ObjectiveBiochemistry and Molecular Biology, a discipline that elucidates life phenomena at the molecular level, serves as a core foundational course in medical education. It provides the theoretical basis for studying other basic and clinical medical subjects, as well as for understanding pathogenesis, disease diagnosis, and treatment. However, its complex content and highly abstract concepts have posed a dual challenge to traditional teaching models: “inefficient instruction” and “inadequate learning outcomes”. Within limited classroom hours, how to engage students and stimulate their intrinsic motivation, and how to help them recognize, understand, and develop a passion for biochemistry from the perspective of the discipline’s essence, have long been key focuses of curriculum research. MethodsUsing the lipid metabolism chapter as an example, this study employs “Rain Classroom”, a generative artificial intelligence (AI)-assisted platform, to support education in four dimensions: teaching, learning, evaluation, and research. In teaching, it assists instructors through virtual experiments, lesson preparation support, knowledge mapping, and assignment design. For learning, it serves as an intelligent study assistant for students, providing automated assignment review, enabling educational resource sharing, and facilitating personalized learning pathways. In evaluation, the platform automates assignment grading, analyzes student performance data, and offers diagnostic feedback and teaching recommendations. In research, it aids educators in collecting and analyzing teaching data, as well as searching for and summarizing relevant literature. ResultsThe results indicate that an educational model integrating teacher-led instruction, student-centered learning, and generative AI assistance significantly enhances teaching quality, students’ self-directed learning abilities, and knowledge mastery. Furthermore, with the support of generative AI, curriculum-based ideological education—focusing on cutting-edge disciplinary advances and topical medical issues—helps cultivate students’ medical spirit of “honoring life and healing the wounded”, thereby fostering the establishment of appropriate professional values. Finally, while generative AI presents both opportunities and challenges for higher education, this study also analyzes potential risks in its teaching applications, emphasizing the need for both instructors and students to avoid over-reliance and to ensure that technological tools consistently serve the fundamental goals of education. ConclusionThis study demonstrates that integrating generative AI, specifically via the “Rain Classroom” platform, can effectively enhance biochemistry education. By supporting teaching, learning, evaluation, and research, this approach improves both educational effectiveness and student outcomes. It also facilitates the incorporation of cutting-edge knowledge and professional ethics, nurturing a patient-centered mindset. Additionally, the study addresses potential implementation risks to ensure that such technological tools remain aligned with the core purpose of education.

Subclinical hypothyroidism (SCH) is a subclinical state of mild hypothyroidism. In recent years, the impact of SCH on multiple systems of the body has gradually attracted attention. Although SCH patients usually do not have obvious clinical symptoms, studies have shown that SCH may be associated with a variety of chronic diseases, such as cardiovascular disease and metabolic syndrome. Due to the complex interrelationship between diabetes mellitus and thyroid disease, researchers have begun to pay attention to the potential impact of SCH on diabetic retinopathy (diabetic retinopathy, DR). This article aims to comprehensively review the current research progress on the impact of SCH on DR, and explore in depth the pathophysiological mechanisms, clinical manifestations, and treatment strategies, providing clinicians with more comprehensive diagnostic and treatment ideas.

OBJECTIVE: Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke (IS). However, the lipid profiles associated with IS have been poorly studied. We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling. METHODS: Serum lipidomic profiling was performed using LC-MS in 20 patients with IS and 20 age- and sex-matched healthy controls. Univariate and multivariate analyses were simultaneously performed to identify the differential lipids. Multiple testing was controlled for using a false discovery rate (FDR) approach. Enrichment analysis was performed using MetaboAnalyst software. RESULTS: Based on the 294 lipids assayed, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used to distinguish patients with IS from healthy controls. Fifty-six differential lipids were identified with an FDR-adjusted P less than 0.05 and variable influences in projection (VIP) greater than 1.0. These lipids were significantly enriched in glycerophospholipid metabolism (FDR-adjusted P = 0.009, impact score = 0.216). CONCLUSIONS Serum lipid profiles differed significantly between patients with IS and healthy controls. Thus, glycerophospholipid metabolism may be involved in the development of IS. These results provide initial evidence that lipid molecules and their related metabolites may serve as new biomarkers and potential therapeutic targets for IS.
Humans ; Pilot Projects ; Lipidomics ; Male ; Female ; Biomarkers/blood* ; Middle Aged ; Ischemic Stroke/blood* ; Aged ; China ; Lipids/blood* ; Adult ; Case-Control Studies ; East Asian People

ObjectiveTo investigate the significance of different non-treatment thresholds or upper limits of normal （ULN） of alanine aminotransferase （ALT） in evaluating significant liver pathological injury in patients with chronic hepatitis B virus （HBV） infection， and to provide guidance for clinical diagnosis and treatment. MethodsThis study was conducted among 733 patients with chronic HBV infection who were hospitalized in Ningbo No. 2 Hospital from January 2015 to December 2023 and underwent liver biopsy and histopathological examination， and all patients had a persistent ALT level of ≤40 U/L and positive HBV DNA （>30 IU/mL）. According to the treatment threshold or ULN of ALT， the patients were divided into group 1 with 575 patients （≤35 U/L for male patients， ≤25 U/L for female patients）， group 2 with 430 patients （≤30 U/L for male patients， ≤19 U/L for female patients）， group 3 with 443 patients （≤27 U/L for male patients， ≤24 U/L for female patients）， group 4 with 446 patients （≤25 U/L）， group 5 with 158 patients （>35 U/L for male patients， >25 U/L for female patients）， and group 6 with 145 patients （>30 — ≤35 U/L for male patients， >19 — ≤25 U/L for female patients）. Groups 2， 5， and 6 were compared to analyze the severity of liver pathological injury in patients with different ALT levels and the constituent ratio of patients with significant liver pathological injury， and groups 1， 2， 3， and 4 were compared to investigate the value of different ULN or non-treatment thresholds of ALT in determining liver inflammation grade （G）， liver fibrosis stage （S）， and the treatment indication based on liver pathology. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test or the Tambane’s test was used for further comparison between two groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； a Ridit analysis was used for comparison of ranked data. A multivariate Logistic regression analysis （forward stepwise） was performed with whether liver pathology met the treatment indication （≥G2 and/or ≥S2） as the dependent variable and related factors with a significant impact on the dependent variable （P <0.05） as the independent variable. The receiver operating characteristic （ROC） curve was plotted， and the area under the ROC curve （AUC）， as well as sensitivity， specificity， positive predictive value， negative predictive value， positive likelihood ratio， and negative likelihood ratio， was used to assess the diagnostic value of different non-treatment thresholds of ALT. ResultsAmong the 733 patients， 259 （35.33%） had ≥G2 liver inflammation， 211 （28.79%） had ≥S2 liver fibrosis， and 306 （41.75%） had treatment indication （≥G2 and/or ≥S2）. There was a significant difference in liver inflammation grade （G0 — G4） between groups 2， 5， and 6 （χ²=22.869， P <0.001）， and there were also significant differences in the constituent ratios of patients with ≥G2 or ≥G3 liver inflammation between the three groups （χ²=21.742 and 14.921， P<0.001 and P=0.001）. There was a significant difference in liver fibrosis stage （S0 — S4） between groups 2， 5， and 6 （χ²=16.565， P<0.001）， and there were also significant differences in the constituent ratios of patients with ≥S2， ≥S3 or S4 liver fibrosis between the three groups （χ²=13.264， 13.050， and 6.260， P=0.001， 0.001， and 0.044）. There were significant differences between groups 2， 5， and 6 in the constituent ratios of patients with or without treatment indication based on liver pathology （χ²=20.728， P<0.001）. There were significant differences between groups 2， 5， and 6 in the constituent ratio of male patients （χ²=24.836， P<0.05）， age （F=5.710， P<0.05）， ALT （F=473.193， P<0.05）， aspartate aminotransferase （AST） （F=107.774， P<0.05）， ALT/AST ratio （F=40.167， P<0.05）， γ-glutamyl transpeptidase （GGT） （H=15.463， P<0.05）， aspartate aminotransferase-to-platelet ratio index （APRI） （H=63.024， P<0.05）， and LIF-5 （5 indicators for liver inflammation and fibrosis） （H=46.397， P<0.05）. In groups 1 — 4， compared with the patients without treatment indication， the patients with treatment indication had a significantly lower constituent ratio of patients with positive HBeAg， significantly lower levels of platelet count （PLT） and HBV DNA， and significantly higher age， ALT， AST， GGT， APRI， FIB-4， and LIF-5 （all P<0.05）. The Logistic regression analysis showed that age （odds ratio ［OR］=1.044， 95% confidence interval ［CI］： 1.025 — 1.063， P<0.001）， GGT （OR=1.022， 95%CI： 1.007 — 1.038， P=0.003）， and HBV DNA （OR=0.839， 95%CI： 0.765 — 0.919， P<0.001） were influencing factors for treatment indication based on liver pathology in group 1； HBeAg （OR=1.978， 95%CI： 1.269 — 3.082， P=0.003）， age （OR=1.048， 95%CI： 1.025 — 1.071， P<0.001）， GGT （OR=1.016， 95%CI： 1.001 — 1.031， P=0.041）， and PLT （OR=0.995， 95%CI： 0.991 — 1.000， P=0.049） were influencing factors in group 2； age （OR=1.040， 95%CI： 1.014 — 1.066， P=0.002）， ALT （OR=1.047， 95%CI： 1.005 — 1.092， P=0.029）， HBV DNA （OR=0.817， 95%CI： 0.736 — 0.907， P<0.001）， and LIF-5 （OR=7.382， 95%CI： 1.151 — 47.330， P=0.035） were influencing factors in group 3； age （OR=1.054， 95%CI： 1.031 — 1.077， P<0.001）， ALT （OR=1.061， 95%CI： 1.016 — 1.107， P=0.008）， and HBV DNA （OR=0.825， 95%CI： 0.743 — 0.917， P<0.001） were influencing factors in group 4. The diagnostic performance for identifying ≥G2 liver inflammation， ≥S2 liver fibrosis， and treatment indication in groups 1 — 4 had an AUC of >0.7； group 1 showed the lowest sensitivity （28.76%） and the highest specificity， positive predictive value， positive likelihood ratio， and negative likelihood ratio in judging treatment indication； group 2 had the highest sensitivity and negative predictive value and the lowest negative likelihood ratio； groups 3 and 4 had similar diagnostic indicators. ConclusionIn patients with chronic HBV infection and a persistently low ALT level， the severity of liver histopathological injury and the constituent ratio of significant liver histopathological injury decrease with the reduction in ALT level. A higher non-treatment threshold or ULN of ALT can help to identify the patients requiring treatment （with a higher specificity）， while a lower non-treatment threshold or ULN of ALT can help to identify the patients who do not require treatment （with a higher sensitivity）.

Objective:To investigate the effect of securinine(SEC)on apoptosis of the human colon cancer cell line SW620,and to elucidate its possible mechanism.Methods:The nude mice with subcutaneously transplanted tumor were divided into control group(n=6),oxaliplatin(OXA)group(n=7),and SEC group(n=7).The volume and mass of subcutaneous tumors in the nude mice were measured in various groups,and the tumor inhibitory rates in various groups were calculated.The SW620 cells were treated with different doses(5-120 μmol·L-1)of SEC for 12,24,48,and 72 h,respectively.Cell counting kit-8(CCK-8)assay was used to assess the survival rates of cells in various groups,and the optimal doses of SEC were confirmed.The SW620 cells were divided into control group,20 μmol·L-1 SEC group,40 μmol·L-1SEC group,and 40 μmol·L-1OXA group.TUNEL staining method and flow cytometry were used to detect the apoptotic rates of cells in various groups.JC-1 staining was used to detect the mitochondrial membrane potentials of cells in various groups,and 2',7'-dichlorodi-hydrofluorescin diacetate(DCFH-DA)fluorescence staining and flow cytometry were used to measure the reactive oxygen species(ROS)levels in the cells in various groups.Western blotting method was used to detect the expression levels of cytochrome C,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),c-Jun N-terminal kinase(JNK),phosphorylated JNK(p-JNK),mitogen-activated protein kinase p38,phosphorylated p38(p-p38),extracellular signal-regulated kinase(ERK)and phosphorylated ERK(p-ERK)proteins in the cells in various groups.Results:Compared with control group,the volume and mass of subcutaneously transplanted tumors in the nude mice in SEC group were significantly decreased(P＜0.05 or P＜0.01 or P＜0.001);the inhibitory rates of tumor in SEC group and OXA group were 20.42％and 6.50％.The CCK-8 assay results showed that compared with 0 μmol·L-1 SEC,when the SEC dose exceeded 20 μmol·L-1,the survival rates of SW620 cells were significantly decreased(P＜0.001).The optimal condition for subsequent experiments was set as doses of 20 μmol·L-1SEC and 40 μmol·L-1SEC,and duration of 24 h.The TUNEL results showed that compared with control group,the apoptotic rates of cells in 20 and 40 μmol·L-1 SEC groups were significantly increased(P＜0.05 or P＜0.001).The results of flow cytometry showed that compared with control group,the apoptotic rate in 40 μmol·L-1SEC group was significantly increased(P＜0.001).The JC-1 staining results showed that compared with control group,the mitochondrial membrane potentials of cells in 20 and 40 μmol·L-1 SEC groups were significantly decreased(P＜0.001).Compared with control group,the levels of ROS detected by DCFH-DA fluorescence staining in the cells of 20 and 40 μmol·L-1 SEC groups and 40 μmol·L-1 OXA group were significantly increased(P＜0.001),while the level of ROS detected by flow cytometry in 40 μmol·L-1SEC group was significantly increased(P＜0.05).Compared with control group,the expression levels of Bcl-2 protein in the cells in 20 and 40 μmol·L-1 SEC groups and 40 μmol·L-1 OXA group were decreased(P＜0.01),while the expression levels of cytochrome C and Bax proteins were increased(P＜0.001).Compared with control group,the ratios of p-JNK/JNK,p-p38/p38 and p-ERK/ERK in 20 and 40 μmol·L-1 SEC groups were significantly increased(P＜0.05 or P＜0.01 or P＜0.001).Conclusion:SEC can inhibit the proliferation of SW620 cells,increase the cellular ROS levels,reduce the mitochondrial membrane potential,and induce the mitochondrial apoptosis;its mechanism may be related to the regulation of the mitogen-activated protein kinase(MAPK)signaling pathway.

This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

The manufacturing process is crucial for ensuring the safety and efficacy of traditional Chinese medicine(TCM) preparations. Using advanced technologies, innovative methods, and new equipment tailored for TCM to enhance the quality control of TCM preparations in the manufacturing process helps to ensure the product quality and foster high-quality development of the TCM industry. Upon current technical requirements, such as Guideline for Studies on Pharmaceutical Changes in Marketed Traditional Chinese Medicine Preparations(Trial) and Guideline for Study on Quality Control in Manufacturing Process of Oral Traditional Chinese Medicine Preparations(Trial), this paper analyzes the characteristics and current development of quality control in the manufacturing process of TCM preparations. It also discusses the significant roles that quality control in manufacturing process plays in ensuring the quality consistency and in the evaluation and decision-making of changes in marketed TCM preparations. Furthermore, to benefit the high-quality development of the TCM industry, this paper offers recommendations for improving quality control of TCM preparations in the manufacturing process and implementing new technologies and methods.
Quality Control ; Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/standards* ; Decision Making ; Humans

Wumei Pills, a classic traditional Chinese medicine(TCM) formula, are widely used in the treatment of biliary ascariasis and diarrhea. In recent years, studies have shown that Wumei Pills have advantages in the treatment of type 2 diabetes mellitus(T2DM), while there are no relevant reports that systematically evaluate the efficacy of Wumei Pills in the treatment of T2DM. This study addresses this issue by systematically evaluating the efficacy and safety of Wumei Pills, aiming to provide an evidence-based basis for clinical practice. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, and VIP were researched for the randomized controlled trial(RCT) involving Wumei Pills for the treatment of T2DM that were published from inception to September 2024. RevMan 5.3 was used for the Meta-analysis of the data. A total of 18 RCTs were included, with a total of 1 437 patients. Meta-analysis produced the following results.(1)Treatment group outperformed control group in terms of overall response rate(RR=1.28, 95%CI[1.14, 1.43], P<0.000 1), fasting blood glucose(FPG)(WMD=-0.69, 95%CI[-0.93,-0.46], P<0.000 01), two-hour postprandial plasma glucose(2hPG)(WMD=-0.74, 95%CI[-1.17,-0.31], P<0.000 7), glycated hemoglobin(HbA1c)(WMD=-0.39, 95%CI[-0.60,-0.18], P=0.000 3), high-density lipoprotein(HDL)(WMD=0.38, 95%CI[0.28, 0.48], P<0.000 01), and body mass index(BMI)(WMD=-1.41, 95%CI[-2.40,-0.42], P=0.005).(2)The two groups had comparable effects regarding total cholesterol(TC)(WMD=-0.53, 95%CI[-1.13, 0.08], P=0.09) and low-density lipoprotein(LDL)(WMD=-0.25, 95%CI[-0.56, 0.06], P=0.12).(3)Triglycerides(TG)(WMD=-0.28,95%CI [-0.59,0.03],P=0.08), sensitivity analysis showed potential reduction effect(WMD=-0.20,95%CI[-0.36,-0.04],P=0.01). Occurrence of adverse drug reaction(RR=0.43,95%CI [0.23,0.80],P=0.007), sensitivity analysis showed significant disappearance(RR=0.56,95%CI[0.26,1.22],P=0.14), suggesting that the efficacy of treatment group was not better than that of control group. The results indicate that the treatment of T2DM with Wumei Pills is greatly related to the improvement of glucose metabolism, lipid metabolism, and clinical efficacy. The findings provide a basis for clinical application of Wumei Pills in treating T2DM, while the conclusion remains to be verified by clinical studies with higher quality.
Humans ; Diabetes Mellitus, Type 2/blood* ; Drugs, Chinese Herbal/administration & dosage* ; Randomized Controlled Trials as Topic ; Blood Glucose/metabolism* ; Hypoglycemic Agents/therapeutic use* ; Treatment Outcome ; Glycated Hemoglobin/metabolism* ; Female

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

The chemical constituents from Cephalotaxus lanceolata were isolated and purified by using multiple chromatographic techniques, including octadecylsilane(ODS), silica gel, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography(HPLC). A total of 17 compounds obtained were identified by using spectroscopic methods such as nuclear magnetic resonance(NMR), mass spectrometry(MS), and ultraviolet(UV) combined with literature data. Compound 1 was a new alkaloid dimer, named cephalancetine E. The known compounds were determined as cephalancetine A(2), 11-hydroxycephalotaxine(3), 4-hydroxycephalotaxine(4), cephalotaxine(5), epicephalotaxine(6), cephalotaxine β-N-oxide(7), acetylcephalotaxine(8), cephalotine A(9), cephalotine B(10), 11-hydroxycephalotaxine hemiketal(11), 3-deoxy-3,11-epoxy-cephalotaxine(12), cephalotaxinone(13), isocephalotaxinone(14), 2,11-epoxy-1,2-dihydro-8-oxo-cephalotaxine(15), cephalotaxamide(16), and drupacine(17), respectively. Compounds 11, 12, and 15 were isolated from the Cephalotaxus genus for the first time. The biological activity was tested for compounds 1-17. The results reveal that compound 17 displays potent inhibitory activities against three human cancer cell lines(HepG-2, MCF-7, and SH-SY5Y).
Cephalotaxus/chemistry* ; Humans ; Cell Line, Tumor ; Drugs, Chinese Herbal/pharmacology* ; Harringtonines/pharmacology* ; Molecular Structure ; Dimerization ; Alkaloids/isolation & purification* ; Magnetic Resonance Spectroscopy