Humans ; Carcinoma, Renal Cell/drug therapy* ; Immunotherapy/adverse effects* ; Kidney Neoplasms/drug therapy* ; Retrospective Studies

Objective: To report the long-term survival of renal cell carcinoma (RCC) patients treated with radical nephrectomy in Sun Yat-sen University Cancer Center. Methods: We retrospectively analyzed the clinical, pathological and follow-up records of 1 367 non-metastatic RCC patients treated with radical nephrectomy from 1999 to 2020 in this center. The primary endpoint of this study was overall survival rate. Survival curves were estimated using the Kaplan-Meier method, and group differences were compared through Log-rank test. Univariate and multivariate Cox analysis were fit to determine the clinical and pathological features associated with overall survival rate. Results: A total of 1 367 patients treated with radical nephrectomy with complete follow-up data were included in the study. The median follow-up time was 52.6 months, and 1 100 patients survived and 267 died, with the median time to overall survival not yet reached. The 5-year and 10-year overall survival rates were 82.8% and 74.9%, respectively. The 5-year and 10-year overall survival rates of Leibovich low-risk patients were 93.3% and 88.2%, respectively; of Leibovich intermediate-risk patients were 82.2% and 72.3%, respectively; and of Leibovich high-risk patients were 50.5% and 30.2%, respectively. There were significant differences in the long-term survival among the three groups (P<0.001). The 10-year overall survival rates for patients with pT1, pT2, pT3 and pT4 RCC were 83.2%, 73.6%, 55.0% and 31.4%, respectively. There were significant differences among pT1, pT2, pT3 and pT4 patients(P<0.001). The 5-year and 10-year overall survival rates of patients with lymph node metastasis were 48.5% and 35.6%, respectively, and those of patients without lymph node metastasis were 85.1% and 77.5%, respectively. There was significant difference in the long-term survival between patients with lymph node metastasis and without lymph node metastasis. The 10-year overall survival rate was 96.2% for nuclear Grade 1, 81.6% for nuclear Grade 2, 60.5% for nuclear Grade 3, and 43.4% for nuclear Grade 4 patients. The difference was statistically significant. There was no significant difference in the long-term survival between patients with localized renal cancer (pT1-2N0M0) who underwent open surgery and minimally invasive surgery (10-year overall survival rate 80.5% vs 85.6%, P=0.160). Multivariate Cox analysis showed that age≥55 years (HR=2.11, 95% CI: 1.50-2.96, P<0.001), T stage(T3+ T4 vs T1a: HR=2.37, 95% CI: 1.26-4.46, P=0.008), local lymph node metastasis (HR=3.04, 95%CI: 1.81-5.09, P<0.001), nuclear grade (G3-G4 vs G1: HR=4.21, 95%CI: 1.51-11.75, P=0.006), tumor necrosis (HR=1.66, 95% CI: 1.17-2.37, P=0.005), sarcomatoid differentiation (HR=2.39, 95% CI: 1.31-4.35, P=0.005) and BMI≥24kg/m(2) (HR=0.56, 95%CI: 0.39-0.80, P=0.001) were independent factors affecting long-term survival after radical nephrectomy. Conclusions: The long-term survival of radical nephrectomy in patients with renal cell carcinoma is satisfactory. Advanced age, higher pathological stage and grade, tumor necrosis and sarcomatoid differentiation were the main adverse factors affecting the prognosis of patients. Higher body mass index was a protective factor for the prognosis of patients.
Humans ; Middle Aged ; Carcinoma, Renal Cell/secondary* ; Lymphatic Metastasis ; Retrospective Studies ; Neoplasm Staging ; Kidney Neoplasms/pathology* ; Prognosis ; Nephrectomy ; Survival Analysis ; Necrosis/surgery* ; Survival Rate