1.Clinical observation of Cervus and Cucumis Polypeptide for Injection in the treatment of knee osteoarthritis
Shunda LI ; Lu XU ; Zhen WANG ; Yong HE ; Yushan ZHANG
Chinese Journal of Biochemical Pharmaceutics 2017;37(9):42-43
Objective To investigate and analyze the efficacy of Cervus and Cucumis Polypeptide for Injection in the treatment of osteoarthritis of the knee. Methods 100 patients with osteoarthritis of knee joint treated in Xinchang people's hospital from February 2015 to May 2017 were selected and randomly divided into the control group and the experimental group, with 50 patients in each group. The control group were treated with oral glucosamine capsules in the treatment of the experimental group, Cervus and Cucumis Polypeptide for Injection palliative treatment, 250 mL saline plus 25g guguatiquwu, oral Nimeilishu capsule. The treatment time of the 2 groups was one month. The therapeutic effects of the experimental group and the control group were compared and analyzed. Results After the corresponding treatment, 4 patients in the experimental group were invalid, 20 cases were effective, and 26 cases were effective. In the control group, 13 patients were ineffective. The effective rate of the experimental group was 92%, which was significantly higher than that of the control group (P<0.05). The IL-1 of the knee joint fluid in the experimental group was (8.01±1.72), and the IL-1 of the knee fluid in the control group was (7.08±0.97). The level of IL-1 in the knee joint fluid of the experimental group was significantly higher than that of the control group, with statistical difference (P<0.05). Conclusion Cervus and Cucumis Polypeptide for Injection is effective in the treatment of osteoarthritis of the knee, and can significantly improve the efficiency of treatment,.
2.The effects of gastrodin on TLR4 expression in microglia induced by ischemia and hypoxia
Shunda LI ; Yongqiang ZHAO ; Xueke YANG ; Shuyu CHEN ; Yan YANG ; Yun YUAN
Chinese Journal of Neuroanatomy 2024;40(1):50-56
Objective:To determine the effect of gastrodin(GAS)on toll-like receptor 4(TLR4)expression in mi-croglia after hypoxic-ischemic brain damage.Methods:Hypoxia-ischemic brain damage(HIBD)model was established in neonatal rat in vivo.Thirty 3 d SD rats of were randomly divided into there groups:Sham group,HIBD model group,HIBD model+gastrodin intervention group(HIBD+G).Oxygen glucose deprivation(OGD)model was established in BV2 cells in vitro,Control group(Control),oxygen glucose deprivation group(OGD),OGD+gastrodin intervention group(OGD+G)were randomly set in vitro.Both Western Blot and immunofluorescence staining techniques were used to detect the expression of TLR4 in cells of each group in vitro and in the left corpus callosum region in vivo.Results:The expression of TLR4 was significantly increased in OGD-induced microglia.After gastrodin intervention,TLR4 expression was decreased significantly(P<0.05).Conclusion:GAS can inhibit the expression of TLR4 in activated microglia and thus play a neuroprotective role in HIBD.
3.Genetically-modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting
Xueshuai WAN ; Karin WISSKIRCHEN ; Tao JIN ; Lu YANG ; Xiaorui WANG ; Xiang’an WU ; Fang LIU ; Yu WU ; Christy MA ; Yong PANG ; Qi LI ; Ke ZHANG ; Ulrike PROTZER ; Shunda DU
Clinical and Molecular Hepatology 2024;30(4):735-755
Background/Aims:
Hepatitis B virus (HBV)-DNA integration in HBV-related hepatocellular carcinoma (HBV-HCC) can be targeted by HBV-specific T cells. SCG101 is an autologous, HBV-specific T-cell product expressing a T-cell receptor (TCR) after lentiviral transduction recognizing the envelope-derived peptide (S20-28) on HLA-A2. We here validated its safety and efficacy preclinically and applied it to an HBV-related HCC patient (NCT05339321).
Methods:
Good Manufacturing Practice-grade manufactured cells were assessed for off-target reactivity and functionality against hepatoma cells. Subsequently, a patient with advanced HBV-HCC (Child-Pugh class A, Barcelona Clinic Liver Cancer stage B, Eastern Cooperative Oncology Group performance status 0, hepatitis B e antigen-, serum hepatitis B surface antigen [HBsAg]+, HBsAg+ hepatocytes 10%) received 7.9×107 cells/kg after lymphodepletion. Safety, T-cell persistence, and antiviral and antitumor efficacy were evaluated.
Results:
SCG101, produced at high numbers in a closed-bag system, showed HBV-specific functionality against HBV-HCC cells in vitro and in vivo. Clinically, treatment was well tolerated, and all adverse events, including transient hepatic damage, were reversible. On day 3, ALT levels increased to 1,404 U/L, and concurrently, serum HBsAg started decreasing by 3.84 log10 and remained <1 IU/mL for over six months. HBsAg-expressing hepatocytes in liver biopsies were undetectable after 73 days. The patient achieved a partial response according to modified RECIST with a >70% reduction in target lesion size. Transferred T cells expanded, developed a stem cell-like memory phenotype, and were still detectable after six months in the patient’s blood.
Conclusions
SCG101 T-cell therapy showed encouraging efficacy and safety in preclinical models and in a patient with primary HBV-HCC and concomitant chronic hepatitis B with the capability to eliminate HBsAg+ cells and achieve sustained tumor control after single dosing.
4.Genetically-modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting
Xueshuai WAN ; Karin WISSKIRCHEN ; Tao JIN ; Lu YANG ; Xiaorui WANG ; Xiang’an WU ; Fang LIU ; Yu WU ; Christy MA ; Yong PANG ; Qi LI ; Ke ZHANG ; Ulrike PROTZER ; Shunda DU
Clinical and Molecular Hepatology 2024;30(4):735-755
Background/Aims:
Hepatitis B virus (HBV)-DNA integration in HBV-related hepatocellular carcinoma (HBV-HCC) can be targeted by HBV-specific T cells. SCG101 is an autologous, HBV-specific T-cell product expressing a T-cell receptor (TCR) after lentiviral transduction recognizing the envelope-derived peptide (S20-28) on HLA-A2. We here validated its safety and efficacy preclinically and applied it to an HBV-related HCC patient (NCT05339321).
Methods:
Good Manufacturing Practice-grade manufactured cells were assessed for off-target reactivity and functionality against hepatoma cells. Subsequently, a patient with advanced HBV-HCC (Child-Pugh class A, Barcelona Clinic Liver Cancer stage B, Eastern Cooperative Oncology Group performance status 0, hepatitis B e antigen-, serum hepatitis B surface antigen [HBsAg]+, HBsAg+ hepatocytes 10%) received 7.9×107 cells/kg after lymphodepletion. Safety, T-cell persistence, and antiviral and antitumor efficacy were evaluated.
Results:
SCG101, produced at high numbers in a closed-bag system, showed HBV-specific functionality against HBV-HCC cells in vitro and in vivo. Clinically, treatment was well tolerated, and all adverse events, including transient hepatic damage, were reversible. On day 3, ALT levels increased to 1,404 U/L, and concurrently, serum HBsAg started decreasing by 3.84 log10 and remained <1 IU/mL for over six months. HBsAg-expressing hepatocytes in liver biopsies were undetectable after 73 days. The patient achieved a partial response according to modified RECIST with a >70% reduction in target lesion size. Transferred T cells expanded, developed a stem cell-like memory phenotype, and were still detectable after six months in the patient’s blood.
Conclusions
SCG101 T-cell therapy showed encouraging efficacy and safety in preclinical models and in a patient with primary HBV-HCC and concomitant chronic hepatitis B with the capability to eliminate HBsAg+ cells and achieve sustained tumor control after single dosing.
5.Genetically-modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting
Xueshuai WAN ; Karin WISSKIRCHEN ; Tao JIN ; Lu YANG ; Xiaorui WANG ; Xiang’an WU ; Fang LIU ; Yu WU ; Christy MA ; Yong PANG ; Qi LI ; Ke ZHANG ; Ulrike PROTZER ; Shunda DU
Clinical and Molecular Hepatology 2024;30(4):735-755
Background/Aims:
Hepatitis B virus (HBV)-DNA integration in HBV-related hepatocellular carcinoma (HBV-HCC) can be targeted by HBV-specific T cells. SCG101 is an autologous, HBV-specific T-cell product expressing a T-cell receptor (TCR) after lentiviral transduction recognizing the envelope-derived peptide (S20-28) on HLA-A2. We here validated its safety and efficacy preclinically and applied it to an HBV-related HCC patient (NCT05339321).
Methods:
Good Manufacturing Practice-grade manufactured cells were assessed for off-target reactivity and functionality against hepatoma cells. Subsequently, a patient with advanced HBV-HCC (Child-Pugh class A, Barcelona Clinic Liver Cancer stage B, Eastern Cooperative Oncology Group performance status 0, hepatitis B e antigen-, serum hepatitis B surface antigen [HBsAg]+, HBsAg+ hepatocytes 10%) received 7.9×107 cells/kg after lymphodepletion. Safety, T-cell persistence, and antiviral and antitumor efficacy were evaluated.
Results:
SCG101, produced at high numbers in a closed-bag system, showed HBV-specific functionality against HBV-HCC cells in vitro and in vivo. Clinically, treatment was well tolerated, and all adverse events, including transient hepatic damage, were reversible. On day 3, ALT levels increased to 1,404 U/L, and concurrently, serum HBsAg started decreasing by 3.84 log10 and remained <1 IU/mL for over six months. HBsAg-expressing hepatocytes in liver biopsies were undetectable after 73 days. The patient achieved a partial response according to modified RECIST with a >70% reduction in target lesion size. Transferred T cells expanded, developed a stem cell-like memory phenotype, and were still detectable after six months in the patient’s blood.
Conclusions
SCG101 T-cell therapy showed encouraging efficacy and safety in preclinical models and in a patient with primary HBV-HCC and concomitant chronic hepatitis B with the capability to eliminate HBsAg+ cells and achieve sustained tumor control after single dosing.
6.Genetically-modified, redirected T cells target hepatitis B surface antigen-positive hepatocytes and hepatocellular carcinoma lesions in a clinical setting
Xueshuai WAN ; Karin WISSKIRCHEN ; Tao JIN ; Lu YANG ; Xiaorui WANG ; Xiang’an WU ; Fang LIU ; Yu WU ; Christy MA ; Yong PANG ; Qi LI ; Ke ZHANG ; Ulrike PROTZER ; Shunda DU
Clinical and Molecular Hepatology 2024;30(4):735-755
Background/Aims:
Hepatitis B virus (HBV)-DNA integration in HBV-related hepatocellular carcinoma (HBV-HCC) can be targeted by HBV-specific T cells. SCG101 is an autologous, HBV-specific T-cell product expressing a T-cell receptor (TCR) after lentiviral transduction recognizing the envelope-derived peptide (S20-28) on HLA-A2. We here validated its safety and efficacy preclinically and applied it to an HBV-related HCC patient (NCT05339321).
Methods:
Good Manufacturing Practice-grade manufactured cells were assessed for off-target reactivity and functionality against hepatoma cells. Subsequently, a patient with advanced HBV-HCC (Child-Pugh class A, Barcelona Clinic Liver Cancer stage B, Eastern Cooperative Oncology Group performance status 0, hepatitis B e antigen-, serum hepatitis B surface antigen [HBsAg]+, HBsAg+ hepatocytes 10%) received 7.9×107 cells/kg after lymphodepletion. Safety, T-cell persistence, and antiviral and antitumor efficacy were evaluated.
Results:
SCG101, produced at high numbers in a closed-bag system, showed HBV-specific functionality against HBV-HCC cells in vitro and in vivo. Clinically, treatment was well tolerated, and all adverse events, including transient hepatic damage, were reversible. On day 3, ALT levels increased to 1,404 U/L, and concurrently, serum HBsAg started decreasing by 3.84 log10 and remained <1 IU/mL for over six months. HBsAg-expressing hepatocytes in liver biopsies were undetectable after 73 days. The patient achieved a partial response according to modified RECIST with a >70% reduction in target lesion size. Transferred T cells expanded, developed a stem cell-like memory phenotype, and were still detectable after six months in the patient’s blood.
Conclusions
SCG101 T-cell therapy showed encouraging efficacy and safety in preclinical models and in a patient with primary HBV-HCC and concomitant chronic hepatitis B with the capability to eliminate HBsAg+ cells and achieve sustained tumor control after single dosing.
7.Construction and practice of standardized workflow and informatization platform for centralized volume-based procurement
Yingying WEI ; Dong LIU ; Xiongzhang YIN ; Hongbin YANG ; Guofang HE ; Fei’e LI ; Shunda CHEN ; Xuepeng GONG
China Pharmacy 2022;33(9):1136-1140
OBJECTIVE To sum marize the pro cedure and informatization construction of centralized volume-based procurement(VBP)in our hospital ,in order to give references for normal development of centralized VBP. METHODS The standardized workflow system was established ,including using flow chart method to establish standardized workflow ,carrying out procedure training and inspection of procedure implementation , and continuously conducting procedure optimization. The information system was developed for the task links that needed a lot of calculation to improve the automation level of information processing. RESULTS & CONCLUSIONS Eight specific work procedures were established in our hospital ,including the work procedures of submitting the demand data of centralized VBP and the implementation of centralized VBP ,and has taken measures such as procedure training ,establishing supervision and inspection system and using auxiliary means to promote the implementation of the procedure ,so as to optimize the procedure and work form. An informatization platform for the clinical task allocation of the agreed purchase quantity of centralized VBP and a supervision platform for the daily use of VBP were also established in our hospital,then the two tasks with a large amount of calculation could be finished. Standardized workflow system and informatization platform construction has improved the operation and supervision efficiency of centralized VBP in our hospital ,ensured the completion of centralized purchase tasks and saved human resources ,which has a certain promotion value.
8.Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria(2024)
Miao CHEN ; Chen YANG ; Ziwei LIU ; Wei CAO ; Bo ZHANG ; Xin LIU ; Jingnan LI ; Wei LIU ; Jie PAN ; Jian WANG ; Yuehong ZHENG ; Yuexin CHEN ; Fangda LI ; Shunda DU ; Cong NING ; Limeng CHEN ; Cai YUE ; Jun NI ; Min PENG ; Xiaoxiao GUO ; Tao WANG ; Hongjun LI ; Rongrong LI ; Tong WU ; Bing HAN ; Shuyang ZHANG ; MULTIDISCIPLINE COLLABORATION GROUP ON RARE DISEASE AT PEKING UNION MEDICAL COLLEGE HOSPITAL
Medical Journal of Peking Union Medical College Hospital 2024;15(5):1011-1028
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the