With the rapid advancement of medical technology and the increasing complexity of clinical environments, competence in clinical ethical decision-making has become an indispensable core competency for exemplary physicians. However, traditional medical ethics education has long been confronted with the persistent challenges of theory-practice dissociation and the disconnect between pedagogical settings and clinical realities. Thus, how to construct a "Clinical Ethics" curriculum that aligns with the objectives of training high-caliber medical professionals has emerged as a critical and challenging issue in current medical education reform. To effectively address this challenge, the Office of Education at Peking University Third Hospital, since 2021, has assembled a multidisciplinary "Clinical Ethics" teaching and management team comprising faculty from Peking University School of Humanities and key clinical specialists from the hospital. In 2022, the "Clinical Ethics" elective course was formally launched for fourth-year students in the eight-year MD program who had completed coursework in "Medical Ethics" and organ-system-based curricula, with the aim of exploring and operationalizing a pre-clinical ethics education model tailored for senior medical students. The course employs a modular instructional design encompassing "theoretical review-case-based deliberation-clinical workshop", which effectively facilitates the deep integration of medical humanities with clinical practice.Following four years of iterative refinement through the "plan-act-observe-reflect" cycle, the course has demonstrated positive outcomes in enhancing students' ethical awareness and decision-making capabilities, and has preliminarily established a sustainable collaborative mechanism among the multidisciplinary faculty team. This article systematically delineates the course development background, pedagogical model and methodological innovations, and the multidisciplinary collaborative framework, alongside reflections and summaries based on implementation outcomes, with the intent of providing references for the future development of "Clinical Ethics" curricula.

ObjectiveFrozen shoulder (FS) is a debilitating musculoskeletal disorder characterized by persistent inflammation and progressive fibrosis of the glenohumeral joint capsule, leading to pain and severely restricted range of motion. Given the limited efficacy of current pharmacotherapies, there is an urgent need for novel anti-fibrotic agents. Guyanxiao Tincture (GYX), a traditional Chinese herbal formula, has shown clinical benefits in alleviating FS symptoms. However, its bioactive constituents and the molecular mechanisms underlying its therapeutic effects remain poorly defined. This study aimed to systematically evaluate the therapeutic efficacy of GYX against FS and to elucidate the mechanisms by which GYX attenuates capsular fibrosis. MethodsA Sprague-Dawley (SD) rat model of FS was established by immobilizing the unilateral shoulder with a plaster cast for 21 d. Following model induction, animals were administered with GYX or its serum-identified bioactive component, icariside F2. The absorbed prototype compounds of GYX in FS rat serum were profiled using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Therapeutic effects were assessed by measuring shoulder range of motion (ROM), histopathological evaluation of the capsule via hematoxylin-eosin staining, and quantification of transforming growth factor‑β1 (TGF-β1) content by ELISA. To explore the underlying mechanisms, transcriptomic profiling of the shoulder capsule was performed using RNA sequencing, and differentially expressed genes were validated by real-time quantitative PCR. Protein expression and localization were examined through immunohistochemistry, immunofluorescence, and Western blot. Protein-protein interaction networks were constructed to identify key regulatory hubs. In vitro, primary shoulder capsule fibroblasts were stimulated with TGF‑β1 to induce a fibrotic phenotype and then treated with icariside F2. The expression of alpha cardiac muscle 1 (ACTC1), α‑smooth muscle actin, and collagen I was subsequently measured. ResultsSerum pharmacochemistry analysis identified icariside F2 as the predominant circulating bioactive component of GYX in FS rats. Both GYX and icariside F2 treatment significantly improved the ROM and ameliorated histopathological lesions, including the attenuation of synovial hyperplasia, inflammatory infiltration, and excessive collagen deposition in the shoulder capsule. Consistently, elevated TGF‑β1 levels in the model group were markedly reduced after the interventions. RNA sequencing revealed that actin ACTC1 was dramatically upregulated in the fibrotic capsule, accompanied by the enrichment of fibrosis-associated pathways such as TGF‑β signaling, focal adhesion, and ECM-receptor interaction. Protein-protein interaction network analysis demonstrated that ACTC1 directly interacts with core fibrotic genes, including Col1a1, Col1a2, Thbs2, and Fn1. Critically, icariside F2 administration significantly reversed the aberrant overexpression of ACTC1 and suppressed the activation of the aforementioned fibrosis-related pathways in vivo. In TGF‑β1-stimulated fibroblasts, icariside F2 dose-dependently downregulated ACTC1 at both the mRNA and protein levels and concurrently decreased the expression of the fibrotic markers α‑smooth muscle actin and collagen I. Immunofluorescence and Western blot further confirmed that icariside F2 attenuated stress fiber formation and collagen production in vitro. ConclusionGYX and its bioactive component icariside F2 effectively alleviate the progression of frozen shoulder by inhibiting capsular fibrosis. Mechanistically, the therapeutic action is functionally linked to the suppression of ACTC1 and its downstream profibrotic signaling cascade, highlighting ACTC1 as a promising therapeutic target for the management of frozen shoulder.

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Objective To investigate the mechanism by which long non-coding RNA(lncRNA)AI662270 regulates insulin resistance in adipocytes in aging mice.Methods(1)Twenty male C57BL/6 mice were randomly divided into youth(4-month-old)group and aged(18-month-old)group(n=10).Mice in youth group were raised to 4 months of age and euthanized by orbital exsanguination under urethane anesthesia,while aged mice were euthanized at 18 months using the same sacrifice method.Epididymal white adipose tissue(eWAT)and liver tissue were rapidly dissected.Western blotting was employed to detect the protein expression levels of tumor suppressor gene 1(p16ink4a)and cyclin-dependent kinase inhibitor p21(p21kip1),RT-qPCR was used to measure the expression of 4 differentially expressed lncRNAs(C4a,AI662270,BATE1 and Gm29719).Mouse embryonic fibroblasts(3T3-L1)were cultured and divided into a normal control group(no treatment after induced differentiation into mature adipocytes)and a senescence model group[doxorubicin(ADR)-treated group;0.2 μmol/L ADR was used to induce senescent adipocytes].β-galactosidase staining was performed to assess adipocyte senescence.RT-qPCR was applied to evaluate the expression of AI662270 and senescence markers(p16ink4a,p21kip1,p53),while Western blotting was utilized to detect the expression levels of phosphorylated H2A histone family member X(γ-H2AX),p16ink4a,and p21kip1 proteins.(2)Hexokinase method was adopted to measure glucose content in mouse serum and 3T3-L1 adipocyte culture medium.RT-qPCR was performed to analyze mRNA expression levels of insulin sensitivity-related gene protein kinase B(Akt),insulin receptor substrate 1(IRS1),phosphatidylinositol 3 kinase(PI3K)and glucose transporter 4(GLUT4)in mouse eWAT and adipocytes.Western blotting was conducted to determine the protein expression levels of IRS 1,PI3K,Akt,and p-Akt.(3)Spearman correlation analysis was applied to examine the correlation between AI662270 expression levels and IRS1/PI3K mRNA expression levels.A low-expression model of AI662270 in senescent adipocytes was constructed,and RT-qPCR was used to verify the knockdown efficiency.Hexokinase method was employed to assess glucose content in the cell culture medium of senescent adipocytes after AI662270 knockdown.RT-qPCR was performed to measure the mRNA expressions of Akt,IRS1,IRS2,and PI3K,while Western blotting was utilized to detect the expressions levels of Akt and p-Akt proteins.(4)Bioinformatics analysis was performed to predict downstream target genes of AI662270 and their binding sites.RT-qPCR and Western blotting were subsequently applied to validate the expression of these downstream target genes following AI662270 knockdown.Results(1)Compared with youth group,the protein expression levels of p16ink4a and p21kip1 in eWAT of aged mice were significantly increased(P＜0.05).Additionally,the expression levels of C4a,AI662270,BATE1,and Gm29719 in both eWAT and liver tissues were significantly increased in aged group(P＜0.05).β-galactosidase staining revealed enhanced blue-green coloration and enlarged,flattened cellular morphology in ADR-treated senescent adipocytes compared with normal control group.Compared with normal control group,ADR-treated senescent adipocytes significantly increased the mRNA expression levels of AI662270,p16ink4a,and p21kip1,and significantly elevated protein expression levels of γ-H2AX,p16ink4a,and p21kip1(P＜0.05).(2)Serum glucose content was significantly higher in aged group mice compared with youth group(P＜0.01),and glucose content in the adipocyte culture medium in ADR group was significantly increased(P＜0.05).The expression levels of IRS1 and PI3K in eWAT in aged group were significantly reduced compared with youth group(P＜0.01).Compared with normal control group,the expression levels of IRS 1 and PI3K in adipocytes in ADR-treated group were also significantly reduced(P＜0.05).(3)Spearman correlation analysis demonstrated that the expression level of AI662270 was negatively correlated with the mRNA expression levels of IRS1 and PI3K(P＜0.05).RT-qPCR showed that AI662270 expression level was significantly reduced in the siAI662270-transfected senescent adipocytes compared with siNC group(P＜0.05),indicating the low expression model of aged adipocytes AI662270 was successfully constructed.Hexokinase assay results showed that glucose content in the cell culture medium was significantly reduced after the AI662270 was knocked down by senescent adipocytes(P＜0.05).Furthermore,the mRNA expression levels of IRS1,IRS2 and PI3K(P＜0.05)and the p-Akt/Akt ratio in senescent adipocytes was significantly increased after knockdown of AI662270(P＜0.01).(4)Bioinformatics analysis predicted miR-3073b-3p as a downstream target gene of AI662270,and heme oxygenase 1(Hmox1)was identified as a target molecule of miR-3073b-3p.The expression level of miR-3073b-3p in senescent adipocytes in siAI662270 group was significantly increased,while the mRNA and protein expression level of Hmox1 were significantly decreased compared with siNC group(P＜0.01).Conclusions Aging significantly increases the expression of AI662270 in eWAT of mice,and the expression of AI662270 was negatively correlated with insulin sensitivity.AI662270 knockdown can reduce glucose content in senescent adipocyte culture medium,upregulate the expression of IRS1 and PI3K,and increase insulin sensitivity in senescent adipocytes,which may be mediated through the AI662270/miR-3073b-3p/Hmox1 pathway.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Aim To explore the mechanism of luteolin in alleviating hepatic fibrosis.Methods C57BL/6 mice were randomly divided into the control group,CCl4 group,silybin group(100 mg·kg-1)and luteo-lin group(100 mg·kg-1).After 10-week modeling and 2-week treatment,the serum levels of aminotrans-ferase and liver histopathology were examined.Hepatic fibrosis and autophagy-related gene expression were as-sessed using immunohistochemistry and immunofluores-cence.Human hepatic stellate cell line(LX2)was cultured and divided into control,TGF-β1(10 mg·L-1),TGF-β1+silybin(40 μmol·L-1),TGF-β1+luteolin(40 μmol·L-1).Fibrotic and autophagy-re-lated markers were analyzed using quantitative real-time PCR,Western blot,immunofluorescence and MDC staining.Results Compared with the CCl4 group,the treatment groups showed significantly improved liver function and reduced hepatic fibrosis,with markedly downregulated COL1A1 and α-SMA expression,and luteolin demonstrated superior efficacy.Compared with TGF-β1 group,luteolin treatment significantly de-creased mRNA levels of COL1A1,ACTA2 and MAP1LC3B,while increasing the mRNA level of SQSTM1,the protein levels of COL1A1 and α-SMA de-creased,p62 was enhanced,the LC3Ⅱ/Ⅰ ratio was downregulated,and autophagy was reduced.These effects of luteolin were reversed by autophagy inducer rapamycin.Conclusion Luteolin alleviates liver fi-brosis by decreasing the autophagy of hepatic stellate cells.

Objective To explore the characteristics and prognosis of follicular lymphoma(FL)with bulky disease under rituximab-based first-line treatment.Methods A retrospective analysis was conducted on 525 FL patients diagnosed between September 2009 and September 2021 who received rituximab as a first-line treat-ment[342 patients received rituximab combined with chemotherapy(R-chemo),183 patients received rituximab plus lenalidomide(R2)].The clinicopathologic characteristics,gene mutations,and prognosis of bulky FL patients were analyzed.Results Compared to non-bulky FL patients,bulky FL patients had a significantly higher proportion of lymph node≥5 sites,≥2 extranodal involvement,bone marrow involvement,elevated LDH,and a higher proportion in the high-risk group of FLIPI1 and FLIPI2.Gene sequencing revealed a significantly higher mutation rate of ZNF608 in bulky FL patients compared to non-bulky FL patients.In patients receiving R-chemo as the first-line treatment,there was no significant difference in progression-free survival(PFS)and overall survival(OS)between bulky and non-bulky FL patients.However,in patients treated with R2,the PFS and OS of bulky FL patients was significantly shorter.Conclusions Bulky FL patients compared to non-bulky FL patients have a significantly higher proportion of high-risk baseline characteristics.For bulky FL at diagnosis,chemo-free regimens require further exploration on the basis of R2.

Objective:To investigate the influence and mechanisms of metformin on the proliferation and apoptosis of human keloid fibroblasts (Fbs).Methods:This study was an experimental research. The keloid tissue was collected from 7 keloid patients (2 males and 5 females, aged 20-65 years, with a disease course of more than 1 year) who underwent keloid excision surgery at the Department of Plastic, Cosmetic and Maxillofacial Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from September 2020 to September 2023. The primary Fbs were isolated and cultured, and cells from passages 3 to 6 were used for experiments. The cells were divided into control group and metformin group, and were cultured in complete medium. The medium for metformin group was supplemented with metformin at a final molarity of 60 mmol/L. The cell counting kit-8 was used to assess the proliferation activity of cells in two groups after 12 and 24 hours of culture, and the proliferation inhibition rate of cells in metformin group after 12 and 24 hours of culture was calculated, with a sample size of 6. The apoptosis detection kit was used to detect the apoptotic distribution of cells in control group after 0 hour (immediately) of culture and in metformin group after 12 and 24 hours of culture, with a sample size of 3. The cell cycle detection kit was used to detect the cycle distribution of cells in two groups after 12 and 24 hours of culture, with a sample size of 3. The eukaryotic mRNA sequencing was performed on suitable number of cells of two groups after 24 hours of culture, and the Kyoto encyclopedia of genes and genomes functional annotation analysis and functional enrichment analysis were performed after screening for differentially expressed genes (DEGs) with significantly differential expression between two groups. Western blotting was conducted to detect the protein expressions of phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR) in the PI3K/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway of cells in two groups after 24 hours of culture, with a sample size of 3.Results:After 12 and 24 hours of culture, the proliferation activity of cells in metformin group was significantly lower than that in control group (with t values of 4.70 and 24.02, respectively, P<0.05); the proliferation activity of cells in metformin group after 24 hours of culture was significantly lower than that after 12 hours of culture within the group ( t=4.73, P<0.05). Compared with that after 12 hours of culture within the group, the proliferation inhibition rate of cells in metformin group was significantly increased after 24 hours of culture ( t=5.29, P<0.05). Compared with that in control group after 0 hour of culture, the proportion of early apoptotic cells in metformin group was significantly increased (with t values of 6.62 and 4.58, respectively, P<0.05), and the proportion of early and late apoptotic cells was significantly increased after 12 and 24 hours of culture (with t values of 4.84 and 3.75, respectively, P<0.05). After 24 hours of culture, the proportion of late apoptotic cells in metformin group was significantly higher than that after 12 hours of culture within the group ( t=4.55, P<0.05). After 12 hours of culture, the proportion of S-phase cells in metformin group was significantly lower than that in control group ( t=5.90, P<0.05). After 24 hours of culture, compared with that in control group, the proportion of G0/G1-phase cells in metformin group was significantly increased ( t=5.36, P<0.05), while the proportion of G2/M-phase cells was significantly decreased ( t=17.63, P<0.05). The proportion of S-phase cells in metformin group after 24 hours of culture was significantly higher than that after 12 hours of culture within the group ( t=7.60, P<0.05). After 24 hours of culture, 4 814 DEGs with significantly differential expression were detected in the cells of metformin group compared with control group. The significantly upregulated and downregulated DEGs were mainly involved in biological functions related to signal transduction, cell growth and death, transport and catabolism, the endocrine system, the immune system, and cancer. The pathways that were significantly enriched with DEGs with significantly differential expression included the cell cycle and DNA replication, with the highest number of genes in the PI3K/Akt signaling pathway. After 24 hours of culture, the protein expressions of PI3K, p-Akt, and p-mTOR of cells in metformin group were 0.190±0.017, 0.170±0.017, and 0.247±0.005, respectively, which were significantly lower than 0.440±0.026, 0.300±0.060, and 0.547±0.025 in control group (with t values of 13.69, 3.61, and 20.12, respectively, P values all <0.05). Conclusions:Metformin can significantly inhibit the proliferation of human keloid Fbs through the PI3K/Akt/mTOR signaling pathway and effectively induce its apoptotic process, thereby exerting antifibrotic effects.