1.Effect of Wenyang Shengji Ointment (温阳生肌膏) on MGO Content and HIF-1a/VEGF Pathway in Wound Tissue of Diabetic Wound Model Rats with Yin Syndrome
Xinyu HUANG ; Li CHEN ; Yarong DING ; Jun WANG ; Shuihua FENG ; Zhongzhi ZHOU
Journal of Traditional Chinese Medicine 2025;66(4):382-389
ObjectiveTo investigate the possible mechanism of Wenyang Shengji Ointment (温阳生肌膏, WSO) in the treatment of diabetic wounds with yin syndrome. MethodsA total of 24 SD rats were randomly divided into a group (n=6) and modeling group (n=18). The modeling group rats were fed with high-fat diet for 14 days and then were injected intraperitoneally with streptozotocin to induce diabetic model. After steroid injection, full-thickness skin defects were created on the back of the rats to establish a diabetic wound with yin syndrome model. The normal group was fed with regular diet, and full-thickness skin defects were created surgically on the back of the rats. The 18 successfully modeled rats were further divided into three groups, the model group, the WSO group, and the Beifuxin (Recombinant Bovine Basic Fibroblast Growth Factor Gel, BX) group, 6 rats in each group. The WSO group was given the ointment to the wound, the Beifuxin group was givne BX gel, and the normal group and model group was disinfected and treated with saline. All groups had their dressings changed once daily for 14 days. Wound healing was recorded on days 0, 3, 7, and 14, and the wound healing rate was calculated on day 3, 7, and 14. On day 14 after treatment, HE staining was performed to observe the pathological morphology of the wound tissue. Western Blot was used to detect the relative protein levels of hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Immunofluorescence was used to measure the fluorescence intensity of HIF-1α in the wound tissue, and ELISA was used to detect the methylglyoxal (MGO) content in the wound tissue. ResultsCompared with the normal group, the model group showed poor wound healing on day 3, 7, and 14, with a low wound healing rate (P<0.01). HE staining showed scab coverage on the wound, with inflammatory cell infiltration and disorganized collagen arrangement. The relative protein levels of VEGF were significantly reduced, while the relative protein levels of HIF-1α and the MGO content significantly increased (P<0.01), and the fluorescence intensity of HIF-1α was enhanced. Compared to the model group, the WSO group and Beifuxin group showed better wound healing on day 3, 7, and 14, with an increased wound healing rate (P<0.01). The wound tissue showed clear and complete epithelial structure, reduced inflammatory cells, mature granulation tissue, and organized collagen arrangement. MGO content was significantly reduced (P<0.01). The relative protein levels of HIF-1α and VEGF both significantly increased in the WSO group, while only VEGF increased in the Beifuxin group (P<0.05 or P<0.01). Compared with the Beifuxin group, the WSO group had a thicker epidermal layer, prominent collagen formation, significantly increased HIF-1α fluorescence expression, reduced MGO content in the wound tissue, and higher relative protein levels of HIF-1α (P<0.05). ConclusionWSO can reduce the accumulation of MGO in diabetic wound tissue with yin syndrome and activate the HIF-1α/VEGF pathway, which could be one of the mechanisms for promoting wound healing.
2.Analyze the risk factors of secondary myocardial injury to acute organophosphorus pesticide poisoning and the predictive value of serum Furin and sTWEAK for it
Rui LI ; Wei ZHU ; Jie XU ; Yarong XIE
International Journal of Laboratory Medicine 2024;45(20):2480-2484
Objective To investigate the risk factors of myocardial injury secondary to acute organophos-phorus pesticide poisoning(AOPP)and the predictive efficacy of serum Furin and soluble tumor necrosis fac-tor-like weak inducer of apoptosis(sTWEAK).Methods A total of 146 AOPP patients admitted to this hos-pital from February 2021 to February 2023 were selected as the research objects.Three days after admission,they were divided into non-myocardial injury group(84 cases)and myocardial injury group(62 cases)accord-ing to whether they had secondary toxic heart disease.The clinical data of all patients were collected.Univari-ate and multivariate Logistic regression analysis were used to explore the risk factors of secondary myocardial injury in AOPP patients.The serum Furin and sTWEAK levels of all patients were detected by enzyme-linked immunosorbent assay.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum Furin and sTWEAK for secondary myocardial injury in AOPP patients.Results Myocardial injury occurred in 62 of 146 AOPP patients,with an incidence of 42.47%.Univariate analysis showed that there were no statistically significant differences in gender,time from medication to admission,and pesticide type between the two groups(P>0.05).Compared with the non-myocardial injury group,the myocardial in-jury group had significantly higher levels of tropomin Ⅰ and creatine kinase isoenzyme and a significantly high-er proportion of patients with age ≥60 years,severe poisoning,and acute physiology and chronic health evalu-ation(APACHE)Ⅱ score ≥20(P<0.05).The serum levels of Furin and sTWEAK in the myocardial injury group were higher than those in the non-myocardial injury group(P<0.05).The area under curve(AUC)of serum Furin and sTWEAK in predicting secondary myocardial injury in AOPP patients was 0.813 and 0.744,respectively.The AUC of combined prediction of the two was 0.896,which was higher than that of each index alone.Multivariate Logistic regression analysis showed that severe poisoning degree(OR=2.054,95%CI 1.256-3.360),APACHE Ⅱ score ≥20 points(OR=2.323,95%CI 1.334-4.046),serum Furin≥129.48 ng/L(OR=3.380,95%CI 1.689-6.766),serum sTWEAK≥845.86 ng/L(OR=4.988,95%CI 2.057-12.097)were risk factors for secondary myocardial injury in AOPP patients(P<0.05).Conclusion Seconda-ry myocardial injury in AOPP patients is related to the degree of poisoning and APACHE Ⅱ score,and the ser-um Furin and sTWEAK levels increase in patients with secondary myocardial injury in AOPP,which have im-portant clinical significance in predicting patients with secondary myocardial injury in AOPP.
3.Analysis of novel gene mutations in a family with hereditary coagulation factor XI deficiency
Rui LI ; Yarong XIE ; Wei ZHU ; Xiaoyan LI ; Hao LIU
Chinese Journal of Laboratory Medicine 2024;47(8):952-957
Objective:To explore the molecular mechanism of clinical bleeding in a family with hereditary coagulation factor Ⅺ (FⅪ) deficiency caused by a novel mutation of the coagulation factor Ⅺ (FⅪ) gene.Methods:A male proband with hereditary coagulation factor XI deficiency who was admitted to Yuncheng Central Hospital Affiliated to Shanxi Medical University due to "adenoid hypertrophy" on February 23, 2023 and his family members (5 people in 3 generations) were selected as research subjects. The clinical data of the proband and family members were collected; the relevant coagulation indexes of all members were tested; those with abnormal coagulation indexes (prolonged activated partial thromboplastin time (APTT), normal thrombin time (PT) and fibrinogen (Fib)) were selected for APTT correction experiment; those with corrected Rosner index (RI) less than 10% were selected to detect FⅪ activity (FⅪ:C) by one-step method, FⅪ antigen (FⅪ:Ag) by ELISA method, and whole exon sequence by Illumina sequencing method. New mutation sites were rated according to the American College of Medical Genetics and Genomics (ACMG) related variation rating guidelines, and bioinformatics software was used to predict the impact of new mutations on protein structure and function.Results:The APTT of the proband, his father and his daughter were all prolonged and their RI were all less than 10%. Further tests revealed that FⅪ:C and FⅪ:Ag of the three were all decreased. Illumina sequencing revealed a new frameshift mutation c.1223dupC (P.Ser409Leufs*32) in exon 11 of FⅪ of the three people, and a missense mutation c.G1253T (p.Gly418Val) in exon 11 of FⅪ of the proband′s father. ACMG rated the new mutation as pathogenic, and c.G1253T was a reported possible pathogenic mutation.Conclusion:The heterozygous frameshift mutation c.1223dupC (P.Ser409Leufs*32) in exon 11 of FⅪ may be the main molecular mechanism of the disease in this family.
4.Effects of embedded guidance technique assisted transconjunctival lower eyelid blepharoplasty
Yarong CHI ; Zhujun LI ; Lin JIN ; Jiuzuo HUANG ; Nanze YU ; Xiao LONG
Chinese Journal of Medical Aesthetics and Cosmetology 2024;30(4):307-311
Objective:To investigate the effect of embedded guidance technique assisted transconjunctival lower eyelid blepharoplasty.Methods:A retrospective study was conducted to include 88 patients who underwent transconjunctival blepharoplasty and tear trough deformity correction with orbital septum fat release and fixation (referred to as transconjunctival lower eyelid blepharoplasty) at the Department of Plastic and Reconstructive Surgery, Peking Union Medical College Hospital, from October 2021 to August 2022. There were 9 male patients (10.23%) and 79 female patients (88.77%), aged 22 to 51 years, with an average age of (34.42±6.17) years. The internal fixation of septum fat flap was assisted with embedded guidance technique, and the Barton grades system was used to evaluate the surgical effect, while the patient satisfaction and complications were collected.Results:The followed-up period is 6-16 months. Before operation, 35 eyes (19.89%) were classified as Barton Ⅰ, 86 eyes (48.86%) were classified as Barton Ⅱ, and 55 eyes (31.25%) were classified as Barton Ⅲ. After transconjunctival lower eyelid blepharoplasty, 151 eyes (85.80%) recovered to Barton grade 0, 22 eyes (12.50%) recovered to grade Ⅰ, 3 eyes (1.70%) recovered to grade Ⅱ, and no case was grade Barton Ⅲ. The patient satisfaction score was (9.14±1.22) points, and 78 patients (88.64%) were very satisfied. Only 6 patients (6.82%) showed mild complications, mainly including postoperative bilateral lower eyelid asymmetry (3 cases), mild bilateral orbital area ecchymosis (2 cases) and mild surface depression at internal fixation position (1 case).Conclusions:The transconjunctival lower eyelid blepharoplasty assisted by the embedded guidance technique achieves favorable results with high patient satisfaction and few complications.
5.Compound ANBP promotes diabetic wound healing by regulating TCA circulation-related enzymes
Wei WANG ; Qian HOU ; Xinling HUANG ; Jun WANG ; Meilin ZOU ; Yarong DING ; Letian GUO ; Chenlei XIE ; Xinyu HUANG ; Li CHEN ; Zhongzhi ZHOU
Chinese Journal of Pathophysiology 2024;40(7):1283-1291
AIM:To investigate the effects of the compound ANBP on wound healing in diabetic rats and ex-plore its mechanism of action.METHODS:Ninety male SD rats were randomly divided into blank,model,compound ANBP,Beifuxin,and nicotinamide mononucleotide(NMN)groups,with 16 rats in each group.Wound healing in each group was observed and samples were taken on days 3,7 and 14 to analyze the wound healing rate.Local histopathological changes were observed using HE and Masson staining.The expressions of pyruvate dehydrogenase E1 subunit alpha 1(PDHA1),citrate synthase(CS),isocitrate dehydrogenase(IDH1)and oxoglutarate dehydrogenase(OGDH)were de-tected through immunofluorescence and Western blot.The number and morphology of mitochondria in the wound tissue were observed using transmission electron microscopy.RESULTS:Histomorphological changes revealed significant im-provement in diabetic wound healing in the blank and compound ANBP groups compared to that of the model group.The wound healing rates of the blank,compound ANBP,Beifuxin,and NMN groups were significantly increased on days 3,7,and 14(P<0.01).Compared to the model group,granulation tissue generation was higher in the other groups,cover-ing the wound defect and producing abundant collagen fibers.At 3,7,and 14 days after intervention,the blank,com-pound ANBP,Beifuxin,and NMN groups showed significantly enhanced fluorescence intensities of TCA cycling-related enzymes PDHA1,CS,IDH1,and OGDH indicating increased expression of these enzymes.The levels of the TCA cy-cling-related enzymes were significantly increased(P<0.01)in the compound ANBP,Beifuxin and NMN groups but were significantly decreased(P<0.01)in the model group.An increase in the number and density of mitochondria and a de-crease in the cavitation rate of mitochondria with improved morphology(P<0.05)was observed in the group treated with compound ANBP.CONCLUSION:Compound ANBP may increase the number of mitochondria,improve mitochondrial morphology and function,upregulate the expression levels of PDHA1,CS,IDH1,and OGDH proteins,and accelerate the regeneration of wound granulation tissue,thus promoting the healing of diabetic wounds in rats.
6.The diagnostic study of second-generation motion correction algorithm in improving the accuracy of CT-derived fractional flow reserve calculations
Wenli YANG ; Ziting LAN ; Lihua YU ; Yarong YU ; Xu DAI ; Shuai ZHANG ; Nianyun LI ; Jiayin ZHANG
Chinese Journal of Radiology 2024;58(7):721-728
Objective:To investigate the diagnostic performance of CT-derived fractional flow reserve (CT-FFR) derived from standard images (STD), images processed by first-generation (SSF1) and second-generation (SSF2) whole-heart motion correction algorithm, respectively.Methods:Patients who underwent both coronary CT angiography (CCTA) and invasive coronary angiography (ICA) with FFR examination within 3 months in Shanghai General Hospital, Shanghai Jiao Tong Univerisity School of Medicine from January 2020 to December 2022 were screened in this retrospective study. Totally of 121 patients (134 lesions) were finally included in the study. CCTA images were reconstructed using iterative reconstruction, iterative reconstruction plus SSF1 and SSF2 algorithms. All images were divided into three groups: STD group, SSF1 group, and SSF2 group. The image quality of the CCTA images was assessed using the Likert scale, and differences between the two groups were compared using the Mann-Whitney U and Kruskal-Wallis test. The correlation and consistency between CT-FFR and FFR were evaluated using Spearman correlation coefficient and Bland-Altman plots. The diagnostic performance of CCTA and CT-FFR from three groups was compared by receiver operating characteristic (ROC) curves. The area under the curve (AUC) was compared using the DeLong test. Results:Compared to the STD group and SSF1 group, the SSF2 group showed the best performance in image quality score (median=3.7). Best correlation ( r=0.652, P<0.001) and consistency (mean difference=0.03) between CT-FFR and FFR were observed in SSF2 group. ROC analysis results revealed that, at the per-lesion level, in the diagnosis of ischemic lesions, the diagnostic performance of CT-FFR in the SSF2 group was significantly better than that of the SSF1 group (AUC=0.88 vs. 0.76, P=0.003), while no significant difference was observed between STD group and SSF1 group ( P=0.125). At the per-patient level, the SSF2 group also demonstrated the highest diagnostic performance. Conclusion:The SSF2 algorithm significantly improved CCTA image quality and enhanced its diagnostic performance for evaluating stenosis severity and CT-FFR calculations.
7.Wenyang-Shengji ointment regulates GRP78/CHOP pathway to inhibit excessive endoplasmic reticulum stress for facilitating diabetic refractory wound repair
Yarong DING ; Shixu ZHENG ; Jun WANG ; Chenlei XIE ; Shuihua FENG ; Zhongzhi ZHOU ; Li CHEN
Chinese Journal of Pathophysiology 2024;40(3):493-501
AIM:To study the regulation of endoplasmic reticulum stress(ERS)using the glucose regulated protein 78(GRP78)/CCAAT/enhancer binding protein homologous protein(CHOP)pathway and explore the related mech-anism of Wenyang-Shengji ointment in facilitating the repair of diabetic refractory wounds.METHODS:To establish a rat model of diabetic refractory wound repair,Sprague-Dawley(SD)rats were fed a high-fat diet and intraperitoneally in-jected with streptozotocin.Subsequently,full-thickness skin defects were induced in the dorsal region of the rats.The ex-periment included 4 groups:normal,model(diabetic refractory wounds),Wenyang-Shengji ointment,and Beifuxin(re-combinant bovine basic fibroblast growth factor gel)groups.The normal and model groups were treated with normal saline after disinfection.In the Wenyang-Shengji ointment and Beifuxin groups,the wounds were topically treated with the re-spective ointments once daily.After 14 d of treatment,wound healing was assessed and quantified using the wound healing rate.Hematoxylin-eosin(HE)staining was employed to examine the micromorphology of the wound tissue.Western blot analysis was performed to measure GRP78,CHOP and caspase-12 levels in the wound tissue.Immunohistochemical analy-sis was used to detect the expression and distribution patterns of GRP78,CHOP and caspase-12 in the wounds.Transmis-sion electron microscopy was used to observe reticulum numbers and swelling.Enzyme-linked immunosorbent assay was used to determine interleukin-1β(IL-1β)level as a pro-inflammatory factor within the wound.RESULTS:Indexes of each group were assessed 14 d after the corresponding intervention.Compared with normal group,the rats in model group exhibited a significant decrease in the wound healing rate(P<0.01),accompanied by increased inflammatory exudation and poor granulation tissue growth.Additionally,there were increases in the expression levels of GRP78,CHOP and cas-pase-12 proteins(P<0.01),as well as a significant elevation in the content of inflammatory factor IL-1β(P<0.01).In contrast,compared with model group,treatment with Wenyang-Shengji ointment resulted in a significant improvement in wound healing rate(P<0.01),reduction in inflammatory exudation,and enhanced granulation tissue growth(P<0.01).Furthermore,there was a notable decrease in the protein expression of GRP78/CHOP/caspase-12 within the wound tissue following treatment with Wenyang-Shengji ointment(P<0.01).The levels of inflammatory factor IL-1β also showed a sig-nificant decrease(P<0.01).CONCLUSION:Wenyang-Shengji promotes the healing of diabetic refractory wounds,which may be associated with the downregulation of the GRP78/CHOP pathway,inhibition of excessive ERS,and reduc-tion in the level of wound cell apoptosis.
8.ERK mediated C-Myc/PD-L1 synergy to investigate tumor suppression effect of Shenqi Yiliu decoction combined with cisplatin in combination with H22 hepatocellular carcinoma tumor bearing mice
Yuping YANG ; Yongqiang DUAN ; Min BAI ; Xin FENG ; Nan ZHOU ; Liren CAO ; Yarong LI ; Lan MA
Chinese Journal of Immunology 2024;40(3):586-591
Objective:To investigate the tumor suppressing effect of Shenqi Yiliu decoction combined with cisplatin via ERK-mediated C-Myc/PD-L1 phase-coordinated pathway on H22 hepatocellular carcinoma tumor-bearing mice and its mechanism.Meth-ods:In 60 SPF-grade male Kunming mice,10 mice were taken as blank group by random number table method,and the other 50 mice were replicated as H22 hepatocellular carcinoma tumor-bearing mouse model.After successful replication of the model,the model mice were randomly divided into model group,cisplatin group[2.5×10-3 g/(kg·3 d)],Shenqi Yiliu decoction low[13.515 g/(kg·d)],me-dium[27.03 g/(kg·d-1)],and high dose[27.030 g/(kg·d)]combined with cisplatin group[2.5×10-3 g/(kg·3 d)],10 mice in each group were treated for 13 d.After 24 h of the last dose,the mice were anesthetized and sacrificed,and the tumor inhibition rate,spleen index and thymus index of each drug group were determined;HE staining was performed to observe the histopathological changes of tumor in mice;ELISA kit was used to detect the contents of EGF and IFN-γ in tumor tissue homogenate;p-ERK1/2,C-Myc and PD-L1 protein expression in tumor tissue were detected by IHC and Western blot;ERK,C-Myc and PD-L1 mRNA expression levels in tumor tissue were detected by RT-PCR.Results:Compared with blank group,the average body mass and spleen index of mice in model group were decreased(P<0.05).Compared with model group,the tumor inhibition effect of each treatment group was obvious,and Shenqi Yiliu decoction combined with cisplatin group inhibited tumor growth in liver cancer mice in a dose-dependent way,im-proved the average body mass,spleen index and thymus index of mice,promoted the necrosis of tumor cells and increased the necrotic area.EGF and IFN-γ contents,P-ERK1/2,C-Myc,PD-L1 protein expressions and ERK,C-Myc,PD-L1 mRNA expression levels were decreased in tumor tissues(P<0.05).Compared with cisplatin group,the therapeutic effect of Shenqi decoction combined with cisplatin in medium and high dose groups was significant,and the difference was statistically significant(P<0.05).Conclusion:Shenqi Yiliu decoction combined with cisplatin effectively inhibited the tumor growth of H22 liver cancer tumor-bearing mice and significantly reduces the expression of C-Myc and PD-L1 proteins in the tumor tissues,which may be through the regulation of ERK signaling path-way-related protein expression to exert tumor suppressive effect.
9.Aesthetic Investigation of the Pretarsal Shows and Morphology of Double Eyelids in Chinese Populations: A Questionnaire-based Survey
Yarong CHI ; Zhujun LI ; Lin JIN ; Nanze YU ; Jiuzuo HUANG ; Xiao LONG
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1334-1341
To explore the ideal pretarsal shows and morphological characteristics of double eyelids in Chinese populations through a morphometric analysis. This study employed a convenience sampling method to survey Chinese adults who did not reside abroad for an extended period (with cumulative overseas stay of over one year). From November 2023 to May 2024, electronic questionnaires were distributed to collect attractiveness ratings of nine different images (including one image featuring single eyelid and eight images with varying pretarsal shows and morphologies of double eyelids). Stratified comparisons were conducted based on gender, age, occupation, etc., to determine the ideal pretarsal show and morphology of double eyelids. Quantitative analysis was performed on the aesthetic features of the nine images depicting double eyelids to validate and elucidate the survey findings. A total of 493 questionnaires were filled out, and 397 valid questionnaires were included for data analysis after quality control. As for the whole cohort, the images feathering 2 mm double eyelid were deemed to be the most attractive, with the in-fold type scoring (3.72±0.97) points and the out-fold type scoring (3.65±1.04) points. The next was 1 mm, followed by 3 mm, single eyelid, and finally, 4 mm. As for morphology, in-fold type achieved higher scores than out-fold type in images with the same pretarsal show. However, statistically significant differences were only found in ratings for the images with 3 mm and 4 mm double eyelids (all This study validates that the pretarsal show of 2 mm and the presence of either an in-fold or out-fold morphology are considered optimal for double eyelids among Chinese individuals. These findings hold significant implications for the planning of double eyelid surgeries, assessment of surgical outcomes, and evaluation of other periocular procedures associated with double eyelid surgeries.
10.Aesthetic Investigation of the Pretarsal Shows and Morphology of Double Eyelids in Chinese Populations: A Questionnaire-based Survey
Yarong CHI ; Zhujun LI ; Lin JIN ; Nanze YU ; Jiuzuo HUANG ; Xiao LONG
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1334-1341
To explore the ideal pretarsal shows and morphological characteristics of double eyelids in Chinese populations through a morphometric analysis. This study employed a convenience sampling method to survey Chinese adults who did not reside abroad for an extended period (with cumulative overseas stay of over one year). From November 2023 to May 2024, electronic questionnaires were distributed to collect attractiveness ratings of nine different images (including one image featuring single eyelid and eight images with varying pretarsal shows and morphologies of double eyelids). Stratified comparisons were conducted based on gender, age, occupation, etc., to determine the ideal pretarsal show and morphology of double eyelids. Quantitative analysis was performed on the aesthetic features of the nine images depicting double eyelids to validate and elucidate the survey findings. A total of 493 questionnaires were filled out, and 397 valid questionnaires were included for data analysis after quality control. As for the whole cohort, the images feathering 2 mm double eyelid were deemed to be the most attractive, with the in-fold type scoring (3.72±0.97) points and the out-fold type scoring (3.65±1.04) points. The next was 1 mm, followed by 3 mm, single eyelid, and finally, 4 mm. As for morphology, in-fold type achieved higher scores than out-fold type in images with the same pretarsal show. However, statistically significant differences were only found in ratings for the images with 3 mm and 4 mm double eyelids (all This study validates that the pretarsal show of 2 mm and the presence of either an in-fold or out-fold morphology are considered optimal for double eyelids among Chinese individuals. These findings hold significant implications for the planning of double eyelid surgeries, assessment of surgical outcomes, and evaluation of other periocular procedures associated with double eyelid surgeries.

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