1.Erratum: Author correction to "SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade" Acta Pharm Sin B 9 (2019) 304-315.
Mingxia ZHAO ; Wenjie GUO ; Yuanyuan WU ; Chenxi YANG ; Liang ZHONG ; Guoliang DENG ; Yuyu ZHU ; Wen LIU ; Yanhong GU ; Yin LU ; Lingdong KONG ; Xiangbao MENG ; Qiang XU ; Yang SUN
Acta Pharmaceutica Sinica B 2025;15(5):2810-2812
[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].
2.Treatment of hypertrophic scars in children with triamcinolone acetonide acetate injection combined with ultra-pulsed CO 2 fractional laser
Jingjing XU ; Jie ZHENG ; Lingdong ZHU ; Beibei NIU
Chinese Journal of Plastic Surgery 2025;41(3):231-239
Objective:To investigate the clinical effect of local injection of triamcinolone acetonide acetate combined with ultra-pulsed CO 2 fractional laser in the treatment of hypertrophic scars in children. Methods:A randomized controlled study method was used. According to the inclusion and exclusion criteria, the subjects were selected from children with hypertrophic scars admitted to the Children’s Hospital Affiliated to Shandong University from January 2022 to September 2023, and were divided into control group and experimental group using random number table method. The control group was treated with ultra-pulsed CO 2 fractional laser. The experimental group was injected with triamcinolone acetonide acetate injection at multiple points into the scar (the ratio of triamcinolone acetonide acetate injection to 2% lidocoin hydrochloride injection was 1∶1), with a distance between the points as 1 cm, and the injection dose was about 0.1 to 0.2 ml/cm 2 according to the degree of scar protrusion. The maximum dose each time was ≤40 mg. CO 2 fractional laser treatment was performed after 10 minutes of cold compress with ice bag. Scars in both groups were treated 3 times, with an interval of 2 to 3 months. Before the treatment and 6 months after the last treatment, the Vancouver scar scale (VSS) was performed on both groups of scars score, the total score was 0 - 15. The higher the score, the more serious the scar hyperplasia was. Six months after the last treatment, the scar treatment effects of the two groups were comprehensively evaluated and divided into 3 levels: markedly effective, effective and ineffective. The total effective rate =(markedly effective + effective) number of cases/total number of cases ×100%. Patient satisfaction was investigated 6 months after the last treatment and divided into 5 levels: very satisfied, satisfied, average, dissatisfied, and very dissatisfied. Satisfaction rate =(very satisfied + satisfied) number of cases/total number of cases ×100%. The occurrence of adverse reactions was recorded throughout the treatment process. Analysis was performed using SPSS 19.0 software. Measurement data were expressed as Mean±SD, inter-group comparisons were performed using independent samples t-test, intra-group comparisons were performed using paired t-test, counting data were expressed as examples and percentages, and comparisons between the two groups were performed using χ2 test. P<0.05 indicated that the difference was statistically significant. Results:A total of 82 children with hypertrophic scars were included, 33 males and 49 females, aged 1 to 15 years old, with an area of 5 to 45 cm 2. The pathogenic factors were trauma, burns, and surgery. The course of disease was 2 to 30 months. Among them, 41 patients in the control group, 16 males and 25 females; the age was (5.8±1.6) years; 41 patients in the experimental group, 17 males and 24 females, the age was (5.6±1.5) years. There were no significant differences in age, gender, scar area, pathogenic factors and course of disease between the two groups ( P>0.05). There was no significant difference in VSS scores between the experimental group and the control group before the treatment [(9.42±1.35) points vs. (9.06±1.57) points, P>0.05]. Six months after the last treatment, there was a significant difference in VSS scores between the experimental group and the control group [(4.12±0.56) points vs. (5.50±0.75) points, P<0.01]. The VSS scores of children in both groups were significantly lower than those before the treatment ( P<0.01). Six months after the last treatment, the comprehensive evaluation result showed that the total effective rate in the experimental group was higher than that in the control group [92.7%(38/41) vs. 75.6%(31/41), P<0.05]. Six months after the last treatment, the patient satisfaction survey showed that the satisfaction rate in the experimental group was higher than that in the control group [87.8%(36/41) vs. 58.5%(24/41), P<0.01]. The main adverse reactions during treatment included edema erythema, skin ruptures, skin atrophy, and vigorous hair growth. There was no significant difference in the incidence of adverse reactions between the experimental group and the control group [12.2%(5/41) vs. 7.3%(3/41), P>0.05]. Conclusion:Local injection of triamcinolone acetonide acetate combined with ultra-pulsed CO 2 fractional laser is more effective in treating children’s hypertrophic scars. It can significantly improve the appearance of scars, reduce clinical symptoms, with fewer adverse reactions, and high patient satisfaction.
3.Treatment of hypertrophic scars in children with triamcinolone acetonide acetate injection combined with ultra-pulsed CO 2 fractional laser
Jingjing XU ; Jie ZHENG ; Lingdong ZHU ; Beibei NIU
Chinese Journal of Plastic Surgery 2025;41(3):231-239
Objective:To investigate the clinical effect of local injection of triamcinolone acetonide acetate combined with ultra-pulsed CO 2 fractional laser in the treatment of hypertrophic scars in children. Methods:A randomized controlled study method was used. According to the inclusion and exclusion criteria, the subjects were selected from children with hypertrophic scars admitted to the Children’s Hospital Affiliated to Shandong University from January 2022 to September 2023, and were divided into control group and experimental group using random number table method. The control group was treated with ultra-pulsed CO 2 fractional laser. The experimental group was injected with triamcinolone acetonide acetate injection at multiple points into the scar (the ratio of triamcinolone acetonide acetate injection to 2% lidocoin hydrochloride injection was 1∶1), with a distance between the points as 1 cm, and the injection dose was about 0.1 to 0.2 ml/cm 2 according to the degree of scar protrusion. The maximum dose each time was ≤40 mg. CO 2 fractional laser treatment was performed after 10 minutes of cold compress with ice bag. Scars in both groups were treated 3 times, with an interval of 2 to 3 months. Before the treatment and 6 months after the last treatment, the Vancouver scar scale (VSS) was performed on both groups of scars score, the total score was 0 - 15. The higher the score, the more serious the scar hyperplasia was. Six months after the last treatment, the scar treatment effects of the two groups were comprehensively evaluated and divided into 3 levels: markedly effective, effective and ineffective. The total effective rate =(markedly effective + effective) number of cases/total number of cases ×100%. Patient satisfaction was investigated 6 months after the last treatment and divided into 5 levels: very satisfied, satisfied, average, dissatisfied, and very dissatisfied. Satisfaction rate =(very satisfied + satisfied) number of cases/total number of cases ×100%. The occurrence of adverse reactions was recorded throughout the treatment process. Analysis was performed using SPSS 19.0 software. Measurement data were expressed as Mean±SD, inter-group comparisons were performed using independent samples t-test, intra-group comparisons were performed using paired t-test, counting data were expressed as examples and percentages, and comparisons between the two groups were performed using χ2 test. P<0.05 indicated that the difference was statistically significant. Results:A total of 82 children with hypertrophic scars were included, 33 males and 49 females, aged 1 to 15 years old, with an area of 5 to 45 cm 2. The pathogenic factors were trauma, burns, and surgery. The course of disease was 2 to 30 months. Among them, 41 patients in the control group, 16 males and 25 females; the age was (5.8±1.6) years; 41 patients in the experimental group, 17 males and 24 females, the age was (5.6±1.5) years. There were no significant differences in age, gender, scar area, pathogenic factors and course of disease between the two groups ( P>0.05). There was no significant difference in VSS scores between the experimental group and the control group before the treatment [(9.42±1.35) points vs. (9.06±1.57) points, P>0.05]. Six months after the last treatment, there was a significant difference in VSS scores between the experimental group and the control group [(4.12±0.56) points vs. (5.50±0.75) points, P<0.01]. The VSS scores of children in both groups were significantly lower than those before the treatment ( P<0.01). Six months after the last treatment, the comprehensive evaluation result showed that the total effective rate in the experimental group was higher than that in the control group [92.7%(38/41) vs. 75.6%(31/41), P<0.05]. Six months after the last treatment, the patient satisfaction survey showed that the satisfaction rate in the experimental group was higher than that in the control group [87.8%(36/41) vs. 58.5%(24/41), P<0.01]. The main adverse reactions during treatment included edema erythema, skin ruptures, skin atrophy, and vigorous hair growth. There was no significant difference in the incidence of adverse reactions between the experimental group and the control group [12.2%(5/41) vs. 7.3%(3/41), P>0.05]. Conclusion:Local injection of triamcinolone acetonide acetate combined with ultra-pulsed CO 2 fractional laser is more effective in treating children’s hypertrophic scars. It can significantly improve the appearance of scars, reduce clinical symptoms, with fewer adverse reactions, and high patient satisfaction.
4.Immunological pathways in viral hepatitis-induced hepato-cellular carcinoma
Lingdong XU ; Yifan XU ; Fei ZHANG ; Pinglong XU ; Lie WANG
Journal of Zhejiang University. Medical sciences 2024;53(1):64-72
Hepatocellular carcinoma(HCC)is a serious neoplastic disease with increasing incidence and mortality,accounting for 90%of all liver cancers.Hepatitis viruses are the major causative agents in the development of HCC.Hepatitis A virus(HAV)primarily causes acute infections,which is associated with HCC to a certain extent,as shown by clinicopathological studies.Chronic hepatitis B virus(HBV)or hepatitis C virus(HCV)infections lead to persistent liver inflammation and cirrhosis,disrupt multiple pathways associated with cellular apoptosis and proliferation,and are the most common viral precursors of HCC.Mutations in the HBV X protein(HBx)gene are closely associated with the incidence of HCC,while the expression of HCV core proteins contributes to hepatocellular lipid accumulation,thereby promoting tumorigenesis.In the clinical setting,hepatitis D virus(HDV)frequently co-infects with HBV,increasing the risk of chronic hepatitis.Hepatitis E virus(HEV)usually causes acute infections.However,chronic infections of HEV have been increasing recently,particularly in immuno-compromised patients and organ transplant recipients,which may increase the risk of progression to cirrhosis and the occurrence of HCC.Early detection,effective intervention and vaccination against these viruses may significantly reduce the incidence of liver cancer,while mechanistic insights into the interplay between hepatitis viruses and HCC may facilitate the development of more effective intervention strategies.This article provides a comprehensive overview of hepatitis viruses and reviews recent advances in research on aberrant hepatic immune responses and the pathogenesis of HCC due to viral infection.
5.Fangchinoline induces antiviral response by suppressing STING degradation
Wang JINYONG ; Xie FANG ; Jia XIN ; Wang XUEJIAO ; Kong LINGDONG ; Li YIYING ; Liang XUE ; Zhang MEIQI ; He YUTING ; Feng WANDI ; Luo TONG ; Wang YAO ; Xu ANLONG
Journal of Pharmaceutical Analysis 2024;14(6):902-913
The stimulator of interferon genes(STING),an integral adaptor protein in the DNA-sensing pathway,plays a pivotal role in the innate immune response against infections.Additionally,it presents a valuable therapeutic target for infectious diseases and cancer.We observed that fangchinoline(Fan),a bis-benzylisoquinoline alkaloid(BBA),effectively impedes the replication of vesicular stomatitis virus(VSV),encephalomyocarditis virus(EMCV),influenza A virus(H1 N1),and herpes simplex virus-1(HSV-1)in vitro.Fan treatment significantly reduced the viral load,attenuated tissue inflammation,and improved survival in a viral sepsis mouse model.Mechanistically,Fan activates the antiviral response in a STING-dependent manner,leading to increased expression of interferon(1FN)and interferon-stimulated genes(ISGs)for potent antiviral effects in vivo and in vitro.Notably,Fan interacts with STING,preventing its degradation and thereby extending the activation of IFN-based antiviral responses.Collectively,our findings highlight the potential of Fan,which elicits antiviral immunity by suppressing STING degra-dation,as a promising candidate for antiviral therapy.
6.New opportunities and challenges of natural products research: When target identification meets single-cell multiomics.
Yuyu ZHU ; Zijun OUYANG ; Haojie DU ; Meijing WANG ; Jiaojiao WANG ; Haiyan SUN ; Lingdong KONG ; Qiang XU ; Hongyue MA ; Yang SUN
Acta Pharmaceutica Sinica B 2022;12(11):4011-4039
Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.
7.SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade.
Mingxia ZHAO ; Wenjie GUO ; Yuanyuan WU ; Chenxi YANG ; Liang ZHONG ; Guoliang DENG ; Yuyu ZHU ; Wen LIU ; Yanhong GU ; Yin LU ; Lingdong KONG ; Xiangbao MENG ; Qiang XU ; Yang SUN
Acta Pharmaceutica Sinica B 2019;9(2):304-315
Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both and . However, whether SHP099-mediated SHP2 inhibition retards tumor growth anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099. Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system. SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8IFN- T cells and the upregulation of cytotoxic T-cell related genes including , which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and anti-PD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growth in two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.
8. Effect of human stromal vascular fraction gel on the treatment of patients with skin depressed scar and its mechanism
Lingdong OU ; Aijun ZHANG ; Ang LI ; Shengjun TAO ; Manman XU ; Qiang LI ; Peisheng JIN
Chinese Journal of Burns 2019;35(12):859-865
Objective:
To observe content of cytokine in human stromal vascular fraction gel (SVF-GEL) and effect of SVF-GEL on biological behaviors of epidermal and dermal cells in vitro and clinical efficacy of SVF-GEL.
Methods:
(1) SVF-GEL was prepared using liposuction aspirates harvested from females who received abdomen liposuction in author′s unit. SVF-GEL (1 mL) and high-glucose Dulbecco′s modified eagle medium (DMEM, 1 mL) were respectively cultured for 24 h with high-glucose DMEM containing 10% fetal calf serum, 10 g/L penicillin, and 10 g/L streptomycin, denoted as SVF-GEL group and negative control group, with 6 samples in each group. Content of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) in the supernatant was determined by enzyme-linked immunosorbent assay. (2) A number of 5×105 human skin fibroblasts (HSF) and HaCaT cells in logarithmic phase were inoculated and cultured in Transwell chambers for 12 h. All Transwell chambers containing cells were divided into SVF-GEL group (0.5 mL SVF-GEL was added for co-culture) and control group (0.5 mL high-glucose DMEM was added for co-culture), with 9 samples in each group for HSF and HaCaT cells. Scratch assay was performed after culture for 24 h, and residual scratch width was observed at post scratch hour (PSH) 0 (immediately), 24, and 48. Cell migration distance was measured at PSH 24 and 48. After culture for 24, 48, and 72 h, the number of living cell was counted using cell counter. (3) From June 2018 to June 2019, SVF-GEL was applied clinically to treat 15 patients with depressed scars on face, including 2 males and 13 females, aged 19 to 42 years. Survival condition of SVF-GEL and whether complications or not were observed 6 months after surgery. Before surgery and 6 months after surgery, depressed degree, color, and pliability of scar were compared. Vancouver Scar Scale (VSS) was employed to access color, vascularity, and pliability before surgery and 6 months after surgery, and total score was calculated. The number of patients with complete satisfaction or satisfaction was counted six months after surgery. Data were processed with analysis of variance of factorial design, paired samples
9.Effect of Heart Rate and Coronary Calcification on the Diagnostic Accuracy of the Dual-Source CT Coronary Angiography in Patients with Suspected Coronary Artery Disease.
Lingdong MENG ; Lianqun CUI ; Yuntao CHENG ; Xiaoyan WU ; Yuansheng TANG ; Yong WANG ; Fayun XU
Korean Journal of Radiology 2009;10(4):347-354
OBJECTIVE: To evaluate the diagnostic accuracy of a dual-source computed tomography (DSCT) coronary angiography, with a particular focus on the effect of heart rate and calcifications. MATERIALS AND METHODS:One hundred and nine patients with suspected coronary disease were divided into 2 groups according to a mean heart rate (< 70 bpm and > or = 70 bpm) and into 3 groups according to the mean Agatston calcium scores (< or = 100, 101-400, and > 400). Next, the effect of heart rate and calcification on the accuracy of coronary artery stenosis detection was analyzed by using an invasive coronary angiography as a reference standard. Coronary segments of less than 1.5 mm in diameter in an American Heart Association (AHA) 15-segment model were independently assessed. RESULTS: The mean heart rate during the scan was 71.8 bpm, whereas the mean Agatston score was 226.5. Of the 1,588 segments examined, 1,533 (97%) were assessable. A total of 17 patients had calcium scores above 400 Agatston U, whereas 50 had heart rates > or = 70 bpm. Overall the sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) for significant stenoses were: 95%, 91%, 65%, and 99% (by segment), respectively and 97%, 90%, 81%, and 91% (by artery), respectively (n = 475). Heart rate showed no significant impact on lesion detection; however, vessel calcification did show a significant impact on accuracy of assessment for coronary segments. The specificity, PPV and accuracy were 96%, 80%, and 96% (by segment), respectively for an Agatston score less than 100% and 99%, 96% and 98% (by artery). For an Agatston score of greater to or equal to 400 the specificity, PPV and accuracy were reduced to 79%, 55%, and 83% (by segment), respectively and to 79%, 69%, and 85% (by artery), respectively. CONCLUSION: The DSCT provides a high rate of accuracy for the detection of significant coronary artery disease, even in patients with high heart rates and evidence of coronary calcification. However, patients with severe coronary calcification (> 400 U) remain a challenge to diagnose.
Calcinosis/*radiography
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Coronary Angiography/methods/*standards
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Coronary Disease/*radiography
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Coronary Vessels/*pathology
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Female
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*Heart Rate
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Humans
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Male
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Middle Aged
;
Predictive Value of Tests
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Sensitivity and Specificity
;
Tomography, X-Ray Computed/methods/*standards

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