1.Polymer-assisted PD-L1 degradation and targeted photodynamic therapy synergize to suppress immunodeficient tumors.
Changyong GUO ; Shipeng HE ; Huaxing SHEN ; Wei CONG ; Jinqiu LI ; Yajing JI ; Wenjing HUANG ; Fei GAO ; Honggang HU
Acta Pharmaceutica Sinica B 2025;15(7):3805-3818
Checkpoint blockade immunotherapy has emerged as a transformative approach in cancer treatment by activating tumor-infiltrating T cells. However, the efficacy of PD-L1 blockade is restricted in "cold" tumors, which are characterized by low immunogenicity, presenting a challenge to immunotherapy. This study introduces an innovative strategy, utilizing cathepsin-cleavable N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-assisted combined photodynamic therapy (PDT) and PD-L1 degradation for the first time, effectively treating T cell-deficient tumors. The degradable main-chain polymer, conjugated with photosensitizer porphyrin, facilitates the accumulation of reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and promoting cytotoxic T lymphocytes (CTLs) infiltration into tumors. Multivalent peptide antagonists of PD-L1 promote PD-L1 degradation in lysosomes through receptor crosslinking, overcoming the adaptive cycling of PD-L1 to the tumor cell surface. These findings demonstrate that polymer-assisted PDT and PD-L1 crosslinking degradation represent a potential novel strategy for anti-tumor immunotherapy, providing valuable tools for expanding immunotherapy applications in immunosuppressive cancers.
2.Research progress on the mechanism of IL-33/ST2 signaling pathway in kidney diseases
Qian WANG ; Changchang LIANG ; Shipeng SHEN ; Maodong LIU ; Lu BAI
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(8):1122-1126
Interleukin-33(IL-33)is a member of the interleukin-1 superfamily and a"warning fac-tor"for inflammation in the body.When cells die or tissues are damaged,IL-33 is released in large quantities and binds to its receptor ST2 to form a complex,exerting various biological effects.IL-33/ST2 signaling pathway is activated in many kidney diseases,such as acute renal injury,obstructive ne-phropathy,diabetes nephropathy,IgA nephropathy,lupus nephritis,and kidney transplantation.It plays an important role in inflammation and renal fibro-sis by regulating the intrinsic and adaptive immune responses of the kidney.This article reviews the re-search progress of IL-33/ST2 signaling in common kidney diseases,hoping to provide new targets and ideas for the treatment of kidney diseases.
3.Investigation on the Survival Status and Economic Burden of Patients with Cryopyrin Associated Periodic Syndrome in China
Lina GUO ; Kexin LI ; Jiayin ZHENG ; Caifeng LI ; Min SHEN ; Shipeng LI ; Ningying MAO ; Xinling WANG ; Linkang LI
Chinese Health Economics 2025;44(1):66-71,78
Objective:To explore the survival status and economic burden of disease for patients with Cryopyrin Associated Periodic Syndrome(CAPS)in China.Methods:From August 2023 to February 2024,a questionnaire survey was conducted on patients who volunteered to participate.The survey included patients'sociodemographic characteristics,current medical treatment status,disease economic burden and life quality.Results:A total of 35 valid questionnaires were collected.The average age of onset for the patients was 5.67 years,and the average duration from onset to confirmed diagnosis was 7.63 years.The average total medical cost per person in the past 12 months was 82 532.79 yuan,which is significantly higher than the national per capita disposable income of China in 2023.Conclusion:CAPS has an early onset and a long duration until diagnosis,with treatment primarily symptomatic,resulting in a heavy disease burden for patients and their families.
4.Research progress on the mechanism of IL-33/ST2 signaling pathway in kidney diseases
Qian WANG ; Changchang LIANG ; Shipeng SHEN ; Maodong LIU ; Lu BAI
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(8):1122-1126
Interleukin-33(IL-33)is a member of the interleukin-1 superfamily and a"warning fac-tor"for inflammation in the body.When cells die or tissues are damaged,IL-33 is released in large quantities and binds to its receptor ST2 to form a complex,exerting various biological effects.IL-33/ST2 signaling pathway is activated in many kidney diseases,such as acute renal injury,obstructive ne-phropathy,diabetes nephropathy,IgA nephropathy,lupus nephritis,and kidney transplantation.It plays an important role in inflammation and renal fibro-sis by regulating the intrinsic and adaptive immune responses of the kidney.This article reviews the re-search progress of IL-33/ST2 signaling in common kidney diseases,hoping to provide new targets and ideas for the treatment of kidney diseases.
5.Investigation on the Survival Status and Economic Burden of Patients with Cryopyrin Associated Periodic Syndrome in China
Lina GUO ; Kexin LI ; Jiayin ZHENG ; Caifeng LI ; Min SHEN ; Shipeng LI ; Ningying MAO ; Xinling WANG ; Linkang LI
Chinese Health Economics 2025;44(1):66-71,78
Objective:To explore the survival status and economic burden of disease for patients with Cryopyrin Associated Periodic Syndrome(CAPS)in China.Methods:From August 2023 to February 2024,a questionnaire survey was conducted on patients who volunteered to participate.The survey included patients'sociodemographic characteristics,current medical treatment status,disease economic burden and life quality.Results:A total of 35 valid questionnaires were collected.The average age of onset for the patients was 5.67 years,and the average duration from onset to confirmed diagnosis was 7.63 years.The average total medical cost per person in the past 12 months was 82 532.79 yuan,which is significantly higher than the national per capita disposable income of China in 2023.Conclusion:CAPS has an early onset and a long duration until diagnosis,with treatment primarily symptomatic,resulting in a heavy disease burden for patients and their families.
6.Effects of Taohong siwu decoction modified granules on podocyte epithelial-mesenchymal-transition and renal fibrosis in rats with diabetic kidney disease
Lu BAI ; Shipeng SHEN ; Su WU ; Shuai GUO ; Maodong LIU
China Pharmacy 2024;35(11):1327-1333
OBJECTIVE To investigate the effects of Taohong siwu decoction modified granules on podocyte epithelial- mesenchymal-transition (EMT) and renal fibrosis in diabetic kidney disease (DKD) model rats. METHODS Eight rats were selected as normal group (ordinary feed); the remaining rats were given a high-glucose and high-fat diet combined with intraperitoneal injection of streptozotocin (35 mg/kg) to induce the DKD model. Model rats were randomly divided into model group, irbesartan group [positive control, 13.5 mg/(kg·d)] and modified Taohong siwu decoction group [6.48 g/(kg·d)], with 8 rats in each group. All groups were given relevant medicine intragastrically, once a day, for 16 consecutive weeks. Twenty-four- hour urinary total protein (24 h UTP) was detected at the end of the 4th, 8th, 12th and 16th week of administration. After the last medication, the body mass, water intake, food intake, urine output, the levels of fasting blood glucose, serum creatinine (Scr) and blood urea nitrogen (BUN) as well as mRNA and protein expressions of P-cadherin, nephrin, α -smooth muscle actin (α-SMA), Wilms’ tumor gene 1 (WT1), transforming growth factor-β1( TGF-β1) and type Ⅳ collagen (Col-Ⅳ) in renal tissue were determined. The pathological and morphological changes in renal tissue were observed and the thickness of the glomerular basement membrane was determined. RESULTS Compared with the model group, 24 h UTP of rats was significantly decreased in modified Taohong siwu decoction group since the 8th weekend (P<0.05); the body weight of rats increased significantly, but the amount of water intake and urine decreased significantly; Scr and BUN level, mRNA expression of α-SMA, mRNA and protein expressions of TGF-β1 and Col-Ⅳ were significantly reduced, while the mRNA expressions of P-cadherin, nephrin and WT1 were increased significantly (P<0.05); the protein deposition of α-SMA was reduced, protein depositions of P-cadherin, nephrin and WT1 were increased; the pathological damage and fibrosis of renal tissue were relieved; the thickness of glomerular basement membrane was decreased significantly (P<0.05). CONCLUSIONS Taohong siwu decoction modified granules can inhibit the EMT of podocyte in DKD model rats, and alleviate renal pathological damage and podocyte damage, thus protecting renal function, and delaying the process of renal fibrosis.
7.Effects of Taohong siwu decoction modified granules on podocyte epithelial-mesenchymal-transition and renal fibrosis in rats with diabetic kidney disease
Lu BAI ; Shipeng SHEN ; Su WU ; Shuai GUO ; Maodong LIU
China Pharmacy 2024;35(11):1327-1333
OBJECTIVE To investigate the effects of Taohong siwu decoction modified granules on podocyte epithelial- mesenchymal-transition (EMT) and renal fibrosis in diabetic kidney disease (DKD) model rats. METHODS Eight rats were selected as normal group (ordinary feed); the remaining rats were given a high-glucose and high-fat diet combined with intraperitoneal injection of streptozotocin (35 mg/kg) to induce the DKD model. Model rats were randomly divided into model group, irbesartan group [positive control, 13.5 mg/(kg·d)] and modified Taohong siwu decoction group [6.48 g/(kg·d)], with 8 rats in each group. All groups were given relevant medicine intragastrically, once a day, for 16 consecutive weeks. Twenty-four- hour urinary total protein (24 h UTP) was detected at the end of the 4th, 8th, 12th and 16th week of administration. After the last medication, the body mass, water intake, food intake, urine output, the levels of fasting blood glucose, serum creatinine (Scr) and blood urea nitrogen (BUN) as well as mRNA and protein expressions of P-cadherin, nephrin, α -smooth muscle actin (α-SMA), Wilms’ tumor gene 1 (WT1), transforming growth factor-β1( TGF-β1) and type Ⅳ collagen (Col-Ⅳ) in renal tissue were determined. The pathological and morphological changes in renal tissue were observed and the thickness of the glomerular basement membrane was determined. RESULTS Compared with the model group, 24 h UTP of rats was significantly decreased in modified Taohong siwu decoction group since the 8th weekend (P<0.05); the body weight of rats increased significantly, but the amount of water intake and urine decreased significantly; Scr and BUN level, mRNA expression of α-SMA, mRNA and protein expressions of TGF-β1 and Col-Ⅳ were significantly reduced, while the mRNA expressions of P-cadherin, nephrin and WT1 were increased significantly (P<0.05); the protein deposition of α-SMA was reduced, protein depositions of P-cadherin, nephrin and WT1 were increased; the pathological damage and fibrosis of renal tissue were relieved; the thickness of glomerular basement membrane was decreased significantly (P<0.05). CONCLUSIONS Taohong siwu decoction modified granules can inhibit the EMT of podocyte in DKD model rats, and alleviate renal pathological damage and podocyte damage, thus protecting renal function, and delaying the process of renal fibrosis.
8.Key role of interferon regulatory factor 1(IRF-1)in regulating liver disease:progress and outlook
CHEN TAO ; LI SHIPENG ; DENG DEWEN ; ZHANG WEIYE ; ZHANG JIANJUN ; SHEN ZHONGYANG
Journal of Zhejiang University. Science. B 2024;25(6):451-470
Interferon regulatory factor 1(IRF-1)is a member of the IRF family.It is the first transcription factor to be identified that could bind to the interferon-stimulated response element(ISRE)on the target gene and displays crucial roles in the interferon-induced signals and pathways.IRF-1,as an important medium,has all of the advantages of full cell cycle regulation,cell death signaling transduction,and reinforcing immune surveillance,which are well documented.Current studies indicate that IRF-1 is of vital importance to the occurrence and evolution of multifarious liver diseases,including but not limited to inhibiting the replication of the hepatitis virus(A/B/C/E),alleviating the progression of liver fibrosis,and aggravating hepatic ischemia-reperfusion injury(HIRI).The tumor suppression of IRF-1 is related to the clinical characteristics of liver cancer patients,which makes it a potential indicator for predicting the prognosis and recurrence of liver cancer;additionally,the latest studies have revealed other effects of IRF-1 such as protection against alcoholic/non-alcoholic fatty liver disease(AFLD/NAFLD),cholangiocarcinoma suppression,and uncommon traits in other liver diseases that had previously received little attention.Intriguingly,several compounds and drugs have featured a protective function in specific liver disease models in which there is significant involvement of the IRF-1 signal.In this paper,we hope to propose a prospective research basis upon which to help decipher translational medicine applications of IRF-1 in liver disease treatment.
9.Intervention effect of Tongxinluo capsule on renal fibrosis in diabetic nephropathy rats
Lu BAI ; Shipeng SHEN ; Qian WANG ; Min LI ; Shuai GUO ; Maodong LIU
China Pharmacy 2023;34(13):1584-1589
OBJECTIVE To explore the intervention effect and related mechanism of Tongxinluo capsule on renal fibrosis in rats with diabetic nephropathy (DN). METHODS Eight rats were selected as control group (ordinary feed), the remaining rats were given high-glucose and high-fat diet combined with ip injection of streptozotocin (35 mg/kg) to induce DN model. Model rats were randomly divided into model group (purified water), irbesartan group (positive control, 14.12 mg/kg) and Tongxinluo capsule group (0.3 g/kg), including 12 rats in the model group and 11 rats for each of the other two groups. All groups were given relevant medicine or water intragastrically, once a day, for 16 consecutive weeks. After the last medication, fasting blood glucose and 24 h urinary total protein (24 h UTP) were detected. Pathological changes in renal cortex of rats in each group were observed. Serum levels of tissue-type plasminogen activator (PA) and plasminogen activator inhibitor 1 (PAI-1) were measured. mRNA expressions of transforming growth factor-β(1 TGF-β1), type Ⅳ collagen(COL-Ⅳ), Wnt4 and β-catenin in renal cortex of rats were detected. The protein depositions or expressions of TGF-β1, COL-Ⅳ, focal adhesion kinase (FAK), integrin-linked kinase (ILK), E-cadherin, PA, PAI-1, Wnt4 and β-catenin in renal cortex of rats were observed or determined. RESULTS Compared with model group, 24 h UTP of rats in Tongxinluo capsule group were all significantly reduced (P<0.05); pathological damage and fibrosis of renal cortex were relieved; the expression of PA in serum and renal cortex was significantly increased, while PAI-1 level was significantly reduced (P<0.05); the depositions of COL-Ⅳ and TGF-β1 in renal cortex were all reduced, and corresponding mRNA expression was decreased significantly (P<0.05); the depositions of ILK and FAK were decreased, while the deposition of E-cadherin was increased; protein and mRNA expressions of Wnt4 and β-catenin were significantly reduced (P<0.05). CONCLUSIONS Tongxinluo capsule can relieve pathological damage to renal tissue and renal fibrosis of DN model rats, and reduce extracellular matrix deposition. The mechanism may be related to regulation of fibrinolytic system activity, the decrease of ILK and FAK expression, and inhibition of Wnt/β-catenin signaling pathway.
10.Application effect of supportive nursing in patients with heart failure
Jun WU ; Fei SHEN ; Shipeng DANG ; Yunle WANG
Chinese Journal of Modern Nursing 2022;28(11):1527-1529
Objective:To explore the application effect of supportive nursing in patients with heart failure.Methods:Using the convenient sampling method, a total of 86 heart failure patients who were admitted to Wuxi People's Hospital from October 2019 to March 2021 were selected as the research objects. According to the random number table method, they were divided into the control group and the observation group, with 43 cases in each group. The control group was given routine nursing, while the observation group was given supportive nursing intervention. The scores of General Self-Efficacy Scale (GSES) and Generic Quality Life Inventory-74 (GQOL-74) were compared between the two groups before and after the intervention.Results:After intervention, the GSES score and GQOL-74 dimension scores of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Supportive nursing can improve self-efficacy and quality of life in patients with heart failure.

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