An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic acid (HA) hydrogels, while effective for rapid filling, suffer from limited duration of support, weak cell adhesion, and an inability to promote collagen regeneration. Silk fibroin (SF), a natural protein from silkworm cocoons, is known for its excellent cell adhesion and collagen-stimulating abilities. However, its limited gelation capability restricts its potential application as a standalone injectable hydrogel. Based on a complementary strategy, this study combines the rapid gelling properties of HA with the collagen regenerative properties of SF to create a co-crosslinked HA-SF hydrogel. The composite hydrogel merges HA's rapid filling effect with SF's strong tissue adhesion and collagen-stimulating abilities. The formulation, physicochemical properties, degradation, biocompatibility, and filling effects of the HA-SF hydrogel were systematically investigated. HA-SF hydrogel exhibits excellent mechanical properties and ensures long-term support while maintaining injectability. Interestingly, after intradermal injection in the UVB-induced photoaging model, HA-SF hydrogel not only enhances hydrogel-cell interaction but also continues to stimulate collagen regeneration, especially type III collagen. This dual action achieves the biological effects of repair and anti-aging while maintaining the filling effect. Proteomic analysis confirms that repair and anti-aging effects are enhanced by the regulation of skin fibroblasts and modulation of amino acid and lipid metabolism. This composite hydrogel holds strong promise for clinical applications, offering a safer, long-lasting, and more natural injectable filler that combines filling, repair, and anti-aging into one system.

ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang ［Yiqi Yangyin Jiedu prescription （YQYYJD）］ in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI）-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD （0， 2， 3， 4， 5， 6， 7， 8 g·L^-1） and cisplatin （0， 3， 6， 9， 12， 15， 18， 21， 24， 27 mg·L^-1） on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 （CCK-8） assay after 24 hours of intervention. The half-maximal inhibitory concentration （IC₅₀） for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group （complete medium）， YQYYJD group （5 g·L^-1）， cisplatin group （12 mg·L^-1）， and combined group （YQYYJD 5 g·L^-1 + cisplatin 12 mg·L^-1）. After 24 hours of intervention， cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay， and cell migration was evaluated by scratch and Transwell assays. Glucose consumption， lactate production， and adenosine triphosphate （ATP） levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins， including hexokinase 2 （HK2）， phosphofructokinase P （PFKP）， pyruvate kinase M2 （PKM2）， lactate dehydrogenase A （LDHA）， glucose transporter 1 （GLUT1）， and monocarboxylate transporter 4 （MCT4）， were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC₅₀ of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L^-1 and 12.91 mg·L^-1， respectively. In terms of cell proliferation， compared with the blank group， the cell survival rate and the number of colonies formed in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in cell survival rate and colony formation （P<0.01）. In terms of cell migration， compared with the blank group， the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane （P<0.01）. In terms of glycolysis， compared with the blank group， glucose consumption， lactate production， and ATP levels in the YQYYJD group， cisplatin group， and combined group were significantly decreased （P<0.01）. Compared with the YQYYJD and cisplatin groups， the combined group showed a further significant reduction in glucose consumption， lactate production， and ATP levels （P<0.05）. Compared with the blank group， the protein expression levels of HK2， PFKP， PKM2， and LDHA in the YQYYJD， cisplatin， and combined groups were significantly decreased （P<0.01）. The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups （P<0.01）. No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes， including HK2， PFKP， PKM2， and LDHA， thereby inhibiting glycolysis.

ObjectiveTo observe the prognosis effect of soluble programmed death ligand-1（sPD-L1） in treating patients with advanced lung adenocarcinoma treated with epidermal growth factor receptor-tyrosine kinase inhibitors（EGFR-TKIs） and the influence of Yiqi Yangyin Jiedu prescription. MethodA prospective cohort-controlled study was conducted to enroll patients treated with EGFR-TKIs in the first line of treatment，who were admitted to the Oncology Department of Longhua Hospital and Shanghai Chest Hospital from May 1^st， 2021 to June 30^th， 2023， and they were evaluated as non-progressive and identified with deficiency of Qi and Yin after one month of treatment. The patients were divided into an exposed group （EGFR-TKIs combined with Yiqi Yangyin Jiedu prescription） and a non-exposed group （EGFR-TKIs alone）according to whether or not they were treated with Yiqi Yangyin Jiedu prescription and were treated until disease progression， or death and intolerable adverse reactions occurred. The enzyme-linked immunosorbent assay （ELISA） was applied to detect the level of sPD-L1 in patients at the time of enrollment and disease progression，and Cox risk proportionality model was used to analyze the independent prognostic factors affecting disease progression of patients treated with EGFR-TKIs. ResultA total of 90 patients （39 in the exposed group and 51 in the non-exposed group） undergoing disease progression after EGFR-TKI treatment were enrolled. At the time of enrolment and after disease progression，the levels of serum sPD-L1 in the 90 patients were 12.06 （27.54） ng·L^-1 and 41.99 （62.93） ng·L^-1，respectively. Compared with that at the time of enrollment， the serum sPD-L1 level in the 90 patients was significantly increased after disease progression （P<0.01）. The serum sPD-L1 level in patients in the exposed group was 12.27 （24.78） ng·L^-1 and 29.57 （61.12）ng·L^-1 respectively at the time of enrolment and after disease progression. In the non-exposed group， patients had serum sPD-L1 levels of 11.81 （28.46） ng·L^-1 and 49.54 （74.12） ng·L^-1 respectively at the time of enrolment and after disease progression. Compared with that at the time of enrollment， the serum sPD-L1 level in the two groups of patients was significantly increased after disease progression （P<0.01）. In addition， compared with that in the non-exposed group， the sPD-L1 level in the exposed group was greatly reduced after disease progression（P<0.01）. Cox multifactorial analysis showed that sPD-L1 level and age at the time of enrolment were associated with patients' progression-free survival（PFS），and that low levels of sPD-L1 （<12.06 ng·L^-1） prolonged the PFS and reduced the risk of disease progression in patients treated with EGFR-TKIs compared with high levels of sPD-L1. ConclusionElevated sPD-L1 level is a poor prognostic factor for the long-term efficacy of EGFR-TKIs，and treatment with Yiqi Yangiin Jiedu prescription can down-regulate sPD-L1 level of patients treated with EGFR-TKIs.

Objective: To explore the feasibility of constructing a lung cancer early-warning risk model based on facial image features, providing novel insights into the early screening of lung cancer. Methods: This study included patients with pulmonary nodules diagnosed at the Physical Examination Center of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 1, 2019 to December 31, 2024, as well as patients with lung cancer diagnosed in the Oncology Departments of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine and Longhua Hospital during the same period. The facial image information of patients with pulmonary nodules and lung cancer was collected using the TFDA-1 tongue and facial diagnosis instrument, and the facial diagnosis features were extracted from it by deep learning technology. Statistical analysis was conducted on the objective facial diagnosis characteristics of the two groups of participants to explore the differences in their facial image characteristics, and the least absolute shrinkage and selection operator (LASSO) regression was used to screen the characteristic variables. Based on the screened feature variables, four machine learning methods: random forest, logistic regression, support vector machine (SVM), and gradient boosting decision tree (GBDT) were used to establish lung cancer classification models independently. Meanwhile, the model performance was evaluated by indicators such as sensitivity, specificity, F1 score, precision, accuracy, the area under the receiver operating characteristic (ROC) curve (AUC), and the area under the precision-recall curve (AP). Results: A total of 1 275 patients with pulmonary nodules and 1 623 patients with lung cancer were included in this study. After propensity score matching (PSM) to adjust for gender and age, 535 patients were finally included in the pulmonary nodule group and the lung cancer group, respectively. There were significant differences in multiple color space metrics (such as R, G, B, V, L, a, b, Cr, H, Y, and Cb) and texture metrics [such as gray-levcl co-occurrence matrix (GLCM)-contrast (CON) and GLCM-inverse different moment (IDM)] between the two groups of individuals with pulmonary nodules and lung cancer (P < 0.05). To construct a classification model, LASSO regression was used to select 63 key features from the initial 136 facial features. Based on this feature set, the SVM model demonstrated the best performance after 10-fold stratified cross-validation. The model achieved an average AUC of 0.8729 and average accuracy of 0.799 0 on the internal test set. Further validation on an independent test set confirmed the model’s robust performance (AUC = 0.823 3, accuracy = 0.729 0), indicating its good generalization ability. Feature importance analysis demonstrated that color space indicators and the whole/lip Cr components (including color-B-0, wholecolor-Cr, and lipcolor-Cr) were the core factors in the model’s classification decisions, while texture indicators [GLCM-angular second moment (ASM)_2, GLCM-IDM_1, GLCM-CON_1, GLCM-entropy (ENT)_2] played an important auxiliary role. Conclusion The facial image features of patients with lung cancer and pulmonary nodules show significant differences in color and texture characteristics in multiple areas. The various models constructed based on facial image features all demonstrate good performance, indicating that facial image features can serve as potential biomarkers for lung cancer risk prediction, providing a non-invasive and feasible new approach for early lung cancer screening.

Objective:In order to effectively educate students on tooth defect diseases and restoration techniques, the teaching and research team at the School of Stomatology of Qingdao University developed an integrated course operative dentistry. This course is specifically designed to align with the undergraduate curriculum reform requirements of "Three Early, Two Multiple and One Integration".Methods:The teaching practice of operative dentistry was conducted with the stomatology undergraduates of grade 2020 and 2021. The course group redesigned the curriculum by reorganizing teaching content, rebuilding teaching resources, reconstructing teaching mode, and reshaping the evaluation system. Evaluation of the curriculum design included test scores, satisfaction questionnaires, and teacher self-evaluation. Statistical analysis was performed using SPSS 27.0 software, including independent sample t-tests for numerical variables and Fisher's exact test or Wilcoxon rank sum test for categorical variables. Results:Through the integrated course learning, 92.68% (38/41) of the students of grade 2020 and 97.44% (38/39) of the students of grade 2021 can basically or completely master various dental defect repair schemes and understand the importance of preserving natural tooth. 82.93% (34/41) of the students of grade 2020 and 100.00% (39/39) of the students of grade 2021 could basically or completely master the key points of various dental defect restorations.Conclusions:Through the practice of teaching, it has been confirmed that the integrated course of operative dentistry is beneficial to students' mastering the knowledge and skills of dental defect diseases and their restoration in a more comprehensive way, and is conducive to the cultivation of clinical thinking, hands-on ability and the patient-centered, comprehensive problem-solving thinking, which is in line with the guidance on the innovation and development of medical education.

Objective:To observe the clinical effect of the Yiqi Yangxue Shengsui Formula in the prevention and treatment of adverse bleeding events caused by platinum-based dual drugs combined with bevacizumab chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods:A prospective, single-center, randomized controlled trial design was adopted. The research subjects were patients with stage Ⅲb-Ⅳb non-squamous NSCLC who were hospitalized at Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from December 2022 to March 2024. Patients who met the inclusion criteria were randomly assigned to the experimental group and the control group in a 1∶1 ratio. The control group received a platinum-based doublet regimen [pemetrexed disodium for injection+cisplatin/carboplatin, or paclitaxel protein-bound for injection+cisplatin/carboplatin] combined with bevacizumab for 4 courses of treatment; the experimental group was treated with the same regimen plus the traditional Chinese medicine Yiqi Yangxue Shengsui Formula, nourishing blood and generating bone marrow. The primary observation index was the incidence and grade of adverse bleeding events during the 4 courses of treatment. The secondary observation indices were the occurrence time and duration of bleeding, the grade of the lowest platelet count during treatment, the platelet count grade at the time of bleeding, and coagulation function indicators. Results:A total of 77 patients were included, with 39 in the experimental group and 38 in the control group. Among them, 29 were male (37.7%) and 48 were female (62.3%); 35 were aged 65 years or older and 42 were younger than 65 years. There were no statistically significant differences between the 2 groups in terms of gender, age, lung cancer stage, pathological type, and chemotherapy drug selection ( P> 0.05). The incidence of adverse bleeding events in the experimental group was significantly lower than that in the control group [17.9%(7/39) vs. 39.5%(15/38), P=0.037]. There was no statistically significant difference in the grading of adverse bleeding events between the 2 groups ( P>0.05). The duration of bleeding in the experimental group was shorter than that in the control group [(2.57±1.13) days vs. (5.67±1.80) days, P<0.001]. The minimum platelet count classification during the treatment period, and the platelet count classification at the time of bleeding in the experimental group were both better than those in the control group ( P<0.05). The prothrombin time and international normalized ratio when bleeding occurred in the experimental group were both lower than those in the control group [(10.96±0.39) s vs. (11.49±0.50) s and 0.97±0.04 vs. 1.02±0.06, P<0.05]. There were no statistically significant differences between the 2 groups of patients in terms of activated partial thromboplastin time, fibrinogen degradation products and D-dimer ( P>0.05). Conclusion:The Yiqi Yangxue Shengsui formula can effectively prevent and treat bleeding adverse events related to platinum-based dual-drug chemotherapy combined with bevacizumab in patients with advanced NSCLC. The mechanism may be related to the increase of platelet count and the improvement of exogenous coagulation function indicators.

Objective:In order to effectively educate students on tooth defect diseases and restoration techniques, the teaching and research team at the School of Stomatology of Qingdao University developed an integrated course operative dentistry. This course is specifically designed to align with the undergraduate curriculum reform requirements of "Three Early, Two Multiple and One Integration".Methods:The teaching practice of operative dentistry was conducted with the stomatology undergraduates of grade 2020 and 2021. The course group redesigned the curriculum by reorganizing teaching content, rebuilding teaching resources, reconstructing teaching mode, and reshaping the evaluation system. Evaluation of the curriculum design included test scores, satisfaction questionnaires, and teacher self-evaluation. Statistical analysis was performed using SPSS 27.0 software, including independent sample t-tests for numerical variables and Fisher's exact test or Wilcoxon rank sum test for categorical variables. Results:Through the integrated course learning, 92.68% (38/41) of the students of grade 2020 and 97.44% (38/39) of the students of grade 2021 can basically or completely master various dental defect repair schemes and understand the importance of preserving natural tooth. 82.93% (34/41) of the students of grade 2020 and 100.00% (39/39) of the students of grade 2021 could basically or completely master the key points of various dental defect restorations.Conclusions:Through the practice of teaching, it has been confirmed that the integrated course of operative dentistry is beneficial to students' mastering the knowledge and skills of dental defect diseases and their restoration in a more comprehensive way, and is conducive to the cultivation of clinical thinking, hands-on ability and the patient-centered, comprehensive problem-solving thinking, which is in line with the guidance on the innovation and development of medical education.

Objective:To observe the clinical effect of the Yiqi Yangxue Shengsui Formula in the prevention and treatment of adverse bleeding events caused by platinum-based dual drugs combined with bevacizumab chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods:A prospective, single-center, randomized controlled trial design was adopted. The research subjects were patients with stage Ⅲb-Ⅳb non-squamous NSCLC who were hospitalized at Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from December 2022 to March 2024. Patients who met the inclusion criteria were randomly assigned to the experimental group and the control group in a 1∶1 ratio. The control group received a platinum-based doublet regimen [pemetrexed disodium for injection+cisplatin/carboplatin, or paclitaxel protein-bound for injection+cisplatin/carboplatin] combined with bevacizumab for 4 courses of treatment; the experimental group was treated with the same regimen plus the traditional Chinese medicine Yiqi Yangxue Shengsui Formula, nourishing blood and generating bone marrow. The primary observation index was the incidence and grade of adverse bleeding events during the 4 courses of treatment. The secondary observation indices were the occurrence time and duration of bleeding, the grade of the lowest platelet count during treatment, the platelet count grade at the time of bleeding, and coagulation function indicators. Results:A total of 77 patients were included, with 39 in the experimental group and 38 in the control group. Among them, 29 were male (37.7%) and 48 were female (62.3%); 35 were aged 65 years or older and 42 were younger than 65 years. There were no statistically significant differences between the 2 groups in terms of gender, age, lung cancer stage, pathological type, and chemotherapy drug selection ( P> 0.05). The incidence of adverse bleeding events in the experimental group was significantly lower than that in the control group [17.9%(7/39) vs. 39.5%(15/38), P=0.037]. There was no statistically significant difference in the grading of adverse bleeding events between the 2 groups ( P>0.05). The duration of bleeding in the experimental group was shorter than that in the control group [(2.57±1.13) days vs. (5.67±1.80) days, P<0.001]. The minimum platelet count classification during the treatment period, and the platelet count classification at the time of bleeding in the experimental group were both better than those in the control group ( P<0.05). The prothrombin time and international normalized ratio when bleeding occurred in the experimental group were both lower than those in the control group [(10.96±0.39) s vs. (11.49±0.50) s and 0.97±0.04 vs. 1.02±0.06, P<0.05]. There were no statistically significant differences between the 2 groups of patients in terms of activated partial thromboplastin time, fibrinogen degradation products and D-dimer ( P>0.05). Conclusion:The Yiqi Yangxue Shengsui formula can effectively prevent and treat bleeding adverse events related to platinum-based dual-drug chemotherapy combined with bevacizumab in patients with advanced NSCLC. The mechanism may be related to the increase of platelet count and the improvement of exogenous coagulation function indicators.

Objective To analyze the objective tongue diagnosis data characteristics of benign and malignant pulmonary nodules and to establish a lung cancer risk warning model based on the logistic regression method.Methods From July 2020 to March 2022,263 lung cancer patients(lung cancer group)from the Oncology Department of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,292 benign pulmonary nodules patients(benign pulmonary nodules group)from the Physical Examination Center of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,and 307 healthy individuals(healthy control group)were selected.TFDA-1 digital tongue diagnostic instrument was used to collect tongue images.Objective diagnostic features of the tongue were obtained through feature extraction technology.The distribution characteristics of the tongue indicators of the three groups of subjects were analyzed.A lung cancer warning model was established based on logistic regression method after feature screening,and the performance of the model was evaluated using sensitivity,specificity,accuracy,and AUC.Results The tongue features of patients in benign pulmonary nodules group were similar to those of the healthy control group,while the tongue features of the lung cancer group differed greatly from those of the healthy control group and benign pulmonary nodules group.The tongue features of lung cancer patients were dark and opaque,the tongue body was reddish,and the tongue coating is thin and yellowish with a greasy texture.The accuracy,sensitivity,specificity and AUC of the lung cancer warning model based on tongue image data were 70.09%,69.94%,70.29%and 0.769,respectively.After adding baseline information to the tongue image data set,the models'performance was improved.The accuracy,sensitivity,specificity and AUC of the new model based on tongue and baseline were 77.30%,75.94%,79.15%and 0.812,respectively.Conclusion The statistical characteristics of objective tongue image data between benign pulmonary nodules and lung cancer patients show significant differences.The lung cancer classification model based on objective tongue data performs well,and the objective tongue diagnosis data in TCM can provide reference for the differential diagnosis of benign pulmonary nodules and lung cancer.

Objective To analyze the differences in the correlation of tongue image indicators among patients with benign lung nodules and lung cancer. Methods From July 1,2020 to March 31,2022,clinical information of lung cancer patients and benign lung nodules patients was collected at the Oncology Department of Longhua Hos-pital Affiliated to Shanghai University of Traditional Chinese Medicine and the Physical Ex-amination Center of Shuguang Hospital Affiliated to Shanghai University of Traditional Chi-nese Medicine,respectively.We obtained tongue images from patients with benign lung nod-ules and lung cancer using the TFDA-1 digital tongue diagnosis instrument,and analyzed these images with the TDAS V2.0 software.The extracted indicators included color space pa-rameters in the Lab system for both the tongue body(TB)and tongue coating(TC)(TB/TC-L,TB/TC-a,and TB/TC-b),textural parameters[TB/TC-contrast(CON),TB/TC-angular second moment(ASM),TB/TC-entropy(ENT),and TB/TC-MEAN],as well as TC parameters(perAll and perPart).The bivariate correlation of TB and TC features was analyzed using Pearson's or Spearman's correlation analysis,and the overall correlation was analyzed using canonical correlation analysis(CCA). Results Samples from 307 patients with benign lung nodules and 276 lung cancer patients were included after excluding outliers and extreme values.Simple correlation analysis indi-cated that the correlation of TB-L with TC-L,TB-b with TC-b,and TB-b with perAll in lung cancer group was higher than that in benign nodules group.Moreover,the correlation of TB-a with TC-a,TB-a with perAll,and the texture parameters of the TB(TB-CON,TB-ASM,TB-ENT,and TB-MEAN)with the texture parameters of the TC(TC-CON,TC-ASM,TC-ENT,and TC-MEAN)in benign nodules group was higher than lung cancer group.CCA further demon-strated a strong correlation between the TB and TC parameters in lung cancer group,with the first and second pairs of typical variables in benign nodules and lung cancer groups indicat-ing correlation coefficients of 0.918 and 0.817(P<0.05),and 0.940 and 0.822(P<0.05),re-spectively. Conclusion Benign lung nodules and lung cancer patients exhibited differences in correla-tion in the L,a,and b values of the TB and TC,as well as the perAll value of the TC,and the texture parameters(TB/TC-CON,TB/TC-ASM,TB/TC-ENT,and TB/TC-MEAN)between the TB and TC.Additionally,there were differences in the overall correlation of the TB and TC be-tween the two groups.Objective tongue diagnosis indicators can effectively assist in the diag-nosis of benign lung nodules and lung cancer,thereby providing a scientific basis for the ear-ly detection,diagnosis,and treatment of lung cancer.