1.Progress on carboxyl-substituted phthalocyanine photosen-sitizers and their drug delivery systems for photodynamic therapy.
Dan SHEN ; Hongjie HUANG ; Jincan CHEN ; Bowen LI ; Zhuo CHEN
Journal of Zhejiang University. Medical sciences 2025;54(4):500-510
Research in photodynamic therapy (PDT) primarily focuses on enhancing light penetration depth, improving oxygen supply, and optimizing photosensitizer delivery. Notably, the delivery efficiency of the photosensitizer is crucial for therapeutic efficacy. Carboxyl-substituted phthalocyanines, as important photosensitizing molecules, possess unique chemical modification sites that enable direct targeted delivery or integration into diverse delivery systems. Their synthesis predominantly employs mixed- or cross-condensation, selective synthesis, and axial modification strategies to introduce carboxyl groups. However, their inherent hydrophobicity significantly hinders effective delivery. To address this limitation, modifications with peptides or quaternary ammonium salt derivatives may facilitate precise delivery to tumor cells and pathogens. With advances in nanotechnology, carboxyl-substituted phthalocyanines can serve as key photosensitizer modules, effectively integrated into nanomaterials such as biomacromolecules, inorganic metals, and polymers for both active and passive delivery. Recently, researchers have exploited the π-π stacking and other intermolecular forces among carboxyl-substituted phthalocyanine molecules to drive their self-assembly into nano-micelles, enabling carrier-free delivery or co-delivery with other therapeutic agents for synergistic effects. This review systematically outlines the synthesis strategies for carboxyl-substituted phthalo-cyanines. Taking mono-carboxyl-substituted zinc phthalocyanine as a model molecule, the performance of three delivery modalities were compared: single-molecule targeted delivery, nanocarrier-encapsulated delivery, and carrier-free self-assembled delivery, in terms of PDT efficacy, biocompatibility, and imaging-guided tracing capabilities, to provide a systematic technical framework for the rational design of novel modular photosensitizers and to advance the clinical translation of PDT in precision oncology and anti-infective therapy.
Photochemotherapy/methods*
;
Indoles/administration & dosage*
;
Isoindoles
;
Photosensitizing Agents/administration & dosage*
;
Drug Delivery Systems
;
Humans
2.Clinical Effects of Pomalidomide-Based Regimen in the Treatment of Relapsed and Refractory Multiple Myeloma.
Man YANG ; Yan HUANG ; Ling-Xiu ZHANG ; Guo-Qing LYU ; Lu-Yao ZHU ; Xian-Kai LIU ; Yan GUO
Journal of Experimental Hematology 2025;33(2):431-436
OBJECTIVE:
To study the clinical effects of pomalidomide-based regimen in the treatment of relapsed and refractory multiple myeloma (RRMM).
METHODS:
60 patients with RRMM in hematology department of the First Affiliated Hospital of Xinxiang Medical University from November 2020 to January 2023 were selected. Among them, 15 cases were treated with PDD regimen (pomalidomide + daratumumab + dexamethasone), and 45 cases were treated with PCD regimen (pomalidomide + cyclophosphamide + dexamethasone). The clinical effects were evaluated.
RESULTS:
The median number of treatment cycles for the entire cohort was 5 (2-11), with an overall response rate (ORR) of 75.0%. The ORR of patients treated with PDD regimen was 73.3%, while the ORR of patients treated with PCD regimen was 75.6%. The ORR of 46 patients with non high-risk cytogenetic abnormalities (non-HRCA) was 86.9%, significantly higher than the 35.7% of 14 patients with HRCA (χ2 =15.031, P < 0.05). The median PFS for all patients was 8.0(95%CI : 6.8-9.1) months and the median OS was 14.0 (95%CI : 11.3-16.7) months. Among patients treated with PDD regimen, the PFS and OS of patients with non-HRCA were significantly higher than those of patients with HRCA [PFS: 7.0(95%CI : 4.6-9.3) months vs 4.0(95%CI : 3.1-4.8) months, χ2 =5.120, P < 0.05; OS: not reached vs 6.0(95%CI : 1.1-10.9) months, χ2 =9.870, P < 0.05]. Among patients treated with PCD regimen, the PFS and OS of patients with non-HRCA were significantly higher than those of patients with HRCA [PFS: 9.0(95%CI : 6.2-11.8) months vs 6.0(95%CI : 5.4-6.6) months, χ2=14.396, P < 0.05; OS: not reached vs 11.0(95%CI : 6.4-15.6) months, χ2 =7.471, P < 0.05].
CONCLUSION
The pomalidomide-based regimen has a good clinical effect and safety in the treatment of RRMM.
Humans
;
Multiple Myeloma/drug therapy*
;
Thalidomide/administration & dosage*
;
Dexamethasone/therapeutic use*
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Female
;
Male
;
Middle Aged
;
Recurrence
;
Aged
;
Cyclophosphamide/therapeutic use*
;
Treatment Outcome
;
Antibodies, Monoclonal
3.Efficacy of Pomalidomide in Multiple Myeloma with Extramedullary Disease.
Ping-Ping ZHANG ; Meng WANG ; Yan-Ping WU ; Jia-Jia LI
Journal of Experimental Hematology 2025;33(2):463-468
OBJECTIVE:
To investigate the efficacy and safety of pomalidomide in the treatment of multiple myeloma (MM) with extramedullary disease (EMD).
METHODS:
The clinical data of 40 pomalidomide-based multiple myeloma patients with extramedullary disease admitted to the Department of Hematology, the First Affiliated Hospital of Bengbu Medical College from February 2019 to August 2023 were retrospectively analyzed.
RESULTS:
Among the 40 patients, 8 were newly diagnosed with EMD and 32 were refractory/relapsed EMD. There were 21 cases with bone-related extramedullary disease (EM-B) and 19 cases with soft tissue-related extramedullary disease (EM-S). Compared with the EM-B group, the EM-S group exhibited lower LDH levels, an elevation in LDH and a shorter progression-free survival(PFS) (11 months vs 21.5 months, P =0.0363). 32 patients completed 3 courses of treatment, and the short-term efficacy was evaluated. There was no significant difference in the rate of use of 3 or more drugs and ASCT treatment between NDMM group and RRMM group (87.50% vs 93.75%, P >0.05; 25.00% vs 15.63%, P >0.05). Compared with the RRMM group, the overall response rate (ORR) of the NDMM patients was significantly higher (83.33% vs 57.70%, P < 0.05). The deep remission rate (VGPR+CR) of the NDMM group was better than that of the RRMM group (50.00% vs 29.62%, P < 0.05), and the non-response rate (SD+PD) of the NDMM group was significantly lower than that of the R/RMM group (33.33% vs 65.38%, P < 0.05), while the partial remission rate (PR) and mortality rate of the NDMM were not significantly different from those of the RRMM group(P >0.05). With a median follow-up of 26 months, the median PFS was 19 months. Univariate analysis showed that EM-S, high-risk genetic abnormalities, induction therapy did not achieve partial response(PR) or better, and more than 2 lines of treatment failure were associated with shorter PFS. Multivariate analysis showed that the best response to induction therapy did not achieve PR or better, EM-S were an independent adverses prognostic factor for PFS. The results of safety analysis showed that 16 cases had hematological adverse events, including 3 cases of grade 3/4 and 13 cases of grade 1/2. The most common non-hematological adverse events were nausea, vomiting, fatigue and abdominal distension, which were mild and tolerable.
CONCLUSION
Pomalidomide-based chemotherapy is effective and well tolerated in MM patients with extramedullary disease.
Humans
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Multiple Myeloma/drug therapy*
;
Thalidomide/therapeutic use*
;
Retrospective Studies
;
Male
;
Female
;
Middle Aged
;
Aged
;
Treatment Outcome
;
Adult
4.Clinical efficacy and safety of vortioxetine as an adjuvant drug for patients with bipolar depression.
Chunxiao DAI ; Yaoyang FU ; Xuanwei LI ; Meihua LIN ; Yinbo LI ; Xiao LI ; Keke HUANG ; Chengcheng ZHOU ; Jian XIE ; Qingwei ZHAO ; Shaohua HU
Journal of Zhejiang University. Science. B 2025;26(1):26-38
OBJECTIVES:
Whether vortioxetine has a utility as an adjuvant drug in the treatment of bipolar depression remains controversial. This study aimed to validate the efficacy and safety of vortioxetine in bipolar depression.
METHODS:
Patients with bipolar Ⅱ depression were enrolled in this prospective, two-center, randomized, 12-week pilot trial. The main indicator for assessing treatment effectiveness was a Montgomery-Asberg Depression Rating Scale (MADRS) of ≥50%. All eligible patients initially received four weeks of lurasidone monotherapy. Patients who responded well continued to receive this kind of monotherapy. However, no-response patients were randomly assigned to either valproate or vortioxetine treatment for eight weeks. By comprehensively comparing the results of MADRS over a period of 4‒12 weeks, a systematic analysis was conducted to determine whether vortioxetine could be used as an adjuvant drug for treating bipolar depression.
RESULTS:
Thirty-seven patients responded to lurasidone monotherapy, and 60 patients were randomly assigned to the valproate or vortioxetine group for eight weeks. After two weeks of combined valproate or vortioxetine treatment, the MADRS score in the vortioxetine group was significantly lower than that in the valproate group. There was no difference in the MADRS scores between the two groups at 8 and 12 weeks. The incidence of side effects did not significantly differ between the valproate and vortioxetine groups. Importantly, three patients in the vortioxetine group appeared to switch to mania or hypomania.
CONCLUSIONS
This study suggested that lurasidone combination with vortioxetine might have potential benefits to bipolar II depression in the early stage, while disease progression should be monitored closely for the risk of switching to mania.
Humans
;
Bipolar Disorder/drug therapy*
;
Vortioxetine/therapeutic use*
;
Male
;
Female
;
Middle Aged
;
Adult
;
Valproic Acid/administration & dosage*
;
Lurasidone Hydrochloride/administration & dosage*
;
Prospective Studies
;
Treatment Outcome
;
Pilot Projects
;
Drug Therapy, Combination
;
Sulfides/therapeutic use*
;
Antidepressive Agents/therapeutic use*
5.Treatment of Idiopathic Multicentric Castleman's Disease With Sequential Thalidomide-Cyclophosphamide-Prednisone After Siltuximab:Report of One Case.
Yue DANG ; Jian LI ; Ya-Ping LUO ; Lu ZHANG
Acta Academiae Medicinae Sinicae 2025;47(3):483-486
Castleman's disease is a rare polyclonal lymphoproliferative disorder.This article reports the diagnosis and treatment of a 45-year-old female patient with idiopathic multicentric Castleman's disease.The patient presented recurrent fever,enlarged lymph nodes,and elevated levels of inflammation markers.After multiple serological examinations and tissue biopsies,she was diagnosed with hyaline vascular-type Castleman's disease.Initially,the patient received siltuximab targeting interleukin-6,which significantly improved her condition.Considering the cost and convenience of long-term treatment,she subsequently switched the therapy to an oral treatment regimen of thalidomide,cyclophosphamide,and prednisone (TCP),which maintained disease control.This report aims to highlight the diagnostic complexity and diversity of treatment options for idiopathic multicentric Castleman's disease,demonstrating the potential of the TCP regimen as a cost-effective treatment choice.
Humans
;
Castleman Disease/drug therapy*
;
Female
;
Middle Aged
;
Thalidomide/therapeutic use*
;
Prednisone/therapeutic use*
;
Cyclophosphamide/therapeutic use*
;
Antibodies, Monoclonal/administration & dosage*
7.Predictors of Hematologic Responses in Patients with Non-Transfusion-Dependent β-Thalassemia Receiving Thalidomide Therapy.
Kun YANG ; Xiao-Lin YIN ; Xiao-Dong LIU ; Fang HUA ; Wei PENG ; Lan LI ; Kun CHEN ; Jin ZHANG ; Shan LUO ; Jian XIAO
Journal of Experimental Hematology 2022;30(5):1519-1526
OBJECTIVE:
To explore the predictors of hematologic responses of non-transfusion-dependent β-thalassemia (NTDT) to thalidomide.
METHODS:
33 patients with NTDT who treated with thalidomide in the 923rd Hospital of the Joint Logistics Support Force of the People's Liberation Army from May 2016 to June 2019 were included in the study. The basic data, hematological indexes, degree of treatment response and genetic background of the patients were analyzed.
RESULTS:
The baseline fetal hemoglobin (HbF) level of main responders (MaR) was significantly higher than that of minor responders (MiR) and no responders (NR) (P=0.001). And the baseline HbF level was positively correlated with hemoglobin increment after treatment (r=0.601). Genetic background analysis showed that the frequencies of the genotype CT of HBG2 rs7482144 (P=0.031), the genotypes CT/CC (P=0.030) and the minor allele C (P=0.015) of HBS1L-MYB rs9399137, the genotypes AT/TT (P=0.030) and the minor allele T (P=0.028) of HBS1L-MYB rs4895440, the genotypes AG/GG (P=0.030) and the minor allele G (P=0.028) of HBS1L-MYB rs4895441 (P=0.030) in MaR group were significantly higher than those in MiR and NR groups. Comparing the area under the ROC curve (AUC) of the above indicators to predict the main response, the results demonstrated that the predictive value of baseline HbF level was significantly better than rs7482144 (0.91 vs 0.72, P=0.003), rs9399137 (0.91 vs 0.74, P=0.022), rs4895440 (0.91 vs 0.74, P=0.023) and rs4895441 (0.91 vs 0.74, P=0.023), but there was no significant difference in the predictive value between combined single nucleotide polymorphisms (SNPs) (0.91 vs 0.88, P=0.658)and baseline HbF combined SNPs (0.91 vs 0.97, P=0.132). The AUC value of baseline HbF predicting the efficacy of thalidomide as the main response was 0.91, the cut-off value was 27.4%, the sensitivity was 100%, and the specificity was 58.3% (P=0.001).
CONCLUSION
The hematologic response of NTDT to thalidomide is variable and complex. Compared to genetic background, baseline HbF may be a simpler and more efficient tool to predict efficacy response.
Fetal Hemoglobin/genetics*
;
Humans
;
MicroRNAs
;
Polymorphism, Single Nucleotide
;
Repressor Proteins/genetics*
;
Thalidomide/therapeutic use*
;
beta-Thalassemia/genetics*
8.A randomized controlled trial of indobufen versus aspirin in the prevention of bridging restenosis after coronary artery bypass grafting.
Chen BAI ; Jing Xing LI ; Yang YU ; Rui LIU ; Ming Xin GAO ; Fan ZHANG ; Hai Yang LI
Chinese Journal of Cardiology 2022;50(5):466-470
Objective: To compare the efficacy and safety between indobufen and aspirin in the prevention of restenosis of bridge vessels at 1 year after off-pump coronary artery bypass grafting. Methods: This study was a prospective cohort study. We selected 152 patients who received coronary artery bypass grafting in Beijing Anzhen Hospital from December 2016 to December 2018. Patients were divided into the indobufen group and the aspirin group. Patients in the aspirin group were treated with aspirin and clopidogrel, and patients in the indobufen group were treated with indobufen and clopidogrel. During the 1-year follow-up, the rate of restenosis of saphenous vein bridge and internal mammary artery bridge, the rate of adverse cardiac events and adverse reactions were compared between the two groups. The levels of fibrinogen (FIB), D-dimer (D-D), thrombomodulin (TM) and thrombin-activatable fibrinolysis inhibitor (TAFI) were compared before and after antiplatelet therapy. Results: There were 76 cases in the indobufen group, including 57 males (75.0%), aged (60.3±6.6) years. There were 76 cases in the aspirin group, including 62 males (81.6%), aged (59.7±7.2) years. Baseline data were comparable between the two groups (P>0.05). During the follow-up, 3 cases were lost to follow up. Follow-up was completed in 74 patients in the indobufen group and 75 in the aspirin group. A total of 268 bridging vessels were grafted in the indobufen group and 272 in the aspirin group. One year after surgery, the patency rates of great saphenous vein bridge and internal mammary artery bridge were 94.5% (189/200) and 97.1% (66/68) in the indobuphen group, and 91.3% (189/207) and 96.9% (63/65) in the aspirin group, respectively. There was no significant difference in patency rate of great saphenous vein bridge and internal mammary artery bridge between the two groups (χ²=0.282, 0.345, P>0.05). The total incidence of adverse cardiac events was 5.4% (4/74) in the indobufen group and 6.7% (5/75) in the aspirin group (χ²=0.126, P>0.05). The overall incidence of gastrointestinal adverse reactions was significantly lower in the indobufen group than in the aspirin group (4.1% (3/74) vs. 13.3% (10/75), χ²=4.547, P<0.05). The levels of FIB, D-D, TM and TAFI in the two groups were lower than those before surgery (P<0.05), and there was no statistical significance between the two groups at baseline and post-operation (P>0.05). Conclusion: The efficacy of indobufen combined with clopidogrel in the prevention of 1-year restenosis after coronary artery bypass graft is similar to that of aspirin combined with clopidogrel, but the incidence of adverse reactions is lower, and the safety is higher in patients treated with indobufen combined with clopidogrel compared to aspirin combined with clopidogrel strategy.
Aspirin/therapeutic use*
;
Clopidogrel/therapeutic use*
;
Coronary Artery Bypass/adverse effects*
;
Drug Therapy, Combination
;
Humans
;
Isoindoles
;
Male
;
Phenylbutyrates
;
Platelet Aggregation Inhibitors/therapeutic use*
;
Prospective Studies
;
Treatment Outcome
9.Synergistic Mechanism of Interferon alpha-1b, Interleukin-2 and Thalidomide for Immune Regulation in Patients with Acute Myeloid Leukemia.
Rui-Hua MI ; Lin CHEN ; Ya-Lan ZHOU ; Dong-Bei LI ; Sha LIU ; Xiao-Jiao WANG ; Jia LIU ; Min-Fang WANG ; Xiao-Miao MA ; Zhi-Chun LI ; Hong-Mian ZHAO ; Yu-Lin XU ; Shu-Xia CHEN ; Hai-Ping YANG ; Zhi-Qiang GUO ; Chun-Lai LUAN ; Shu-Li GUO ; Qing-Lin SONG ; Xu-Dong WEI
Journal of Experimental Hematology 2021;29(1):26-31
OBJECTIVE:
To explore the synergistic immunomodulatory mechanism of interferon alpha-1b, interleukin-2 and thalidomide (ITI) regimen on patients with acute myeloid leukemia (AML).
METHODS:
Sixty eight untreated de novo or relapsed or refractory or maintenance therapy patients with AML admitted in the Affiliated Cancer Hospital of Zhengzhou University and the other 11 medical units from March 2016 to May 2019 were treated with ITI regimen. Peripheral blood specimen per patient was collected into EDTA-K3 anticoagulation vacuum tube before the administration of ITI and 3 months after the treatment; peripheral blood lymphocyte subsets and perforin and Granzyme B expression were analyzed by using flow cytometry; the levels of VEGF, IFN-γ, TNF-α and IL-6 in the plasma were detected by using a cytometric bead array. Thirty-five healthy subjects from the hospital physical examination centre were selected as normal controls.
RESULTS:
The ratio of CD4
CONCLUSION
The ITI regimen can raise the ratio of CD4
CD8-Positive T-Lymphocytes
;
Humans
;
Interferon-alpha
;
Interleukin-2
;
Leukemia, Myeloid, Acute/drug therapy*
;
Perforin
;
Thalidomide

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