Objective To develop an ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method to simultaneously determine 10 main components, including berberine, phellodendrine, specnuezhenide, mangiferin, loganin, paeoniflorin, geniposide, baicalin, and acteoside in Compound Dihuang oral solution. Methods An UPLC-MS/MS method was established with an ACQUITY UPLC BEH-C18 （2.1 mm×100 mm, 1.7 μm）column and mobile phase of 0.1% formic water（A）-methanol solution（B） in a gradient elution manner. The flow rate of mobile phase was 0.2 ml/min.The temperature of column was 30℃. The injection volume was 2 μl. The MS detection was in MRM mode. Results 10 components in Compound Dihuang oral solution had a good linear relationship within their concentration range,and the precision, repeatability, stability and recovery met the requirements. The contents of berberine, phellodendrine, specnuezhenide, mangiferin, loganin, paeoniflorin, geniposide, baicalin, and acteoside in 7 batches of samples were （89.7-95.6） μg/ml, （164.0-177.7） μg/ml, （540.0-610.0） μg/ml, （408.7-429.0） μg/ml, （726.0-825.0） μg/ml, （503.7-572.0） μg/ml, （1380.0-1540.0） μg/ml, （2596.7-2896.7) μg/ml, （4866.7-5520.0) μg/ml, （61.8-67.2) μg/ml, respectively. Conclusion The established method was easy to be repeated and operated. The contents of 10 components in Compound Dihuang oral solution could be determined quickly and accurately, which provided a reference for the quality control of hospital preparation.

ObjectiveTo investigate the effect of Yunkang oral liquid on postpartum kidney deficiency in mice. MethodPostpartum mice were randomized into model and low-dose （6 mL·kg^-1）， medium-dose （9 mL·kg^-1）， and high-dose （12 mL·kg^-1） Yunkang oral liquid groups. The mouse model of postpartum kidney deficiency was established by sleep deprivation combined with forced swimming. Another 9 female ICR mice were selected as the normal control group. The mice were administrated with Yunkang oral liquid during the period of modeling. The levels of estradiol （E₂）， progesterone （P）， follicle-stimulating hormone （FSH）， and luteinizing hormone （LH） in the serum were measured by the enzyme-linked immunosorbent assay. The morphological changes of ovaries and uterus were observed by hematoxylin-eosin （HE） staining， and the expression of transforming growth factor （TGF）-β and Smad2/3 was determined by immunohistochemistry and Western blotting. ResultThe mice in the model group showed prolonged estrous cycle， reduced voluntary activity， dorsal temperature， grip strength， and bone strength， and whitening tongue coating. Compared with the model group， Yunkang oral liquid shortened the estrous cycle， increased the voluntary activity， dorsal temperature， grip strength， and bone strength， and alleviated the whitening of tongue coating. Moreover， it elevated the E₂ and P levels and lowered the FSH and LH levels in the serum， decreased ovarian follicular atresia rate， promoted uterine repair， and down-regulated the expression of TGF-β and Smad2/3 in the ovarian and uterine tissues. ConclusionYunkang oral liquid can ameliorate postpartum kidney deficiency in mice by regulating the TGF-β/Smads signaling pathway.

Pharmaceutical excipients, as an indispensable part of drug preparation, play crucial roles as drug carriers, improving drug release, ensuring drug stability, and enhancing patient compliance. Traditional Chinese Medicine (TCM) boasts a rich developmental history. With the modernization of technology, the deep integration of pharmacy, chemistry, and materials science has provided broader opportunities for innovative research in TCM. Simultaneously, the demand for high-quality excipients has become increasingly critical.This paper aims to review current research and applications of excipients in TCM preparations, including pre-mixed and co-processed excipients, modified excipients, and the unification of drugs and excipients, such as flavoring agents, fillers, penetration enhancers, and delivery systems. A meticulous synthesis and analysis of existing research aims to provide a reference for selecting excipients in TCM preparations, stimulate innovation in excipient development for TCM, and advocate for the development of personalized excipients.

Objective To investigate the relationship between systemic immune-inflammation index (SII)and lower extremity vascular disease in patients with type 2 diabetes mellitus (T2DM).Methods A cross-sectional study was conducted on 390 T2DM patients admitted in our department from January 2013 to January 2024.According to the diagnostic criteria for lower extremity vascular disease in T2DM patients,they were divided into a lower extremity vascular disease group (n=158)and a control group (n=232).General data and results of laboratory tests were compared between the 2 groups.Spearman correlation analysis was used to identify the related factors for lower extremity vascular diseases in T2DM patients.The correlation between SII and lower extremity vascular diseases in T2DM patients was analyzed using the Row Mean Scores and Cochran-Armitage Trend analysis.Multivariate logistic regression analysis was applied to identify the risk factors for lower limb vascular lesions in T2DM patients.Receiver operating characteristic (ROC)curve was plotted to evaluate the diagnostic efficacy of SII for lower extremity vascular disease in the patients.Results Compared with T2DMpatients without lower extremity vascular disease,those with lower extremity vascular disease were older,had higher levels of total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),SII,larger proportion of carotid vascular lesions,and increased proportion of no-taking statins.The lower extremity vascular disease in T2DM patients was positively correlated with SII/100 (r=0.429,P<0.001),age (r=0.517,P<0.001),TC (r=0.161,P=0.001),LDL-C (r=0.117,P=0.021),carotid artery lesions (r=0.101,P=0.047),no-taking statins (r=0.266,P<0.001).Logistic regression analysis showed that SII,age,LDL-C,and no-taking statins were the risk factors for lower extremity vascular lesions in T2DM patients (P<0.01).The area under the curve (AUC)value of SII combined with age,LDL-C,and no-taking statins in predicting lower extremity vascular disease in T2DM patients was 0.896.Conclusion SII is not only a risk factor,but also a simple marker for lower extremity vascular disease in T2DM patients,suggesting that inflammatory response plays an important role in the occurrence and development of lower extremity vascular disease in T2DM.

Over-expression of glutathione S-transferase(GST)can promote Cisplatin resistance in hepatocellular carcinoma(HCC)treatment.Hence,inhibiting GST is an attractive strategy to improve Cisplatin sensi-tivity in HCC therapy.Although several synthesized GST inhibitors have been developed,the side effects and narrow spectrum for anticancer seriously limit their clinical application.Considering the abundance of natural compounds with anticancer activity,this study developed a rapid fluorescence technique to screen"green"natural GST inhibitors with high specificity.The fluorescence assay demonstrated that schisanlactone B(hereafter abbreviated as C1)isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo.Importantly,C1 can selectively kill HCC cells from normal liver cells,effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression.Considering the high GST levels in HCC patients,this compound demon-strated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.

Objective:To investigate the expression level of serum microRNA-122-5p (miR-122-5p) in elderly patients with chronic atrophic gastritis (CAG) and its correlation with inflammatory factors and disease severity.Methods:A total of 120 CAG patients admitted to our hospital from Dec. 2019 to Dec. 2021 were selected as as the experimental group. According to the gastric mucosa pathological score, the patients were grouped into 58 cases with normal condition and 62 cases with severe condition. Another 105 patients with chronic non-atrophic gastritis during the same period were included as the control group. The expression level of serum miR-122-5p was detected by qRT-PCR, the level of serum hs-CRP was detected by immunoturbidimetry, the levels of serum TNF-α and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA), and the correlation of serum miR-122-5p expression level with hs-CRP, IL-6, TNF-α and disease severity in CAG patients was analyzed by Pearson method. Logistic regression was used to analyze the risk factors of affecting CAG.Results:There were no significant differences in gender, age, or the proportion of patients with smoking history between the CAG group and the control group ( P>0.05). The proportions of drinking and Hp positive patients in the CAG group were 52.50% and 62.50%, which were significantly higher than those in the control group (25.71%, 43.80%) ( P<0.05) ; The serum levels of miR-122-5p, hs-CRP, IL-6, and TNF-α in the CAG group were (2.31±0.42), (24.89±4.56) mg/L, (39.26±7.68) ng/mL, and (85.42±9.65) pg/ml, respectively, which were significantly higher than the control group [ (1.05±0.12), (16.54±3.85) mg/L, (22.39±5.21) ng/ml, (862.34±7.46) pg/ml] ( P<0.05) ; Serum hs-CRP, IL-6, TNF-αlevels, miR-122-5p expression levels, Hp positive infection rate and pathological score in patients with severe CAG disease were (28.14±3.21) mg/L, (44.55±5.73) ng/ml, (93.42±8.81) pg/ml, 2.74±0.30, 72.58%, (4.30±1.20) points, respectively, which were significantly higher than those of patients with normal disease [ (21.42±3.67) mg/L, (33.61±5.54) ng/ml, (76.87±7.59) pg/mL, 1.85±0.36, 51.72%, (1.60±0.30) points] ( P<0.05) ; correlation analysis showed that serum miR-122-5p expression level in CAG patients was positively correlated with hs-CRP, IL-6, TNF-α and disease severity ( r=0.475, 0.453, 0.505, 0.563, P<0.001). Multivariate logistic analysis showed that Hp positive infection ( OR=2.527, 95% CI=1.125-5.678), miR-122-5p ( OR=2.323, 95% CI=1.341-4.025) were independent risk factors for CAG ( P<0.05) . Conclusion:The expression level of serum miR-122-5p in elderly patients with CAG is increased, which is related to serum inflammatory factors, disease severity and Hp infection, and may be a marker for the diagnosis of CAG.

OBJECTIVE To study the unknown impurity in potassium aspartate and magnesium aspartate injection by heart-cutting two-dimensional liquid chromatography coupled with Quadrupole time-of-flight mass spectrometry (2D-LC-Q-TOF-MS). METHODS The Waters ACQUITY UPLC 2D system and Xevo G2-XS QTof-MS system were used. One- dimensional chromatographic conditions were as listed. An Agilent ZORBAX-NH2 column was used, and potassium dihydrogen thophosphate(0.05 mol·L-1)-acetonitrile(37∶63) as the mobile phase, at a flow rate of 1.3 mL·min-1. The detection wavelength was set at 200 nm. Two-dimensional chromatographic conditions were as listed. A Waters ACQUITY UPLC HSS T3 column was used, and 0.1% formic acid solution(ESI+)/5 mmol·L-1 ammonium formate(ESI-) as the mobile phase A, and acetonitrile as the mobile phase B, in gradient mode. The mass spectrometry used an electro spray ionization source(ESI) for positive and negative ion mode detection. RESULTS Combined the high resolution mass, MS2 fragment ions and the UNIFI software, the possible structure of the unknown impurity in potassium aspartate and magnesium aspartate injection was infered. CONCLUSION The 2D-LC-Q-TOF-MS method can be used to identify impurities in potassium aspartate and magnesium aspartate injection, which provides reference for the improvement of quality control and process optimization of potassium aspartate and magnesium aspartate injection.

OBJECTIVE：To provide method reference for scientifically eva luating the rationality of the use of saxagliptin . METHODS：Based on the drug instructions ，clinical guidelines ，clinical pathways ，related references ，clinical endocrinology department and pharmaceutical experts of a hospital jointly discussed and formulated the evaluation criteria for the rationality of the use of saxagliptin. AHP method was used to assign weights to various indexes of evaluation criteria ；TOPSIS method was used to analyze the use of saxagliptin of 106 cases in the hospital during Nov. 2018-Apr. 2019 retrospectively and evaluate rational drug use. RESULTS ：A total of 6 primary indicators and 12 secondary indicators were established. The first three indicators with a relatively high index weight were indications （with a weight of 0.25），dose and adjustment of administration （with a weight of 0.21）and frequency of administration （with a weight of 0.15）. Among 106 cases，39.6％ of drug use were reasonable ，51.0％ were basically reasonable and 9.4％ were unreasonable. Evaluation results made by weighted TOPSIS were consistent with the actual situation. CONCLUSIONS ：TOPSIS method weighted by AHP is reasonable and feasible for evaluating the rationality of saxagliptin use.

Objective To investigate the effect of enriched environment (EE) on behavior and expression of mitogenactivated protein kinase phosphatase-1 (MKP-1) in hippocampus of depression rats induced by chronic unpredicted mild stress (CUS) and to provide clues for the molecular mechanism of treating depression.Methods Forty Sprague-Dawley rats were randomly divided into control group,CUS group,fluoxetine group and EE group,with 10 rats in each group.The rats in CUS group,fluoxetine group and EE group were given 8 weeks of CUS,and from the fifth week,the rats in EE group and fluoxetine group were given EE and fluoxetine for 4 weeks,respectively.The changes of behavioristic of the rats in the four groups were evaluated by body mass gain,open field test,and sucrose preference.The expression of MKP-1 in hippocampus was detected by Western blot.Results There was no significant difference in body mass,distance of horizontal movement,the number of upright,the times of passing through the grid and sucrose preference index among the four groups(P ＞ 0.05).After modeling,compared with the control group,the body mass gain,distance of horizontal movement,the number of up-right,the times of passing through the grid and sucrose preference index in the CUS group,fluoxetine group and EE group were decreased significantly(P ＜ 0.05);there was no significant difference in the body mass gain,distance of horizontal movement,the number of up-right,the times of passing through the grid and sucrose preference index among the CUS group,fluoxetine group and EE group(P ＞ 0.05).After intervening by fluoxetine and EE,the body mass gain,distance of horizontal movement,the number of up-right,the times of passing through the grid and sucrose preference index in the CUS group were lower than those in the control group(P ＜0.05);but there was no significant difference in the body mass gain,distance of horizontal movement,the number of up-right,the times of passing through the grid and sucrose preference index between the control group and the fluoxetine group and EE group(P ＞ 0.05).Compared with the CUS group,the body mass gain,distance of horizontal movement,the number of up-right,the times of passing through the grid and sucrose preference index in the fluoxetine group and EE group were higher(P ＜ 0.05);there was no significant difference in the body mass gain,distance of horizontal movement,the number of up-right,the times of passing through the grid and sucrose preference index between the fluoxetine group and EE group (P ＞ 0.05).The expression of MKP-1 in hippocampus of CUS group and EE group was higher than that in the control group (P ＜0.05).There was no significant difference in the expression of MKP-1 in hippocampus between the fluoxetine group and control group(P ＞ 0.05).Compared with the CUS group,the expression of MKP-1 in hippocampus in the fluoxetine group decreased (P ＜ 0.05).There was no significant difference in the expression of MKP-1 in hippocampus between the EE group and CUS group(P ＞0.05).Compared with the fluoxetine group,the expression of MKP-1 in hippocampus in the EE group was higher(P ＜ 0.05).Conclusion EE can significantly improve depressive symptoms in rats,but it has no significant effect on MKP-1 protein expression in hippocampus,and EE may not act on depression by affecting MKP-1.

Pathology is a subject that studies the etiology,pathogenesis,pathological changes,progression and outcome of diseases.Pathology links the basic research and clinical practice and is an important part of translational medicine.In order to cultivate qualified pathological graduates with solid pathological theories and the abilities of proposing and addressing scientific hypotheses from pathological morphology changes,we employ modularized special training to divide the pathology training courses into morphology learning module,article searching and reading module,project design module,experiment operation module and scientific presentation module.The training contents among these modules are relatively independent but closely connected,and compose a strategy that aims to improve the scientific innovation ability of pathological graduates.