Process analytical technology(PAT) is a key means for digital transformation and upgrading of the traditional Chinese medicine(TCM) manufacturing process, serving as an important guarantee for consistent and controllable TCM product quality. Near-infrared(NIR) spectroscopy has become the core technology for measuring the TCM manufacturing process. By incorporating NIR spectroscopy into PAT and starting from the construction of a smart platform for the TCM manufacturing process, this paper systematically described the development history and innovative application of the combination of NIR spectroscopy with chemometrics in measuring the TCM manufacturing process by the research team over the past two decades. Additionally, it explored the application of a validation method based on accuracy profile(AP) in the practice of NIR spectroscopy. Furthermore, the software development progress driven by NIR spectroscopy supported by modeling technology was analyzed, and the prospect of integrating NIR spectroscopy in smart factory control platforms was exemplified with the construction practices of related platforms. By integrating with the smart platform, NIR spectroscopy could improve production efficiency and guarantee product quality. Finally, the prospect of the smart platform application in measuring the TCM manufacturing process was projected. It is believed that the software development for NIR spectroscopy and the smart manufacturing platform will provide strong technical support for TCM digitalization and industrialization.
Spectroscopy, Near-Infrared/methods* ; Drugs, Chinese Herbal/analysis* ; Software ; Medicine, Chinese Traditional ; Quality Control

This paper aimed to use non-targeted urine metabolomics to reveal the potential biomarkers of toxicity in rats with hepatic injury induced by aqueous extracts of Dictamni Cortex(ADC). Forty-eight SD rats were randomly assigned to a blank group and high-dose, medium-dose, and low-dose ADC groups, with 12 rats in each group(half male and half female), and they were administered orally for four weeks. The hepatic injury in SD rats was assessed by body weight, liver weight/index, biochemical index, L-glutathione(GSH), malondialdehyde(MDA), and pathological alterations. The qPCR was utilized to determine the expression of metabolic enzymes in the liver and inflammatory factors. Differential metabolites were screened using principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA), followed by a metabolic pathway analysis. The Mantel test was performed to assess differential metabolites and abnormally expressed biochemical indexes, obtaining potential biomarkers. The high-dose ADC group showed a decrease in body weight and an increase in liver weight and index, resulting in hepatic inflammatory cell infiltration and hepatic steatosis. In addition, this group showed elevated levels of MDA, cytochrome P450(CYP) 3A1, interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α), as well as lower levels of alanine transaminase(ALT) and GSH. A total of 76 differential metabolites were screened from the blank and high-dose ADC groups, which were mainly involved in the pentose phosphate pathway, tryptophan metabolism, purine metabolism, pentose and glucuronic acid interconversion, galactose metabolism, glutathione metabolism, and other pathways. The Mantel test identified biomarkers of hepatotoxicity induced by ADC in SD rats, including glycineamideribotide, dIDP, and galactosylglycerol. In summary, ADC induced hepatotoxicity by disrupting glucose metabolism, ferroptosis, purine metabolism, and other pathways in rats, and glycineamideribotide, dIDP, and galactosylglycerol could be employed as the biomarkers of its toxicity.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Metabolomics ; Biomarkers/metabolism* ; Liver/metabolism* ; Drugs, Chinese Herbal/adverse effects* ; Female ; Chemical and Drug Induced Liver Injury/metabolism* ; Glutathione/metabolism* ; Humans

OBJECTIVE: To investigate the effect of 5-hydroxytryptamine (5-HT) on the proliferation, apoptosis and colony-forming unit-megakaryocyte (CFU-MK) of Meg-01 cells and its possible mechanisms. METHODS: The uptake and metabolism of 5-HT in Meg-01 cells were analysed by reverse-phase high-performance liquid chromatography (RP-HPLC) with electrochemical detection. The expression of 5-HT2B receptor (5-HT2BR) in megakaryocytes was detected by immunofluorescence staining. The cell proliferation and viability were measured by MTT and Trypan blue staining after Meg-01 cells were single-cultured or co-cultured with different concentrations of 5-HT/5-HT2BR inhibitor Ketanserin for 48 h. Meg-01 cells were incubated with 5-HT/ Ketanserin for 72 h, then the flow cytometry was used to detect early apoptosis of the cells and the activity of caspase-3. Using CFU-MK assay to investigate the effect of 5-HT on the differentiation of megakaryocytes. RESULTS: 5-HT could be uptaken by Meg-01 cells, and metabolized into 5-hydroxyindoleacetic acid (5-HIAA). The expression of 5-HT2BR on megakaryocytes could be detected after immunofluorescence staining. 5-HT could promote the proliferation of Meg-01 cells at a dose-dependent manner (r =0.82), with the most significant effect observed at a concentration of 200 nmol/L (P < 0.001). Trypan blue staining also indicated that 200 nmol/L 5-HT had the most significant effect on the viability of Meg-01 cells (P < 0.05). The proliferation of Meg-01 cells treated with 5-HT was increased compared with the untreated control (P < 0.001), while the combination of 5-HT with ketanserin downregulated this effect. 5-HT significantly reduced the early apoptosis rate (P < 0.001) and caspase-3 activity (P < 0.05) of Meg-01 cells, while addition of ketanserin significantly increased the early apoptosis rate of Meg-01 cells (P < 0.001) and caspase-3 activity also increased to some extent. 5-HT promoted the formation of CFU-MK in bone marrow cells in a dose-dependent manner (r =0.89). The addition of ketanserin reduced the promoting effect of 5-HT on CFU-MK formation (P < 0.01). CONCLUSION There may be monoamine oxidase present in megakaryocytes, which can metabolize and decompose 5-HT into 5-HIAA. 5-HT may promote the proliferation and differentiation of megakaryocytes through 5-HT2BR. Besides, 5-HT can also reduce the apoptosis of megakaryocytes, and its anti-apoptotic effect may be mediated by 5-HT2BR and caspase-3 pathways.
Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Megakaryocytes/metabolism* ; Serotonin/pharmacology* ; Humans ; Receptor, Serotonin, 5-HT2B/metabolism* ; Caspase 3/metabolism* ; Cell Differentiation

OBJECTIVE: To investigate the effect of TBL1XR1 mutation on cell biological characteristics of diffuse large B-cell lymphoma (DLBCL). METHODS: The TBL1XR1 overexpression vector was constructed and DNA sequencing was performed to determine the mutation status. The effect of TBL1XR1 mutation on apoptosis of DLBCL cell line was detected by flow cytometry and TUNEL fluorescence assay; CCK-8 assay was used to detect the effect of TBL1XR1 mutation on cell proliferation; Transwell assay was used to detect the effect of TBL1XR1 mutation on cell migration and invasion; Western blot was used to detect the effect of TBL1XR1 mutation on the expression level of epithelial-mesenchymal transition (EMT) related proteins. RESULTS: The TBL1XR1 overexpression plasmid was successfully constructed. The in vitro experimental results showed that TBL1XR1 mutation had no significant effect on apoptosis of DLBCL cells. Compared with the control group, TBL1XR1 mutation enhanced cell proliferation, migration and invasion of DLBCL cells. TBL1XR1 gene mutation significantly increased the expression of N-cadherin protein, while the expression of E-cadherin protein decreased. CONCLUSION TBL1XR1 mutation plays a role in promoting tumor cell proliferation, migration and invasion in DLBCL. TBL1XR1 could be considered as a potential target for DLBCL therapy in future research.
Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Cell Proliferation ; Mutation ; Receptors, Cytoplasmic and Nuclear/genetics* ; Apoptosis ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Cell Movement ; Repressor Proteins/genetics* ; Nuclear Proteins/genetics* ; Cadherins/metabolism*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Based on the interaction between supramolecule of traditional Chinese medicine and enterobacteria, the material basis of Rhei Radix et Rhizoma and Coptidis Rhizoma was explored. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) were used to characterize the morphological differences of Rhubarb single decoction, Coptis single decoction and Rhubarb and Coptis co-decoction. An in vitro antibacterial model (E. coli, E. faecium and B. subtilis) was established to evaluate the damage effect of the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma on enterobacteria. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the changes of chemical components of single decoctions and co-decoctions. The co-decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma was turbid after decocting. The spherical particles of 300-400 nm were observed under SEM, and the co-decoction was more uniform and stable than that of single decoction. The interaction between supramolecules formed after the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma and enterobacteria was significantly different from that of single decoction. In the process of interaction between supramolecules and enterobacteria, the spherical state was maintained, and the medicinal ingredients in Coptidis Rhizoma or Rhei Radix et Rhizoma were blocked, which could effectively alleviate the damage to enterobacteria. This study provided a reference for subsequent studies on the regulation of intestinal flora homeostasis by the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma.

Objective To screen the optimal regimen of Chinese medicine combined with hormones for the treatment of premature ovarian failure(POF)using network meta-analysis and to provide an evidence-based basis for the clinical treatment of POF.Methods The randomized controlled trials(RCTs)of Chinese medicine combined with hormones in the treatment of POF were retrieved from thhe domestic and oversea databases of CNKI,VIP,Wanfang,CBM,PubMed,Cochrane,Embase,and Web of Science.The quality of the literature was assessed using the tools for analysis of bias recommended by Cochrane Reviewer's Handbook and by Jadad scale scores.Rstudio and StataSE 15.1 statistical software were used to perform network meta-analysis and graphical presentation of the data.Results A total of 50 RCTs were included,covering 8 intervention methods.The overall risk of bias of the included studies was low,but the quality of the literature was generally low.The results of network meta-analysis showed that,in terms of the effective rate,the intervetion of 7 various Chinese medicines combined with hormone was superior to the conventional treatment(hormone replacement therapy,HRT)in the control group,and Nuangong Qiwei Powder+HRT was superior to the remaining 6 kinds of Chinese medicines combined with HRT;with reference to the values of the surface under the cumulative ranking curve(SUCRA),the efficiencies of the effective rate of the 8 intervention methods in descending order were Nuangong Qiwei Powder+ HRT(SUCRA=81.2),Zishen Yutai Pills + HRT(SUCRA=80.0),modified Zuogui Pills + HRT(SUCRA= 66.1),Ankun Zhongzi Pills + HRT(SUCRA=49.6),Kuntai Capsules + HRT(SUCRA=45.2),modified Erxian Decoction + HRT(SUCRA=39.5),Liuwei Dihuang Pills + HRT(SUCRA=37.4)and HRT(SUCRA=1.0).In terms of improving serum follicle-stimulating hormone(FSH)levels,modified Zuogui Pills + HRT was superior to the remaining 7 intervention methods;with reference to the values of the SUCRA,the efficiencies of the 8 intervention methods in descending order were modified Zuogui Pills + HRT(SUCRA=97.0),HRT(SUCRA= 77.9),Liuwei Dihuang Pills + HRT(SUCRA=76.6),Kuntai Capsules + HRT(SUCRA=46.5),Nuangong Qiwei Powder+HRT(SUCRA=38.9),Ankun Zhongzi Pills + HRT(SUCRA=29.9),modified Erxian Decoction + HRT(SUCRA=18.1),and Zishen Yutai Pills + HRT(SUCRA=15.1).Conclusion All kinds of Chinese medicines combined with HRT exert stronger effect on improving the primary outcome indicators than HRT alone for the treatment of POF.The intervention with Nuangong Qiwei Powder+HRT exerts the highest probability of the optimal regimen for enhancing the efficiency,and the intervention with Zuogui Pills + HRT exerts the highest probability of the optimal regimen for lowering the serum FSH level.However,due to the low quality of the included studies,more rigorously-designed,large sample-size,and high-quality randomized controlled trials need to be conducted in the future to provide conclusive evidence-based evidence.

Objective To investigate the rate of germline variants in patients with pancreatic cancer and clinical characteristics related with germline variants.Methods A total of 271 patients diagnosed with pancreatic cancer were enrolled in this study.Germline variants of 21 tumor susceptibility genes were detected by next-generation sequencing,and the relationship between germline variants and clinical factors such as age of onset,family history and personal history was analyzed.Results The rate of germline P/LP variants was 6.3%in unselected pancreatic cancer patients,but was high as 17.1%in genetic high-risk group patients(those with a family or personal history of cancer,or early-onset).Genes with higher frequency of germline variants in pancreatic cancer patients were PALB2,BRCA2,and ATM.Conclusion The rate of germline variants in overall pancreatic cancer patients is not high,but it increases significantly in genetic high-risk group,proving the importance of clinical factors in the screening of hereditary pancreatic cancer.