As people’s attention to health continues to increase, the market demand for traditional Chinese medicine (TCM) is growing steadily. The quality and safety of Chinese medicinal materials have attracted unprecedented social attention. In particular, the issue of exogenous harmful residue pollution in TCM has become a hot topic of concern for both regulatory authorities and society. The Chinese Pharmacopoeia 2025 Edition further refines the detection methods and limit standards for exogenous harmful residues in TCM. This not only reflects China’s high-level emphasis on the quality and safety of TCM but also demonstrates the continuous progress made by China in the field of TCM safety supervision. Basis on this study, by systematically reviewing the development history of the detection standards for exogenous harmful residues in TCM and analyzing the revisions and updates of these detection standards in the Chinese Pharmacopoeia 2025 Edition, deeply explores the key points of the changes in the monitoring standards for exogenous harmful residues in TCM in the Chinese Pharmacopoeia 2025 Edition. Moreover, it interprets the future development directions of the detection of exogenous residues in TCM, aiming to provide a reference for the formulation of TCM safety supervision policies.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Objective To investigate the effect of microRNA(miR)-4645-5p on the proliferation,invasion and epithelial-mesenchymal transition of esophageal cancer cells by targeting mucin 16(MUC16)and its mo-lecular mechanism.Methods The expression of miR-4645-5p in esophageal cancer tissues was analyzed online by TCGA database.The expression level of miR-4645-5p in esophageal cancer cell lines was analyzed by fluo-rescent real-time fluorescence quantitative polymerase chain reaction(qPCR).KYSE-30 cells were transfected with miR-4645-5p mimic and negative control mimic by lipofection technology,and were divided into miR-4645-5p group and control mimic group.The proliferation ability,migration ability and invasion ability of transfected KYSE-30 cells were analyzed by CCK-8 method,scratch test and Transwell test respectively.The target gene of miR-4645-5p was predicted by the bioinformatics website,and the binding of miR-4645-5p to the target gene was detected by the dual-luciferase reporter gene assay.The expression level of MUC16 mR-NA was detected by qPCR,and the protein expression levels of MUC16,transcription factor-1(ZEB-1),zonal atresia protein(ZO-1),tight junction protein-1(Claudin-1)and α-smooth muscle actin(α-SMA)were detected by Western blotting.Results The expression level of miR-4645-5p in esophageal cancer tissues was signifi-cantly lower than that in adjacent tissues(P＜0.01).Compared with HET-1 A,the expression of miR-4645-5p was lower in esophageal cancer cell lines(P＜0.05).After overexpression of miR-4645-5p,the proliferation a-bility of KYSE-30 cells was significantly reduced(P＜0.05),the migration ability was significantly reduced(P＜0.01)and the invasion ability was significantly reduced(P＜0.01).miR-4645-5p targeted and negatively regulated the expression of MUC16 mRNA(P＜0.01).After overexpression of miR-4645-5p,the protein ex-pression levels of MUC16,ZEB-1 and α-SMA were all down-regulated,and the protein expression levels of ZO-1 and Claudin-1 were up-regulated.Conclusion miR-4645-5p regulates the malignant biological behavior of esophageal cancer KYSE-30 cells by targeting MUC16.

BACKGROUND:Studies demonstrated that miR-135a-5p was highly expressed in mouse embryonic palatal mesenchymal cells with cleft palate induced by dexamethasone.The primary cilium and its mediated Shh signaling pathway were involved in the autophagy of mouse embryonic palatal mesenchymal cells.It is speculated that miR-135a-5p may regulate autophagy in mouse embryonic palatal mesenchymal cells through primary cilia and its mediated Shh signaling pathway. OBJECTIVE:To investigate the regulatory effect of miR-135a-5p on autophagy of mouse embryonic palatal mesenchymal cells. METHODS:In vitro,palatal mesenchymal cells from C57BL/6J mouse embryos were extracted and cultured.Cell transfections were set up as follows:(1)the cells were divided into control group,miR-135a-5p negative control group and miR-135a-5p mimic group;(2)NC+miR-NC group,KIF3B overexpression group,and miR-135a-5p+KIF3B group:qRT-PCR was performed to verify transfection efficiency of miR-135a-5p and KIF3B.A transmission electron microscope was used to observe the number of autophagosome/autophagolysosome in the cells of each group.The degree of fluorescence expression of autophagy marker LC3B was determined by the immunofluorescence technique.The protein expression of KIF3B,LC3 and P62 was determined by western blot assay.(3)The cells were divided into miR-135a-5p negative control group,and SAG treated group,and SAG+miR-135a-5p group.qRT-PCR was used to detect the mRNA expression levels of Gli3,a key transcription factor downstream of Shh signaling.The protein expressions of autophagy-related proteins LC3 and P62 were detected by western blot assay. RESULTS AND CONCLUSION:(1)After overexpression of miR-135a-5p,the number of autophagosome/autophagolysosome was significantly increased(P<0.01).The fluorescence density of LC3B increased significantly(P<0.01);the protein expression of KIF3B and P62 decreased(P<0.01),and the protein expression of LC3 increased.(2)After overexpression of KIF3B,the number of autophagosome/autophagolysosome was significantly decreased(P<0.01);the fluorescence density of LC3B was decreased(P<0.01);the protein expression of P62 was increased(P<0.01),and the protein expression of LC3 was decreased(P<0.01).Targeted expression of KIF3B was inhibited by miR-135a-5p(P<0.01);the number of autophagosome/autophagolysosome,the fluorescence intensity of LC3B as well as the protein expression of LC3 were reversed(P<0.01)and the protein expression of P62 was decreased(P<0.01).(3)SAG significantly increased the mRNA expression of Gli3(P<0.01),increased the protein expression of P62(P<0.01),and decreased the protein expression of LC3(P<0.01).When miR-135a-5p was added,Gli3 mRNA expression was significantly decreased(P<0.01);P62 protein expression was decreased(P<0.01),and LC3 protein expression was reversed(P<0.01).(4)These results indicate that miR-135a-5p targets the inhibition of KIF3B and promotes autophagy in mouse embryonic mesenchymal cells possibly by negatively regulating the Shh signaling pathway.

Objective Hippocampal atrophy is a clinically important marker for the diagnosis of many psychiatric disorders such as Alzheimer’s disease‚ so accurate segmentation of the hippocampus is an important scientific issue. With the development of deep learning‚ a large number of advanced automatic segmentation method have been proposed. However‚ 3D hippocampal segmentation is still challenging due to the effects of various noises in MRI and unclear boundaries between various classes of the hippocampus. Therefore‚ the aim of this paper is to propose new method to segment the hippocampal head‚ body‚ and tail more accurately. Methods To overcome these challenges‚ this paper proposed two strategies. One was the spatial and frequency domain features adaptive fusion strategy‚ which reduced the influence of noise on feature extraction by automatically selecting the appropriate frequency combination through fast Fourier transform and convolution. The other was an inter-class boundary region enhancement strategy‚ which allowed the network to focus on learning the boundary regions by weighting the loss function of the boundary regions between each class to achieve the goal of pinpointing the boundaries and regulating the size of the hippocampal head‚ body and tail. Results Experiments performed on a 50-case teenager brain MRI dataset show that our method achieves state-of-the-art hippocampal segmentation. Hippocampal head‚ body and tail had been improved compared to the existing method. Ablation experiments demonstrated the effectiveness of our two proposed strategies‚ and we also validated that the network had a strong generalization ability on a 260-case Task04_Hippocampus dataset. It was shown that the method proposed in this paper could be used in more hippocampal segmentation scenarios. Conclusion The method proposed in this paper can help clinicians to observe hippocampal atrophy more clearly and accomplish more accurate diagnosis and follow-up of the condition.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective To investigate the neuroprotective effect and potential mechanism of rehabilitation training combined with citicoline on cerebral hemorrhage model in mice based on Keap1/Nrf2/ARE signaling pathway.Methods The C57BL/6 male mice were randomly divided into sham operation group(sham operation treatment),model group(right caudate putamen hemorrhage model induced by type Ⅶcollagenase),choline group(model+choline 64 mg·kg-1),rehabilitation training group(rehabilitation training)and combined group(model+rehabilitation training+choline 64 mg·kg-1).The study observed the modified neurological severity score(mNSS)in mice with cerebral hemorrhage;colorimetric assays were used to detect the expression of malondialdehyde(MDA),superoxide dismutase(SOD)and catalase(CAT)in brain tissues;protein imprinting and reverse transcription-quantitative polymerase chain reaction were employed to assess the expression of Kelch-like ECH-associated protein 1(Keap1),nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE),heme oxygenase-1(HO-1),quinone oxidoreductase 1(NQ01)proteins and mRNA in brain tissues.Results The mNSS scores of sham operation group,model group,citicoline group,rehabilitation training group and combined group were 0,1.56±0.73,1.00±0.00,0.78±0.44 and 0.67±0.50;the MDA contents were(6.93±0.92),(22.97±0.77),(19.26±1.73),(13.21±0.78)and(7.25±0.97)nmol·mgprot-1;the relative expression of Keap1 protein were 0.79±0.03,1.02±0.04,0.95±0.10,0.90±0.09 and 0.86±0.05;the relative expression levels of Nrf2 protein were 0.94±0.12,0.71±0.08,0.90±0.07,0.98±0.12 and 1.33±0.25.There were significant differences in the above indexes between the model group and the sham operation group(P＜0.05,P＜0.01);there were significant differences between the citicoline group and the rehabilitation training group,the model group(P＜0.05,P＜0.01);there were significant differences between the combined group and the citicoline group,the rehabilitation training group except for protein expression of Keap1(all P＜0.01).Conclusion Rehabilitation training and citicoline can reduce the symptoms of neurological deficits in mice with cerebral hemorrhage.The mechanism way be that they can activate the Keap1/Nrf2/ARE signaling pathway to exert anti-oxidative stress,and the combined effect is the best.

Objective To develop a two-dimensional liquid chromatographic method for rifapentine blood concentration determination.Methods The blood concentration of rifapentine was determined by a novel two-dimensional liquid chromatography(2D-LC)with a one-dimensional column:Aston SC2T(3.5 mm ×50.0 mm,5 μm);a two-dimensional column:Aston SCB(4.6 mm ×250.0 mm,5 μm);the temperature of the column was 40 ℃;the flow rate was 1.0 mL·min-1;the detection wavelength was 335 nm;the injection volume was 300 μL.The specificity,standard curve and lower limit of quantification,precision and recovery,and stability of the method were investigated.The method was used to determine the blood concentration of rifapentine in tuberculosis patients.Results Rifapentine showed good linearity within 0.33-18.62 μg·mL-1 with the standard curve equation of y=2.68 x 105x-5 850.36(r=0.997),the recoveries were 99.81％-105.08％,and the intra-and inter-day precision were ≤4.84％.The results of rifapentine blood concentration measurements in tuberculosis patients were in the range of 0.10-54.70μg·mL-1,and 64.74％were within the therapeutic window concentration range(8-30 μg·mL-1).Conclusion The method is easy to operate,has high sensitivity,low detection limit and high specificity,and is suitable for clinical blood concentration determination.Individual differences in the administration of rifapentine in tuberculosis patients are large,and blood concentration monitoring is required for individualized treatment.

Objective To investigate the effects of total flavones from Oxytropis falcata Bunge on hepatic fibrosis(HF)induced by carbon tetrachloride and liver transforming growth factor(TGF-β)/Smad signaling pathway.Methods Forty-eight male rats were randomly divided into normal group(intraperitoneal injection of peanut oil,intragastric administration of 0.9％NaCl),model group(intraperitoneal injection of 40％CC14 peanut oil solution induced HF model,intragastric administration of 0.9％NaCl),positive control group(modeling,intragastric administration of 0.2 mg·kg-1 of colchicine),experimental-L,-M,-H groups(modeling,intragastric administration of 100,200 and 400 mg·kg-1 of total flavonoid extract of Oxytropis falcata Bunge),8 individuals in each group,for 4 consecutive weeks.The histopathological changes were observed by hematoxylin-eosin and Masson staining.Serum liver function and liver fibrosis were measured;erum inflammatory factors were detected;fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine gene expression in liver.Results The pathological injury of liver tissue in the model group was serious,and a large number of inflammatory factors and collagen fibers were accumulated,while the rest of the treatment groups had different degrees of remission.In normal group,model group,positive control group,experimental-L,-M,-H groups,glutamic-pyruvic transaminase levels were(49.28±12.44),(5 885.42±948.37),(4 454.60±489.27),(4 650.47±843.53),(3 761.75±887.30)and(3 544.90±1 066.75)μg·L-1;glutamic-oxaloacetic transaminase levels were(186.90±46.89),(5 936.23±793.81),(3 971.37±780.28),(4 360.30±863.35),(3 943.10±439.47)and(3 971.38±631.08)μg·L-1;hyaluronic acid levels were(45.08±17.16),(104.32±36.06),(66.83±20.09),(70.30±21.07),(60.00±9.68)and(59.02±10.73)μg·L-1;laminin levels were(23.13±3.89),(60.85±13.66),(35.67±9.92),(39.98±9.39),(36.55±12.21)and(34.68±24.83)μg·L-1;type Ⅲ procollagen level were(24.98±5.34),(82.58±30.14),(40.70±16.14),(51.08±23.21),(43.60±12.48)and(44.20±11.66)p±g·L-1;interleukin(IL)-1β levels were(37.63±1.24),(46.10±3.23),(39.22±2.36),(41.33±0.93),(40.25±2.04)and(39.18±2.23)pg·mL-1;tumor necrosis factor-α levels were(314.58±20.56),(383.71±16.97),(349.00±7.93),(348.88±25.11),(325.75±27.84)and(335.07±21.33)pg·mL-1;TGF-β1 mRNA expression of relative quantity respectively were 1.00±0.00,60.99±15.70,9.61±1.59,7.37±1.09,6.41±0.64,6.87±1.09;Smad7 mRNA relative expression were 1.00±0.00,0.34±0.05,0.21±0.03,0.35±0.02,0.38±0.02,0.42±0.03.The above indexes in the model group were compared with the normal group,and the above indexes in the experimental-M,-H groups were compared with the model group,and the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Total flavonoids of Oxytropis falcata Bunge have protective effects on CC14-induced liver fibrosis in rats,and the mechanism may be related to the regulation of TGF-β/Smad pathway.

AIM To investigate the variation rules of main secondary metabolites in Hedysari Radix before and after rubbing strip.METHODS UPLC-MS/MS was adopted in the content determination of formononetin,ononin,calycosin,calycosin-7-glucoside,medicarpin,genistein,luteolin,liquiritigenin,isoliquiritigenin,vanillic acid,ferulic acid,γ-aminobutyric acid,adenosine and betaine,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used for chemical pattern recognition to explore differential components.RESULTS After rubbing strip,formononetin,calycosin,liquiritigenin and γ-aminobutynic acid demonstrated increased contents,along with decreased contents of ononin,calycosin-7-glucoside and vanillic acid.The samples with and without rubbing strip were clustered into two types,calycosin-7-glucoside,formononetin,γ-aminobutynic acid,vanillic acid,calycosin-7-glucoside and formononetin were differential components.CONCLUSION This experiment clarifies the differences of chemical constituents in Hedysari Radix before and after rubbing strip,which can provide a reference for the research on rubbing strip mechanism of other medicinal materials.