Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

OBJECTIVE: To retrospectively analyze the clinical data of newly diagnosed acute myeloid leukemia (AML) patients treated with venetoclax combined with azacitidine (Ven/Aza) or standard "3+7" regimen and similar regimens, collect real-world study data, compare the treatment response and adverse events between the two regimens, as well as perform survival analysis. METHODS: To retrospectively analyze the efficacy, survival, and adverse reactions of newly diagnosed AML patients treated with Ven/Aza (24 cases) and "3+7" regimens (117 cases ) in our hospital from September 2009 to March 2023, as well as factors influencing outcomes. A propensity score matching (PSM) was performed on age and Eastern Cooperative Oncology Group performance status (ECOG PS) to obtain a 1:1 matched cohort of 20 pairs, and the efficacy and survival before and after the matching were compared. RESULTS: The median age of patients in the Ven/Aza group was 69 years, while that in the "3+7" group was 56 years (P <0.001). Objective remission rate (ORR) was 62.5% in Ven/Aza group and 74.8% in "3+7" group (P >0.05). The median overall survival (OS) in the Ven/Aza group was 522 days, while that in the "3+7" group was 1 002 days (P >0.05). After controlling the two variables of age and ECOG PS, a PSM cohort of 20 pairs was obtained, in which the ORR was 65% in Ven/Aza group and 60% in "3+7" group (P >0.05). The median OS was 522 days and 629 days, and median progression-free survival (PFS) was 531 days and 198 days between the two groups, respectively. There were no statistically significant differences in OS and PFS between the two groups (both P >0.05). Additionally, the incidence of adverse events in the Ven/Aza group was significantly reduced. CONCLUSION The overall cohort shows that the "3+7" regimen has advantages in efficacy and survival, but Ven/Aza regimen is relatively safer. After performing PSM on age and ECOG PS, the Ven/Aza group showed improved efficacy, and a longer median PFS compared to "3+7" group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Retrospective Studies ; Sulfonamides/administration & dosage* ; Azacitidine/administration & dosage* ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Aged ; Middle Aged ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
Animals ; Hesperidin/therapeutic use* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Male ; Stress, Psychological/drug therapy* ; Brain/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Serotonin/metabolism* ; Gastrointestinal Microbiome/drug effects* ; Behavior, Animal/drug effects* ; Rats ; Brain-Gut Axis/drug effects* ; Chronic Disease ; Colon/drug effects*

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Objective To explore the relationship between triglyceride-glucose(TyG)index and hypertension in patients with cerebral hemorrhage.Methods A total of 1718 patients with cere-bral hemorrhage admitted to our hospital from January,2013 to May,2023 were enrolled in this study.According to the TyG index quartile,437 cases were assigned into Q1 group(≤8.375),424 cases into Q2 group(TyG index 8.376～8.737),429 cases into Q3 group(TyG index 8.738～9.087),and 428 cases into Q4 group(≥9.088).The general clinical data were compared in the four groups.Logistic regression analysis was used to study the correlation between TyG index and hy-pertension.Results There were significant differences among the four groups in terms of age,hy-pertension,diabetes,SBP,DBP,TC,TG,HDL-C,LDL-C,FBG,glycated hemoglobin and TyG in-dex(P＜0.05,P＜0.01).Logistic regression analysis showed that when the TyG index was a con-tinuous variable,it was significantly correlated with the risk of hypertension(OR=1.999,95％CI:1.393-2.869,P=0.001).When the index was used as a categorical variable,with Q1as a ref-erence,TyG index in Q3 and Q4 was associated with an increase in OR of hypertension(OR=1.869,95％CI:1.220-2.865,P=0.004;OR=1.844,95％CI:1.125-3.020,P=0.015).After ad-justing cofounders,the association of TyG index and risk of hypertension was stronger in the fe-males(OR=2.618,95％CI:1.312-5.221,P=0.006)than the males(OR=1.783,95％CI:1.151-2.761,P=0.010),and in the patients ≥65 years old(OR=3.277,95％CI:1.600-6.741,P=0.001)than those＜65 years old(OR=1.782,95％CI:1.076-2.949,P=0.025).Conclusion TyG index is closely associated with hypertension in patients with cerebral hemorrhage,especially in women and elderly.

Objective:To investigate the expression of LINC01088 in breast cancer and its effects on cell prolifera-tion,migration,and invasion.Methods:GEPIA and bc-GenExMiner were used to analyze the correlation between LINC01088 expression levels and clinical characteristics as well as prognosis.The expression of LINC01088 in MCF10A and MDA-MB-231,BT-549,MCF7 were detected by Real-time PCR.The effect of LINC01088 on the biological func-tion of breast cancer cells was examined by overexpressing LINC01088 in breast cancer cells.Cell proliferation was as-sessed using the Incucyte assay,while cell migration and invasion were evaluated using Transwell assays.Western blot-ting was employed to detect the expression of proteins associated with cell proliferation and metastasis.Results:LINC01088 expression was significantly lower in breast cancer tissues compared to normal breast tissues(P<0.05).Data from the bc-GenExMiner database revealed higher LINC01088 expression in HER2 positive patients(P<0.0001),corre-lating with longer overall survival(P=0.0006)and disease-free survival(P=0.0002).The mRNA expression level of LINC01088 in normal breast epithelial cell line was higher than that in breast cancer cell lines(P<0.05).Overexpression of LINC01088 significantly reduced proliferation,migration,and invasion in three breast cancer cell lines(P<0.01).Addi-tionally,LINC01088 upregulated p21 and p27(P<0.01),while downregulating Snail,Slug,PI3K,and phosphorylated Akt(P<0.05).Conclusion:LINC01088 expression was significantly reduced in human breast cancer.In vitro,LINC01088 in-hibited the proliferation,migration,and invasion of breast cancer cells.This effect may be attributed to its role in sup-pressing the PI3K-AKT pathway and epithelial-mesenchymal transition.

Objective:To investigate the expression of LINC01088 in breast cancer and its effects on cell prolifera-tion,migration,and invasion.Methods:GEPIA and bc-GenExMiner were used to analyze the correlation between LINC01088 expression levels and clinical characteristics as well as prognosis.The expression of LINC01088 in MCF10A and MDA-MB-231,BT-549,MCF7 were detected by Real-time PCR.The effect of LINC01088 on the biological func-tion of breast cancer cells was examined by overexpressing LINC01088 in breast cancer cells.Cell proliferation was as-sessed using the Incucyte assay,while cell migration and invasion were evaluated using Transwell assays.Western blot-ting was employed to detect the expression of proteins associated with cell proliferation and metastasis.Results:LINC01088 expression was significantly lower in breast cancer tissues compared to normal breast tissues(P<0.05).Data from the bc-GenExMiner database revealed higher LINC01088 expression in HER2 positive patients(P<0.0001),corre-lating with longer overall survival(P=0.0006)and disease-free survival(P=0.0002).The mRNA expression level of LINC01088 in normal breast epithelial cell line was higher than that in breast cancer cell lines(P<0.05).Overexpression of LINC01088 significantly reduced proliferation,migration,and invasion in three breast cancer cell lines(P<0.01).Addi-tionally,LINC01088 upregulated p21 and p27(P<0.01),while downregulating Snail,Slug,PI3K,and phosphorylated Akt(P<0.05).Conclusion:LINC01088 expression was significantly reduced in human breast cancer.In vitro,LINC01088 in-hibited the proliferation,migration,and invasion of breast cancer cells.This effect may be attributed to its role in sup-pressing the PI3K-AKT pathway and epithelial-mesenchymal transition.

Objective To explore the relationship between triglyceride-glucose(TyG)index and hypertension in patients with cerebral hemorrhage.Methods A total of 1718 patients with cere-bral hemorrhage admitted to our hospital from January,2013 to May,2023 were enrolled in this study.According to the TyG index quartile,437 cases were assigned into Q1 group(≤8.375),424 cases into Q2 group(TyG index 8.376～8.737),429 cases into Q3 group(TyG index 8.738～9.087),and 428 cases into Q4 group(≥9.088).The general clinical data were compared in the four groups.Logistic regression analysis was used to study the correlation between TyG index and hy-pertension.Results There were significant differences among the four groups in terms of age,hy-pertension,diabetes,SBP,DBP,TC,TG,HDL-C,LDL-C,FBG,glycated hemoglobin and TyG in-dex(P＜0.05,P＜0.01).Logistic regression analysis showed that when the TyG index was a con-tinuous variable,it was significantly correlated with the risk of hypertension(OR=1.999,95％CI:1.393-2.869,P=0.001).When the index was used as a categorical variable,with Q1as a ref-erence,TyG index in Q3 and Q4 was associated with an increase in OR of hypertension(OR=1.869,95％CI:1.220-2.865,P=0.004;OR=1.844,95％CI:1.125-3.020,P=0.015).After ad-justing cofounders,the association of TyG index and risk of hypertension was stronger in the fe-males(OR=2.618,95％CI:1.312-5.221,P=0.006)than the males(OR=1.783,95％CI:1.151-2.761,P=0.010),and in the patients ≥65 years old(OR=3.277,95％CI:1.600-6.741,P=0.001)than those＜65 years old(OR=1.782,95％CI:1.076-2.949,P=0.025).Conclusion TyG index is closely associated with hypertension in patients with cerebral hemorrhage,especially in women and elderly.

Objective:To investigate the predictive value of morphology,immunology,and cytogenetics for isocitrate dehydrogenase 1 and 2(IDH1/2)gene mutation in newly diagnosed acute myeloid leukemia(AML)patients.Methods:The clinical data of 186 newly diagnosed AML patients(except M3 subtype)in the First People's Hospital of Changzhou were retrospectively analyzed,and the variables associated with IDH1/2 mutation in patients were screened using LASSO regression to construct a multivariate logistic regression analysis model.The Bootstrap method was used for internal validation of the model and nomograms were used to visualize the model,and receiver operating characteristic(ROC)curve was used to evaluate the predictive performance of the model.Results:A total of 60 AML patients had IDH1/2 mutation at initial diagnosis.LASSO regression screened 9 predictive variables associated with IDH1/2 mutation,including CD7,CD56,CD11b,CD15,CD64,HLA-DR,platelet count ≥ 50 × 109/L,isolated+8 and normal karyotype.The nomogram and ROC curve were plotted based on the above 9 variables.The area under the ROC curve(AUC)of the training set and the validation set were 0.871 and 0.806,respectively.Internal validation showed that the nomogram had good predictive ability.Conclusion:The prediction model based on MIC typing constructed in this study has a good predictive ability for the presence of IDH1/2 mutations in newly diagnosed AML patients and has important clinical application value when the gene mutation detection results are unavailable.

Objective:To explore the risk factors affecting the survival and efficacy of patients with acute myeloid leukemia with myelodysplasia-related changes(AML-MRC)transformed from myelodysplastic syndrome(MDS).Methods:The clinical data of 60 patients with AML-MRC transformed from MDS who hospitalized in The Third Affiliated Hospital of Soochow University from January 2010 to December 2021 were retrospectively analyzed.The demographic data and laboratory parameters,cytogenetic karyotypes,target genes of AML detected by next generation sequence,risk stratification,treatment regimen,therapeutic efficacy and survival outcome were documented.Rank sum test and Chi-square test or Fisher exact test were used to compare the survival and efficacy.The effects of clinical parameters,risk stratification and treatment regimens on the survival and efficacy of the AML-MRC patients were analyzed by univariate and multivariate analysis.Results:The median overall survival(OS)of the AML-MRC patients was 4.5 months,the 1-year OS rate was 28.3％,and the complete remission(CR)rate after treatment was 33.3％.The univariate analysis showed that age≥60 years,leukocytosis,severe thrombocytopenia,poor-risk group and only accepted hypomethylating agents(HMAs)or supportive therapy were the risk factors affecting OS.COX multivariate analysis showed that thrombocytopenia(HR=4.46),HMAs therapy(compared to transplantation,HR=10.47),supportive therapy(compared to transplantation,HR=25.80)and poor-risk group(compared to medium-risk group,HR=13.86)were independent hazard factors for median OS of patients with AML-MRC.The univariate analysis showed that the risk factors affecting 1-year OS in patients with AML-MRC were age ≥ 60 years,thrombocytopenia,time of transformation from MDS to AML(TTA)≥3 months,fibrinogen-albumin ratio index(FARI)≥ 0.07,CONUT score≥5,poor-risk group and supportive therapy.Binary logistic regression analysis showed that the independent risk factors for 1-year OS in AML-MRC patients were age ≥ 60 years(HR=11.23),thrombocytopenia(HR=8.71),FARI ≥ 0.07(HR=5.19)and poor-risk group(HR=14.00).The risk factors affecting CR of AML-MRC patients in univariate analysis were age ≥ 60 years,thrombocytopenia,FARI ≥ 0.1,CONUT score ≥ 5,poor-risk group and supportive therapy,while binary logistic regression analysis showed that age ≥ 60 years(HR=7.35),CONUT score ≥ 5(HR=9.60),thrombocytopenia(HR=12.05)and poor-risk group(HR=32.5)were independent risk factors affecting CR of the patients.Conclusion:The OS of AML-MRC patients is poor,old age(≥ 60 years old),supportive therapy,HMA therapy,poor-risk,thrombocytopenia,FARI ≥ 0.07 and CONUT score ≥ 5 may be associated with poor prognosis.